Commentary

Disorders of hyperpigmentation—melasma, postinflammatory hyperpigmentation, lichen planus pigmentosus, erythema dyschromicum perstans, and pigmented contact dermatitis, among others—are common and challenging to treat. Although they can affect individuals of all skin types, they most commonly are seen in skin of color; in fact, dyspigmentation is one of the most common chief concerns for which individuals of color see a dermatologist.^1,2

For many years, hydroquinone (HQ) was one of the main options available for use as a lightening agent. Although effective, it has the risk of causing irritant dermatitis, potentially leading to further dyspigmentation, in addition to the risk of ochronosis with long-term use. It remains an important and useful treatment for pigmentary disorders, but there are numerous other lightening agents that also can be considered in the treatment of disorders of hyperpigmentation.

Herein, we provide recommendations for traditional and newer non-HQ lightening agents that can be considered when treating disorders of hyperpigmentation.

Traditional Non-HQ Lightening Agents

Retinoids—Retinoids are topical vitamin A derivatives that have been used safely and effectively for decades in the treatment of pigmentary disorders. Retinoids have multiple mechanisms of action in improving pigmentation. In addition to impeding tyrosinase induction, they inhibit pigment transfer to keratinocytes and lead to accelerated pigment loss due to epidermal shedding.³ Over-the-counter formulations include retinol, retinaldehyde, and adapalene. Prescription formulations include tretinoin and tazarotene in different strengths and vehicle formulations.⁴

Glycolic Acid—Glycolic acid is derived from sugarcane and is considered an α-hydroxy acid that leads to rapid desquamation of pigmented keratinocytes.⁵ Glycolic acid can not only be used in chemical peels but also in topical creams. It is the most common α-hydroxy acid peel and is sometimes paired with HQ and other topical lightening agents for increased penetration. Glycolic acid peels are available in concentrations of 20% to 70% and can be used at various depths. When used incorrectly, it can cause redness, burning, and even skin discoloration; however, when used at the proper concentrations and depth according to Fitzpatrick skin type, there typically are no notable adverse effects, and clinical results are favorable.

Kojic Acid—Kojic acid is a natural metabolite derived from fungi and is widely used in Asian countries. It works by inhibiting the catecholase activity of tyrosinase⁶ and typically is available in concentrations of 1% to 4%. A study suggested that a concentration of 1% or less typically is safe to use for prolonged periods without adverse effects. Although not more effective than HQ as a monotherapy, kojic acid has been shown to haveimproved efficacy when used in combination with other lightening agents.⁷

Azelaic Acid—Azelaic acid works by inhibiting tyrosinase, mitochondrial oxidoreductase activation, and DNA synthesis. It preferentially targets heavily pigmented melanocytes and possesses anti-inflammatory and antibacterial properties.⁸ A 20% concentration of azelaic acid was compared to HQ 4% for the treatment of melasma, and results revealed that the liposomal form of azelaic acid was considerably more tolerable than HQ 4% and also more effective.⁹

Licorice Extracts—Licorice extracts have been safely used in several cosmeceutical skin lightening products.¹⁰ The main active compounds in licorice root are glabridin and liquiritin, which work to disperse melanin. These compounds often are used topically at concentrations of 10% to 40%. A study by Amer and Metwalli¹¹ found that topical liquiritin produced a reduction of pigmentary intensity, with 80% of patients showing an excellent response, which was described as no difference between the previously pigmented area and the normal skin surrounding it.

Aloesin—Aloesin is a low-molecular-weight glycoprotein found in aloe vera plants. Its mechanism of action includes competitive inhibition of the dihydroxyphenylalanine oxidation site, resulting in the inhibition of tyrosinase.¹² It often is combined with arbutin for an enhanced lightening effect.

Niacinamide—Niacinamide is a form of vitamin B₃ that works by suppressing the transfer of melanosomes to keratinocytes.¹³ In addition to its skin lightening effects, it also is photoprotective and antimicrobial, and its tolerability and safety have led to its inclusion in many cosmeceutical and prescription products.¹⁴

Ascorbic Acid—Ascorbic acid affects the monopherase activity of tyrosinase, thus reducing the synthesis of melanin. It also serves as an antioxidant in the skin by preventing the production of free radicals that can induce melanogenesis.¹⁵ Although it tends to be well tolerated with a low adverse effect profile, its relative instability and varying permeability can present a challenge. It is less effective as a monotherapy, so it often is combined with other lightening ingredients for greater efficacy.

Corticosteroids—Topical corticosteroids are anti-inflammatory and impact melanogenesis, though the mechanism of action of the latter has not been fully elucidated.^16,17 Low- to mid-potency topical steroids often are used in conjunction with skin lightening products to diminish irritation and decrease inflammation.¹⁸ However, prolonged use of corticosteroids can lead to cutaneous adverse effects such as striae, hypopigmentation, and acne, as well as systemic side effects if there is sufficient absorption over time.

Soybean Extracts—Soybean extracts contain serine protease inhibitors that reduce the transfer of melanosomes into keratinocytes by inhibiting the PAR-2 (protease-activated receptor 2) pathway.^19,20

Ellagic Acid—Ellagic acid is found in common plants such as eucalyptus and strawberry as well as green tea.²¹ It works as an antioxidant and decreases melanogenesis through inhibition of tyrosinase activity.

Paper Mulberry—Paper mulberry extract comes from the roots of the Broussonetia papyrifera tree and functions by inhibiting tyrosinase activity. It is widely used in South Africa and Europe.²²

Resveratrol—Resveratrol is an ingredient extracted from Morus alba L and functions as an antimelanogentic agent by directly inhibiting tyrosinase as well as transcriptional and posttranscriptional processing of tyrosinase.²³ It also holds antiproliferative, anti-inflammatory, and antioxidant properties and has widely been used for antiaging and skin lightening purposes.²⁴

Newer Non-HQ Lightening Agents

Silymarin—Silymarin (also known as milk thistle [Silybum marianum]), is a polyphenolic flavonoid that possesses anticarcinogenic, antioxidant, and anti-inflammatory properties. It prevents melanin production in a dose-dependent manner by inhibiting levodopa (L-dopa) oxidation activity of tyrosinase and also reduces the expression of tyrosinase protein.²⁵ In combination with vitamins C and E and hexylresorcinol, silymarin has been found to reduce the effects of photodamage, brighten skin, improve evenness and lines, as well as improve global facial appearance.²⁶

Malassezin—Malassezin is an indole produced by Malessezia furfur yeast and has recently been investigated for melanogenesis suppression. Grimes et al²⁷ assessed the efficacy of topical malassezin in 7 patients with facial hyperpigmentation applied twice daily for 14 weeks. Punch biopsies were taken at weeks 0, 8, 14, and 22. Biopsies from weeks 8 and 14 demonstrated reduced epidermal melanin compared to baseline in all participants; however, at 22 weeks, biopsies showed no difference in melanin content compared to baseline, indicating a temporary process induced by the malassezin.²⁷ More clinical studies are needed to investigate this further.

N-acetyl-glucosamine—N-acetyl-glucosamine is an aminosaccharide that inhibits the glycosylation of tyrosinase as well as its function in melanogenesis.²⁸ It is synthesized and included in topical products for wound healing, rhytides, moisturization, and pigmentation disorders.

Topical Tranexamic Acid—Tranexamic acid traditionally has been used orally for the treatment of menorrhagia but also has been found to be beneficial as a therapy for hyperpigmentation and erythema. Tranexamic acid interferes with plasmin activity, thus indirectly inhibiting melanogenesis while also inhibiting angiogenesis by targeting vascular endothelial growth factor (VEGF) receptors.²⁹ It also leads to an increase in the levels of β-endorphin and μ-opioid receptors as well as the expression of estrogen receptor β on the surface of mast cells.³⁰ Its oral benefit led to the development of topical formulations, typically in 2% to 5% concentrations. It has proven particularly beneficial in the treatment of melasma due to its effects on improving pigmentation, erythema, and skin barrier function.³¹ Topical tranexamic acid has a relatively high safety profile, with minor side effects such as transient skin irritation and erythema being reported.³²

Cysteamine—Cysteamine inhibits tyrosinase, peroxidase, and chelating copper ions necessary for melanogenesis. It has proven to be effective in treating melasma and chronic severe postinflammatory hyperpigmentation when used in a 5% cream formulation.^33,34 Lima et al³⁵ were the first to compare the effects of topical cysteamine to HQ in the treatment of facial melasma. They found that the mean reduction in modified Melasma Area and Severity Index score was 24% for cysteamine and 41% for HQ after 60 days. There were no severe adverse effects with either treatment group.³⁵

Final Thoughts

Hydroquinone remains the gold standard for treatment of hyperpigmentation; however, its side-effect profile and risk of ochronosis with long-term use has ushered in various other safe and effective skin lightening agents that can be used as monotherapies or in combination with other lightening agents. Many of these products also can be used effectively with procedural treatments such as chemical peels, lasers, and microneedling for enhanced absorption and efficacy. As newer agents are developed, additional well-designed studies will be needed to determine their safety and efficacy in different skin types as well as their role in the treatment of pigmentary disorders.

Disorders of hyperpigmentation—melasma, postinflammatory hyperpigmentation, lichen planus pigmentosus, erythema dyschromicum perstans, and pigmented contact dermatitis, among others—are common and challenging to treat. Although they can affect individuals of all skin types, they most commonly are seen in skin of color; in fact, dyspigmentation is one of the most common chief concerns for which individuals of color see a dermatologist.^1,2

For many years, hydroquinone (HQ) was one of the main options available for use as a lightening agent. Although effective, it has the risk of causing irritant dermatitis, potentially leading to further dyspigmentation, in addition to the risk of ochronosis with long-term use. It remains an important and useful treatment for pigmentary disorders, but there are numerous other lightening agents that also can be considered in the treatment of disorders of hyperpigmentation.

Herein, we provide recommendations for traditional and newer non-HQ lightening agents that can be considered when treating disorders of hyperpigmentation.

Traditional Non-HQ Lightening Agents

Retinoids—Retinoids are topical vitamin A derivatives that have been used safely and effectively for decades in the treatment of pigmentary disorders. Retinoids have multiple mechanisms of action in improving pigmentation. In addition to impeding tyrosinase induction, they inhibit pigment transfer to keratinocytes and lead to accelerated pigment loss due to epidermal shedding.³ Over-the-counter formulations include retinol, retinaldehyde, and adapalene. Prescription formulations include tretinoin and tazarotene in different strengths and vehicle formulations.⁴

Glycolic Acid—Glycolic acid is derived from sugarcane and is considered an α-hydroxy acid that leads to rapid desquamation of pigmented keratinocytes.⁵ Glycolic acid can not only be used in chemical peels but also in topical creams. It is the most common α-hydroxy acid peel and is sometimes paired with HQ and other topical lightening agents for increased penetration. Glycolic acid peels are available in concentrations of 20% to 70% and can be used at various depths. When used incorrectly, it can cause redness, burning, and even skin discoloration; however, when used at the proper concentrations and depth according to Fitzpatrick skin type, there typically are no notable adverse effects, and clinical results are favorable.

Kojic Acid—Kojic acid is a natural metabolite derived from fungi and is widely used in Asian countries. It works by inhibiting the catecholase activity of tyrosinase⁶ and typically is available in concentrations of 1% to 4%. A study suggested that a concentration of 1% or less typically is safe to use for prolonged periods without adverse effects. Although not more effective than HQ as a monotherapy, kojic acid has been shown to haveimproved efficacy when used in combination with other lightening agents.⁷

Azelaic Acid—Azelaic acid works by inhibiting tyrosinase, mitochondrial oxidoreductase activation, and DNA synthesis. It preferentially targets heavily pigmented melanocytes and possesses anti-inflammatory and antibacterial properties.⁸ A 20% concentration of azelaic acid was compared to HQ 4% for the treatment of melasma, and results revealed that the liposomal form of azelaic acid was considerably more tolerable than HQ 4% and also more effective.⁹

Licorice Extracts—Licorice extracts have been safely used in several cosmeceutical skin lightening products.¹⁰ The main active compounds in licorice root are glabridin and liquiritin, which work to disperse melanin. These compounds often are used topically at concentrations of 10% to 40%. A study by Amer and Metwalli¹¹ found that topical liquiritin produced a reduction of pigmentary intensity, with 80% of patients showing an excellent response, which was described as no difference between the previously pigmented area and the normal skin surrounding it.

Aloesin—Aloesin is a low-molecular-weight glycoprotein found in aloe vera plants. Its mechanism of action includes competitive inhibition of the dihydroxyphenylalanine oxidation site, resulting in the inhibition of tyrosinase.¹² It often is combined with arbutin for an enhanced lightening effect.

Niacinamide—Niacinamide is a form of vitamin B₃ that works by suppressing the transfer of melanosomes to keratinocytes.¹³ In addition to its skin lightening effects, it also is photoprotective and antimicrobial, and its tolerability and safety have led to its inclusion in many cosmeceutical and prescription products.¹⁴

Ascorbic Acid—Ascorbic acid affects the monopherase activity of tyrosinase, thus reducing the synthesis of melanin. It also serves as an antioxidant in the skin by preventing the production of free radicals that can induce melanogenesis.¹⁵ Although it tends to be well tolerated with a low adverse effect profile, its relative instability and varying permeability can present a challenge. It is less effective as a monotherapy, so it often is combined with other lightening ingredients for greater efficacy.

Corticosteroids—Topical corticosteroids are anti-inflammatory and impact melanogenesis, though the mechanism of action of the latter has not been fully elucidated.^16,17 Low- to mid-potency topical steroids often are used in conjunction with skin lightening products to diminish irritation and decrease inflammation.¹⁸ However, prolonged use of corticosteroids can lead to cutaneous adverse effects such as striae, hypopigmentation, and acne, as well as systemic side effects if there is sufficient absorption over time.

Soybean Extracts—Soybean extracts contain serine protease inhibitors that reduce the transfer of melanosomes into keratinocytes by inhibiting the PAR-2 (protease-activated receptor 2) pathway.^19,20

Ellagic Acid—Ellagic acid is found in common plants such as eucalyptus and strawberry as well as green tea.²¹ It works as an antioxidant and decreases melanogenesis through inhibition of tyrosinase activity.

Paper Mulberry—Paper mulberry extract comes from the roots of the Broussonetia papyrifera tree and functions by inhibiting tyrosinase activity. It is widely used in South Africa and Europe.²²

Resveratrol—Resveratrol is an ingredient extracted from Morus alba L and functions as an antimelanogentic agent by directly inhibiting tyrosinase as well as transcriptional and posttranscriptional processing of tyrosinase.²³ It also holds antiproliferative, anti-inflammatory, and antioxidant properties and has widely been used for antiaging and skin lightening purposes.²⁴

Newer Non-HQ Lightening Agents

Silymarin—Silymarin (also known as milk thistle [Silybum marianum]), is a polyphenolic flavonoid that possesses anticarcinogenic, antioxidant, and anti-inflammatory properties. It prevents melanin production in a dose-dependent manner by inhibiting levodopa (L-dopa) oxidation activity of tyrosinase and also reduces the expression of tyrosinase protein.²⁵ In combination with vitamins C and E and hexylresorcinol, silymarin has been found to reduce the effects of photodamage, brighten skin, improve evenness and lines, as well as improve global facial appearance.²⁶

Malassezin—Malassezin is an indole produced by Malessezia furfur yeast and has recently been investigated for melanogenesis suppression. Grimes et al²⁷ assessed the efficacy of topical malassezin in 7 patients with facial hyperpigmentation applied twice daily for 14 weeks. Punch biopsies were taken at weeks 0, 8, 14, and 22. Biopsies from weeks 8 and 14 demonstrated reduced epidermal melanin compared to baseline in all participants; however, at 22 weeks, biopsies showed no difference in melanin content compared to baseline, indicating a temporary process induced by the malassezin.²⁷ More clinical studies are needed to investigate this further.

N-acetyl-glucosamine—N-acetyl-glucosamine is an aminosaccharide that inhibits the glycosylation of tyrosinase as well as its function in melanogenesis.²⁸ It is synthesized and included in topical products for wound healing, rhytides, moisturization, and pigmentation disorders.

Topical Tranexamic Acid—Tranexamic acid traditionally has been used orally for the treatment of menorrhagia but also has been found to be beneficial as a therapy for hyperpigmentation and erythema. Tranexamic acid interferes with plasmin activity, thus indirectly inhibiting melanogenesis while also inhibiting angiogenesis by targeting vascular endothelial growth factor (VEGF) receptors.²⁹ It also leads to an increase in the levels of β-endorphin and μ-opioid receptors as well as the expression of estrogen receptor β on the surface of mast cells.³⁰ Its oral benefit led to the development of topical formulations, typically in 2% to 5% concentrations. It has proven particularly beneficial in the treatment of melasma due to its effects on improving pigmentation, erythema, and skin barrier function.³¹ Topical tranexamic acid has a relatively high safety profile, with minor side effects such as transient skin irritation and erythema being reported.³²

Cysteamine—Cysteamine inhibits tyrosinase, peroxidase, and chelating copper ions necessary for melanogenesis. It has proven to be effective in treating melasma and chronic severe postinflammatory hyperpigmentation when used in a 5% cream formulation.^33,34 Lima et al³⁵ were the first to compare the effects of topical cysteamine to HQ in the treatment of facial melasma. They found that the mean reduction in modified Melasma Area and Severity Index score was 24% for cysteamine and 41% for HQ after 60 days. There were no severe adverse effects with either treatment group.³⁵

Final Thoughts

Hydroquinone remains the gold standard for treatment of hyperpigmentation; however, its side-effect profile and risk of ochronosis with long-term use has ushered in various other safe and effective skin lightening agents that can be used as monotherapies or in combination with other lightening agents. Many of these products also can be used effectively with procedural treatments such as chemical peels, lasers, and microneedling for enhanced absorption and efficacy. As newer agents are developed, additional well-designed studies will be needed to determine their safety and efficacy in different skin types as well as their role in the treatment of pigmentary disorders.

Disorders of hyperpigmentation—melasma, postinflammatory hyperpigmentation, lichen planus pigmentosus, erythema dyschromicum perstans, and pigmented contact dermatitis, among others—are common and challenging to treat. Although they can affect individuals of all skin types, they most commonly are seen in skin of color; in fact, dyspigmentation is one of the most common chief concerns for which individuals of color see a dermatologist.^1,2

For many years, hydroquinone (HQ) was one of the main options available for use as a lightening agent. Although effective, it has the risk of causing irritant dermatitis, potentially leading to further dyspigmentation, in addition to the risk of ochronosis with long-term use. It remains an important and useful treatment for pigmentary disorders, but there are numerous other lightening agents that also can be considered in the treatment of disorders of hyperpigmentation.

Herein, we provide recommendations for traditional and newer non-HQ lightening agents that can be considered when treating disorders of hyperpigmentation.

Traditional Non-HQ Lightening Agents

Retinoids—Retinoids are topical vitamin A derivatives that have been used safely and effectively for decades in the treatment of pigmentary disorders. Retinoids have multiple mechanisms of action in improving pigmentation. In addition to impeding tyrosinase induction, they inhibit pigment transfer to keratinocytes and lead to accelerated pigment loss due to epidermal shedding.³ Over-the-counter formulations include retinol, retinaldehyde, and adapalene. Prescription formulations include tretinoin and tazarotene in different strengths and vehicle formulations.⁴

Glycolic Acid—Glycolic acid is derived from sugarcane and is considered an α-hydroxy acid that leads to rapid desquamation of pigmented keratinocytes.⁵ Glycolic acid can not only be used in chemical peels but also in topical creams. It is the most common α-hydroxy acid peel and is sometimes paired with HQ and other topical lightening agents for increased penetration. Glycolic acid peels are available in concentrations of 20% to 70% and can be used at various depths. When used incorrectly, it can cause redness, burning, and even skin discoloration; however, when used at the proper concentrations and depth according to Fitzpatrick skin type, there typically are no notable adverse effects, and clinical results are favorable.

Kojic Acid—Kojic acid is a natural metabolite derived from fungi and is widely used in Asian countries. It works by inhibiting the catecholase activity of tyrosinase⁶ and typically is available in concentrations of 1% to 4%. A study suggested that a concentration of 1% or less typically is safe to use for prolonged periods without adverse effects. Although not more effective than HQ as a monotherapy, kojic acid has been shown to haveimproved efficacy when used in combination with other lightening agents.⁷

Azelaic Acid—Azelaic acid works by inhibiting tyrosinase, mitochondrial oxidoreductase activation, and DNA synthesis. It preferentially targets heavily pigmented melanocytes and possesses anti-inflammatory and antibacterial properties.⁸ A 20% concentration of azelaic acid was compared to HQ 4% for the treatment of melasma, and results revealed that the liposomal form of azelaic acid was considerably more tolerable than HQ 4% and also more effective.⁹

Licorice Extracts—Licorice extracts have been safely used in several cosmeceutical skin lightening products.¹⁰ The main active compounds in licorice root are glabridin and liquiritin, which work to disperse melanin. These compounds often are used topically at concentrations of 10% to 40%. A study by Amer and Metwalli¹¹ found that topical liquiritin produced a reduction of pigmentary intensity, with 80% of patients showing an excellent response, which was described as no difference between the previously pigmented area and the normal skin surrounding it.

Aloesin—Aloesin is a low-molecular-weight glycoprotein found in aloe vera plants. Its mechanism of action includes competitive inhibition of the dihydroxyphenylalanine oxidation site, resulting in the inhibition of tyrosinase.¹² It often is combined with arbutin for an enhanced lightening effect.

Niacinamide—Niacinamide is a form of vitamin B₃ that works by suppressing the transfer of melanosomes to keratinocytes.¹³ In addition to its skin lightening effects, it also is photoprotective and antimicrobial, and its tolerability and safety have led to its inclusion in many cosmeceutical and prescription products.¹⁴

Ascorbic Acid—Ascorbic acid affects the monopherase activity of tyrosinase, thus reducing the synthesis of melanin. It also serves as an antioxidant in the skin by preventing the production of free radicals that can induce melanogenesis.¹⁵ Although it tends to be well tolerated with a low adverse effect profile, its relative instability and varying permeability can present a challenge. It is less effective as a monotherapy, so it often is combined with other lightening ingredients for greater efficacy.

Corticosteroids—Topical corticosteroids are anti-inflammatory and impact melanogenesis, though the mechanism of action of the latter has not been fully elucidated.^16,17 Low- to mid-potency topical steroids often are used in conjunction with skin lightening products to diminish irritation and decrease inflammation.¹⁸ However, prolonged use of corticosteroids can lead to cutaneous adverse effects such as striae, hypopigmentation, and acne, as well as systemic side effects if there is sufficient absorption over time.

Soybean Extracts—Soybean extracts contain serine protease inhibitors that reduce the transfer of melanosomes into keratinocytes by inhibiting the PAR-2 (protease-activated receptor 2) pathway.^19,20

Ellagic Acid—Ellagic acid is found in common plants such as eucalyptus and strawberry as well as green tea.²¹ It works as an antioxidant and decreases melanogenesis through inhibition of tyrosinase activity.

Paper Mulberry—Paper mulberry extract comes from the roots of the Broussonetia papyrifera tree and functions by inhibiting tyrosinase activity. It is widely used in South Africa and Europe.²²

Resveratrol—Resveratrol is an ingredient extracted from Morus alba L and functions as an antimelanogentic agent by directly inhibiting tyrosinase as well as transcriptional and posttranscriptional processing of tyrosinase.²³ It also holds antiproliferative, anti-inflammatory, and antioxidant properties and has widely been used for antiaging and skin lightening purposes.²⁴

Newer Non-HQ Lightening Agents

Silymarin—Silymarin (also known as milk thistle [Silybum marianum]), is a polyphenolic flavonoid that possesses anticarcinogenic, antioxidant, and anti-inflammatory properties. It prevents melanin production in a dose-dependent manner by inhibiting levodopa (L-dopa) oxidation activity of tyrosinase and also reduces the expression of tyrosinase protein.²⁵ In combination with vitamins C and E and hexylresorcinol, silymarin has been found to reduce the effects of photodamage, brighten skin, improve evenness and lines, as well as improve global facial appearance.²⁶

Malassezin—Malassezin is an indole produced by Malessezia furfur yeast and has recently been investigated for melanogenesis suppression. Grimes et al²⁷ assessed the efficacy of topical malassezin in 7 patients with facial hyperpigmentation applied twice daily for 14 weeks. Punch biopsies were taken at weeks 0, 8, 14, and 22. Biopsies from weeks 8 and 14 demonstrated reduced epidermal melanin compared to baseline in all participants; however, at 22 weeks, biopsies showed no difference in melanin content compared to baseline, indicating a temporary process induced by the malassezin.²⁷ More clinical studies are needed to investigate this further.

N-acetyl-glucosamine—N-acetyl-glucosamine is an aminosaccharide that inhibits the glycosylation of tyrosinase as well as its function in melanogenesis.²⁸ It is synthesized and included in topical products for wound healing, rhytides, moisturization, and pigmentation disorders.

Topical Tranexamic Acid—Tranexamic acid traditionally has been used orally for the treatment of menorrhagia but also has been found to be beneficial as a therapy for hyperpigmentation and erythema. Tranexamic acid interferes with plasmin activity, thus indirectly inhibiting melanogenesis while also inhibiting angiogenesis by targeting vascular endothelial growth factor (VEGF) receptors.²⁹ It also leads to an increase in the levels of β-endorphin and μ-opioid receptors as well as the expression of estrogen receptor β on the surface of mast cells.³⁰ Its oral benefit led to the development of topical formulations, typically in 2% to 5% concentrations. It has proven particularly beneficial in the treatment of melasma due to its effects on improving pigmentation, erythema, and skin barrier function.³¹ Topical tranexamic acid has a relatively high safety profile, with minor side effects such as transient skin irritation and erythema being reported.³²

Cysteamine—Cysteamine inhibits tyrosinase, peroxidase, and chelating copper ions necessary for melanogenesis. It has proven to be effective in treating melasma and chronic severe postinflammatory hyperpigmentation when used in a 5% cream formulation.^33,34 Lima et al³⁵ were the first to compare the effects of topical cysteamine to HQ in the treatment of facial melasma. They found that the mean reduction in modified Melasma Area and Severity Index score was 24% for cysteamine and 41% for HQ after 60 days. There were no severe adverse effects with either treatment group.³⁵

Final Thoughts

Hydroquinone remains the gold standard for treatment of hyperpigmentation; however, its side-effect profile and risk of ochronosis with long-term use has ushered in various other safe and effective skin lightening agents that can be used as monotherapies or in combination with other lightening agents. Many of these products also can be used effectively with procedural treatments such as chemical peels, lasers, and microneedling for enhanced absorption and efficacy. As newer agents are developed, additional well-designed studies will be needed to determine their safety and efficacy in different skin types as well as their role in the treatment of pigmentary disorders.

As a physician who has had a career-long obsession with the underappreciated value of sleep, a recent study published in the journal Child Development caught my eye. The findings presented by a group of Australian-based psychologists and educators suggest a positive association between napping and learning by preschool children. While the study itself relied on a very small sample and may not prove to be repeatable, the authors included in their introduction an excellent discussion of a large collection of recent studies supporting the educational benefit of sleep in general and napping in particular.

Although sleep seems to finally be receiving some of the attention it deserves, I am still concerned that as a profession we are failing to give it the appropriate weight at our health maintenance visits. This is particularly true of napping. Understandably, napping doesn’t feel urgent to parents in those turbulent first 4 or 5 months of night wakings and erratic settling. However, as a child approaches the 6-month milestone, napping is a topic ripe for well-considered anticipatory guidance.

When the recurrent cycles of awake-eat-sleep begin to develop into a somewhat predictable pattern and solid food is introduced, it’s time to suggest to parents a strategy that will encourage a napping pattern that will hopefully habituate into toddlerhood and beyond.

It can begin simply as a matter of defining the feeding in the middle of the day as lunch and then programming the period immediately following that meal as a siesta – a segment of the day completely reserved for rest. Many warm-weather countries have been using this strategy for centuries. Try to go to the pharmacy to pick up a prescription at 2 o’clock in the afternoon in rural Spain. It just ain’t gonna happen.

Most adults and children I know seem to be sleepy during this midday postprandial period. It makes more than a little sense to harness this natural drowsiness into creating a napping habit. However, the challenge for many young families is controlling their schedule to create a period of time when nothing else is going on in the child’s environment, leaving sleep as the only option. For some parents this requires the discipline to pause their own lives long enough so that the children realize that they aren’t missing out on something fun. This means no TV, no phone conversations, no visitors. Obviously, it also means not scheduling any appointments during this siesta period. Skilled day care providers have been doing this for years. But the message hasn’t seeped into the general population and sadly I occasionally see mothers with toddlers in the grocery store at 1 in the afternoon.

Once the nap/siesta is firmly welded to lunch, this gives the parent the ability to make minor adjustments that reflect the child’s stamina. If the child seems to be tiring/getting grumpy, serve up lunch a bit early and the restorative nap follows. As the child gets older and his or her stamina improves he or she may not be sleepy but the siesta remains as a quiet time. Some days it may be a nap, some days just a rest for an hour. By counseling parents to define the period after lunch as a siesta you will be helping them avoid that dreaded transition period called “giving up the nap.”

You may already be including this strategy in your anticipatory guidance. It may help to add to your advice the accumulating evidence that napping may play an important role in the child’s development and education.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

As a physician who has had a career-long obsession with the underappreciated value of sleep, a recent study published in the journal Child Development caught my eye. The findings presented by a group of Australian-based psychologists and educators suggest a positive association between napping and learning by preschool children. While the study itself relied on a very small sample and may not prove to be repeatable, the authors included in their introduction an excellent discussion of a large collection of recent studies supporting the educational benefit of sleep in general and napping in particular.

Although sleep seems to finally be receiving some of the attention it deserves, I am still concerned that as a profession we are failing to give it the appropriate weight at our health maintenance visits. This is particularly true of napping. Understandably, napping doesn’t feel urgent to parents in those turbulent first 4 or 5 months of night wakings and erratic settling. However, as a child approaches the 6-month milestone, napping is a topic ripe for well-considered anticipatory guidance.

When the recurrent cycles of awake-eat-sleep begin to develop into a somewhat predictable pattern and solid food is introduced, it’s time to suggest to parents a strategy that will encourage a napping pattern that will hopefully habituate into toddlerhood and beyond.

It can begin simply as a matter of defining the feeding in the middle of the day as lunch and then programming the period immediately following that meal as a siesta – a segment of the day completely reserved for rest. Many warm-weather countries have been using this strategy for centuries. Try to go to the pharmacy to pick up a prescription at 2 o’clock in the afternoon in rural Spain. It just ain’t gonna happen.

Most adults and children I know seem to be sleepy during this midday postprandial period. It makes more than a little sense to harness this natural drowsiness into creating a napping habit. However, the challenge for many young families is controlling their schedule to create a period of time when nothing else is going on in the child’s environment, leaving sleep as the only option. For some parents this requires the discipline to pause their own lives long enough so that the children realize that they aren’t missing out on something fun. This means no TV, no phone conversations, no visitors. Obviously, it also means not scheduling any appointments during this siesta period. Skilled day care providers have been doing this for years. But the message hasn’t seeped into the general population and sadly I occasionally see mothers with toddlers in the grocery store at 1 in the afternoon.

Once the nap/siesta is firmly welded to lunch, this gives the parent the ability to make minor adjustments that reflect the child’s stamina. If the child seems to be tiring/getting grumpy, serve up lunch a bit early and the restorative nap follows. As the child gets older and his or her stamina improves he or she may not be sleepy but the siesta remains as a quiet time. Some days it may be a nap, some days just a rest for an hour. By counseling parents to define the period after lunch as a siesta you will be helping them avoid that dreaded transition period called “giving up the nap.”

You may already be including this strategy in your anticipatory guidance. It may help to add to your advice the accumulating evidence that napping may play an important role in the child’s development and education.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

As a physician who has had a career-long obsession with the underappreciated value of sleep, a recent study published in the journal Child Development caught my eye. The findings presented by a group of Australian-based psychologists and educators suggest a positive association between napping and learning by preschool children. While the study itself relied on a very small sample and may not prove to be repeatable, the authors included in their introduction an excellent discussion of a large collection of recent studies supporting the educational benefit of sleep in general and napping in particular.

Although sleep seems to finally be receiving some of the attention it deserves, I am still concerned that as a profession we are failing to give it the appropriate weight at our health maintenance visits. This is particularly true of napping. Understandably, napping doesn’t feel urgent to parents in those turbulent first 4 or 5 months of night wakings and erratic settling. However, as a child approaches the 6-month milestone, napping is a topic ripe for well-considered anticipatory guidance.

When the recurrent cycles of awake-eat-sleep begin to develop into a somewhat predictable pattern and solid food is introduced, it’s time to suggest to parents a strategy that will encourage a napping pattern that will hopefully habituate into toddlerhood and beyond.

It can begin simply as a matter of defining the feeding in the middle of the day as lunch and then programming the period immediately following that meal as a siesta – a segment of the day completely reserved for rest. Many warm-weather countries have been using this strategy for centuries. Try to go to the pharmacy to pick up a prescription at 2 o’clock in the afternoon in rural Spain. It just ain’t gonna happen.

Most adults and children I know seem to be sleepy during this midday postprandial period. It makes more than a little sense to harness this natural drowsiness into creating a napping habit. However, the challenge for many young families is controlling their schedule to create a period of time when nothing else is going on in the child’s environment, leaving sleep as the only option. For some parents this requires the discipline to pause their own lives long enough so that the children realize that they aren’t missing out on something fun. This means no TV, no phone conversations, no visitors. Obviously, it also means not scheduling any appointments during this siesta period. Skilled day care providers have been doing this for years. But the message hasn’t seeped into the general population and sadly I occasionally see mothers with toddlers in the grocery store at 1 in the afternoon.

Once the nap/siesta is firmly welded to lunch, this gives the parent the ability to make minor adjustments that reflect the child’s stamina. If the child seems to be tiring/getting grumpy, serve up lunch a bit early and the restorative nap follows. As the child gets older and his or her stamina improves he or she may not be sleepy but the siesta remains as a quiet time. Some days it may be a nap, some days just a rest for an hour. By counseling parents to define the period after lunch as a siesta you will be helping them avoid that dreaded transition period called “giving up the nap.”

You may already be including this strategy in your anticipatory guidance. It may help to add to your advice the accumulating evidence that napping may play an important role in the child’s development and education.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Now hot off the press from the “always-guessed-it-was-true-but-now-you-know-it” department comes a multinational study that looked at childhood cardiovascular risk factors and longevity.

Using data collected from individuals in Finland, Australia, and the United States the International Childhood Cardiovascular Cohorts Consortium Outcomes Study investigators sought links between subjects’ body mass index, systolic blood pressure, total cholesterol, blood triglyceride level, and smoking in childhood with cardiovascular disease and outcomes as they aged into adulthood.

The children were initially enrolled in the 1970s and 1980s. The adult evaluations were done in 2015-2019 when the subjects’ average age was 46. Of the 40,000 individuals who originally entered the study, 800 were found to have cardiovascular events of which over 300 had resulted in death. I found these numbers a bit surprising given the relatively young age at which the follow-up data were collected.

What was less surprising is that people with higher than normal values for all five risk factors as children had nearly three times the risk of cardiovascular disease as adults. Researchers found that smoking at a young age was biggest risk factor with body mass index, systolic blood pressure, blood triglycerides, and cholesterol following in descending order. They also found that adults who were obese as children had triple the risk of cardiovascular disease as adults. High blood pressure in childhood doubled the risk.

It will be interesting to see if and how these trends change as the study population ages. It could be that the effect of these childhood risk factors is blunted as the those segments at the highest risk die off and/or risk- associated behaviors adopted in adulthood become more prominent. But, it feels more likely that the childhood risk factors will remain as major contributors.

Is this just another ho-hum-told-you-so study or does it have some special relevance for us as pediatricians? At a minimum these findings should inspire us to stick with our calling to commit ourselves to the health of children. A healthy adult population is clearly our legacy.

Of course the two individual risk factors in childhood that appear to be the most potent in adulthood, obesity and smoking, are also the most frustrating for pediatricians to address. However, the study suggests that we should rejoice in those few successes when we achieve them. Childhood obesity has been a tough nut to crack. On the other hand, the societal change that has made great strides in adult smoking over the last half century should encourage us that our work with the pediatric population will eventually bring rewards.

Smoking and obesity can include components of both patient and parental behavior. Monitoring cholesterol, triglycerides, and blood pressure hinges on our behavior as providers. Although there have been recent recommendations that we be more attentive, we don’t have a strong history when it comes to detecting and addressing high blood pressure in children. This study should serve as an another reminder to take blood pressure more seriously.

I was surprised and somewhat disappointed that I first learned about the results of this study in an email newsletter from the medical school I attended. I would have hoped that a paper like this from a well known peer-reviewed journal with a clear message about the relationship of childhood health and longevity should have been picked up quickly by the lay press. Again, this leaves it to us to promote the message that the health of children is important in and of itself but plays a critical role in the health of adults.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Now hot off the press from the “always-guessed-it-was-true-but-now-you-know-it” department comes a multinational study that looked at childhood cardiovascular risk factors and longevity.

Using data collected from individuals in Finland, Australia, and the United States the International Childhood Cardiovascular Cohorts Consortium Outcomes Study investigators sought links between subjects’ body mass index, systolic blood pressure, total cholesterol, blood triglyceride level, and smoking in childhood with cardiovascular disease and outcomes as they aged into adulthood.

The children were initially enrolled in the 1970s and 1980s. The adult evaluations were done in 2015-2019 when the subjects’ average age was 46. Of the 40,000 individuals who originally entered the study, 800 were found to have cardiovascular events of which over 300 had resulted in death. I found these numbers a bit surprising given the relatively young age at which the follow-up data were collected.

What was less surprising is that people with higher than normal values for all five risk factors as children had nearly three times the risk of cardiovascular disease as adults. Researchers found that smoking at a young age was biggest risk factor with body mass index, systolic blood pressure, blood triglycerides, and cholesterol following in descending order. They also found that adults who were obese as children had triple the risk of cardiovascular disease as adults. High blood pressure in childhood doubled the risk.

It will be interesting to see if and how these trends change as the study population ages. It could be that the effect of these childhood risk factors is blunted as the those segments at the highest risk die off and/or risk- associated behaviors adopted in adulthood become more prominent. But, it feels more likely that the childhood risk factors will remain as major contributors.

Is this just another ho-hum-told-you-so study or does it have some special relevance for us as pediatricians? At a minimum these findings should inspire us to stick with our calling to commit ourselves to the health of children. A healthy adult population is clearly our legacy.

Of course the two individual risk factors in childhood that appear to be the most potent in adulthood, obesity and smoking, are also the most frustrating for pediatricians to address. However, the study suggests that we should rejoice in those few successes when we achieve them. Childhood obesity has been a tough nut to crack. On the other hand, the societal change that has made great strides in adult smoking over the last half century should encourage us that our work with the pediatric population will eventually bring rewards.

Smoking and obesity can include components of both patient and parental behavior. Monitoring cholesterol, triglycerides, and blood pressure hinges on our behavior as providers. Although there have been recent recommendations that we be more attentive, we don’t have a strong history when it comes to detecting and addressing high blood pressure in children. This study should serve as an another reminder to take blood pressure more seriously.

I was surprised and somewhat disappointed that I first learned about the results of this study in an email newsletter from the medical school I attended. I would have hoped that a paper like this from a well known peer-reviewed journal with a clear message about the relationship of childhood health and longevity should have been picked up quickly by the lay press. Again, this leaves it to us to promote the message that the health of children is important in and of itself but plays a critical role in the health of adults.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Now hot off the press from the “always-guessed-it-was-true-but-now-you-know-it” department comes a multinational study that looked at childhood cardiovascular risk factors and longevity.

Using data collected from individuals in Finland, Australia, and the United States the International Childhood Cardiovascular Cohorts Consortium Outcomes Study investigators sought links between subjects’ body mass index, systolic blood pressure, total cholesterol, blood triglyceride level, and smoking in childhood with cardiovascular disease and outcomes as they aged into adulthood.

The children were initially enrolled in the 1970s and 1980s. The adult evaluations were done in 2015-2019 when the subjects’ average age was 46. Of the 40,000 individuals who originally entered the study, 800 were found to have cardiovascular events of which over 300 had resulted in death. I found these numbers a bit surprising given the relatively young age at which the follow-up data were collected.

What was less surprising is that people with higher than normal values for all five risk factors as children had nearly three times the risk of cardiovascular disease as adults. Researchers found that smoking at a young age was biggest risk factor with body mass index, systolic blood pressure, blood triglycerides, and cholesterol following in descending order. They also found that adults who were obese as children had triple the risk of cardiovascular disease as adults. High blood pressure in childhood doubled the risk.

It will be interesting to see if and how these trends change as the study population ages. It could be that the effect of these childhood risk factors is blunted as the those segments at the highest risk die off and/or risk- associated behaviors adopted in adulthood become more prominent. But, it feels more likely that the childhood risk factors will remain as major contributors.

Is this just another ho-hum-told-you-so study or does it have some special relevance for us as pediatricians? At a minimum these findings should inspire us to stick with our calling to commit ourselves to the health of children. A healthy adult population is clearly our legacy.

Of course the two individual risk factors in childhood that appear to be the most potent in adulthood, obesity and smoking, are also the most frustrating for pediatricians to address. However, the study suggests that we should rejoice in those few successes when we achieve them. Childhood obesity has been a tough nut to crack. On the other hand, the societal change that has made great strides in adult smoking over the last half century should encourage us that our work with the pediatric population will eventually bring rewards.

Smoking and obesity can include components of both patient and parental behavior. Monitoring cholesterol, triglycerides, and blood pressure hinges on our behavior as providers. Although there have been recent recommendations that we be more attentive, we don’t have a strong history when it comes to detecting and addressing high blood pressure in children. This study should serve as an another reminder to take blood pressure more seriously.

I was surprised and somewhat disappointed that I first learned about the results of this study in an email newsletter from the medical school I attended. I would have hoped that a paper like this from a well known peer-reviewed journal with a clear message about the relationship of childhood health and longevity should have been picked up quickly by the lay press. Again, this leaves it to us to promote the message that the health of children is important in and of itself but plays a critical role in the health of adults.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Mental illness has been waiting in the wings for years; ignored, ridiculed, minimized, and stigmatized. Those who succumbed to it tried to lend testimonials, but to no avail. Those who were spared its effects remained in disbelief. So, it stayed on the sidelines, growing in intensity and breadth, yet stifled by the masses, until 2 years ago.

In March 2020, when COVID-19 became a pandemic, the importance of mental health finally became undeniable. As the pandemic’s effects progressed and wreaked havoc on our nation, our mental illness rates simultaneously surged. This surge paralleled that of the COVID-19 pandemic’s and in fact, contributed to a secondary crisis, allowing mental health to finally be addressed and gain center stage status.

But “mental health” is not easily defined, as it takes on many forms and is expressed in a variety of ways and via a myriad of symptoms. It does not discriminate by gender, race, age, socioeconomic status, educational level, profession, religion, or geography. At times, mental health status is consistent but at other times it can fluctuate in intensity, duration, and expression. It can be difficult to manage, yet there are various treatment modalities that can be implemented to lessen the impact of mental illness. Stressful events seem to potentiate its manifestation and yet, there are times it seems to appear spontaneously, much as an uninvited guest.

Mental health has a strong synergistic relationship with physical health, as they are very interdependent and allow us to function at our best only when they are both operating optimally. It should come as no surprise then, that the COVID-19 pandemic contributed to the exponential surge of mental illnesses. Capitalizing on its nondiscriminatory nature, mental illness impacted a large segment of the population – both those suffering from COVID-19 as well as those treating them.

As the nation starts to heal from the immediate and lingering physical and emotional consequences of the COVID-19 pandemic, President Biden has chosen to address and try to meet the needs of the health care heroes, the healers. The signing of H.R. 1667, the Dr. Lorna Breen Health Care Provider Protection Act into law on March 18, 2022, showed dedication to the health care community that has given tirelessly to our nation during the COVID-19 pandemic, and is itself recuperating from that effort.

Taking a top-down approach is essential to assuring the health of the nation. If our healers are not healthy, physically and mentally, they will not be able treat those whom they are dedicated to helping. Openly discussing and acknowledging the mental health problems of health care workers as a community makes it okay to not be okay. It normalizes the need for health care workers to prioritize their own mental health. It can also start to ease the fear of professional backlash or repercussions for practicing self-care.

I, for one, am very grateful for the prioritizing and promoting of the importance of mental health and wellness amongst health care workers. This helps to reduce the stigma of mental illness, helps us understand its impact, and allows us to formulate strategies and solutions to address its effects. The time has come.

Dr. Jarkon is a psychiatrist and director of the Center for Behavioral Health at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y.

Mental illness has been waiting in the wings for years; ignored, ridiculed, minimized, and stigmatized. Those who succumbed to it tried to lend testimonials, but to no avail. Those who were spared its effects remained in disbelief. So, it stayed on the sidelines, growing in intensity and breadth, yet stifled by the masses, until 2 years ago.

In March 2020, when COVID-19 became a pandemic, the importance of mental health finally became undeniable. As the pandemic’s effects progressed and wreaked havoc on our nation, our mental illness rates simultaneously surged. This surge paralleled that of the COVID-19 pandemic’s and in fact, contributed to a secondary crisis, allowing mental health to finally be addressed and gain center stage status.

But “mental health” is not easily defined, as it takes on many forms and is expressed in a variety of ways and via a myriad of symptoms. It does not discriminate by gender, race, age, socioeconomic status, educational level, profession, religion, or geography. At times, mental health status is consistent but at other times it can fluctuate in intensity, duration, and expression. It can be difficult to manage, yet there are various treatment modalities that can be implemented to lessen the impact of mental illness. Stressful events seem to potentiate its manifestation and yet, there are times it seems to appear spontaneously, much as an uninvited guest.

Mental health has a strong synergistic relationship with physical health, as they are very interdependent and allow us to function at our best only when they are both operating optimally. It should come as no surprise then, that the COVID-19 pandemic contributed to the exponential surge of mental illnesses. Capitalizing on its nondiscriminatory nature, mental illness impacted a large segment of the population – both those suffering from COVID-19 as well as those treating them.

As the nation starts to heal from the immediate and lingering physical and emotional consequences of the COVID-19 pandemic, President Biden has chosen to address and try to meet the needs of the health care heroes, the healers. The signing of H.R. 1667, the Dr. Lorna Breen Health Care Provider Protection Act into law on March 18, 2022, showed dedication to the health care community that has given tirelessly to our nation during the COVID-19 pandemic, and is itself recuperating from that effort.

Taking a top-down approach is essential to assuring the health of the nation. If our healers are not healthy, physically and mentally, they will not be able treat those whom they are dedicated to helping. Openly discussing and acknowledging the mental health problems of health care workers as a community makes it okay to not be okay. It normalizes the need for health care workers to prioritize their own mental health. It can also start to ease the fear of professional backlash or repercussions for practicing self-care.

I, for one, am very grateful for the prioritizing and promoting of the importance of mental health and wellness amongst health care workers. This helps to reduce the stigma of mental illness, helps us understand its impact, and allows us to formulate strategies and solutions to address its effects. The time has come.

Dr. Jarkon is a psychiatrist and director of the Center for Behavioral Health at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y.

Mental illness has been waiting in the wings for years; ignored, ridiculed, minimized, and stigmatized. Those who succumbed to it tried to lend testimonials, but to no avail. Those who were spared its effects remained in disbelief. So, it stayed on the sidelines, growing in intensity and breadth, yet stifled by the masses, until 2 years ago.

In March 2020, when COVID-19 became a pandemic, the importance of mental health finally became undeniable. As the pandemic’s effects progressed and wreaked havoc on our nation, our mental illness rates simultaneously surged. This surge paralleled that of the COVID-19 pandemic’s and in fact, contributed to a secondary crisis, allowing mental health to finally be addressed and gain center stage status.

But “mental health” is not easily defined, as it takes on many forms and is expressed in a variety of ways and via a myriad of symptoms. It does not discriminate by gender, race, age, socioeconomic status, educational level, profession, religion, or geography. At times, mental health status is consistent but at other times it can fluctuate in intensity, duration, and expression. It can be difficult to manage, yet there are various treatment modalities that can be implemented to lessen the impact of mental illness. Stressful events seem to potentiate its manifestation and yet, there are times it seems to appear spontaneously, much as an uninvited guest.

Mental health has a strong synergistic relationship with physical health, as they are very interdependent and allow us to function at our best only when they are both operating optimally. It should come as no surprise then, that the COVID-19 pandemic contributed to the exponential surge of mental illnesses. Capitalizing on its nondiscriminatory nature, mental illness impacted a large segment of the population – both those suffering from COVID-19 as well as those treating them.

As the nation starts to heal from the immediate and lingering physical and emotional consequences of the COVID-19 pandemic, President Biden has chosen to address and try to meet the needs of the health care heroes, the healers. The signing of H.R. 1667, the Dr. Lorna Breen Health Care Provider Protection Act into law on March 18, 2022, showed dedication to the health care community that has given tirelessly to our nation during the COVID-19 pandemic, and is itself recuperating from that effort.

Taking a top-down approach is essential to assuring the health of the nation. If our healers are not healthy, physically and mentally, they will not be able treat those whom they are dedicated to helping. Openly discussing and acknowledging the mental health problems of health care workers as a community makes it okay to not be okay. It normalizes the need for health care workers to prioritize their own mental health. It can also start to ease the fear of professional backlash or repercussions for practicing self-care.

I, for one, am very grateful for the prioritizing and promoting of the importance of mental health and wellness amongst health care workers. This helps to reduce the stigma of mental illness, helps us understand its impact, and allows us to formulate strategies and solutions to address its effects. The time has come.

Dr. Jarkon is a psychiatrist and director of the Center for Behavioral Health at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y.

I suspect that you have heard or read about the recent study in the Journal of Neuroscience that claims to have discovered evidence that as children become teenagers, their brains begin to tune out their mother’s voices. The story appeared in at least 10 Internet news sources including the American Academy of Pediatrics’ daily briefing.

Based on functional MRI studies by a group at Stanford (Calif.) University, the researchers found that while in general, teenagers became more attentive to all voices as they reached puberty, novel voices were favored over the maternal voices that had flooded their environment as younger children. Of course none of this comes as a surprise to anyone who has parented a teenager or spent any time trying to communicate with adolescents. Although we all must be a bit careful not to put too much stock in functional MRI studies, these findings do suggest a physiologic basis for the peer pressure that becomes one of the hallmarks of adolescence. I wouldn’t be surprised if some clever entrepreneur has already begun using MRI to search for just the right tonal qualities that will make the perfect Internet influencer.

But, will these MRI studies help parents who have already thrown up their arms and admitted defeat mumbling, “He’s stopped listening to me?” The more observant parents already realized long ago that their words were often the least effective tools in their tool kit when it comes to modifying behavior.

Just listen in any neighborhood playground or grocery store to how often you hear a parent trying to get a toddler or young child to correct a misbehavior using threats or promises that you and everyone else within earshot knows will never be followed by any consequence. How often do you see a parent modeling behaviors that they expect their children to avoid?

Some more “enlightened” parents will avoid threats and instead attempt to engage in a dialogue with their misbehaving child hoping that a rational discussion with a sleep-deprived toddler in full tantrum mode can convince the youngster to self-correct.

I’m sure you learned and may have even used the playground retort “sticks and stones may break my bones but words will never hurt me.” Of course more untrue words were never spoken. Words can hurt and they can scar. But words and threats can also be hollow and will fall on ears deafened by months and years during which there were no consequences. It is certainly nice to know that there is some physiologic correlation to what we all suspected. The good news is that teenagers are still listening to us, although they are increasingly more interested in what their peers and the rest of the world has to say.

What the study fails to point out is that while teenagers may still be listening to us their behavior is molded not so much by what we say but how we as parents and adults behave. Have we parented in a way in which our words are followed up with appropriate consequences? And, more importantly, have we modeled behavior that matches our words? We need to help parents realize that words can be important but parenting by example is the gold standard.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

I suspect that you have heard or read about the recent study in the Journal of Neuroscience that claims to have discovered evidence that as children become teenagers, their brains begin to tune out their mother’s voices. The story appeared in at least 10 Internet news sources including the American Academy of Pediatrics’ daily briefing.

Based on functional MRI studies by a group at Stanford (Calif.) University, the researchers found that while in general, teenagers became more attentive to all voices as they reached puberty, novel voices were favored over the maternal voices that had flooded their environment as younger children. Of course none of this comes as a surprise to anyone who has parented a teenager or spent any time trying to communicate with adolescents. Although we all must be a bit careful not to put too much stock in functional MRI studies, these findings do suggest a physiologic basis for the peer pressure that becomes one of the hallmarks of adolescence. I wouldn’t be surprised if some clever entrepreneur has already begun using MRI to search for just the right tonal qualities that will make the perfect Internet influencer.

But, will these MRI studies help parents who have already thrown up their arms and admitted defeat mumbling, “He’s stopped listening to me?” The more observant parents already realized long ago that their words were often the least effective tools in their tool kit when it comes to modifying behavior.

Just listen in any neighborhood playground or grocery store to how often you hear a parent trying to get a toddler or young child to correct a misbehavior using threats or promises that you and everyone else within earshot knows will never be followed by any consequence. How often do you see a parent modeling behaviors that they expect their children to avoid?

Some more “enlightened” parents will avoid threats and instead attempt to engage in a dialogue with their misbehaving child hoping that a rational discussion with a sleep-deprived toddler in full tantrum mode can convince the youngster to self-correct.

I’m sure you learned and may have even used the playground retort “sticks and stones may break my bones but words will never hurt me.” Of course more untrue words were never spoken. Words can hurt and they can scar. But words and threats can also be hollow and will fall on ears deafened by months and years during which there were no consequences. It is certainly nice to know that there is some physiologic correlation to what we all suspected. The good news is that teenagers are still listening to us, although they are increasingly more interested in what their peers and the rest of the world has to say.

What the study fails to point out is that while teenagers may still be listening to us their behavior is molded not so much by what we say but how we as parents and adults behave. Have we parented in a way in which our words are followed up with appropriate consequences? And, more importantly, have we modeled behavior that matches our words? We need to help parents realize that words can be important but parenting by example is the gold standard.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

I suspect that you have heard or read about the recent study in the Journal of Neuroscience that claims to have discovered evidence that as children become teenagers, their brains begin to tune out their mother’s voices. The story appeared in at least 10 Internet news sources including the American Academy of Pediatrics’ daily briefing.

Based on functional MRI studies by a group at Stanford (Calif.) University, the researchers found that while in general, teenagers became more attentive to all voices as they reached puberty, novel voices were favored over the maternal voices that had flooded their environment as younger children. Of course none of this comes as a surprise to anyone who has parented a teenager or spent any time trying to communicate with adolescents. Although we all must be a bit careful not to put too much stock in functional MRI studies, these findings do suggest a physiologic basis for the peer pressure that becomes one of the hallmarks of adolescence. I wouldn’t be surprised if some clever entrepreneur has already begun using MRI to search for just the right tonal qualities that will make the perfect Internet influencer.

But, will these MRI studies help parents who have already thrown up their arms and admitted defeat mumbling, “He’s stopped listening to me?” The more observant parents already realized long ago that their words were often the least effective tools in their tool kit when it comes to modifying behavior.

Just listen in any neighborhood playground or grocery store to how often you hear a parent trying to get a toddler or young child to correct a misbehavior using threats or promises that you and everyone else within earshot knows will never be followed by any consequence. How often do you see a parent modeling behaviors that they expect their children to avoid?

Some more “enlightened” parents will avoid threats and instead attempt to engage in a dialogue with their misbehaving child hoping that a rational discussion with a sleep-deprived toddler in full tantrum mode can convince the youngster to self-correct.

I’m sure you learned and may have even used the playground retort “sticks and stones may break my bones but words will never hurt me.” Of course more untrue words were never spoken. Words can hurt and they can scar. But words and threats can also be hollow and will fall on ears deafened by months and years during which there were no consequences. It is certainly nice to know that there is some physiologic correlation to what we all suspected. The good news is that teenagers are still listening to us, although they are increasingly more interested in what their peers and the rest of the world has to say.

What the study fails to point out is that while teenagers may still be listening to us their behavior is molded not so much by what we say but how we as parents and adults behave. Have we parented in a way in which our words are followed up with appropriate consequences? And, more importantly, have we modeled behavior that matches our words? We need to help parents realize that words can be important but parenting by example is the gold standard.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

I have become obsessed with the reality that the unprecedented national shortage of formula is keeping some families from adequately feeding their infants and young children. I am deeply concerned, both as a family medicine physician and a new mother, about the heartbreaking stories that I’ve heard from parents of all socioeconomic backgrounds. New mothers, unable to breastfeed for a multitude of reasons, find themselves standing in front of empty store shelves, in tears.

In recent months, many health care providers have had patients disclose that they are diluting ready-to-feed formula or mixing powdered formula with more water than instructed to make it go further. Some parents are giving cow’s milk to their children at too young an age because they can’t find formula. Others are foregoing milk altogether and feeding their children beverages such as juice or soda. All of these practices can threaten a child’s life, growth, and development.
 

When breastfeeding isn’t possible

We all know that human milk is the optimal, most nutritionally complete food source for newborn babies and infants. It can improve dental health and neurodevelopmental outcomes, as well as reduce the risk for asthma, eczema, diabetes, and obesity. An added benefit during the COVID-19 pandemic has been providing newborn infants with a boost of immunity before they are able to be vaccinated against SARS-CoV-2 infection.

But lactation and breastfeeding aren’t possible for everyone. Earlier this year, when my daughter was born more than a month prematurely, I worried that I would be unable to breastfeed her. The complications of prematurity can interfere with establishing lactation, and my daughter spent some time in the neonatal intensive care unit (NICU), requiring frequent feedings to treat hypoglycemia. She also lacked the muscle strength or coordination to latch on to the breast, so she was fed my colostrum and donor breast milk by bottle.

Not knowing when my mature milk would come in, my family scoured the retail stores for formula while I was still recovering from delivery. My daughter needed a specific type of high-calorie formula for premature infants. Eventually, my mother found one can of this powdered formula. The hospital also sent us home with 16 oz of ready-to-feed samples and enough donor breastmilk to last 24 hours at home. We considered ourselves lucky. The fear and anxiety about being able to feed my baby still stands out in my mind.
 

Pumping and sharing

Over the next few months, out of necessity, I became an “exclusively pumping” mother. My daughter, unable to latch, drank my pumped milk from a bottle. My body started to produce more milk than she needed in a day. In an effort to pay it forward and to put my extra milk to use, I became a human-milk donor. I underwent rigorous screening, including testing for infectious diseases such as HIV and hepatitis C. I was approved to donate to our local hospital’s milk bank, helping other families in the NICU feed their babies. Through informal connections on the internet, I also provide expressed milk to another mother in the community who is unable to lactate. To date, I’ve donated more than 1,500 oz of human milk (and counting).

The practice of human-milk donation dates back millennia with wet-nursing, when children were breastfed by someone other than their biological mothers: relatives, friends, or even strangers. The first milk bank in the United States opened in Boston in the early 20th century. In 1980, the World Health Organization and the United Nations Children’s Fund released a joint statement supporting the use of human-donor milk as the first alternative if the biological mother is unable to breastfeed. Donor milk is a safe option for families who cannot provide their own human milk to their children.
 

Human-milk banks

More than 30 nonprofit milk banks now operate in the United States. Because their mission is primarily to meet the needs of sick and hospitalized children rather than the general public, these milk banks are an impractical solution to the national formula shortage. Although families with healthy children can purchase donor milk with a prescription, supplies are scarce, and insurance doesn’t cover the cost.

Milk provided by formal human-milk banks is considered safe. Certain infections such as HIV and hepatitis can be transmitted through human milk. However, milk banks screen their donors and safely pasteurize and store donated breastmilk, following standard protocols. The risk of contracting an illness from banked donor milk is very low. The American Academy of Pediatrics recommends accepting donor milk only from a milk bank.
 

Informal human-milk donation

An increasingly popular alternative to formal human-milk banks is informal human-milk sharing. But many people, including health care professionals, hold misconceptions about how informal milk donation works. Today’s informal milk donation looks very different from age-old wet-nursing: Moms in support groups, often via social media, are requesting pumped milk from one another. (Note that this definition of “informal human-milk donation” does not include selling or purchasing human milk.)

Although the safety of sharing pumped human milk this way cannot be guaranteed, a harm-reduction approach is warranted, especially in view of the current formula scarcity.

I believe that medical professionals have a responsibility to raise awareness and dispel myths about donor breast milk. Many physicians acknowledge that informal milk sharing is common but rarely recommend it to patients. Whether they are donors or recipients, families who choose to participate need to be educated about how to go about the process as safely as possible.

Patients who are considering accepting informally donated human milk should ask key questions of the donor to gauge the risk of pathogens or other harmful substances being passed to their babies:

• What medications do you take?
• What supplements do you take?
• What recreational drugs do you take?
• Any recent travel?
• Any tattoos and if so, how recent?
• How much alcohol do you drink and how often?
• Have you been diagnosed with any infections?
• Any recent illness?
• How do you pump your breast milk?
• How do you store your breast milk?
• When was the available milk pumped?

We can help families by offering our medical expertise, allowing them to make an informed decision about whether to accept donated human milk. Clinicians can encourage patients and their families to use resources like the Infant Risk Center, which provides evidence-based information about medication safety and breast milk.

If your lactating patient is considering donating milk through informal channels to a family in need, encourage them to be open and honest about their medical history and lifestyle habits. If they cannot be transparent, they should not donate. A mutual level of respect and honesty can ensure the safety of those they hope to help. It is also important to counsel prospective milk donors to notify their milk recipients of any new illnesses, substance use, medications, travel, tattoos, or changes to their medical history.

Finally, encourage lactating patients who are able to do so to donate their extra milk to local nonprofit milk banks to increase the availability of screened, pasteurized breast milk in the community.

As a physician and mother, I hope that U.S. families will be less vulnerable to future formula shortages. Human milk is an ideal food source, but not everyone can lactate. Though not perfect, human milk donated outside of formal milk banks offers a safer alternative to diluting formula or feeding other unsuitable beverages to infants and children. As health care professionals, we need to counsel our patients about how to engage in this practice safely.

Dr. Mieses Malchuk is assistant professor in the department of family medicine at the University of North Carolina at Chapel Hill and a board-certified family physician and attending physician at UNC Health in Chapel Hill. She has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The 2022 Pediatric Academic Societies meeting included an excellent session on the acute and delayed effects of COVID-19 on children’s hearts. Data on the risk for cardiac injury during acute COVID-19, return-to-play guidelines after COVID-19–related heart injury, and post–vaccine-associated myocarditis were reviewed.

COVID-induced cardiac injury

The risk for COVID-induced cardiac injury is directly associated with age. Recent Centers for Disease Control and Prevention data revealed a “myocarditis or pericarditis” rate in the range of 12-17 cases per 100,000 SARS-CoV-2 infections among male children aged 5-11 years (lower rates for females); the rate jumps to 50-65 cases per 100,000 infections among male children aged 12-17 years. So cardiac injury caused by acute COVID-19 appears rare, but the risk is clearly associated with male sex and adolescent age.

Return to play after COVID-19

Clinicians may be pressed by patients and parents for advice on return to play after illness with COVID-19. In July 2020, the American College of Cardiology published an algorithm that has been adjusted over time, most recently in 2022 by the American Academy of Pediatrics. These algorithms stratify recommendations by degree of illness. One rule of thumb: Patients with severe COVID-19 (ICU care or multisystem inflammatory syndrome in children [MIS-C]) have only one box on the algorithm, and that is to rest for 3-6 months and only return to usual activity after cardiac clearance. Moderate disease (defined as ≥ 4 days of fever > 100.4 °F; ≥ 1 week of myalgia, chills, lethargy, or any non-ICU hospital stay; and no evidence of MIS-C) require undergoing an ECG to look for cardiac dysfunction, followed by at least 10 days of rest if the ECG is negative or referral for cardiac evaluation if either ECG or exam by a pediatric cardiologist is abnormal.

Clinicians can perhaps be more permissible with patients who are younger or who have had less severe disease. For example, if a patient aged younger than 12 years is asymptomatic with routine activity at the time of evaluation, an ECG is not indicated. For patients aged 12-15 years who are asymptomatic at the time of evaluation but participate in a high-intensity sport, clinicians might consider obtaining an ECG. As few as 3 days of rest might be enough for select patients who are asymptomatic at presentation. For other patients, clinicians should work with parents to introduce activity gradually and make it clear to parents that any activity intolerance requires quick reevaluation. On existing athlete registries, no deaths that are attributable to post–COVID-19 cardiac effects have been confirmed in children; however, all data presented during the session were from prior to the Omicron variant surge in early 2022, so more information may be forthcoming.
 

Considerations for MIS-C

Among children experiencing MIS-C, 35% had ECG changes, 40% exhibited left ventricular systolic or diastolic dysfunction, and 30% had mitral regurgitation, meaning that a large percentage of patients with MIS-C show some degree of cardiac dysfunction. Unfortunately, we are still in the data-gathering phase for long-term outcomes. Functional parameters tend to improve within a week, and most patients will return to normal cardiac function by 3-4 months.

Return to play after MIS-C is quite different from that for acute COVID-19. Patients with MIS-C should be treated much like other patients with myocarditis with an expected return to play in 3-6 months and only after cardiac follow-up. Another good-to-remember recommendation is to delay COVID-19 vaccination for at least 90 days after an episode of MIS-C.
 

Vaccine-related myocarditis

Once again, older age appears to be a risk factor because most patients with postvaccine myocarditis have been in their mid-teens to early 20s, with events more likely after the second vaccine dose and also more likely in male children (4:1 ratio to female children). No deaths have occurred from postvaccination myocarditis in patients younger than 30 years. Still, many individuals have exhibited residual MRI enhancement in the cardiac tissue for some time after experiencing postvaccination myocarditis; it’s currently unclear whether that has clinical implications. By comparison, CDC data demonstrates convincingly that the risk for cardiac effects is much greater after acute COVID-19 than after COVID-19 vaccination, with risk ratios often higher than 20, depending on age and condition (for example, myocarditis vs. pericarditis). Data are still insufficient to determine whether clinicians should recommend or avoid COVID-19 vaccination in children with congenital heart disease.

In summary, administering COVID-19 vaccines requires a great deal of shared decision-making with parents, and the clinician’s role is to educate parents about all potential risks related to both the vaccine and COVID-19 illness. Research has consistently shown that acute COVID-19 myocarditis and myocarditis associated with MIS-C are much more likely to occur in unvaccinated youth and more likely than postvaccination myocarditis, regardless of age.

William T. Basco, Jr., MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

A version of this article first appeared on Medscape.com.

The 2022 Pediatric Academic Societies meeting included an excellent session on the acute and delayed effects of COVID-19 on children’s hearts. Data on the risk for cardiac injury during acute COVID-19, return-to-play guidelines after COVID-19–related heart injury, and post–vaccine-associated myocarditis were reviewed.

COVID-induced cardiac injury

The risk for COVID-induced cardiac injury is directly associated with age. Recent Centers for Disease Control and Prevention data revealed a “myocarditis or pericarditis” rate in the range of 12-17 cases per 100,000 SARS-CoV-2 infections among male children aged 5-11 years (lower rates for females); the rate jumps to 50-65 cases per 100,000 infections among male children aged 12-17 years. So cardiac injury caused by acute COVID-19 appears rare, but the risk is clearly associated with male sex and adolescent age.

Return to play after COVID-19

Clinicians may be pressed by patients and parents for advice on return to play after illness with COVID-19. In July 2020, the American College of Cardiology published an algorithm that has been adjusted over time, most recently in 2022 by the American Academy of Pediatrics. These algorithms stratify recommendations by degree of illness. One rule of thumb: Patients with severe COVID-19 (ICU care or multisystem inflammatory syndrome in children [MIS-C]) have only one box on the algorithm, and that is to rest for 3-6 months and only return to usual activity after cardiac clearance. Moderate disease (defined as ≥ 4 days of fever > 100.4 °F; ≥ 1 week of myalgia, chills, lethargy, or any non-ICU hospital stay; and no evidence of MIS-C) require undergoing an ECG to look for cardiac dysfunction, followed by at least 10 days of rest if the ECG is negative or referral for cardiac evaluation if either ECG or exam by a pediatric cardiologist is abnormal.

Clinicians can perhaps be more permissible with patients who are younger or who have had less severe disease. For example, if a patient aged younger than 12 years is asymptomatic with routine activity at the time of evaluation, an ECG is not indicated. For patients aged 12-15 years who are asymptomatic at the time of evaluation but participate in a high-intensity sport, clinicians might consider obtaining an ECG. As few as 3 days of rest might be enough for select patients who are asymptomatic at presentation. For other patients, clinicians should work with parents to introduce activity gradually and make it clear to parents that any activity intolerance requires quick reevaluation. On existing athlete registries, no deaths that are attributable to post–COVID-19 cardiac effects have been confirmed in children; however, all data presented during the session were from prior to the Omicron variant surge in early 2022, so more information may be forthcoming.
 

Considerations for MIS-C

Among children experiencing MIS-C, 35% had ECG changes, 40% exhibited left ventricular systolic or diastolic dysfunction, and 30% had mitral regurgitation, meaning that a large percentage of patients with MIS-C show some degree of cardiac dysfunction. Unfortunately, we are still in the data-gathering phase for long-term outcomes. Functional parameters tend to improve within a week, and most patients will return to normal cardiac function by 3-4 months.

Return to play after MIS-C is quite different from that for acute COVID-19. Patients with MIS-C should be treated much like other patients with myocarditis with an expected return to play in 3-6 months and only after cardiac follow-up. Another good-to-remember recommendation is to delay COVID-19 vaccination for at least 90 days after an episode of MIS-C.
 

Vaccine-related myocarditis

Once again, older age appears to be a risk factor because most patients with postvaccine myocarditis have been in their mid-teens to early 20s, with events more likely after the second vaccine dose and also more likely in male children (4:1 ratio to female children). No deaths have occurred from postvaccination myocarditis in patients younger than 30 years. Still, many individuals have exhibited residual MRI enhancement in the cardiac tissue for some time after experiencing postvaccination myocarditis; it’s currently unclear whether that has clinical implications. By comparison, CDC data demonstrates convincingly that the risk for cardiac effects is much greater after acute COVID-19 than after COVID-19 vaccination, with risk ratios often higher than 20, depending on age and condition (for example, myocarditis vs. pericarditis). Data are still insufficient to determine whether clinicians should recommend or avoid COVID-19 vaccination in children with congenital heart disease.

In summary, administering COVID-19 vaccines requires a great deal of shared decision-making with parents, and the clinician’s role is to educate parents about all potential risks related to both the vaccine and COVID-19 illness. Research has consistently shown that acute COVID-19 myocarditis and myocarditis associated with MIS-C are much more likely to occur in unvaccinated youth and more likely than postvaccination myocarditis, regardless of age.

William T. Basco, Jr., MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

A version of this article first appeared on Medscape.com.

The 2022 Pediatric Academic Societies meeting included an excellent session on the acute and delayed effects of COVID-19 on children’s hearts. Data on the risk for cardiac injury during acute COVID-19, return-to-play guidelines after COVID-19–related heart injury, and post–vaccine-associated myocarditis were reviewed.

COVID-induced cardiac injury

The risk for COVID-induced cardiac injury is directly associated with age. Recent Centers for Disease Control and Prevention data revealed a “myocarditis or pericarditis” rate in the range of 12-17 cases per 100,000 SARS-CoV-2 infections among male children aged 5-11 years (lower rates for females); the rate jumps to 50-65 cases per 100,000 infections among male children aged 12-17 years. So cardiac injury caused by acute COVID-19 appears rare, but the risk is clearly associated with male sex and adolescent age.

Return to play after COVID-19

Clinicians may be pressed by patients and parents for advice on return to play after illness with COVID-19. In July 2020, the American College of Cardiology published an algorithm that has been adjusted over time, most recently in 2022 by the American Academy of Pediatrics. These algorithms stratify recommendations by degree of illness. One rule of thumb: Patients with severe COVID-19 (ICU care or multisystem inflammatory syndrome in children [MIS-C]) have only one box on the algorithm, and that is to rest for 3-6 months and only return to usual activity after cardiac clearance. Moderate disease (defined as ≥ 4 days of fever > 100.4 °F; ≥ 1 week of myalgia, chills, lethargy, or any non-ICU hospital stay; and no evidence of MIS-C) require undergoing an ECG to look for cardiac dysfunction, followed by at least 10 days of rest if the ECG is negative or referral for cardiac evaluation if either ECG or exam by a pediatric cardiologist is abnormal.

Clinicians can perhaps be more permissible with patients who are younger or who have had less severe disease. For example, if a patient aged younger than 12 years is asymptomatic with routine activity at the time of evaluation, an ECG is not indicated. For patients aged 12-15 years who are asymptomatic at the time of evaluation but participate in a high-intensity sport, clinicians might consider obtaining an ECG. As few as 3 days of rest might be enough for select patients who are asymptomatic at presentation. For other patients, clinicians should work with parents to introduce activity gradually and make it clear to parents that any activity intolerance requires quick reevaluation. On existing athlete registries, no deaths that are attributable to post–COVID-19 cardiac effects have been confirmed in children; however, all data presented during the session were from prior to the Omicron variant surge in early 2022, so more information may be forthcoming.
 

Considerations for MIS-C

Among children experiencing MIS-C, 35% had ECG changes, 40% exhibited left ventricular systolic or diastolic dysfunction, and 30% had mitral regurgitation, meaning that a large percentage of patients with MIS-C show some degree of cardiac dysfunction. Unfortunately, we are still in the data-gathering phase for long-term outcomes. Functional parameters tend to improve within a week, and most patients will return to normal cardiac function by 3-4 months.

Return to play after MIS-C is quite different from that for acute COVID-19. Patients with MIS-C should be treated much like other patients with myocarditis with an expected return to play in 3-6 months and only after cardiac follow-up. Another good-to-remember recommendation is to delay COVID-19 vaccination for at least 90 days after an episode of MIS-C.
 

Vaccine-related myocarditis

Once again, older age appears to be a risk factor because most patients with postvaccine myocarditis have been in their mid-teens to early 20s, with events more likely after the second vaccine dose and also more likely in male children (4:1 ratio to female children). No deaths have occurred from postvaccination myocarditis in patients younger than 30 years. Still, many individuals have exhibited residual MRI enhancement in the cardiac tissue for some time after experiencing postvaccination myocarditis; it’s currently unclear whether that has clinical implications. By comparison, CDC data demonstrates convincingly that the risk for cardiac effects is much greater after acute COVID-19 than after COVID-19 vaccination, with risk ratios often higher than 20, depending on age and condition (for example, myocarditis vs. pericarditis). Data are still insufficient to determine whether clinicians should recommend or avoid COVID-19 vaccination in children with congenital heart disease.

In summary, administering COVID-19 vaccines requires a great deal of shared decision-making with parents, and the clinician’s role is to educate parents about all potential risks related to both the vaccine and COVID-19 illness. Research has consistently shown that acute COVID-19 myocarditis and myocarditis associated with MIS-C are much more likely to occur in unvaccinated youth and more likely than postvaccination myocarditis, regardless of age.

William T. Basco, Jr., MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

A version of this article first appeared on Medscape.com.

I had an early attraction to newspapers. As a child growing up in Jersey City, N.J., I delivered them door-to-door. I was editor-in-chief of my high school newspaper and worked as a copy boy and sports reporter on the daily Jersey Journal. At Princeton, I joined the University Press Club, working as a string reporter for the New York Herald Tribune, Philadelphia Inquirer, and Associated Press.

I thought I might become a journalist, but medicine was too strong a calling. During my GI elective as a senior medical resident at New York Hospital, I was able to work with some of the first commercial fiberoptic instruments, which presaged my academic career in endoscopic innovation. I was editor-in-chief of Gastrointestinal Endoscopy from 1988 to 1996, and have been the consulting editor for GI Endoscopy Clinics of North America since 1997.

As the first editor-in-chief of GI & Hepatology News, I had the opportunity to combine a background in peer review with my early newspaper experience. My vision for the new publication was to provide information curated and vetted by experts, in contrast to the torrent pouring down from the Internet that was (pertinent to our specialty) “indigestible.” I put in much effort selecting stories provided by Elsevier Global Medical News, especially in constructing the front page. AGA Institute provided strong support, allowing me to choose an editorial board covering all subspecialties. I wanted to highlight the excitement of researchers balanced by expert review and commentary. The digital version added search features, and I tried to promote the “browse factor” that would also encourage advertising, critical to the success of any newspaper. At the end of my term, I felt I had laid a strong foundation, and have been delighted to see the publication continue to thrive.
 

Charles Lightdale, MD, is professor of medicine at Columbia University Medical Center in New York. He disclosed having no conflicts of interest.

I had an early attraction to newspapers. As a child growing up in Jersey City, N.J., I delivered them door-to-door. I was editor-in-chief of my high school newspaper and worked as a copy boy and sports reporter on the daily Jersey Journal. At Princeton, I joined the University Press Club, working as a string reporter for the New York Herald Tribune, Philadelphia Inquirer, and Associated Press.

I thought I might become a journalist, but medicine was too strong a calling. During my GI elective as a senior medical resident at New York Hospital, I was able to work with some of the first commercial fiberoptic instruments, which presaged my academic career in endoscopic innovation. I was editor-in-chief of Gastrointestinal Endoscopy from 1988 to 1996, and have been the consulting editor for GI Endoscopy Clinics of North America since 1997.

As the first editor-in-chief of GI & Hepatology News, I had the opportunity to combine a background in peer review with my early newspaper experience. My vision for the new publication was to provide information curated and vetted by experts, in contrast to the torrent pouring down from the Internet that was (pertinent to our specialty) “indigestible.” I put in much effort selecting stories provided by Elsevier Global Medical News, especially in constructing the front page. AGA Institute provided strong support, allowing me to choose an editorial board covering all subspecialties. I wanted to highlight the excitement of researchers balanced by expert review and commentary. The digital version added search features, and I tried to promote the “browse factor” that would also encourage advertising, critical to the success of any newspaper. At the end of my term, I felt I had laid a strong foundation, and have been delighted to see the publication continue to thrive.
 

Charles Lightdale, MD, is professor of medicine at Columbia University Medical Center in New York. He disclosed having no conflicts of interest.

I had an early attraction to newspapers. As a child growing up in Jersey City, N.J., I delivered them door-to-door. I was editor-in-chief of my high school newspaper and worked as a copy boy and sports reporter on the daily Jersey Journal. At Princeton, I joined the University Press Club, working as a string reporter for the New York Herald Tribune, Philadelphia Inquirer, and Associated Press.

I thought I might become a journalist, but medicine was too strong a calling. During my GI elective as a senior medical resident at New York Hospital, I was able to work with some of the first commercial fiberoptic instruments, which presaged my academic career in endoscopic innovation. I was editor-in-chief of Gastrointestinal Endoscopy from 1988 to 1996, and have been the consulting editor for GI Endoscopy Clinics of North America since 1997.

As the first editor-in-chief of GI & Hepatology News, I had the opportunity to combine a background in peer review with my early newspaper experience. My vision for the new publication was to provide information curated and vetted by experts, in contrast to the torrent pouring down from the Internet that was (pertinent to our specialty) “indigestible.” I put in much effort selecting stories provided by Elsevier Global Medical News, especially in constructing the front page. AGA Institute provided strong support, allowing me to choose an editorial board covering all subspecialties. I wanted to highlight the excitement of researchers balanced by expert review and commentary. The digital version added search features, and I tried to promote the “browse factor” that would also encourage advertising, critical to the success of any newspaper. At the end of my term, I felt I had laid a strong foundation, and have been delighted to see the publication continue to thrive.
 

Charles Lightdale, MD, is professor of medicine at Columbia University Medical Center in New York. He disclosed having no conflicts of interest.

There is a need to connect mental and physical symptoms in the diagnosis and treatment of psychiatric disorders. Obviously, we are not yet equipped to clearly recognize which neurotransmitters cause which symptoms. The science of defining the underlying mechanisms is lagging behind the clinical needs. However, in this article, we present a few hypothetical clinical cases to emphasize a possible way of analyzing symptoms in order to identify underlying pathology and guide more effective treatment. Our descriptions do not reflect the entire set of symptoms caused by these neurotransmitters; we created them based on what is presently known (or suspected). Additional research is needed to confirm or disprove the hypotheses we present.

In Part 1 (Current Psychiatry, May 2022), we argued that for depression, anxiety, psychosis, and bipolar disorder, development and approval of medications is currently based on descriptive diagnoses, with disregard to the various underlying causes of those conditions. Similar to how the many types of pneumonia are treated differently based on the specific infective agent, we suggested there are various types of depression or chronic pain based on the underlying neuro­transmitter pathology. Such an approach may be extrapolated to anxiety, psychosis, or bipolar disorder, although those conditions are outside the scope of this article. In Part 1, we described serotonin- and dopamine-associated mental and physical symptoms that suggest distinctly different types of depression or chronic pain, and we suggested specific ways of treating those described conditions. Part 2 reflects on pathology that is possibly connected to endorphin and norepinephrine dysfunction. Table 1 outlines medical and psychiatric symptoms that likely reflect endorphin excess^1-16 and deficiency,^1,16-24 and Table 2 lists symptoms that likely reflect norepinephrine excess^16,25-30and deficiency.^16,26,31-39 It is worth noting that both the quantity of neurotransmitters as well as the quality of the transmission (as in receptors, cellular pumps, and distribution mechanisms) are important.

Endorphin excess (Table 1^1-16)

Ms. R is a frustrated chronic pain patient who bitterly complains that despite having seen more than 20 physicians, she does not have an answer to what causes her “all over” pain and headache.^4,5,11 She does not believe that all her laboratory test are normal, and insists that “something is missing.” She aches all over but says she can actually tolerate more pain than others and experiences only a little discomfort during an electromyogram or dental interventions. Though Ms. R is not very susceptible to acute pain,^4,5,9,16 pain all over without an identifiable cause is part of her life.^4,5,11 She says that listening to music and social interactions help decrease her pain.^4,5,10 Ms. R states that opioid medications do not help her pain, though she has a history of opioid overuse and opioid-induced hyperalgesia.^6,11,16

Ms. R tends to overdo pleasureful activities to achieve satisfaction.² She says exercise is particularly satisfying, to the point that she experiences euphoria and a loss of time.⁹ She is angry that her neurologist suggested she see a psychiatrist. Her depression bothers her more than her anxiety.^2,5,7

Ms. R clearly has a self-image problem, alternating between high and low self-esteem. She has a low appetite^1,12,14-16 and sleeps excessively.^2,4,7,9,10 Her mother privately tells you that Ms. R has a history of childhood sexual abuse and lagged in life due to a lack of motivation. Ms. R used to self-mutilate “to feel normal.”¹² Her primary care physician chronically addresses Ms. R’s poorly explained cholestasis and pruritus⁸ as well as dysregulation of blood pressure and heart rate, both of which tend to be low.^12,13,16

Impression. Ms. R shows multiple symptoms associated with endorphin excess. A trial of an opioid antagonist may be reasonable. Dopamine blockade helps with endorphin suppression and also may be used for this patient. Using a low starting dose and a slow titration of such medications would be beneficial due to frequent intolerance issues, especially nausea. Gamma aminobutyric acid-ergic medications modulate the opioid system and may be considered. A serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine may help patients such as Ms. R to control mood and pain through norepinephrine’s influence on endorphins.

Endorphin deficiency (Table 1^1,16-24)

Mr. J complains of low back pain, diffuse body pain, depression, and moodiness.^19,20,24 He is sluggish and plagued by psychomotor retardation.²⁴ All his life, a heightened perception of pain has caused him problems,^19,20 but has not stopped him from engaging in self-mutilation.²⁴ His “unexplained” pain and general body aches seem to be associated with objectively verifiable pain generators (such as bruises and surgical procedures) but this pain is in excess of what would generally be expected. Mr. J describes his low back pain as mild degenerative disc disease and is eager to explain that his wife’s spine is more diseased, yet she has no back pain.

Continue to: Mr. J responds to treatment...

Mr. J responds to treatment with opioids^16,20 but comments that his mood, and not necessarily his pain, improves when he takes these medications.²⁰ He tends to overuse his pain medications, and had run into trouble with his previous pain management physician. Nitrous oxide is remarkably effective during dental procedures.¹⁹ Acupuncture helps to control his pain and mood.¹⁷ Exercise is also rewarding.¹⁸

Mr. J has difficulty achieving orgasm, a decreased sexual drive, and emotional sensitivity.²⁴ He is impulsive.^19,20,24 His baseline mood is low-grade; anxiety bothers him more than depression.^23,24 Mr. J is thin, has a poor appetite,^1,16 and sleeps poorly.²⁴ His primary care physician struggles to help Mr. J to control dysregulation of his heart rate, blood pressure,²¹ and urinary retention,^16,22 as well as episodes of hypoglycemia.^1,16 He reluctantly admits to abusing alcohol, but explains that it helps with his mood and pain better than his prescribed medications.^18,23

Impression. Mr. J exhibits multiple symptoms associated with endorphin deficiency. Short-term use of opioids is warranted, but he should avoid long-term opioid use, and he and his physician should work together to establish strict control of their intake. Buprenorphine would be the opioid of choice for such a patient. Psychiatric treatment, including for alcohol use disorder, should be a mandatory part of his treatment regimen. Behavioral therapy with a focus on finding healthy ways to achieve gratification would be effective. Alternative treatments such as acupuncture may be of value.

Norepinephrine excess (Table 2^16,25-30)

Mr. G comes to the office irritable and angry^28,30 because no one can help him with his intractable headaches.^16,25 He is pale, his breathing is noisy, and he licks his dry lips while sweating.^16,25 His wife is shy and seems to be afraid of her husband, who is easily irritated and edgy.^28,30 His heart rate and blood pressure are high; he has a history of palpitations and chest pain.^16,25 When unhappy, he gets pale, sweaty, tremulous, and nauseous.^16,25 He masks his anxiety with aggression and has impaired concentration, restless sleep, muscle tension, muscle cramps, and abdominal cramps.^27,28,30 Mr. G suffers from frequent nausea.^16,25 His neck is stiff and pupils are dilated; he clenches his teeth and uses a mouth guard for correction of temporomandibular joint disorder.^16,25 His sleep apnea is poorly controlled because he feels entrapped when he uses a continuous positive airway pressure machine.²⁹ He blames his wife for his premature ejaculation and says that she gives him goosebumps.²⁵ His hypervigilance and hyperarousal are torturous to his wife.^27,30 Despite his overall angry state, Mr. G is also constantly fearful.^28,30 He is almost never hungry, does not like crowds, hates your waiting area, and is vocal about his dislike of doctors being late “all the time.”^26,28,30

Comment. Norepinephrine and dopamine functions are connected through common neuronal and glial uptake mechanisms. This is a foundation of norepinephrine excess symptoms crossing over with symptoms of dopamine deficiency.

Continue to: Impression

Impression. Mr. G shows multiple symptoms associated with norepinephrine excess. It is important to avoid caffeine intake in patients with clinical signs of excessive norepinephrine. Beta-blockers and alpha-2 agonists work well in patients such as Mr. G. Benzodiazepines indirectly decrease norepinephrine activity, but need to be used carefully due to the potential for misuse and addiction. In particular, short-acting benzodiazepines such as alprazolam and lorazepam must be avoided due to the induction of CNS instability with rapidly changing medication blood levels. Chlordiazepoxide may be a good choice for a patient such as Mr. G because it has the fewest adverse effects and the lowest abuse potential compared with other benzodiazepines. Avoid SNRIs in such a patient. Using mood-stabilizing antipsychotic medications may be especially warranted in treating Mr. G’s depression and pain.

Norepinephrine deficiency (Table 2^16,26,31-39)

Two years ago, Ms. A was diagnosed with chronic fatigue³¹ and fibromyalgia. She also had been diagnosed with depression and attention-deficit/hyperactivity disorder (ADHD). She presents with concerns of “brain fog,” no energy, low sex drive, and daytime sleepiness.^33,35 Allodynia is widespread.^16,36,37 Ms. A suffers from bulimia; she eats once a day but is still overweight.²⁶ She has orthostatic hypotension in addition to baseline low blood pressure and bradycardia.^16,38,39 Her pupils are almost pinpoint, even when she does not take opioid medications.¹⁶ Her skin is dry and her hair is brittle; deep tendon reflexes are weakened, and her muscle tone is decreased.¹⁶ Ms. A’s constant low mood drives her to drink excessive amounts of caffeine, which she says “helps with daytime sleepiness but does not last”^32,33 and causes heart rhythm problems³⁸ and dyspepsia.¹⁶ She sees that her headaches and body pain are associated with her caffeine intake, but refuses to stop taking caffeine. Her low interest in life and general passivity have caused her many problems, though the problems themselves do not make her feel much.^31,32,39 She is rather indifferent to pleasurable activities, including sex.³¹ Her response to exciting experiences is blunted,³² but she is still frequently tearful.³⁴ Ms. A’s mood does not improve with selective serotonin reuptake inhibitors; she has tried many. She says that she would not come to see a physician, but “my mom told me to.” She resents that her family thinks she is lazy^31,32,39 and blames her ADHD for underperformance in life.^32,33 Ms. A has a family history of chronic pain and Alzheimer disease, and the longer she experiences pain, the worse her memory.³⁵

Comment. As mentioned earlier, because of the norepinephrine/dopamine relationship, symptoms of excess dopamine overlap with symptoms of norepinephrine deficiency.

Impression. Ms. A shows multiple symptoms associated with norepinephrine deficiency. The use of noradrenergic antidepressants (such as SNRIs and mirtazapine)²⁶ and stimulants may be warranted. Physical exercise, participating in social activities, massage, acupuncture, and family support may help with Ms. A’s pain as well as her depression, as might vasopressors.

In Part 3, we will address gamma aminobutyric acid and glutamate.

Bottom Line

Both high and low levels of endorphins and norepinephrine may be associated with certain psychiatric and medical symptoms and disorders. An astute clinician may judge which neurotransmitter is dysfunctional based on the patient’s presentation, and tailor treatment accordingly.

Related Resources

• Arbuck DM, Salmerón JM, Mueller R. Neurotransmitter-based diagnosis and treatment: a hypothesis (Part 1). Current Psychiatry. 2022;21(5):30-36. doi:10.12788/cp.0242

Drug Brand Names

Alprazolam • Xanax
Chlordiazepoxide • Librium
Lorazepam • Ativan
Mirtazapine • Remeron

There is a need to connect mental and physical symptoms in the diagnosis and treatment of psychiatric disorders. Obviously, we are not yet equipped to clearly recognize which neurotransmitters cause which symptoms. The science of defining the underlying mechanisms is lagging behind the clinical needs. However, in this article, we present a few hypothetical clinical cases to emphasize a possible way of analyzing symptoms in order to identify underlying pathology and guide more effective treatment. Our descriptions do not reflect the entire set of symptoms caused by these neurotransmitters; we created them based on what is presently known (or suspected). Additional research is needed to confirm or disprove the hypotheses we present.

In Part 1 (Current Psychiatry, May 2022), we argued that for depression, anxiety, psychosis, and bipolar disorder, development and approval of medications is currently based on descriptive diagnoses, with disregard to the various underlying causes of those conditions. Similar to how the many types of pneumonia are treated differently based on the specific infective agent, we suggested there are various types of depression or chronic pain based on the underlying neuro­transmitter pathology. Such an approach may be extrapolated to anxiety, psychosis, or bipolar disorder, although those conditions are outside the scope of this article. In Part 1, we described serotonin- and dopamine-associated mental and physical symptoms that suggest distinctly different types of depression or chronic pain, and we suggested specific ways of treating those described conditions. Part 2 reflects on pathology that is possibly connected to endorphin and norepinephrine dysfunction. Table 1 outlines medical and psychiatric symptoms that likely reflect endorphin excess^1-16 and deficiency,^1,16-24 and Table 2 lists symptoms that likely reflect norepinephrine excess^16,25-30and deficiency.^16,26,31-39 It is worth noting that both the quantity of neurotransmitters as well as the quality of the transmission (as in receptors, cellular pumps, and distribution mechanisms) are important.

Endorphin excess (Table 1^1-16)

Ms. R is a frustrated chronic pain patient who bitterly complains that despite having seen more than 20 physicians, she does not have an answer to what causes her “all over” pain and headache.^4,5,11 She does not believe that all her laboratory test are normal, and insists that “something is missing.” She aches all over but says she can actually tolerate more pain than others and experiences only a little discomfort during an electromyogram or dental interventions. Though Ms. R is not very susceptible to acute pain,^4,5,9,16 pain all over without an identifiable cause is part of her life.^4,5,11 She says that listening to music and social interactions help decrease her pain.^4,5,10 Ms. R states that opioid medications do not help her pain, though she has a history of opioid overuse and opioid-induced hyperalgesia.^6,11,16

Ms. R tends to overdo pleasureful activities to achieve satisfaction.² She says exercise is particularly satisfying, to the point that she experiences euphoria and a loss of time.⁹ She is angry that her neurologist suggested she see a psychiatrist. Her depression bothers her more than her anxiety.^2,5,7

Ms. R clearly has a self-image problem, alternating between high and low self-esteem. She has a low appetite^1,12,14-16 and sleeps excessively.^2,4,7,9,10 Her mother privately tells you that Ms. R has a history of childhood sexual abuse and lagged in life due to a lack of motivation. Ms. R used to self-mutilate “to feel normal.”¹² Her primary care physician chronically addresses Ms. R’s poorly explained cholestasis and pruritus⁸ as well as dysregulation of blood pressure and heart rate, both of which tend to be low.^12,13,16

Impression. Ms. R shows multiple symptoms associated with endorphin excess. A trial of an opioid antagonist may be reasonable. Dopamine blockade helps with endorphin suppression and also may be used for this patient. Using a low starting dose and a slow titration of such medications would be beneficial due to frequent intolerance issues, especially nausea. Gamma aminobutyric acid-ergic medications modulate the opioid system and may be considered. A serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine may help patients such as Ms. R to control mood and pain through norepinephrine’s influence on endorphins.

Endorphin deficiency (Table 1^1,16-24)

Mr. J complains of low back pain, diffuse body pain, depression, and moodiness.^19,20,24 He is sluggish and plagued by psychomotor retardation.²⁴ All his life, a heightened perception of pain has caused him problems,^19,20 but has not stopped him from engaging in self-mutilation.²⁴ His “unexplained” pain and general body aches seem to be associated with objectively verifiable pain generators (such as bruises and surgical procedures) but this pain is in excess of what would generally be expected. Mr. J describes his low back pain as mild degenerative disc disease and is eager to explain that his wife’s spine is more diseased, yet she has no back pain.

Continue to: Mr. J responds to treatment...

Mr. J responds to treatment with opioids^16,20 but comments that his mood, and not necessarily his pain, improves when he takes these medications.²⁰ He tends to overuse his pain medications, and had run into trouble with his previous pain management physician. Nitrous oxide is remarkably effective during dental procedures.¹⁹ Acupuncture helps to control his pain and mood.¹⁷ Exercise is also rewarding.¹⁸

Mr. J has difficulty achieving orgasm, a decreased sexual drive, and emotional sensitivity.²⁴ He is impulsive.^19,20,24 His baseline mood is low-grade; anxiety bothers him more than depression.^23,24 Mr. J is thin, has a poor appetite,^1,16 and sleeps poorly.²⁴ His primary care physician struggles to help Mr. J to control dysregulation of his heart rate, blood pressure,²¹ and urinary retention,^16,22 as well as episodes of hypoglycemia.^1,16 He reluctantly admits to abusing alcohol, but explains that it helps with his mood and pain better than his prescribed medications.^18,23

Impression. Mr. J exhibits multiple symptoms associated with endorphin deficiency. Short-term use of opioids is warranted, but he should avoid long-term opioid use, and he and his physician should work together to establish strict control of their intake. Buprenorphine would be the opioid of choice for such a patient. Psychiatric treatment, including for alcohol use disorder, should be a mandatory part of his treatment regimen. Behavioral therapy with a focus on finding healthy ways to achieve gratification would be effective. Alternative treatments such as acupuncture may be of value.

Norepinephrine excess (Table 2^16,25-30)

Mr. G comes to the office irritable and angry^28,30 because no one can help him with his intractable headaches.^16,25 He is pale, his breathing is noisy, and he licks his dry lips while sweating.^16,25 His wife is shy and seems to be afraid of her husband, who is easily irritated and edgy.^28,30 His heart rate and blood pressure are high; he has a history of palpitations and chest pain.^16,25 When unhappy, he gets pale, sweaty, tremulous, and nauseous.^16,25 He masks his anxiety with aggression and has impaired concentration, restless sleep, muscle tension, muscle cramps, and abdominal cramps.^27,28,30 Mr. G suffers from frequent nausea.^16,25 His neck is stiff and pupils are dilated; he clenches his teeth and uses a mouth guard for correction of temporomandibular joint disorder.^16,25 His sleep apnea is poorly controlled because he feels entrapped when he uses a continuous positive airway pressure machine.²⁹ He blames his wife for his premature ejaculation and says that she gives him goosebumps.²⁵ His hypervigilance and hyperarousal are torturous to his wife.^27,30 Despite his overall angry state, Mr. G is also constantly fearful.^28,30 He is almost never hungry, does not like crowds, hates your waiting area, and is vocal about his dislike of doctors being late “all the time.”^26,28,30

Comment. Norepinephrine and dopamine functions are connected through common neuronal and glial uptake mechanisms. This is a foundation of norepinephrine excess symptoms crossing over with symptoms of dopamine deficiency.

Continue to: Impression

Impression. Mr. G shows multiple symptoms associated with norepinephrine excess. It is important to avoid caffeine intake in patients with clinical signs of excessive norepinephrine. Beta-blockers and alpha-2 agonists work well in patients such as Mr. G. Benzodiazepines indirectly decrease norepinephrine activity, but need to be used carefully due to the potential for misuse and addiction. In particular, short-acting benzodiazepines such as alprazolam and lorazepam must be avoided due to the induction of CNS instability with rapidly changing medication blood levels. Chlordiazepoxide may be a good choice for a patient such as Mr. G because it has the fewest adverse effects and the lowest abuse potential compared with other benzodiazepines. Avoid SNRIs in such a patient. Using mood-stabilizing antipsychotic medications may be especially warranted in treating Mr. G’s depression and pain.

Norepinephrine deficiency (Table 2^16,26,31-39)

Two years ago, Ms. A was diagnosed with chronic fatigue³¹ and fibromyalgia. She also had been diagnosed with depression and attention-deficit/hyperactivity disorder (ADHD). She presents with concerns of “brain fog,” no energy, low sex drive, and daytime sleepiness.^33,35 Allodynia is widespread.^16,36,37 Ms. A suffers from bulimia; she eats once a day but is still overweight.²⁶ She has orthostatic hypotension in addition to baseline low blood pressure and bradycardia.^16,38,39 Her pupils are almost pinpoint, even when she does not take opioid medications.¹⁶ Her skin is dry and her hair is brittle; deep tendon reflexes are weakened, and her muscle tone is decreased.¹⁶ Ms. A’s constant low mood drives her to drink excessive amounts of caffeine, which she says “helps with daytime sleepiness but does not last”^32,33 and causes heart rhythm problems³⁸ and dyspepsia.¹⁶ She sees that her headaches and body pain are associated with her caffeine intake, but refuses to stop taking caffeine. Her low interest in life and general passivity have caused her many problems, though the problems themselves do not make her feel much.^31,32,39 She is rather indifferent to pleasurable activities, including sex.³¹ Her response to exciting experiences is blunted,³² but she is still frequently tearful.³⁴ Ms. A’s mood does not improve with selective serotonin reuptake inhibitors; she has tried many. She says that she would not come to see a physician, but “my mom told me to.” She resents that her family thinks she is lazy^31,32,39 and blames her ADHD for underperformance in life.^32,33 Ms. A has a family history of chronic pain and Alzheimer disease, and the longer she experiences pain, the worse her memory.³⁵

Comment. As mentioned earlier, because of the norepinephrine/dopamine relationship, symptoms of excess dopamine overlap with symptoms of norepinephrine deficiency.

Impression. Ms. A shows multiple symptoms associated with norepinephrine deficiency. The use of noradrenergic antidepressants (such as SNRIs and mirtazapine)²⁶ and stimulants may be warranted. Physical exercise, participating in social activities, massage, acupuncture, and family support may help with Ms. A’s pain as well as her depression, as might vasopressors.

In Part 3, we will address gamma aminobutyric acid and glutamate.

Bottom Line

Both high and low levels of endorphins and norepinephrine may be associated with certain psychiatric and medical symptoms and disorders. An astute clinician may judge which neurotransmitter is dysfunctional based on the patient’s presentation, and tailor treatment accordingly.

Related Resources

• Arbuck DM, Salmerón JM, Mueller R. Neurotransmitter-based diagnosis and treatment: a hypothesis (Part 1). Current Psychiatry. 2022;21(5):30-36. doi:10.12788/cp.0242

Drug Brand Names

Alprazolam • Xanax
Chlordiazepoxide • Librium
Lorazepam • Ativan
Mirtazapine • Remeron

There is a need to connect mental and physical symptoms in the diagnosis and treatment of psychiatric disorders. Obviously, we are not yet equipped to clearly recognize which neurotransmitters cause which symptoms. The science of defining the underlying mechanisms is lagging behind the clinical needs. However, in this article, we present a few hypothetical clinical cases to emphasize a possible way of analyzing symptoms in order to identify underlying pathology and guide more effective treatment. Our descriptions do not reflect the entire set of symptoms caused by these neurotransmitters; we created them based on what is presently known (or suspected). Additional research is needed to confirm or disprove the hypotheses we present.

In Part 1 (Current Psychiatry, May 2022), we argued that for depression, anxiety, psychosis, and bipolar disorder, development and approval of medications is currently based on descriptive diagnoses, with disregard to the various underlying causes of those conditions. Similar to how the many types of pneumonia are treated differently based on the specific infective agent, we suggested there are various types of depression or chronic pain based on the underlying neuro­transmitter pathology. Such an approach may be extrapolated to anxiety, psychosis, or bipolar disorder, although those conditions are outside the scope of this article. In Part 1, we described serotonin- and dopamine-associated mental and physical symptoms that suggest distinctly different types of depression or chronic pain, and we suggested specific ways of treating those described conditions. Part 2 reflects on pathology that is possibly connected to endorphin and norepinephrine dysfunction. Table 1 outlines medical and psychiatric symptoms that likely reflect endorphin excess^1-16 and deficiency,^1,16-24 and Table 2 lists symptoms that likely reflect norepinephrine excess^16,25-30and deficiency.^16,26,31-39 It is worth noting that both the quantity of neurotransmitters as well as the quality of the transmission (as in receptors, cellular pumps, and distribution mechanisms) are important.

Endorphin excess (Table 1^1-16)

Ms. R is a frustrated chronic pain patient who bitterly complains that despite having seen more than 20 physicians, she does not have an answer to what causes her “all over” pain and headache.^4,5,11 She does not believe that all her laboratory test are normal, and insists that “something is missing.” She aches all over but says she can actually tolerate more pain than others and experiences only a little discomfort during an electromyogram or dental interventions. Though Ms. R is not very susceptible to acute pain,^4,5,9,16 pain all over without an identifiable cause is part of her life.^4,5,11 She says that listening to music and social interactions help decrease her pain.^4,5,10 Ms. R states that opioid medications do not help her pain, though she has a history of opioid overuse and opioid-induced hyperalgesia.^6,11,16

Ms. R tends to overdo pleasureful activities to achieve satisfaction.² She says exercise is particularly satisfying, to the point that she experiences euphoria and a loss of time.⁹ She is angry that her neurologist suggested she see a psychiatrist. Her depression bothers her more than her anxiety.^2,5,7

Ms. R clearly has a self-image problem, alternating between high and low self-esteem. She has a low appetite^1,12,14-16 and sleeps excessively.^2,4,7,9,10 Her mother privately tells you that Ms. R has a history of childhood sexual abuse and lagged in life due to a lack of motivation. Ms. R used to self-mutilate “to feel normal.”¹² Her primary care physician chronically addresses Ms. R’s poorly explained cholestasis and pruritus⁸ as well as dysregulation of blood pressure and heart rate, both of which tend to be low.^12,13,16

Impression. Ms. R shows multiple symptoms associated with endorphin excess. A trial of an opioid antagonist may be reasonable. Dopamine blockade helps with endorphin suppression and also may be used for this patient. Using a low starting dose and a slow titration of such medications would be beneficial due to frequent intolerance issues, especially nausea. Gamma aminobutyric acid-ergic medications modulate the opioid system and may be considered. A serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine may help patients such as Ms. R to control mood and pain through norepinephrine’s influence on endorphins.

Endorphin deficiency (Table 1^1,16-24)

Mr. J complains of low back pain, diffuse body pain, depression, and moodiness.^19,20,24 He is sluggish and plagued by psychomotor retardation.²⁴ All his life, a heightened perception of pain has caused him problems,^19,20 but has not stopped him from engaging in self-mutilation.²⁴ His “unexplained” pain and general body aches seem to be associated with objectively verifiable pain generators (such as bruises and surgical procedures) but this pain is in excess of what would generally be expected. Mr. J describes his low back pain as mild degenerative disc disease and is eager to explain that his wife’s spine is more diseased, yet she has no back pain.

Continue to: Mr. J responds to treatment...

Mr. J responds to treatment with opioids^16,20 but comments that his mood, and not necessarily his pain, improves when he takes these medications.²⁰ He tends to overuse his pain medications, and had run into trouble with his previous pain management physician. Nitrous oxide is remarkably effective during dental procedures.¹⁹ Acupuncture helps to control his pain and mood.¹⁷ Exercise is also rewarding.¹⁸

Mr. J has difficulty achieving orgasm, a decreased sexual drive, and emotional sensitivity.²⁴ He is impulsive.^19,20,24 His baseline mood is low-grade; anxiety bothers him more than depression.^23,24 Mr. J is thin, has a poor appetite,^1,16 and sleeps poorly.²⁴ His primary care physician struggles to help Mr. J to control dysregulation of his heart rate, blood pressure,²¹ and urinary retention,^16,22 as well as episodes of hypoglycemia.^1,16 He reluctantly admits to abusing alcohol, but explains that it helps with his mood and pain better than his prescribed medications.^18,23

Impression. Mr. J exhibits multiple symptoms associated with endorphin deficiency. Short-term use of opioids is warranted, but he should avoid long-term opioid use, and he and his physician should work together to establish strict control of their intake. Buprenorphine would be the opioid of choice for such a patient. Psychiatric treatment, including for alcohol use disorder, should be a mandatory part of his treatment regimen. Behavioral therapy with a focus on finding healthy ways to achieve gratification would be effective. Alternative treatments such as acupuncture may be of value.

Norepinephrine excess (Table 2^16,25-30)

Mr. G comes to the office irritable and angry^28,30 because no one can help him with his intractable headaches.^16,25 He is pale, his breathing is noisy, and he licks his dry lips while sweating.^16,25 His wife is shy and seems to be afraid of her husband, who is easily irritated and edgy.^28,30 His heart rate and blood pressure are high; he has a history of palpitations and chest pain.^16,25 When unhappy, he gets pale, sweaty, tremulous, and nauseous.^16,25 He masks his anxiety with aggression and has impaired concentration, restless sleep, muscle tension, muscle cramps, and abdominal cramps.^27,28,30 Mr. G suffers from frequent nausea.^16,25 His neck is stiff and pupils are dilated; he clenches his teeth and uses a mouth guard for correction of temporomandibular joint disorder.^16,25 His sleep apnea is poorly controlled because he feels entrapped when he uses a continuous positive airway pressure machine.²⁹ He blames his wife for his premature ejaculation and says that she gives him goosebumps.²⁵ His hypervigilance and hyperarousal are torturous to his wife.^27,30 Despite his overall angry state, Mr. G is also constantly fearful.^28,30 He is almost never hungry, does not like crowds, hates your waiting area, and is vocal about his dislike of doctors being late “all the time.”^26,28,30

Comment. Norepinephrine and dopamine functions are connected through common neuronal and glial uptake mechanisms. This is a foundation of norepinephrine excess symptoms crossing over with symptoms of dopamine deficiency.

Continue to: Impression

Impression. Mr. G shows multiple symptoms associated with norepinephrine excess. It is important to avoid caffeine intake in patients with clinical signs of excessive norepinephrine. Beta-blockers and alpha-2 agonists work well in patients such as Mr. G. Benzodiazepines indirectly decrease norepinephrine activity, but need to be used carefully due to the potential for misuse and addiction. In particular, short-acting benzodiazepines such as alprazolam and lorazepam must be avoided due to the induction of CNS instability with rapidly changing medication blood levels. Chlordiazepoxide may be a good choice for a patient such as Mr. G because it has the fewest adverse effects and the lowest abuse potential compared with other benzodiazepines. Avoid SNRIs in such a patient. Using mood-stabilizing antipsychotic medications may be especially warranted in treating Mr. G’s depression and pain.

Norepinephrine deficiency (Table 2^16,26,31-39)

Two years ago, Ms. A was diagnosed with chronic fatigue³¹ and fibromyalgia. She also had been diagnosed with depression and attention-deficit/hyperactivity disorder (ADHD). She presents with concerns of “brain fog,” no energy, low sex drive, and daytime sleepiness.^33,35 Allodynia is widespread.^16,36,37 Ms. A suffers from bulimia; she eats once a day but is still overweight.²⁶ She has orthostatic hypotension in addition to baseline low blood pressure and bradycardia.^16,38,39 Her pupils are almost pinpoint, even when she does not take opioid medications.¹⁶ Her skin is dry and her hair is brittle; deep tendon reflexes are weakened, and her muscle tone is decreased.¹⁶ Ms. A’s constant low mood drives her to drink excessive amounts of caffeine, which she says “helps with daytime sleepiness but does not last”^32,33 and causes heart rhythm problems³⁸ and dyspepsia.¹⁶ She sees that her headaches and body pain are associated with her caffeine intake, but refuses to stop taking caffeine. Her low interest in life and general passivity have caused her many problems, though the problems themselves do not make her feel much.^31,32,39 She is rather indifferent to pleasurable activities, including sex.³¹ Her response to exciting experiences is blunted,³² but she is still frequently tearful.³⁴ Ms. A’s mood does not improve with selective serotonin reuptake inhibitors; she has tried many. She says that she would not come to see a physician, but “my mom told me to.” She resents that her family thinks she is lazy^31,32,39 and blames her ADHD for underperformance in life.^32,33 Ms. A has a family history of chronic pain and Alzheimer disease, and the longer she experiences pain, the worse her memory.³⁵

Comment. As mentioned earlier, because of the norepinephrine/dopamine relationship, symptoms of excess dopamine overlap with symptoms of norepinephrine deficiency.

Impression. Ms. A shows multiple symptoms associated with norepinephrine deficiency. The use of noradrenergic antidepressants (such as SNRIs and mirtazapine)²⁶ and stimulants may be warranted. Physical exercise, participating in social activities, massage, acupuncture, and family support may help with Ms. A’s pain as well as her depression, as might vasopressors.

In Part 3, we will address gamma aminobutyric acid and glutamate.

Bottom Line

Both high and low levels of endorphins and norepinephrine may be associated with certain psychiatric and medical symptoms and disorders. An astute clinician may judge which neurotransmitter is dysfunctional based on the patient’s presentation, and tailor treatment accordingly.

Related Resources

• Arbuck DM, Salmerón JM, Mueller R. Neurotransmitter-based diagnosis and treatment: a hypothesis (Part 1). Current Psychiatry. 2022;21(5):30-36. doi:10.12788/cp.0242

Drug Brand Names

Alprazolam • Xanax
Chlordiazepoxide • Librium
Lorazepam • Ativan
Mirtazapine • Remeron

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.

Having witnessed the devastating impact of stigma on patients with mental illness throughout my psychiatric career, I am fed up and disgusted with this malevolent scourge.

I regard the stigma that engulfs neuropsychiatric disorders as a malignancy that mutilates patients’ souls and hastens their mortality.

Stigma is hate speech

How would you feel if you had a serious medical illness, a disabling brain disorder such as schizophrenia, depression, or anxiety, and people refer to you with pejorative and insulting terms such as crazy, deranged, lunatic, unhinged, nutty, insane, wacky, berserk, cuckoo, bonkers, flaky, screwball, or unglued? This is hate speech generated by stigma against people with mental illness. Individuals with heart disease, cancer, or diabetes never get called such disgraceful and stigmatizing terms that shame, stain, besmirch, and scar them, which happens daily to persons with psychiatric brain disorders.

The damage and harm of the discriminatory stigma on our patients is multifaceted. It is painful, detrimental, pernicious, and deleterious. It is corrosive to their spirits, crippling to their self-image, and subversive to their self-confidence. Hate speech is not simply words, but a menacing weapon that assaults the core humanity of medically ill psychiatric patients.

Although hate speech is punishable by law, there are rarely any legal actions against those who hurl hate speech at psychiatric patients every day. Society has institutionalized the stigma of mental illness and takes it in stride instead of recognizing it as an illegal, harmful act.

Long before the stresses of the COVID-19 pandemic, 43% of the population had been shown to experience a diagnosable psychiatric disorder over the course of their life.¹ Thus, tens of millions of people are burdened by stigma and the hate speech associated with it. This is directly related to massive ignorance about mental illness being the result of a neurobiological condition due to either genetic or intrauterine adverse events that disrupt brain development. Delusions and hallucinations are symptoms of a malfunctioning brain, depression is not a sign of personal weakness, anxiety is the most prevalent mental disorder in the world, and obsessive-compulsive disorder (OCD) is not odd behavior but the result of dysfunction of neural circuits. Correcting public misperceptions about psychiatric brain disorders can mitigate stigma, but it has yet to happen.

Stigma is a hate crime

Stigma can accelerate physical death and premature mortality. Many studies have confirmed that persons with schizophrenia do not receive basic primary care treatments for the life-shortening medical conditions that often afflict them, such as diabetes, dyslipidemia, and hypertension.² Stigma is responsible for a significant disparity of medical^3-5 and intensive care⁶ among individuals with mental illness compared to the general population. It’s no wonder most psychiatric disorders are associated with accelerated mortality.⁷ A recent study during the pandemic by Balasuriya et al⁸ reported that patients with depression had poor access to care. Stigma interferes with or delays necessary medical care, leading to clinical deterioration and unnecessary, preventable death. Stigma shortens life and is a hate crime.

Continue to: The extremely high suicide rates...

The extremely high suicide rates among individuals with serious mental illness, who live under the oppressiveness of stigma, is another example of how stigma is a hate crime that can cause patients with psychiatric disorders to give up and end their lives. Zaheer et al⁹ found that young patients with schizophrenia had an astronomical suicide rate compared to the general population (1 in 52 in individuals with schizophrenia, compared to 12 in 100,000 in the general population, roughly a 200-fold increase!). This is clearly a consequence of stigma and discrimination,¹⁰ which leads to demoralization, shame, loneliness, distress, and hopelessness. Stigma can be fatal, and that makes it a hate crime.

Stigma also limits vocational opportunities for individuals with mental illness. They are either not hired, or quickly fired. Even highly educated professionals such as physicians, nurses, lawyers, or teachers can lose their jobs if they divulge a history of a psychiatric disorder or alcohol or substance abuse, regardless of whether they are receiving treatment and are medically in remission. Even highly qualified politicians have been deemed “ineligible” for higher office if they disclose a history of psychiatric treatment. Stigma is loaded with outrageous discrimination that deprives our patients of “the pursuit of happiness,” a fundamental constitutional right.

Stigma surrounding the mental health professions

Stigma also engulfs mental health professionals, simply because they deal with psychiatric patients every day. In a classic article titled “The Enigma of Stigma,”¹¹ Dr. Paul Fink, past president of the American Psychiatric Association (1988-1989), described how psychiatrists are perceived as “different” from other physicians by the public and by the media. He said psychiatrists are tarred by the same brush as their patients as “undesirables” in society. And movies such as Psycho and One Flew Over the Cuckoo’s Nest reinforce the stigma against both psychiatric patients and the psychiatrists and nurses who treat them. The health care system that carves out “behavioral health” from the umbrella of “medical care” further accentuates the stigma by portraying the “separateness” of psychiatry, a genuine medical specialty, from its fellow medical disciplines. This becomes fodder for the antipsychiatry movement at every turn and can even lead to questioning the existence of mental illness, as Thomas Szasz¹² did by declaring that mental illness is a myth and describing psychiatry as “the science of lies.” No other medical specialty endures abuse and insults like psychiatry, and that’s a direct result of stigma.

Extinguishing stigma is a societal imperative

So what can be done to squelch stigma and defeat it once and for all, so that psychiatric patients can be treated with dignity and compassion, like people with cancer, heart attacks, diabetes, or brain tumors? The pandemic, terrible as it has been for the entire world, did have the silver lining of raising awareness about the ubiquity of psychiatric symptoms, such as anxiety and depression, across all ages, genders, educational and religious backgrounds, and socioeconomic classes. But there should also be a robust legal battle against the damaging effects of stigma. There are laws to sanction and penalize hate speech and hate crimes that must be implemented when stigma is documented. There are also parity laws, but they have no teeth and have not ameliorated the insurance discrepancies and economic burden of psychiatric disorders. A bold step would be to reclassify serious psychiatric brain disorders (schizophrenia, bipolar disorder, major depressive disorder, OCD, attention-deficit/hyperactivity disorder, generalized anxiety disorder/panic attacks, and borderline personality disorder) as neurologic disorders, which would automatically give patients with these disorders broad access to medical care, which happened when autism was reclassified as a neurologic disorder. Finally, a much more intensive public education must be disseminated about the neurobiological etiologies, brain structure, and function in psychiatric disorders, and the psychiatric symptoms associated with all neurologic disorders. Regrettably, empathy can be difficult to teach.

Stigma is hate speech and a hate crime. It must be permanently eliminated by effective laws and by erasing the widespread ignorance about the medical and neurologic roots of mental disorders, and by emphasizing the fact that they are as treatable as other general medical conditions.