Despite much progress, major depressive disorder (MDD) continues to be a challenging and life-threatening neuropsychiatric disorder. It is highly prevalent and afflicts tens of millions of Americans.

It is also ranked as the No. 1 disabling medical (not just psychiatric) condition by the World Health Organization.¹ A significant proportion of patients with MDD do not respond adequately to several rounds of antidepressant medications,² and many are labeled as having “treatment-resistant depression” (TRD).

In a previous article, I provocatively proposed that TRD is a myth.³ What I meant is that in a heterogeneous syndrome such as depression, failure to respond to 1, 2, or even 3 antidepressants should not imply TRD, because there is a “right treatment” that has not yet been identified for a given depressed patient. Most of those labeled as TRD have simply not yet received the pharmacotherapy or somatic therapy with the requisite mechanism of action for their variant of depression within a heterogeneous syndrome. IV ketamine, which, astonishingly, often reverses severe TRD of chronic duration within a few hours, is a prime example of why the term TRD is often used prematurely. Ketamine’s mechanism of action (immediate neuroplasticity via glutamate N-methyl-d-aspartate receptor antagonism, and stimulation of the mammalian target of rapamycin [mTOR]) was not recognized for decades because of the obsession with the monoamine model of depression.

Some clinicians may not be aware of the abundance of mechanisms of action currently available for the treatment of MDD as well as bipolar depression. Many practitioners, in both psychiatry and primary care, usually start the treatment of depression with a selective serotonin reuptake inhibitor, and if that does not produce a response or remission, they might switch to a serotonin-norepinephrine reuptake inhibitor. If that does not control the patient’s depressive symptoms, they start entertaining the notion that the patient may have TRD, not realizing that they have barely scratched the surface of the many therapeutic options and mechanisms of action, one of which could be the “best match” for a given patient.⁴

There will come a day when “precision psychiatry” finally arrives, and specific biomarkers will be developed to identify the “right” treatment for each patient within the heterogenous syndrome of depression.⁵ Until that day arrives, the treatment of depression will continue to be a process of trial and error, and hit or miss. But research will eventually discover genetic, neuro­chemical, neurophysiological, neuro­imaging, or neuroimmune biomarkers that will rapidly guide clinicians to the correct treatment. This is critical to avoid inordinate delays in achieving remission and avert the ever-present risk of suicidal behavior.

The Table⁶ provides an overview of the numerous treatments currently available to manage depression. All increase brain-derived neurotrophic factor and restore healthy neuroplasticity and neuro­genesis, which are impaired in MDD and currently believed to be a final common pathway for all depression treatments.⁷

These 41 therapeutic approaches to treating MDD or bipolar depression reflect the heterogeneity of mechanisms of action to address an equally heterogeneous syndrome. This implies that clinicians have a wide array of on-label options to manage patients with depression, aiming for remission, not just a good response, which typically is defined as a ≥50% reduction in total score on one of the validated rating scales used to quantify depression severity, such as the Montgomery-Åsberg Depression Rating Scale, Hamilton Depression Rating Scale, or Calgary Depression Scale for Schizophrenia.

Continue to: When several FDA-approved pharmacotherapies...

When several FDA-approved pharmacotherapies fall short and produce a suboptimal response, clinicians can resort to other treatment options known to have a higher efficacy than oral antidepressants. These include electroconvulsive therapy, repetitive transcranial magnetic stimulation, and vagus nerve stimulation. Other on-label options include adjunctive therapy with one of the approved second-generation antipsychotic agents or with adjunctive esketamine.

But if the patient still does not improve, one of many emerging off-label treatment options may work. One of the exciting new discoveries is the hallucinogen psilocybin, whose mechanism of action is truly unique. Unlike standard antidepressant medications, which modulate neurotransmitters, psilocybin increases the brain’s network flexibility, decreases the modularity of several key brain networks (especially the default-brain network, or DMN), and alters the dark and distorted mental perspective of depression to a much healthier and optimistic outlook about the self and the world.⁸ Such novel breakthroughs in the treatment of severe depression will shed some unprecedented insights into the core neurobiology of depression, and may lead to early intervention and prevention.

As the saying goes, all roads lead to Rome. Psychiatric clinicians should rejoice that there are abundant approaches and therapeutic mechanisms to relieve their severely melancholic (and often suicidal) patients from the grips of this disabling and life-altering brain syndrome.

Despite much progress, major depressive disorder (MDD) continues to be a challenging and life-threatening neuropsychiatric disorder. It is highly prevalent and afflicts tens of millions of Americans.

It is also ranked as the No. 1 disabling medical (not just psychiatric) condition by the World Health Organization.¹ A significant proportion of patients with MDD do not respond adequately to several rounds of antidepressant medications,² and many are labeled as having “treatment-resistant depression” (TRD).

In a previous article, I provocatively proposed that TRD is a myth.³ What I meant is that in a heterogeneous syndrome such as depression, failure to respond to 1, 2, or even 3 antidepressants should not imply TRD, because there is a “right treatment” that has not yet been identified for a given depressed patient. Most of those labeled as TRD have simply not yet received the pharmacotherapy or somatic therapy with the requisite mechanism of action for their variant of depression within a heterogeneous syndrome. IV ketamine, which, astonishingly, often reverses severe TRD of chronic duration within a few hours, is a prime example of why the term TRD is often used prematurely. Ketamine’s mechanism of action (immediate neuroplasticity via glutamate N-methyl-d-aspartate receptor antagonism, and stimulation of the mammalian target of rapamycin [mTOR]) was not recognized for decades because of the obsession with the monoamine model of depression.

Some clinicians may not be aware of the abundance of mechanisms of action currently available for the treatment of MDD as well as bipolar depression. Many practitioners, in both psychiatry and primary care, usually start the treatment of depression with a selective serotonin reuptake inhibitor, and if that does not produce a response or remission, they might switch to a serotonin-norepinephrine reuptake inhibitor. If that does not control the patient’s depressive symptoms, they start entertaining the notion that the patient may have TRD, not realizing that they have barely scratched the surface of the many therapeutic options and mechanisms of action, one of which could be the “best match” for a given patient.⁴

There will come a day when “precision psychiatry” finally arrives, and specific biomarkers will be developed to identify the “right” treatment for each patient within the heterogenous syndrome of depression.⁵ Until that day arrives, the treatment of depression will continue to be a process of trial and error, and hit or miss. But research will eventually discover genetic, neuro­chemical, neurophysiological, neuro­imaging, or neuroimmune biomarkers that will rapidly guide clinicians to the correct treatment. This is critical to avoid inordinate delays in achieving remission and avert the ever-present risk of suicidal behavior.

The Table⁶ provides an overview of the numerous treatments currently available to manage depression. All increase brain-derived neurotrophic factor and restore healthy neuroplasticity and neuro­genesis, which are impaired in MDD and currently believed to be a final common pathway for all depression treatments.⁷

These 41 therapeutic approaches to treating MDD or bipolar depression reflect the heterogeneity of mechanisms of action to address an equally heterogeneous syndrome. This implies that clinicians have a wide array of on-label options to manage patients with depression, aiming for remission, not just a good response, which typically is defined as a ≥50% reduction in total score on one of the validated rating scales used to quantify depression severity, such as the Montgomery-Åsberg Depression Rating Scale, Hamilton Depression Rating Scale, or Calgary Depression Scale for Schizophrenia.

Continue to: When several FDA-approved pharmacotherapies...

When several FDA-approved pharmacotherapies fall short and produce a suboptimal response, clinicians can resort to other treatment options known to have a higher efficacy than oral antidepressants. These include electroconvulsive therapy, repetitive transcranial magnetic stimulation, and vagus nerve stimulation. Other on-label options include adjunctive therapy with one of the approved second-generation antipsychotic agents or with adjunctive esketamine.

But if the patient still does not improve, one of many emerging off-label treatment options may work. One of the exciting new discoveries is the hallucinogen psilocybin, whose mechanism of action is truly unique. Unlike standard antidepressant medications, which modulate neurotransmitters, psilocybin increases the brain’s network flexibility, decreases the modularity of several key brain networks (especially the default-brain network, or DMN), and alters the dark and distorted mental perspective of depression to a much healthier and optimistic outlook about the self and the world.⁸ Such novel breakthroughs in the treatment of severe depression will shed some unprecedented insights into the core neurobiology of depression, and may lead to early intervention and prevention.

As the saying goes, all roads lead to Rome. Psychiatric clinicians should rejoice that there are abundant approaches and therapeutic mechanisms to relieve their severely melancholic (and often suicidal) patients from the grips of this disabling and life-altering brain syndrome.

Despite much progress, major depressive disorder (MDD) continues to be a challenging and life-threatening neuropsychiatric disorder. It is highly prevalent and afflicts tens of millions of Americans.

It is also ranked as the No. 1 disabling medical (not just psychiatric) condition by the World Health Organization.¹ A significant proportion of patients with MDD do not respond adequately to several rounds of antidepressant medications,² and many are labeled as having “treatment-resistant depression” (TRD).

In a previous article, I provocatively proposed that TRD is a myth.³ What I meant is that in a heterogeneous syndrome such as depression, failure to respond to 1, 2, or even 3 antidepressants should not imply TRD, because there is a “right treatment” that has not yet been identified for a given depressed patient. Most of those labeled as TRD have simply not yet received the pharmacotherapy or somatic therapy with the requisite mechanism of action for their variant of depression within a heterogeneous syndrome. IV ketamine, which, astonishingly, often reverses severe TRD of chronic duration within a few hours, is a prime example of why the term TRD is often used prematurely. Ketamine’s mechanism of action (immediate neuroplasticity via glutamate N-methyl-d-aspartate receptor antagonism, and stimulation of the mammalian target of rapamycin [mTOR]) was not recognized for decades because of the obsession with the monoamine model of depression.

Some clinicians may not be aware of the abundance of mechanisms of action currently available for the treatment of MDD as well as bipolar depression. Many practitioners, in both psychiatry and primary care, usually start the treatment of depression with a selective serotonin reuptake inhibitor, and if that does not produce a response or remission, they might switch to a serotonin-norepinephrine reuptake inhibitor. If that does not control the patient’s depressive symptoms, they start entertaining the notion that the patient may have TRD, not realizing that they have barely scratched the surface of the many therapeutic options and mechanisms of action, one of which could be the “best match” for a given patient.⁴

There will come a day when “precision psychiatry” finally arrives, and specific biomarkers will be developed to identify the “right” treatment for each patient within the heterogenous syndrome of depression.⁵ Until that day arrives, the treatment of depression will continue to be a process of trial and error, and hit or miss. But research will eventually discover genetic, neuro­chemical, neurophysiological, neuro­imaging, or neuroimmune biomarkers that will rapidly guide clinicians to the correct treatment. This is critical to avoid inordinate delays in achieving remission and avert the ever-present risk of suicidal behavior.

The Table⁶ provides an overview of the numerous treatments currently available to manage depression. All increase brain-derived neurotrophic factor and restore healthy neuroplasticity and neuro­genesis, which are impaired in MDD and currently believed to be a final common pathway for all depression treatments.⁷

These 41 therapeutic approaches to treating MDD or bipolar depression reflect the heterogeneity of mechanisms of action to address an equally heterogeneous syndrome. This implies that clinicians have a wide array of on-label options to manage patients with depression, aiming for remission, not just a good response, which typically is defined as a ≥50% reduction in total score on one of the validated rating scales used to quantify depression severity, such as the Montgomery-Åsberg Depression Rating Scale, Hamilton Depression Rating Scale, or Calgary Depression Scale for Schizophrenia.

Continue to: When several FDA-approved pharmacotherapies...

When several FDA-approved pharmacotherapies fall short and produce a suboptimal response, clinicians can resort to other treatment options known to have a higher efficacy than oral antidepressants. These include electroconvulsive therapy, repetitive transcranial magnetic stimulation, and vagus nerve stimulation. Other on-label options include adjunctive therapy with one of the approved second-generation antipsychotic agents or with adjunctive esketamine.

But if the patient still does not improve, one of many emerging off-label treatment options may work. One of the exciting new discoveries is the hallucinogen psilocybin, whose mechanism of action is truly unique. Unlike standard antidepressant medications, which modulate neurotransmitters, psilocybin increases the brain’s network flexibility, decreases the modularity of several key brain networks (especially the default-brain network, or DMN), and alters the dark and distorted mental perspective of depression to a much healthier and optimistic outlook about the self and the world.⁸ Such novel breakthroughs in the treatment of severe depression will shed some unprecedented insights into the core neurobiology of depression, and may lead to early intervention and prevention.

As the saying goes, all roads lead to Rome. Psychiatric clinicians should rejoice that there are abundant approaches and therapeutic mechanisms to relieve their severely melancholic (and often suicidal) patients from the grips of this disabling and life-altering brain syndrome.

Ms. B, age 60, presents to the clinic with high blood pressure, hyperlipidemia, type 2 diabetes mellitus, depression, and anxiety. Her blood pressure is 138/82 mm Hg and pulse is 70 beats per minute. Her body mass index (BMI) is 41, which indicates she is obese. She has always struggled with her weight and has tried diet and lifestyle modifications, as well as medications, for the past 5 years with no success. Her current medication regimen includes lisinopril 40 mg daily, amlodipine 5 mg daily, atorvastatin 40 mg daily, metformin 500 mg twice daily, dulaglutide 0.75 mg weekly, lithium 600 mg daily, venlafaxine extended-release (XR) 150 mg daily, and alprazolam 0.5 mg as needed up to twice daily. Due to Ms. B’s BMI and because she has ≥1 comorbid health condition, her primary care physician refers her to a gastro­enterologist to discuss gastric bypass surgery options.

Ms. B is scheduled for Roux-en-Y gastric bypass surgery. You need to determine if any changes should be made to her psycho­tropic medications after she undergoes this surgery.

There are multiple types of bariatric surgeries, including Roux-en-Y gastric bypass, sleeve gastrectomy, laparoscopic adjustable gastric band, and biliopancreatic diversion with duodenal switch (BPD/DS) (Figure^1-4). These procedures all restrict the stomach’s capacity to hold food. In most cases, they also bypass areas of absorption in the intestine and cause increased secretion of hormones in the gut, including (but not limited to) peptide­-YY (PYY) and glucagon-like peptide 1 (GLP-1). These hormonal changes impact several factors, including satiety, hunger, and blood sugar levels.⁵

Roux-en-Y is commonly referred to as the gold standard of weight loss surgery. It divides the top of the stomach into a smaller stomach pouch that connects directly to the small intestine to facilitate smaller meals and alters the release of gut hormones. Additionally, a segment of the small intestine that normally absorbs nutrients and medications is completely bypassed. In contrast, the sleeve gastrectomy removes approximately 80% of the stomach, consequently reducing the amount of food that can be consumed. The greatest impact of the sleeve gastrectomy procedure appears to result from changes in gut hormones. The adjustable gastric band procedure works by placing a band around the upper portion of the stomach to create a small pouch above the band to satisfy hunger with a smaller amount of food. Lastly, BPD/DS is a procedure that creates a tubular stomach pouch and bypasses a large portion of the small intestine. Like the gastric bypass and sleeve gastrectomy, BPD/DS affects gut hormones impacting hunger, satiety, and blood sugar control.

How bariatric surgery can affect drug absorption

As illustrated in the Table,^6-19 each type of bariatric surgery may impact drug absorption differently depending on the mechanism by which the stomach is restricted.

Drug malabsorption is a concern for clinicians with patients who have undergone bariatric surgery. There is limited research measuring changes in psychotropic exposure and outcomes following bariatric surgery. A 2009 literature review by Padwal et al⁷ found that one-third of the 26 studies evaluated provided evidence of decreased absorption following bariatric surgery in patients taking medications that had intrinsic poor absorption, high lipophilicity, and/or undergo enterohepatic recirculation. In a review that included a small study of patients taking selective serotonin reuptake inhibitors or venlafaxine, Godini et al⁸ demonstrated that although there was a notable decrease in drug absorption closely following the surgery, drug absorption recovered for some patients 1 month after Roux-en-Y surgery. These reviews suggest patients who have undergone any form of bariatric surgery must be observed closely because drug absorption may vary based on the individual, the medication administered, and the amount of time postprocedure.

Until more research becomes available, current evidence supports recommendations to assist patients who have a decreased ability to absorb medications after gastric bypass surgery by switching from an extended-release formulation to an immediate-release or solution formulation. This allows patients to rely less on gastric mixing and unpredictable changes in drug release from extended- or controlled-release formulations.

Continue to: Aside from altered...

Aside from altered pharmacokinetics after bariatric surgery, many patients experience an increased risk of self-harm and suicide.²⁰ Therefore, a continued emphasis on and reinforcement of proper antidepressant use and adjustment in these patients is important. This can be facilitated through frequent follow-up visits, either in-person or via telehealth.

Understanding the effect of bariatric surgery on drug absorption is critical to identifying a potential need to adjust a medication dose or formulation after the surgery. Available evidence and data suggest it is reasonable to switch from an extended- or sustained-release formulation to an immediate-release formulation, and to monitor patients more frequently immediately following the surgery.

CASE CONTINUED

Immediately following surgery, Ms. B’s care team adjusts her medication regimen. To account for the change in her stomach size and composition, and therefore its absorption process, the team changes the venlafaxine dosage from venlafaxine XR 150 mg daily to venlafaxine immediate-release 75 mg twice daily. Ms. B is also monitored more frequently following the procedure to determine if additional adjustments to her medication dosage or therapy frequency are necessary. Eight weeks following surgery, Ms. B has lost 16 pounds and is reintroducing more solid foods into her diet. She struggles with some increased anxiety and depression approximately 1 month after surgery, but that improves after her clinicians decide to increase the venlafaxine dose to 75 mg 3 times a day. Her lithium level was also monitored more closely for the first month after the procedure to decrease the risk of lithium toxicity.

Related Resources

• Colvin C, Tsia W, Silverman AL, et al. Nothing up his sleeve: decompensation after bariatric surgery. Current Psychiatry. 2021;20(4):15-19. doi:10.12788/cp.010

Drug Brand Names

Alprazolam • Xanax
Amlodipine • Norvasc
Atorvastatin • Lipitor
Dulaglutide • Trulicity
Lisinopril • Zestril, Prinivil
Lithium • Eskalith, Lithobid
Metformin • Glucophage
Olanzapine • Zyprexa
Venlafaxine • Effexor

Ms. B, age 60, presents to the clinic with high blood pressure, hyperlipidemia, type 2 diabetes mellitus, depression, and anxiety. Her blood pressure is 138/82 mm Hg and pulse is 70 beats per minute. Her body mass index (BMI) is 41, which indicates she is obese. She has always struggled with her weight and has tried diet and lifestyle modifications, as well as medications, for the past 5 years with no success. Her current medication regimen includes lisinopril 40 mg daily, amlodipine 5 mg daily, atorvastatin 40 mg daily, metformin 500 mg twice daily, dulaglutide 0.75 mg weekly, lithium 600 mg daily, venlafaxine extended-release (XR) 150 mg daily, and alprazolam 0.5 mg as needed up to twice daily. Due to Ms. B’s BMI and because she has ≥1 comorbid health condition, her primary care physician refers her to a gastro­enterologist to discuss gastric bypass surgery options.

Ms. B is scheduled for Roux-en-Y gastric bypass surgery. You need to determine if any changes should be made to her psycho­tropic medications after she undergoes this surgery.

There are multiple types of bariatric surgeries, including Roux-en-Y gastric bypass, sleeve gastrectomy, laparoscopic adjustable gastric band, and biliopancreatic diversion with duodenal switch (BPD/DS) (Figure^1-4). These procedures all restrict the stomach’s capacity to hold food. In most cases, they also bypass areas of absorption in the intestine and cause increased secretion of hormones in the gut, including (but not limited to) peptide­-YY (PYY) and glucagon-like peptide 1 (GLP-1). These hormonal changes impact several factors, including satiety, hunger, and blood sugar levels.⁵

Roux-en-Y is commonly referred to as the gold standard of weight loss surgery. It divides the top of the stomach into a smaller stomach pouch that connects directly to the small intestine to facilitate smaller meals and alters the release of gut hormones. Additionally, a segment of the small intestine that normally absorbs nutrients and medications is completely bypassed. In contrast, the sleeve gastrectomy removes approximately 80% of the stomach, consequently reducing the amount of food that can be consumed. The greatest impact of the sleeve gastrectomy procedure appears to result from changes in gut hormones. The adjustable gastric band procedure works by placing a band around the upper portion of the stomach to create a small pouch above the band to satisfy hunger with a smaller amount of food. Lastly, BPD/DS is a procedure that creates a tubular stomach pouch and bypasses a large portion of the small intestine. Like the gastric bypass and sleeve gastrectomy, BPD/DS affects gut hormones impacting hunger, satiety, and blood sugar control.

How bariatric surgery can affect drug absorption

As illustrated in the Table,^6-19 each type of bariatric surgery may impact drug absorption differently depending on the mechanism by which the stomach is restricted.

Drug malabsorption is a concern for clinicians with patients who have undergone bariatric surgery. There is limited research measuring changes in psychotropic exposure and outcomes following bariatric surgery. A 2009 literature review by Padwal et al⁷ found that one-third of the 26 studies evaluated provided evidence of decreased absorption following bariatric surgery in patients taking medications that had intrinsic poor absorption, high lipophilicity, and/or undergo enterohepatic recirculation. In a review that included a small study of patients taking selective serotonin reuptake inhibitors or venlafaxine, Godini et al⁸ demonstrated that although there was a notable decrease in drug absorption closely following the surgery, drug absorption recovered for some patients 1 month after Roux-en-Y surgery. These reviews suggest patients who have undergone any form of bariatric surgery must be observed closely because drug absorption may vary based on the individual, the medication administered, and the amount of time postprocedure.

Until more research becomes available, current evidence supports recommendations to assist patients who have a decreased ability to absorb medications after gastric bypass surgery by switching from an extended-release formulation to an immediate-release or solution formulation. This allows patients to rely less on gastric mixing and unpredictable changes in drug release from extended- or controlled-release formulations.

Continue to: Aside from altered...

Aside from altered pharmacokinetics after bariatric surgery, many patients experience an increased risk of self-harm and suicide.²⁰ Therefore, a continued emphasis on and reinforcement of proper antidepressant use and adjustment in these patients is important. This can be facilitated through frequent follow-up visits, either in-person or via telehealth.

Understanding the effect of bariatric surgery on drug absorption is critical to identifying a potential need to adjust a medication dose or formulation after the surgery. Available evidence and data suggest it is reasonable to switch from an extended- or sustained-release formulation to an immediate-release formulation, and to monitor patients more frequently immediately following the surgery.

CASE CONTINUED

Immediately following surgery, Ms. B’s care team adjusts her medication regimen. To account for the change in her stomach size and composition, and therefore its absorption process, the team changes the venlafaxine dosage from venlafaxine XR 150 mg daily to venlafaxine immediate-release 75 mg twice daily. Ms. B is also monitored more frequently following the procedure to determine if additional adjustments to her medication dosage or therapy frequency are necessary. Eight weeks following surgery, Ms. B has lost 16 pounds and is reintroducing more solid foods into her diet. She struggles with some increased anxiety and depression approximately 1 month after surgery, but that improves after her clinicians decide to increase the venlafaxine dose to 75 mg 3 times a day. Her lithium level was also monitored more closely for the first month after the procedure to decrease the risk of lithium toxicity.

Related Resources

• Colvin C, Tsia W, Silverman AL, et al. Nothing up his sleeve: decompensation after bariatric surgery. Current Psychiatry. 2021;20(4):15-19. doi:10.12788/cp.010

Drug Brand Names

Alprazolam • Xanax
Amlodipine • Norvasc
Atorvastatin • Lipitor
Dulaglutide • Trulicity
Lisinopril • Zestril, Prinivil
Lithium • Eskalith, Lithobid
Metformin • Glucophage
Olanzapine • Zyprexa
Venlafaxine • Effexor

Ms. B, age 60, presents to the clinic with high blood pressure, hyperlipidemia, type 2 diabetes mellitus, depression, and anxiety. Her blood pressure is 138/82 mm Hg and pulse is 70 beats per minute. Her body mass index (BMI) is 41, which indicates she is obese. She has always struggled with her weight and has tried diet and lifestyle modifications, as well as medications, for the past 5 years with no success. Her current medication regimen includes lisinopril 40 mg daily, amlodipine 5 mg daily, atorvastatin 40 mg daily, metformin 500 mg twice daily, dulaglutide 0.75 mg weekly, lithium 600 mg daily, venlafaxine extended-release (XR) 150 mg daily, and alprazolam 0.5 mg as needed up to twice daily. Due to Ms. B’s BMI and because she has ≥1 comorbid health condition, her primary care physician refers her to a gastro­enterologist to discuss gastric bypass surgery options.

Ms. B is scheduled for Roux-en-Y gastric bypass surgery. You need to determine if any changes should be made to her psycho­tropic medications after she undergoes this surgery.

There are multiple types of bariatric surgeries, including Roux-en-Y gastric bypass, sleeve gastrectomy, laparoscopic adjustable gastric band, and biliopancreatic diversion with duodenal switch (BPD/DS) (Figure^1-4). These procedures all restrict the stomach’s capacity to hold food. In most cases, they also bypass areas of absorption in the intestine and cause increased secretion of hormones in the gut, including (but not limited to) peptide­-YY (PYY) and glucagon-like peptide 1 (GLP-1). These hormonal changes impact several factors, including satiety, hunger, and blood sugar levels.⁵

Roux-en-Y is commonly referred to as the gold standard of weight loss surgery. It divides the top of the stomach into a smaller stomach pouch that connects directly to the small intestine to facilitate smaller meals and alters the release of gut hormones. Additionally, a segment of the small intestine that normally absorbs nutrients and medications is completely bypassed. In contrast, the sleeve gastrectomy removes approximately 80% of the stomach, consequently reducing the amount of food that can be consumed. The greatest impact of the sleeve gastrectomy procedure appears to result from changes in gut hormones. The adjustable gastric band procedure works by placing a band around the upper portion of the stomach to create a small pouch above the band to satisfy hunger with a smaller amount of food. Lastly, BPD/DS is a procedure that creates a tubular stomach pouch and bypasses a large portion of the small intestine. Like the gastric bypass and sleeve gastrectomy, BPD/DS affects gut hormones impacting hunger, satiety, and blood sugar control.

How bariatric surgery can affect drug absorption

As illustrated in the Table,^6-19 each type of bariatric surgery may impact drug absorption differently depending on the mechanism by which the stomach is restricted.

Drug malabsorption is a concern for clinicians with patients who have undergone bariatric surgery. There is limited research measuring changes in psychotropic exposure and outcomes following bariatric surgery. A 2009 literature review by Padwal et al⁷ found that one-third of the 26 studies evaluated provided evidence of decreased absorption following bariatric surgery in patients taking medications that had intrinsic poor absorption, high lipophilicity, and/or undergo enterohepatic recirculation. In a review that included a small study of patients taking selective serotonin reuptake inhibitors or venlafaxine, Godini et al⁸ demonstrated that although there was a notable decrease in drug absorption closely following the surgery, drug absorption recovered for some patients 1 month after Roux-en-Y surgery. These reviews suggest patients who have undergone any form of bariatric surgery must be observed closely because drug absorption may vary based on the individual, the medication administered, and the amount of time postprocedure.

Until more research becomes available, current evidence supports recommendations to assist patients who have a decreased ability to absorb medications after gastric bypass surgery by switching from an extended-release formulation to an immediate-release or solution formulation. This allows patients to rely less on gastric mixing and unpredictable changes in drug release from extended- or controlled-release formulations.

Continue to: Aside from altered...

Aside from altered pharmacokinetics after bariatric surgery, many patients experience an increased risk of self-harm and suicide.²⁰ Therefore, a continued emphasis on and reinforcement of proper antidepressant use and adjustment in these patients is important. This can be facilitated through frequent follow-up visits, either in-person or via telehealth.

Understanding the effect of bariatric surgery on drug absorption is critical to identifying a potential need to adjust a medication dose or formulation after the surgery. Available evidence and data suggest it is reasonable to switch from an extended- or sustained-release formulation to an immediate-release formulation, and to monitor patients more frequently immediately following the surgery.

CASE CONTINUED

Immediately following surgery, Ms. B’s care team adjusts her medication regimen. To account for the change in her stomach size and composition, and therefore its absorption process, the team changes the venlafaxine dosage from venlafaxine XR 150 mg daily to venlafaxine immediate-release 75 mg twice daily. Ms. B is also monitored more frequently following the procedure to determine if additional adjustments to her medication dosage or therapy frequency are necessary. Eight weeks following surgery, Ms. B has lost 16 pounds and is reintroducing more solid foods into her diet. She struggles with some increased anxiety and depression approximately 1 month after surgery, but that improves after her clinicians decide to increase the venlafaxine dose to 75 mg 3 times a day. Her lithium level was also monitored more closely for the first month after the procedure to decrease the risk of lithium toxicity.

Related Resources

• Colvin C, Tsia W, Silverman AL, et al. Nothing up his sleeve: decompensation after bariatric surgery. Current Psychiatry. 2021;20(4):15-19. doi:10.12788/cp.010

Drug Brand Names

Alprazolam • Xanax
Amlodipine • Norvasc
Atorvastatin • Lipitor
Dulaglutide • Trulicity
Lisinopril • Zestril, Prinivil
Lithium • Eskalith, Lithobid
Metformin • Glucophage
Olanzapine • Zyprexa
Venlafaxine • Effexor

CASE Psychotic episode in a patient with HIV

Mr. F, age 32, has schizophrenia and HIV. He presents to the emergency department with auditory and visual hallucinations in addition to paranoia. The treatment team refers him to the state psychiatric facility on an involuntary hold. Mr. F has had multiple previous hospitalizations, none of which had resulted in successful treatment. According to his most recent records, Mr. F failed to improve while taking olanzapine. Upon examination, Mr. F reports he hears command auditory hallucinations to hurt others and endorses paranoia. He is agitated, with a constricted affect, and his thought content is paranoid, disorganized, and circumstantial. Mr. F provides vague and evasive answers upon admission. His physical examination is unremarkable. He has an eighth-grade education level and limited insight into his illnesses. His Positive and Negative Syndrome Scale (PANSS) score is 122, indicating severe symptoms. The PANSS score is formulated based on 30 items, each scored between 1 and 7. Higher scores indicate more severe symptoms.

[polldaddy:11167946]

The authors’ observations

Compared to other medically ill patients, those with AIDS are 7 times more likely to experience EPS associated with antipsychotics. This may be a result of HIV infiltration of the basal ganglia causing regional changes that predispose these patients to EPS.

[polldaddy:11167948]

TREATMENT Haloperidol and antiretroviral therapy

The treatment team decides to start Mr. F on haloperidol for his psychotic symptoms as well as bictegravir, emtricitabine, and tenofovir for HIV. One week after admission, the team starts Mr. F on haloperidol decanoate 150 mg IM, and continues oral haloperidol and antiretroviral therapy. Mr. F reports some improvement in his hallucinations and appears to have reduced paranoia. He attends psychotherapy treatment groups over the next several days and scores 80 on a retrospective PANSS assessment (Figure 1). Mr. F receives haloperidol decanoate 200 mg IM 28 days after his first dose, and his oral haloperidol dose is reduced.

During the following 2 weeks, Mr. F endorses continued improvement of his symptoms and insight and begins discharge planning by calling his sister to discuss living arrangements. However, his mental state begins to decline; he becomes paranoid, withdrawn, and irritable, and endorses increased hallucinations. His PANSS score is 87, and he scores 11 on the Montreal Cognitive Assessment (MoCA), indicating moderate cognitive impairment. MoCA scores range from 0 to 30, with scores <10 indicating severe impairment, 10 to 17 indicating moderate impairment, 18 to 25 indicating mild impairment, and 26 to 30 considered normal. Figure 2 shows a timeline of Mr. F’s MoCA scores during treatment.

The treatment team increases the dose of haloperidol, and Mr. F continues to receive haloperidol deaconate injections monthly. After an adequate trial of haloperidol, the patient exhibits only partial response to treatment—his symptoms wax and wane—and he continues to display limited insight into both his mental illness and HIV diagnosis. Another PANSS assessment yields an essentially unchanged score of 88.

After a discussion of risks and benefits, Mr. F consents to initiating clozapine. The treatment team starts clozapine 25 mg/d and increases the dosage to 400 mg in the evening with a concomitant clozapine level of 487 ng/mL. Mr. F’s absolute neutrophil count was within normal limits (2,500 to 6,000 µL) during this period for weekly complete blood cell count monitoring. Over the next few weeks, his MoCA score increases to 17 and PANSS score decreases to 52. Haloperidol decanoate 200 mg IM is discontinued 3 days after Mr. F received a dose of clozapine 400 mg at bedtime. After an additional 2 weeks of clozapine at the same dosage, Mr. F scores 20 on the MoCA, an increase of 9 points from his baseline score while receiving haloperidol. There is a washout period for haloperidol decanoate and oral haloperidol before he completes a third MoCA. Mr. F participates in a discussion regarding his HIV diagnosis and the importance of consistently continuing treatment for this chronic infection. After some education, he has a better understanding of his condition and is more insightful about wanting to remain compliant with clozapine and bictegravir, emtricitabine, and tenofovir for his HIV.

The authors’ observations

Many patients receive treatment for comorbid HIV and schizophrenia. Patients with schizophrenia and other psychoses are at increased risk of contracting HIV due to numerous psychosocial factors, including an increased frequency of illicit drug use as well as an increased propensity for high-risk sexual behaviors secondary to impaired neurocognitive functioning, delusions, and victimization.¹ In addition to deficits in functioning related to psychiatric illness, patients with HIV also experience virus-related neurocognitive insults. After crossing the blood-brain barrier, HIV viral proteins circulate in the blood, inducing brain endothelial cells to release cytokines, causing neuroinflammation.²

Continue to: Recently, inflammation and inflammatory...

Recently, inflammation and inflammatory biomarkers have become an important topic of psychiatric research. A meta-analysis by Fraguas et al³ concluded that greater inflammation and oxidative stress might lead to poorer outcomes in patients with first-episode psychosis. Based on this evidence, inflammation associated with untreated HIV infection may compound the pre-existing neurocognitive decline seen in patients with schizophrenia and other psychoses, thereby contributing to poor outcomes and treatment-resistant pathology.

Clozapine has been the superior treatment for refractory and nonrefractory schizophrenia.⁴ Factor et al⁵ report there are limited basal ganglia reserves in patients with HIV, which make clozapine the preferred option due to its low potential for causing EPS.

In this case, starting Mr. F on clozapine and titrating to therapeutic blood levels was associated with improved MoCA scores. Low MoCA scores could be due to untreated HIV, as well as inadequately treated psychosis. For Mr. F, improved MoCA scores were associated with increased insight into his HIV. It is important to note that Mr. F’s improved MoCA score also coincided with discontinuing monthly haloperidol decanoate injections. Haloperidol and its metabolites are believed to cause some neuro­toxicity at high doses, and can contribute to cognitive impairment. This may partially explain the increased MoCA score after Mr. F stopped receiving haloperidol decanoate monthly injections.⁶ For the first time, he felt the need to be on antiretroviral therapy for his HIV, and was able to understand the chronic nature of HIV infection.

The benefit of clozapine treatment for patients with schizophrenia and comorbid HIV extends beyond symptomatic control. Long-term and consistent treatment of schizophrenia can be a stepping stone for improving many psychosocial factors. Improved insight allows patients to better understand their illness, treatment regimen, and follow-up needs. Improved self-care contributes to increased adherence to treatment regimens and overall health.

It is likely that patients who are consistently treated for schizophrenia will also have an increased capacity to understand their HIV diagnosis. With gained understanding, patients may be more likely to adhere to highly active antiretroviral therapy (HAART) for HIV and attend follow-up appointments with infectious disease or primary care physicians. Furthermore, with adherence to HAART therapy, patients can enjoy improved quality and duration of life by raising CD4 counts and preventing progression to AIDS and AIDS-related infections.

Continue to: In the case of...

In the case of Mr. F, we noted significant improvement in MoCA scores following treatment with clozapine. This led to improved insight into understanding the chronicity of HIV, understanding the complications of not being treated, and adherence to HAART medication. Improved cognition, as evidenced by an increased MoCA score, can significantly improve patient insight and adherence with medication.⁷ Insight into illness is particularly important when managing a patient with a chronic infectious illness such as HIV, where consistency with the medication regimen can decrease mortality and improve quality of life.⁸ Furthermore, with close monitoring, clozapine was a safe treatment option for this patient with HIV and schizophrenia.

Bottom Line

Patients with schizophrenia are at an increased risk of contracting HIV, and untreated schizophrenia decreases the likelihood patients will adhere to highly active antiretroviral therapy (HAART). Clozapine treatment in comorbid HIV and schizophrenia can improve cognition and insight into HIV diagnosis, possibly increasing the likelihood patients will remain compliant with HAART.

Related Resources

• Diduch MN, Campbell RH, Borovicka M, et al. Treating psychosis in patients with HIV/AIDS. Current Psychiatry. 2018;17(5):35-36,41-44,46.

Drug Brand Names

Bictegravir, emtricitabine, and tenofovir • Biktarvy
Clozapine • Clozaril
Haloperidol • Haldol
Haloperidol decanoate • Haldol decanoate
Olanzapine • Zyprexa
Ziprasidone • Geodon

CASE Psychotic episode in a patient with HIV

Mr. F, age 32, has schizophrenia and HIV. He presents to the emergency department with auditory and visual hallucinations in addition to paranoia. The treatment team refers him to the state psychiatric facility on an involuntary hold. Mr. F has had multiple previous hospitalizations, none of which had resulted in successful treatment. According to his most recent records, Mr. F failed to improve while taking olanzapine. Upon examination, Mr. F reports he hears command auditory hallucinations to hurt others and endorses paranoia. He is agitated, with a constricted affect, and his thought content is paranoid, disorganized, and circumstantial. Mr. F provides vague and evasive answers upon admission. His physical examination is unremarkable. He has an eighth-grade education level and limited insight into his illnesses. His Positive and Negative Syndrome Scale (PANSS) score is 122, indicating severe symptoms. The PANSS score is formulated based on 30 items, each scored between 1 and 7. Higher scores indicate more severe symptoms.

[polldaddy:11167946]

The authors’ observations

Compared to other medically ill patients, those with AIDS are 7 times more likely to experience EPS associated with antipsychotics. This may be a result of HIV infiltration of the basal ganglia causing regional changes that predispose these patients to EPS.

[polldaddy:11167948]

TREATMENT Haloperidol and antiretroviral therapy

The treatment team decides to start Mr. F on haloperidol for his psychotic symptoms as well as bictegravir, emtricitabine, and tenofovir for HIV. One week after admission, the team starts Mr. F on haloperidol decanoate 150 mg IM, and continues oral haloperidol and antiretroviral therapy. Mr. F reports some improvement in his hallucinations and appears to have reduced paranoia. He attends psychotherapy treatment groups over the next several days and scores 80 on a retrospective PANSS assessment (Figure 1). Mr. F receives haloperidol decanoate 200 mg IM 28 days after his first dose, and his oral haloperidol dose is reduced.

During the following 2 weeks, Mr. F endorses continued improvement of his symptoms and insight and begins discharge planning by calling his sister to discuss living arrangements. However, his mental state begins to decline; he becomes paranoid, withdrawn, and irritable, and endorses increased hallucinations. His PANSS score is 87, and he scores 11 on the Montreal Cognitive Assessment (MoCA), indicating moderate cognitive impairment. MoCA scores range from 0 to 30, with scores <10 indicating severe impairment, 10 to 17 indicating moderate impairment, 18 to 25 indicating mild impairment, and 26 to 30 considered normal. Figure 2 shows a timeline of Mr. F’s MoCA scores during treatment.

The treatment team increases the dose of haloperidol, and Mr. F continues to receive haloperidol deaconate injections monthly. After an adequate trial of haloperidol, the patient exhibits only partial response to treatment—his symptoms wax and wane—and he continues to display limited insight into both his mental illness and HIV diagnosis. Another PANSS assessment yields an essentially unchanged score of 88.

After a discussion of risks and benefits, Mr. F consents to initiating clozapine. The treatment team starts clozapine 25 mg/d and increases the dosage to 400 mg in the evening with a concomitant clozapine level of 487 ng/mL. Mr. F’s absolute neutrophil count was within normal limits (2,500 to 6,000 µL) during this period for weekly complete blood cell count monitoring. Over the next few weeks, his MoCA score increases to 17 and PANSS score decreases to 52. Haloperidol decanoate 200 mg IM is discontinued 3 days after Mr. F received a dose of clozapine 400 mg at bedtime. After an additional 2 weeks of clozapine at the same dosage, Mr. F scores 20 on the MoCA, an increase of 9 points from his baseline score while receiving haloperidol. There is a washout period for haloperidol decanoate and oral haloperidol before he completes a third MoCA. Mr. F participates in a discussion regarding his HIV diagnosis and the importance of consistently continuing treatment for this chronic infection. After some education, he has a better understanding of his condition and is more insightful about wanting to remain compliant with clozapine and bictegravir, emtricitabine, and tenofovir for his HIV.

The authors’ observations

Many patients receive treatment for comorbid HIV and schizophrenia. Patients with schizophrenia and other psychoses are at increased risk of contracting HIV due to numerous psychosocial factors, including an increased frequency of illicit drug use as well as an increased propensity for high-risk sexual behaviors secondary to impaired neurocognitive functioning, delusions, and victimization.¹ In addition to deficits in functioning related to psychiatric illness, patients with HIV also experience virus-related neurocognitive insults. After crossing the blood-brain barrier, HIV viral proteins circulate in the blood, inducing brain endothelial cells to release cytokines, causing neuroinflammation.²

Continue to: Recently, inflammation and inflammatory...

Recently, inflammation and inflammatory biomarkers have become an important topic of psychiatric research. A meta-analysis by Fraguas et al³ concluded that greater inflammation and oxidative stress might lead to poorer outcomes in patients with first-episode psychosis. Based on this evidence, inflammation associated with untreated HIV infection may compound the pre-existing neurocognitive decline seen in patients with schizophrenia and other psychoses, thereby contributing to poor outcomes and treatment-resistant pathology.

Clozapine has been the superior treatment for refractory and nonrefractory schizophrenia.⁴ Factor et al⁵ report there are limited basal ganglia reserves in patients with HIV, which make clozapine the preferred option due to its low potential for causing EPS.

In this case, starting Mr. F on clozapine and titrating to therapeutic blood levels was associated with improved MoCA scores. Low MoCA scores could be due to untreated HIV, as well as inadequately treated psychosis. For Mr. F, improved MoCA scores were associated with increased insight into his HIV. It is important to note that Mr. F’s improved MoCA score also coincided with discontinuing monthly haloperidol decanoate injections. Haloperidol and its metabolites are believed to cause some neuro­toxicity at high doses, and can contribute to cognitive impairment. This may partially explain the increased MoCA score after Mr. F stopped receiving haloperidol decanoate monthly injections.⁶ For the first time, he felt the need to be on antiretroviral therapy for his HIV, and was able to understand the chronic nature of HIV infection.

The benefit of clozapine treatment for patients with schizophrenia and comorbid HIV extends beyond symptomatic control. Long-term and consistent treatment of schizophrenia can be a stepping stone for improving many psychosocial factors. Improved insight allows patients to better understand their illness, treatment regimen, and follow-up needs. Improved self-care contributes to increased adherence to treatment regimens and overall health.

It is likely that patients who are consistently treated for schizophrenia will also have an increased capacity to understand their HIV diagnosis. With gained understanding, patients may be more likely to adhere to highly active antiretroviral therapy (HAART) for HIV and attend follow-up appointments with infectious disease or primary care physicians. Furthermore, with adherence to HAART therapy, patients can enjoy improved quality and duration of life by raising CD4 counts and preventing progression to AIDS and AIDS-related infections.

Continue to: In the case of...

In the case of Mr. F, we noted significant improvement in MoCA scores following treatment with clozapine. This led to improved insight into understanding the chronicity of HIV, understanding the complications of not being treated, and adherence to HAART medication. Improved cognition, as evidenced by an increased MoCA score, can significantly improve patient insight and adherence with medication.⁷ Insight into illness is particularly important when managing a patient with a chronic infectious illness such as HIV, where consistency with the medication regimen can decrease mortality and improve quality of life.⁸ Furthermore, with close monitoring, clozapine was a safe treatment option for this patient with HIV and schizophrenia.

Bottom Line

Patients with schizophrenia are at an increased risk of contracting HIV, and untreated schizophrenia decreases the likelihood patients will adhere to highly active antiretroviral therapy (HAART). Clozapine treatment in comorbid HIV and schizophrenia can improve cognition and insight into HIV diagnosis, possibly increasing the likelihood patients will remain compliant with HAART.

Related Resources

• Diduch MN, Campbell RH, Borovicka M, et al. Treating psychosis in patients with HIV/AIDS. Current Psychiatry. 2018;17(5):35-36,41-44,46.

Drug Brand Names

Bictegravir, emtricitabine, and tenofovir • Biktarvy
Clozapine • Clozaril
Haloperidol • Haldol
Haloperidol decanoate • Haldol decanoate
Olanzapine • Zyprexa
Ziprasidone • Geodon

CASE Psychotic episode in a patient with HIV

Mr. F, age 32, has schizophrenia and HIV. He presents to the emergency department with auditory and visual hallucinations in addition to paranoia. The treatment team refers him to the state psychiatric facility on an involuntary hold. Mr. F has had multiple previous hospitalizations, none of which had resulted in successful treatment. According to his most recent records, Mr. F failed to improve while taking olanzapine. Upon examination, Mr. F reports he hears command auditory hallucinations to hurt others and endorses paranoia. He is agitated, with a constricted affect, and his thought content is paranoid, disorganized, and circumstantial. Mr. F provides vague and evasive answers upon admission. His physical examination is unremarkable. He has an eighth-grade education level and limited insight into his illnesses. His Positive and Negative Syndrome Scale (PANSS) score is 122, indicating severe symptoms. The PANSS score is formulated based on 30 items, each scored between 1 and 7. Higher scores indicate more severe symptoms.

[polldaddy:11167946]

The authors’ observations

Compared to other medically ill patients, those with AIDS are 7 times more likely to experience EPS associated with antipsychotics. This may be a result of HIV infiltration of the basal ganglia causing regional changes that predispose these patients to EPS.

[polldaddy:11167948]

TREATMENT Haloperidol and antiretroviral therapy

The treatment team decides to start Mr. F on haloperidol for his psychotic symptoms as well as bictegravir, emtricitabine, and tenofovir for HIV. One week after admission, the team starts Mr. F on haloperidol decanoate 150 mg IM, and continues oral haloperidol and antiretroviral therapy. Mr. F reports some improvement in his hallucinations and appears to have reduced paranoia. He attends psychotherapy treatment groups over the next several days and scores 80 on a retrospective PANSS assessment (Figure 1). Mr. F receives haloperidol decanoate 200 mg IM 28 days after his first dose, and his oral haloperidol dose is reduced.

During the following 2 weeks, Mr. F endorses continued improvement of his symptoms and insight and begins discharge planning by calling his sister to discuss living arrangements. However, his mental state begins to decline; he becomes paranoid, withdrawn, and irritable, and endorses increased hallucinations. His PANSS score is 87, and he scores 11 on the Montreal Cognitive Assessment (MoCA), indicating moderate cognitive impairment. MoCA scores range from 0 to 30, with scores <10 indicating severe impairment, 10 to 17 indicating moderate impairment, 18 to 25 indicating mild impairment, and 26 to 30 considered normal. Figure 2 shows a timeline of Mr. F’s MoCA scores during treatment.

The treatment team increases the dose of haloperidol, and Mr. F continues to receive haloperidol deaconate injections monthly. After an adequate trial of haloperidol, the patient exhibits only partial response to treatment—his symptoms wax and wane—and he continues to display limited insight into both his mental illness and HIV diagnosis. Another PANSS assessment yields an essentially unchanged score of 88.

After a discussion of risks and benefits, Mr. F consents to initiating clozapine. The treatment team starts clozapine 25 mg/d and increases the dosage to 400 mg in the evening with a concomitant clozapine level of 487 ng/mL. Mr. F’s absolute neutrophil count was within normal limits (2,500 to 6,000 µL) during this period for weekly complete blood cell count monitoring. Over the next few weeks, his MoCA score increases to 17 and PANSS score decreases to 52. Haloperidol decanoate 200 mg IM is discontinued 3 days after Mr. F received a dose of clozapine 400 mg at bedtime. After an additional 2 weeks of clozapine at the same dosage, Mr. F scores 20 on the MoCA, an increase of 9 points from his baseline score while receiving haloperidol. There is a washout period for haloperidol decanoate and oral haloperidol before he completes a third MoCA. Mr. F participates in a discussion regarding his HIV diagnosis and the importance of consistently continuing treatment for this chronic infection. After some education, he has a better understanding of his condition and is more insightful about wanting to remain compliant with clozapine and bictegravir, emtricitabine, and tenofovir for his HIV.

The authors’ observations

Many patients receive treatment for comorbid HIV and schizophrenia. Patients with schizophrenia and other psychoses are at increased risk of contracting HIV due to numerous psychosocial factors, including an increased frequency of illicit drug use as well as an increased propensity for high-risk sexual behaviors secondary to impaired neurocognitive functioning, delusions, and victimization.¹ In addition to deficits in functioning related to psychiatric illness, patients with HIV also experience virus-related neurocognitive insults. After crossing the blood-brain barrier, HIV viral proteins circulate in the blood, inducing brain endothelial cells to release cytokines, causing neuroinflammation.²

Continue to: Recently, inflammation and inflammatory...

Recently, inflammation and inflammatory biomarkers have become an important topic of psychiatric research. A meta-analysis by Fraguas et al³ concluded that greater inflammation and oxidative stress might lead to poorer outcomes in patients with first-episode psychosis. Based on this evidence, inflammation associated with untreated HIV infection may compound the pre-existing neurocognitive decline seen in patients with schizophrenia and other psychoses, thereby contributing to poor outcomes and treatment-resistant pathology.

Clozapine has been the superior treatment for refractory and nonrefractory schizophrenia.⁴ Factor et al⁵ report there are limited basal ganglia reserves in patients with HIV, which make clozapine the preferred option due to its low potential for causing EPS.

In this case, starting Mr. F on clozapine and titrating to therapeutic blood levels was associated with improved MoCA scores. Low MoCA scores could be due to untreated HIV, as well as inadequately treated psychosis. For Mr. F, improved MoCA scores were associated with increased insight into his HIV. It is important to note that Mr. F’s improved MoCA score also coincided with discontinuing monthly haloperidol decanoate injections. Haloperidol and its metabolites are believed to cause some neuro­toxicity at high doses, and can contribute to cognitive impairment. This may partially explain the increased MoCA score after Mr. F stopped receiving haloperidol decanoate monthly injections.⁶ For the first time, he felt the need to be on antiretroviral therapy for his HIV, and was able to understand the chronic nature of HIV infection.

The benefit of clozapine treatment for patients with schizophrenia and comorbid HIV extends beyond symptomatic control. Long-term and consistent treatment of schizophrenia can be a stepping stone for improving many psychosocial factors. Improved insight allows patients to better understand their illness, treatment regimen, and follow-up needs. Improved self-care contributes to increased adherence to treatment regimens and overall health.

It is likely that patients who are consistently treated for schizophrenia will also have an increased capacity to understand their HIV diagnosis. With gained understanding, patients may be more likely to adhere to highly active antiretroviral therapy (HAART) for HIV and attend follow-up appointments with infectious disease or primary care physicians. Furthermore, with adherence to HAART therapy, patients can enjoy improved quality and duration of life by raising CD4 counts and preventing progression to AIDS and AIDS-related infections.

Continue to: In the case of...

In the case of Mr. F, we noted significant improvement in MoCA scores following treatment with clozapine. This led to improved insight into understanding the chronicity of HIV, understanding the complications of not being treated, and adherence to HAART medication. Improved cognition, as evidenced by an increased MoCA score, can significantly improve patient insight and adherence with medication.⁷ Insight into illness is particularly important when managing a patient with a chronic infectious illness such as HIV, where consistency with the medication regimen can decrease mortality and improve quality of life.⁸ Furthermore, with close monitoring, clozapine was a safe treatment option for this patient with HIV and schizophrenia.

Bottom Line

Patients with schizophrenia are at an increased risk of contracting HIV, and untreated schizophrenia decreases the likelihood patients will adhere to highly active antiretroviral therapy (HAART). Clozapine treatment in comorbid HIV and schizophrenia can improve cognition and insight into HIV diagnosis, possibly increasing the likelihood patients will remain compliant with HAART.

Related Resources

• Diduch MN, Campbell RH, Borovicka M, et al. Treating psychosis in patients with HIV/AIDS. Current Psychiatry. 2018;17(5):35-36,41-44,46.

Drug Brand Names

Bictegravir, emtricitabine, and tenofovir • Biktarvy
Clozapine • Clozaril
Haloperidol • Haldol
Haloperidol decanoate • Haldol decanoate
Olanzapine • Zyprexa
Ziprasidone • Geodon

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

My father, Morty Sosland, MD, was a psychiatrist in a community health setting when he was diagnosed with amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease) in April 2020. He continued to work until February 2021 and credits his ongoing resilience to what he refers to as “the 3 Hs”: hope, help, and humor. Although he can no longer speak, I was able to interview him over the advanced technology that is text messaging.

Sarah: Hi, Dad.

Morty: It’s Doctor Dad to you.

Sarah: I guess we are starting with humor, then?

Humor

Research has demonstrated that humor can have serious health benefits, such as decreasing stress-making hormones and altering dopamine activity.¹ For individuals facing a life-threatening illness, humor can help them gain a sense of perspective in a situation that would otherwise feel overwhelming.

Sarah: I feel like a lot of the humor you used with patients was to help them gain perspective.

Continue to: Morty

Morty: Yes. I’d have to know the client well enough, though—and timing is important. My patients would come to me with a long list of challenges they had faced in the week, and I would say, “But besides that, everything’s good?”

Sarah: And besides the ALS, everything’s good?

Morty: Exactly. I’d also use magic or math tricks to make kids like coming to therapy or to reinforce important concepts.

Sarah: How has humor helped you cope?

Morty: Thinking about things in humorous ways has always been helpful. I used to say my Olympic sport was walking to the dining room with my walker. Unfortunately, I can’t do that anymore, so now my Olympic sport is getting out of bed. It’s a team sport.

Sarah: And that’s a good segue to…

Help

Countless studies have shown the impact of social support on health. Good social support can increase resilience, protect against mental illness, and even increase life expectancy.² Support becomes even more critical when you are physically dependent on others due to illness.

Continue to: Sarah

Sarah: Was it difficult for you to accept help at first?

Morty: I would say yes—but at the same time, I accepted it because the illness was so shocking. I learned early on this was a fight that my family would also fight alongside me.

Sarah: I remember you would quote Fred Rogers.

Morty: Actually, it was Fred Rogers’ mother. She would tell her son during hard times, “Look for the helpers. You will always find people who are helping.” Helpers can be family members, friends, doctors, and aides, as well as others who have the same illness.

Hope

In the face of all life’s challenges, hope is important, but in the face of a life-threatening illness, hope must be multifaceted.³ In addition to hope for a cure, patients may focus their hopes on deepening relationships, maintaining dignity, or living each day to its fullest.

Morty: Early on in this illness, I chose to set a positive tone when I told people. I would say I have the top doctors and there is more research now than ever. Years ago, I wrote a children’s book with the mantra, “I say I can, I make a plan, I get right to it and then I do it.”⁴ My plan is to be around for at least 30 more years.

Sarah: Do you think it’s possible to hold acceptance and hope at the same time?

Morty: Acceptance and hope are not easy, but possible. I get down about this illness. In my dreams, I walk and talk, and most mornings I wake up and see my wheelchair and I think this is absurd or a different choice word. But I focus on the things I still can do, and that gives me a feeling of hope. I can read the latest research, I can enjoy moments of laughter, and I can spend time with my family and close friends.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

My father, Morty Sosland, MD, was a psychiatrist in a community health setting when he was diagnosed with amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease) in April 2020. He continued to work until February 2021 and credits his ongoing resilience to what he refers to as “the 3 Hs”: hope, help, and humor. Although he can no longer speak, I was able to interview him over the advanced technology that is text messaging.

Sarah: Hi, Dad.

Morty: It’s Doctor Dad to you.

Sarah: I guess we are starting with humor, then?

Humor

Research has demonstrated that humor can have serious health benefits, such as decreasing stress-making hormones and altering dopamine activity.¹ For individuals facing a life-threatening illness, humor can help them gain a sense of perspective in a situation that would otherwise feel overwhelming.

Sarah: I feel like a lot of the humor you used with patients was to help them gain perspective.

Continue to: Morty

Morty: Yes. I’d have to know the client well enough, though—and timing is important. My patients would come to me with a long list of challenges they had faced in the week, and I would say, “But besides that, everything’s good?”

Sarah: And besides the ALS, everything’s good?

Morty: Exactly. I’d also use magic or math tricks to make kids like coming to therapy or to reinforce important concepts.

Sarah: How has humor helped you cope?

Morty: Thinking about things in humorous ways has always been helpful. I used to say my Olympic sport was walking to the dining room with my walker. Unfortunately, I can’t do that anymore, so now my Olympic sport is getting out of bed. It’s a team sport.

Sarah: And that’s a good segue to…

Help

Countless studies have shown the impact of social support on health. Good social support can increase resilience, protect against mental illness, and even increase life expectancy.² Support becomes even more critical when you are physically dependent on others due to illness.

Continue to: Sarah

Sarah: Was it difficult for you to accept help at first?

Morty: I would say yes—but at the same time, I accepted it because the illness was so shocking. I learned early on this was a fight that my family would also fight alongside me.

Sarah: I remember you would quote Fred Rogers.

Morty: Actually, it was Fred Rogers’ mother. She would tell her son during hard times, “Look for the helpers. You will always find people who are helping.” Helpers can be family members, friends, doctors, and aides, as well as others who have the same illness.

Hope

In the face of all life’s challenges, hope is important, but in the face of a life-threatening illness, hope must be multifaceted.³ In addition to hope for a cure, patients may focus their hopes on deepening relationships, maintaining dignity, or living each day to its fullest.

Morty: Early on in this illness, I chose to set a positive tone when I told people. I would say I have the top doctors and there is more research now than ever. Years ago, I wrote a children’s book with the mantra, “I say I can, I make a plan, I get right to it and then I do it.”⁴ My plan is to be around for at least 30 more years.

Sarah: Do you think it’s possible to hold acceptance and hope at the same time?

Morty: Acceptance and hope are not easy, but possible. I get down about this illness. In my dreams, I walk and talk, and most mornings I wake up and see my wheelchair and I think this is absurd or a different choice word. But I focus on the things I still can do, and that gives me a feeling of hope. I can read the latest research, I can enjoy moments of laughter, and I can spend time with my family and close friends.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

My father, Morty Sosland, MD, was a psychiatrist in a community health setting when he was diagnosed with amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease) in April 2020. He continued to work until February 2021 and credits his ongoing resilience to what he refers to as “the 3 Hs”: hope, help, and humor. Although he can no longer speak, I was able to interview him over the advanced technology that is text messaging.

Sarah: Hi, Dad.

Morty: It’s Doctor Dad to you.

Sarah: I guess we are starting with humor, then?

Humor

Research has demonstrated that humor can have serious health benefits, such as decreasing stress-making hormones and altering dopamine activity.¹ For individuals facing a life-threatening illness, humor can help them gain a sense of perspective in a situation that would otherwise feel overwhelming.

Sarah: I feel like a lot of the humor you used with patients was to help them gain perspective.

Continue to: Morty

Morty: Yes. I’d have to know the client well enough, though—and timing is important. My patients would come to me with a long list of challenges they had faced in the week, and I would say, “But besides that, everything’s good?”

Sarah: And besides the ALS, everything’s good?

Morty: Exactly. I’d also use magic or math tricks to make kids like coming to therapy or to reinforce important concepts.

Sarah: How has humor helped you cope?

Morty: Thinking about things in humorous ways has always been helpful. I used to say my Olympic sport was walking to the dining room with my walker. Unfortunately, I can’t do that anymore, so now my Olympic sport is getting out of bed. It’s a team sport.

Sarah: And that’s a good segue to…

Help

Countless studies have shown the impact of social support on health. Good social support can increase resilience, protect against mental illness, and even increase life expectancy.² Support becomes even more critical when you are physically dependent on others due to illness.

Continue to: Sarah

Sarah: Was it difficult for you to accept help at first?

Morty: I would say yes—but at the same time, I accepted it because the illness was so shocking. I learned early on this was a fight that my family would also fight alongside me.

Sarah: I remember you would quote Fred Rogers.

Morty: Actually, it was Fred Rogers’ mother. She would tell her son during hard times, “Look for the helpers. You will always find people who are helping.” Helpers can be family members, friends, doctors, and aides, as well as others who have the same illness.

Hope

In the face of all life’s challenges, hope is important, but in the face of a life-threatening illness, hope must be multifaceted.³ In addition to hope for a cure, patients may focus their hopes on deepening relationships, maintaining dignity, or living each day to its fullest.

Morty: Early on in this illness, I chose to set a positive tone when I told people. I would say I have the top doctors and there is more research now than ever. Years ago, I wrote a children’s book with the mantra, “I say I can, I make a plan, I get right to it and then I do it.”⁴ My plan is to be around for at least 30 more years.

Sarah: Do you think it’s possible to hold acceptance and hope at the same time?

Morty: Acceptance and hope are not easy, but possible. I get down about this illness. In my dreams, I walk and talk, and most mornings I wake up and see my wheelchair and I think this is absurd or a different choice word. But I focus on the things I still can do, and that gives me a feeling of hope. I can read the latest research, I can enjoy moments of laughter, and I can spend time with my family and close friends.

Approximately half of pregnancies in the United States are unplanned, and approximately one-fifth of pregnancies end in elective termination.¹ Psychiatrists who treat women of childbearing potential should understand critical aspects of abortion that could affect their patients’ mental health.

Discuss the potential for pregnancy with your patients. Individuals with psychiatric illness are less likely to adhere to contraceptive methods and are more likely to have unplanned pregnancies and detect pregnancies late.² Women receiving psychiatric care could be at risk of not detecting pregnancy early enough to meet state laws that restrict the time frames in which abortions are allowed.

Understand that patients face barriers to abortion. Almost immediately after the Supreme Court overturned Roe v Wade in June 2022, abortion became illegal in several states. Even if abortion remains legal and available in your jurisdiction, patients could face barriers, including strict limits on abortion timing, monetary and travel challenges, preabortion counseling mandates, and timely access to an abortion provider.

Know that most patients can provide informed consent. Most patients with psychiatric illness have capacity to make medical decisions, including whether to consent to an abortion. Pro forma assessment is not necessary. Assessing capacity to consent to abortion should be the same as any other capacity assessment. If a woman lacks medical decision-making capacity, a substitute decision-maker must be used.

Recognize that ambivalence is normal. Even when a woman is certain about her decision to terminate a pregnancy, she might experience ambivalence. Ambivalence about important life decisions is common and should be validated and explored.³

Be aware of bias. As psychiatrists, we must ensure that our personal opinions about abortion do not impact patient care. An impartial and nondirective approach is key, and any effort to persuade or manipulate a woman’s decision is unethical. Because women with mental illness might be vulnerable to coercion, it is important to ensure that the woman’s choice is voluntary.

Accurately communicate information about mental health and abortion to your patients. Abortion does not worsen mental health. Research on abortion and mental health is rife with poorly designed studies that contain methodological flaws, including failure to control for confounding effects, such as pre-existing mental illness, and inadequate control group comparisons.⁴ For example, the correct comparison group in which to consider mental health outcomes for women who are seeking an abortion is those who sought an abortion but were not able to have one—not women with planned and desired pregnancies. The best predictor of postabortion mental wellness is preabortion mental health.⁵ Well-designed studies, such as the Turnaway Study, have demonstrated that abortion does not cause a significant increase in mental illness.⁶ The Turnaway Study was a well-designed, prospective study of thousands of women who obtained a wanted abortion. It compared many outcomes, including mental health, among women who wanted an abortion vs women who could not obtain a wanted abortion.

Continue to: Know that patients might not receive accurate information about the risks and impact of abortion

Know that patients might not receive accurate information about the risks and impact of abortion. A number of states have requirements—known as “informed consent laws”—that mandate physicians to provide state-authored informational packets about the risks and alternatives to abortion to patients seeking abortions. Some of this information is scientifically inaccurate, which poses a significant ethical dilemma for doctors who must choose between legal requirements and an obligation to scientific integrity.⁷

Recognize that abortion being illegal could negatively impact mental health. The consequences of being forced to carry out an unwanted pregnancy are profound. Women unable to obtain an abortion are more likely to have adverse health and pregnancy outcomes, live in poverty, stay with an abusive partner, and have difficulty bonding with the child.⁶ Abortion is highly stigmatized in the United States, and belonging to a stigmatized group is a risk factor for adverse mental health sequalae, including anxiety, depression, substance use, and cognitive deficits.^4-6

Stay up-to-date on your state’s abortion laws. The legal landscape regarding abortion is changing rapidly, and it is important to stay abreast of these changes.

Restrictions on abortion likely will significantly affect women with psychiatric illness. As psychiatrists, we must be aware of the impact of the country’s changing laws will have on our patients and their mental health.

Approximately half of pregnancies in the United States are unplanned, and approximately one-fifth of pregnancies end in elective termination.¹ Psychiatrists who treat women of childbearing potential should understand critical aspects of abortion that could affect their patients’ mental health.

Discuss the potential for pregnancy with your patients. Individuals with psychiatric illness are less likely to adhere to contraceptive methods and are more likely to have unplanned pregnancies and detect pregnancies late.² Women receiving psychiatric care could be at risk of not detecting pregnancy early enough to meet state laws that restrict the time frames in which abortions are allowed.

Understand that patients face barriers to abortion. Almost immediately after the Supreme Court overturned Roe v Wade in June 2022, abortion became illegal in several states. Even if abortion remains legal and available in your jurisdiction, patients could face barriers, including strict limits on abortion timing, monetary and travel challenges, preabortion counseling mandates, and timely access to an abortion provider.

Know that most patients can provide informed consent. Most patients with psychiatric illness have capacity to make medical decisions, including whether to consent to an abortion. Pro forma assessment is not necessary. Assessing capacity to consent to abortion should be the same as any other capacity assessment. If a woman lacks medical decision-making capacity, a substitute decision-maker must be used.

Recognize that ambivalence is normal. Even when a woman is certain about her decision to terminate a pregnancy, she might experience ambivalence. Ambivalence about important life decisions is common and should be validated and explored.³

Be aware of bias. As psychiatrists, we must ensure that our personal opinions about abortion do not impact patient care. An impartial and nondirective approach is key, and any effort to persuade or manipulate a woman’s decision is unethical. Because women with mental illness might be vulnerable to coercion, it is important to ensure that the woman’s choice is voluntary.

Accurately communicate information about mental health and abortion to your patients. Abortion does not worsen mental health. Research on abortion and mental health is rife with poorly designed studies that contain methodological flaws, including failure to control for confounding effects, such as pre-existing mental illness, and inadequate control group comparisons.⁴ For example, the correct comparison group in which to consider mental health outcomes for women who are seeking an abortion is those who sought an abortion but were not able to have one—not women with planned and desired pregnancies. The best predictor of postabortion mental wellness is preabortion mental health.⁵ Well-designed studies, such as the Turnaway Study, have demonstrated that abortion does not cause a significant increase in mental illness.⁶ The Turnaway Study was a well-designed, prospective study of thousands of women who obtained a wanted abortion. It compared many outcomes, including mental health, among women who wanted an abortion vs women who could not obtain a wanted abortion.

Continue to: Know that patients might not receive accurate information about the risks and impact of abortion

Know that patients might not receive accurate information about the risks and impact of abortion. A number of states have requirements—known as “informed consent laws”—that mandate physicians to provide state-authored informational packets about the risks and alternatives to abortion to patients seeking abortions. Some of this information is scientifically inaccurate, which poses a significant ethical dilemma for doctors who must choose between legal requirements and an obligation to scientific integrity.⁷

Recognize that abortion being illegal could negatively impact mental health. The consequences of being forced to carry out an unwanted pregnancy are profound. Women unable to obtain an abortion are more likely to have adverse health and pregnancy outcomes, live in poverty, stay with an abusive partner, and have difficulty bonding with the child.⁶ Abortion is highly stigmatized in the United States, and belonging to a stigmatized group is a risk factor for adverse mental health sequalae, including anxiety, depression, substance use, and cognitive deficits.^4-6

Stay up-to-date on your state’s abortion laws. The legal landscape regarding abortion is changing rapidly, and it is important to stay abreast of these changes.

Restrictions on abortion likely will significantly affect women with psychiatric illness. As psychiatrists, we must be aware of the impact of the country’s changing laws will have on our patients and their mental health.

Approximately half of pregnancies in the United States are unplanned, and approximately one-fifth of pregnancies end in elective termination.¹ Psychiatrists who treat women of childbearing potential should understand critical aspects of abortion that could affect their patients’ mental health.

Discuss the potential for pregnancy with your patients. Individuals with psychiatric illness are less likely to adhere to contraceptive methods and are more likely to have unplanned pregnancies and detect pregnancies late.² Women receiving psychiatric care could be at risk of not detecting pregnancy early enough to meet state laws that restrict the time frames in which abortions are allowed.

Understand that patients face barriers to abortion. Almost immediately after the Supreme Court overturned Roe v Wade in June 2022, abortion became illegal in several states. Even if abortion remains legal and available in your jurisdiction, patients could face barriers, including strict limits on abortion timing, monetary and travel challenges, preabortion counseling mandates, and timely access to an abortion provider.

Know that most patients can provide informed consent. Most patients with psychiatric illness have capacity to make medical decisions, including whether to consent to an abortion. Pro forma assessment is not necessary. Assessing capacity to consent to abortion should be the same as any other capacity assessment. If a woman lacks medical decision-making capacity, a substitute decision-maker must be used.

Recognize that ambivalence is normal. Even when a woman is certain about her decision to terminate a pregnancy, she might experience ambivalence. Ambivalence about important life decisions is common and should be validated and explored.³

Be aware of bias. As psychiatrists, we must ensure that our personal opinions about abortion do not impact patient care. An impartial and nondirective approach is key, and any effort to persuade or manipulate a woman’s decision is unethical. Because women with mental illness might be vulnerable to coercion, it is important to ensure that the woman’s choice is voluntary.

Accurately communicate information about mental health and abortion to your patients. Abortion does not worsen mental health. Research on abortion and mental health is rife with poorly designed studies that contain methodological flaws, including failure to control for confounding effects, such as pre-existing mental illness, and inadequate control group comparisons.⁴ For example, the correct comparison group in which to consider mental health outcomes for women who are seeking an abortion is those who sought an abortion but were not able to have one—not women with planned and desired pregnancies. The best predictor of postabortion mental wellness is preabortion mental health.⁵ Well-designed studies, such as the Turnaway Study, have demonstrated that abortion does not cause a significant increase in mental illness.⁶ The Turnaway Study was a well-designed, prospective study of thousands of women who obtained a wanted abortion. It compared many outcomes, including mental health, among women who wanted an abortion vs women who could not obtain a wanted abortion.

Continue to: Know that patients might not receive accurate information about the risks and impact of abortion

Know that patients might not receive accurate information about the risks and impact of abortion. A number of states have requirements—known as “informed consent laws”—that mandate physicians to provide state-authored informational packets about the risks and alternatives to abortion to patients seeking abortions. Some of this information is scientifically inaccurate, which poses a significant ethical dilemma for doctors who must choose between legal requirements and an obligation to scientific integrity.⁷

Recognize that abortion being illegal could negatively impact mental health. The consequences of being forced to carry out an unwanted pregnancy are profound. Women unable to obtain an abortion are more likely to have adverse health and pregnancy outcomes, live in poverty, stay with an abusive partner, and have difficulty bonding with the child.⁶ Abortion is highly stigmatized in the United States, and belonging to a stigmatized group is a risk factor for adverse mental health sequalae, including anxiety, depression, substance use, and cognitive deficits.^4-6

Stay up-to-date on your state’s abortion laws. The legal landscape regarding abortion is changing rapidly, and it is important to stay abreast of these changes.

Restrictions on abortion likely will significantly affect women with psychiatric illness. As psychiatrists, we must be aware of the impact of the country’s changing laws will have on our patients and their mental health.

While the COVID-19 pandemic has impacted the mental health of a wide range of individuals, its adverse effects have been particularly detrimental to adolescents. In this article, I discuss evidence that shows the effects of the pandemic on adolescent patients, potential reasons for this increased distress, and what types of coping mechanisms adolescents have used to counter these effects.

Increases in multiple measures of psychopathology

Multiple online surveys and other studies have documented the pandemic’s impact on younger individuals. In the United States, visits to emergency departments by pediatric patients increased in the months after the first lockdown period.¹ Several studies found increased rates of anxiety and depression among adolescents during the COVID-19 pandemic.^2,3 In an online survey of 359 children and 3,254 adolescents in China, 22% of respondents reported that they experienced depressive symptoms.³ In an online survey of 1,054 Canadian adolescents, 43% said they were “very concerned” about the pandemic.⁴ In an online survey of 7,353 adolescents in the United States, 37% reported suicidal ideation during the pandemic compared to 17% in 2017.⁵ A Chinese study found that smartphone and internet addiction was significantly associated with increased levels of depressive symptoms during the pandemic.³ In a survey in the Philippines, 16.3% of adolescents reported moderate-to-severe psychological impairment during the pandemic; the rates of COVID-19–related anxiety were higher among girls vs boys.⁶ Alcohol and cannabis use increased among Canadian adolescents during the pandemic, according to an online survey.⁷ Adolescents with anorexia nervosa reported a 70% increase in poor eating habits and more thoughts associated with eating disorders during the pandemic.⁸ A Danish study found that children and adolescents newly diagnosed with obsessive-compulsive disorder (OCD) or who had completed treatment exhibited worsening OCD, anxiety, and depressive symptoms during the pandemic.⁹ An online survey of 6,196 Chinese adolescents found that those with a higher number of pre-pandemic adverse childhood experiences, such as abuse and neglect, had elevated posttraumatic stress symptoms and anxiety during the onset of the pandemic.¹⁰

Underlying causes of pandemic-induced distress

Limited social connectedness during the pandemic is a major reason for distress among adolescents. A review of 80 studies found that social isolation and loneliness as a result of social distancing and quarantining were associated with an increased risk of depression, anxiety, suicidal ideation, and self-harm.¹¹ Parents’ stress about the risks of COVID-19 was correlated with worsening mental health in their adolescent children.¹² A Chinese study found that the amount of time students spent on smartphones and social media doubled during the pandemic.¹³ In an online survey of 7,890 Chinese adolescents, greater social media, internet, and smartphone use was associated with increased anxiety and depression.¹⁴ This may be in part the result of adolescents spending time reading COVID-related news.

Coping mechanisms to increase well-being

Researchers have identified several positive coping mechanisms adolescents employed during the pandemic. Although some data suggest that increased internet use raises the risk of COVID-related distress, for certain adolescents, using social media to stay connected with friends and relatives was a buffer for feelings of loneliness and might have increased mental well-being.¹⁵ Other common coping mechanisms include relying on faith, volunteering, and starting new hobbies.¹⁶ During the pandemic, there were higher rates of playing outside and increased physical activity, which correlated with positive mental health outcomes.¹⁶ An online survey of 1,040 adolescents found that those who looked to the future optimistically and confidently had a higher health-related quality of life.¹⁷

Continuing an emphasis on adolescent well-being

Although data are limited, adolescents can continue to use these coping mechanisms to maintain their well-being, even if COVID-related restrictions are lifted or reimplemented. During these difficult times, it is imperative for adolescents to get the mental health services they need, and for psychiatric clinicians to continue to find avenues to promote resilience and mental wellness among young patients.

While the COVID-19 pandemic has impacted the mental health of a wide range of individuals, its adverse effects have been particularly detrimental to adolescents. In this article, I discuss evidence that shows the effects of the pandemic on adolescent patients, potential reasons for this increased distress, and what types of coping mechanisms adolescents have used to counter these effects.

Increases in multiple measures of psychopathology

Multiple online surveys and other studies have documented the pandemic’s impact on younger individuals. In the United States, visits to emergency departments by pediatric patients increased in the months after the first lockdown period.¹ Several studies found increased rates of anxiety and depression among adolescents during the COVID-19 pandemic.^2,3 In an online survey of 359 children and 3,254 adolescents in China, 22% of respondents reported that they experienced depressive symptoms.³ In an online survey of 1,054 Canadian adolescents, 43% said they were “very concerned” about the pandemic.⁴ In an online survey of 7,353 adolescents in the United States, 37% reported suicidal ideation during the pandemic compared to 17% in 2017.⁵ A Chinese study found that smartphone and internet addiction was significantly associated with increased levels of depressive symptoms during the pandemic.³ In a survey in the Philippines, 16.3% of adolescents reported moderate-to-severe psychological impairment during the pandemic; the rates of COVID-19–related anxiety were higher among girls vs boys.⁶ Alcohol and cannabis use increased among Canadian adolescents during the pandemic, according to an online survey.⁷ Adolescents with anorexia nervosa reported a 70% increase in poor eating habits and more thoughts associated with eating disorders during the pandemic.⁸ A Danish study found that children and adolescents newly diagnosed with obsessive-compulsive disorder (OCD) or who had completed treatment exhibited worsening OCD, anxiety, and depressive symptoms during the pandemic.⁹ An online survey of 6,196 Chinese adolescents found that those with a higher number of pre-pandemic adverse childhood experiences, such as abuse and neglect, had elevated posttraumatic stress symptoms and anxiety during the onset of the pandemic.¹⁰

Underlying causes of pandemic-induced distress

Limited social connectedness during the pandemic is a major reason for distress among adolescents. A review of 80 studies found that social isolation and loneliness as a result of social distancing and quarantining were associated with an increased risk of depression, anxiety, suicidal ideation, and self-harm.¹¹ Parents’ stress about the risks of COVID-19 was correlated with worsening mental health in their adolescent children.¹² A Chinese study found that the amount of time students spent on smartphones and social media doubled during the pandemic.¹³ In an online survey of 7,890 Chinese adolescents, greater social media, internet, and smartphone use was associated with increased anxiety and depression.¹⁴ This may be in part the result of adolescents spending time reading COVID-related news.

Coping mechanisms to increase well-being

Researchers have identified several positive coping mechanisms adolescents employed during the pandemic. Although some data suggest that increased internet use raises the risk of COVID-related distress, for certain adolescents, using social media to stay connected with friends and relatives was a buffer for feelings of loneliness and might have increased mental well-being.¹⁵ Other common coping mechanisms include relying on faith, volunteering, and starting new hobbies.¹⁶ During the pandemic, there were higher rates of playing outside and increased physical activity, which correlated with positive mental health outcomes.¹⁶ An online survey of 1,040 adolescents found that those who looked to the future optimistically and confidently had a higher health-related quality of life.¹⁷

Continuing an emphasis on adolescent well-being

Although data are limited, adolescents can continue to use these coping mechanisms to maintain their well-being, even if COVID-related restrictions are lifted or reimplemented. During these difficult times, it is imperative for adolescents to get the mental health services they need, and for psychiatric clinicians to continue to find avenues to promote resilience and mental wellness among young patients.

While the COVID-19 pandemic has impacted the mental health of a wide range of individuals, its adverse effects have been particularly detrimental to adolescents. In this article, I discuss evidence that shows the effects of the pandemic on adolescent patients, potential reasons for this increased distress, and what types of coping mechanisms adolescents have used to counter these effects.

Increases in multiple measures of psychopathology

Multiple online surveys and other studies have documented the pandemic’s impact on younger individuals. In the United States, visits to emergency departments by pediatric patients increased in the months after the first lockdown period.¹ Several studies found increased rates of anxiety and depression among adolescents during the COVID-19 pandemic.^2,3 In an online survey of 359 children and 3,254 adolescents in China, 22% of respondents reported that they experienced depressive symptoms.³ In an online survey of 1,054 Canadian adolescents, 43% said they were “very concerned” about the pandemic.⁴ In an online survey of 7,353 adolescents in the United States, 37% reported suicidal ideation during the pandemic compared to 17% in 2017.⁵ A Chinese study found that smartphone and internet addiction was significantly associated with increased levels of depressive symptoms during the pandemic.³ In a survey in the Philippines, 16.3% of adolescents reported moderate-to-severe psychological impairment during the pandemic; the rates of COVID-19–related anxiety were higher among girls vs boys.⁶ Alcohol and cannabis use increased among Canadian adolescents during the pandemic, according to an online survey.⁷ Adolescents with anorexia nervosa reported a 70% increase in poor eating habits and more thoughts associated with eating disorders during the pandemic.⁸ A Danish study found that children and adolescents newly diagnosed with obsessive-compulsive disorder (OCD) or who had completed treatment exhibited worsening OCD, anxiety, and depressive symptoms during the pandemic.⁹ An online survey of 6,196 Chinese adolescents found that those with a higher number of pre-pandemic adverse childhood experiences, such as abuse and neglect, had elevated posttraumatic stress symptoms and anxiety during the onset of the pandemic.¹⁰

Underlying causes of pandemic-induced distress

Limited social connectedness during the pandemic is a major reason for distress among adolescents. A review of 80 studies found that social isolation and loneliness as a result of social distancing and quarantining were associated with an increased risk of depression, anxiety, suicidal ideation, and self-harm.¹¹ Parents’ stress about the risks of COVID-19 was correlated with worsening mental health in their adolescent children.¹² A Chinese study found that the amount of time students spent on smartphones and social media doubled during the pandemic.¹³ In an online survey of 7,890 Chinese adolescents, greater social media, internet, and smartphone use was associated with increased anxiety and depression.¹⁴ This may be in part the result of adolescents spending time reading COVID-related news.

Coping mechanisms to increase well-being

Researchers have identified several positive coping mechanisms adolescents employed during the pandemic. Although some data suggest that increased internet use raises the risk of COVID-related distress, for certain adolescents, using social media to stay connected with friends and relatives was a buffer for feelings of loneliness and might have increased mental well-being.¹⁵ Other common coping mechanisms include relying on faith, volunteering, and starting new hobbies.¹⁶ During the pandemic, there were higher rates of playing outside and increased physical activity, which correlated with positive mental health outcomes.¹⁶ An online survey of 1,040 adolescents found that those who looked to the future optimistically and confidently had a higher health-related quality of life.¹⁷

Continuing an emphasis on adolescent well-being

Although data are limited, adolescents can continue to use these coping mechanisms to maintain their well-being, even if COVID-related restrictions are lifted or reimplemented. During these difficult times, it is imperative for adolescents to get the mental health services they need, and for psychiatric clinicians to continue to find avenues to promote resilience and mental wellness among young patients.

I just finished reading your editorial “A PSYCHIATRIC MANIFESTO: Stigma is hate speech and a hate crime” (Current Psychiatry, June 2022, p. 6-8, doi:10.12788/cp.0258) and had to send you this email. Our teenage son spent the last 3 years struggling with anxiety, depression, and a mood disorder. He has experienced a long hospitalization, has been in partial hospitalization programs and rehab, and now is in a therapeutic day school. Your article brought tears to my eyes because you articulated exactly what I have been feeling as a mother of a teen who struggles with mental health issues.

Our son went from an honor roll student before the pandemic to a child I barely recognized. Approximately 6 months into the pandemic, he was using drugs, vaping nicotine, destroying our property, and eloping at night. The journey of watching his decline and getting him help was agonizing. But the stigma around what was happening to him was an entirely separate animal.

Our society vilifies, ridicules, dismisses, and often makes fun of those with mental health issues. I experience it daily with my son and am on constant guard to shoot down any comments and to calmly teach those who say such cruel things. But the shame my son feels is the most devastating part. Although we keep reminding him that his condition is a medical condition like diabetes or heart disease, for a teenage boy, that makes no sense. He just wants to be “normal.” And living in a world that rarely represents mental illness this way, it’s almost a lost cause to get him to let go of this shame. All we can do is love him, be there for him, support him, and do what we can to educate those around us about the stigma of mental illness.

What a powerful and accurate article. Thank you for putting into words what I have been thinking and feeling, and for being as outraged as we are at how this vulnerable population is treated. My husband is a psychiatrist and we live in an affluent urban area, so we are not in the middle of nowhere with no knowledge of what is happening to our son. And despite that, we still suffer from the stigma.

Thank you, Dr. Nasrallah.

Name withheld 

I need to take a moment to thank you for your editorial about stigma being hate speech and a hate crime. I really agree with you, and I think the way you formulated and articulated this message is very compelling.

I have focused on normalizing mental health differences among entrepreneurs as a destigmatization strategy (see https://www.sciencedirect.com/science/article/pii/S0883902622000027 and https://link.springer.com/article/10.1007/s11187-018-0059-8). Entrepreneurs clearly illustrate the fallacy of stigma. As a simple example, Elon Musk—the wealthiest person in the world—talks openly about being autistic, and possibly bipolar. These mental health differences help him create jobs and contribute to our shared prosperity. Nothing to be ashamed of there.

Thanks again for being such an effective advocate.

Michael A. Freeman, MD
Kentfield, California

Continue to: Thank you...

Thank you so much for your “Psychiatric Manifesto.” I will do my best to disseminate it amongst colleagues, patients, friends, family, and as many others as possible.

Daniel N. Pistone, MD
San Francisco, California

Once again, your words hit the pin on the head.

Robert W. Pollack, MD, ABPN, DLFAPA
Fort Myers, Florida

I just finished reading your editorial “A PSYCHIATRIC MANIFESTO: Stigma is hate speech and a hate crime” (Current Psychiatry, June 2022, p. 6-8, doi:10.12788/cp.0258) and had to send you this email. Our teenage son spent the last 3 years struggling with anxiety, depression, and a mood disorder. He has experienced a long hospitalization, has been in partial hospitalization programs and rehab, and now is in a therapeutic day school. Your article brought tears to my eyes because you articulated exactly what I have been feeling as a mother of a teen who struggles with mental health issues.

Our son went from an honor roll student before the pandemic to a child I barely recognized. Approximately 6 months into the pandemic, he was using drugs, vaping nicotine, destroying our property, and eloping at night. The journey of watching his decline and getting him help was agonizing. But the stigma around what was happening to him was an entirely separate animal.

Our society vilifies, ridicules, dismisses, and often makes fun of those with mental health issues. I experience it daily with my son and am on constant guard to shoot down any comments and to calmly teach those who say such cruel things. But the shame my son feels is the most devastating part. Although we keep reminding him that his condition is a medical condition like diabetes or heart disease, for a teenage boy, that makes no sense. He just wants to be “normal.” And living in a world that rarely represents mental illness this way, it’s almost a lost cause to get him to let go of this shame. All we can do is love him, be there for him, support him, and do what we can to educate those around us about the stigma of mental illness.

What a powerful and accurate article. Thank you for putting into words what I have been thinking and feeling, and for being as outraged as we are at how this vulnerable population is treated. My husband is a psychiatrist and we live in an affluent urban area, so we are not in the middle of nowhere with no knowledge of what is happening to our son. And despite that, we still suffer from the stigma.

Thank you, Dr. Nasrallah.

Name withheld 

I need to take a moment to thank you for your editorial about stigma being hate speech and a hate crime. I really agree with you, and I think the way you formulated and articulated this message is very compelling.

I have focused on normalizing mental health differences among entrepreneurs as a destigmatization strategy (see https://www.sciencedirect.com/science/article/pii/S0883902622000027 and https://link.springer.com/article/10.1007/s11187-018-0059-8). Entrepreneurs clearly illustrate the fallacy of stigma. As a simple example, Elon Musk—the wealthiest person in the world—talks openly about being autistic, and possibly bipolar. These mental health differences help him create jobs and contribute to our shared prosperity. Nothing to be ashamed of there.

Thanks again for being such an effective advocate.

Michael A. Freeman, MD
Kentfield, California

Continue to: Thank you...

Thank you so much for your “Psychiatric Manifesto.” I will do my best to disseminate it amongst colleagues, patients, friends, family, and as many others as possible.

Daniel N. Pistone, MD
San Francisco, California

Once again, your words hit the pin on the head.

Robert W. Pollack, MD, ABPN, DLFAPA
Fort Myers, Florida

I just finished reading your editorial “A PSYCHIATRIC MANIFESTO: Stigma is hate speech and a hate crime” (Current Psychiatry, June 2022, p. 6-8, doi:10.12788/cp.0258) and had to send you this email. Our teenage son spent the last 3 years struggling with anxiety, depression, and a mood disorder. He has experienced a long hospitalization, has been in partial hospitalization programs and rehab, and now is in a therapeutic day school. Your article brought tears to my eyes because you articulated exactly what I have been feeling as a mother of a teen who struggles with mental health issues.

Our son went from an honor roll student before the pandemic to a child I barely recognized. Approximately 6 months into the pandemic, he was using drugs, vaping nicotine, destroying our property, and eloping at night. The journey of watching his decline and getting him help was agonizing. But the stigma around what was happening to him was an entirely separate animal.

Our society vilifies, ridicules, dismisses, and often makes fun of those with mental health issues. I experience it daily with my son and am on constant guard to shoot down any comments and to calmly teach those who say such cruel things. But the shame my son feels is the most devastating part. Although we keep reminding him that his condition is a medical condition like diabetes or heart disease, for a teenage boy, that makes no sense. He just wants to be “normal.” And living in a world that rarely represents mental illness this way, it’s almost a lost cause to get him to let go of this shame. All we can do is love him, be there for him, support him, and do what we can to educate those around us about the stigma of mental illness.

What a powerful and accurate article. Thank you for putting into words what I have been thinking and feeling, and for being as outraged as we are at how this vulnerable population is treated. My husband is a psychiatrist and we live in an affluent urban area, so we are not in the middle of nowhere with no knowledge of what is happening to our son. And despite that, we still suffer from the stigma.

Thank you, Dr. Nasrallah.

Name withheld 

I need to take a moment to thank you for your editorial about stigma being hate speech and a hate crime. I really agree with you, and I think the way you formulated and articulated this message is very compelling.

I have focused on normalizing mental health differences among entrepreneurs as a destigmatization strategy (see https://www.sciencedirect.com/science/article/pii/S0883902622000027 and https://link.springer.com/article/10.1007/s11187-018-0059-8). Entrepreneurs clearly illustrate the fallacy of stigma. As a simple example, Elon Musk—the wealthiest person in the world—talks openly about being autistic, and possibly bipolar. These mental health differences help him create jobs and contribute to our shared prosperity. Nothing to be ashamed of there.

Thanks again for being such an effective advocate.

Michael A. Freeman, MD
Kentfield, California

Continue to: Thank you...

Thank you so much for your “Psychiatric Manifesto.” I will do my best to disseminate it amongst colleagues, patients, friends, family, and as many others as possible.

Daniel N. Pistone, MD
San Francisco, California

Once again, your words hit the pin on the head.

Robert W. Pollack, MD, ABPN, DLFAPA
Fort Myers, Florida

During the closing arguments in a $10 million malpractice trial, attorney Robert McKenna III told jurors the claims against his client, a gastroenterologist, were baseless and equivalent to “extortion.” The patient’s family blamed the gastroenterologist for their father’s death, alleging the doctor perforated his colon during insertion of a feeding tube. 

“I take pride in what I do, and I’ve got to tell you, in the 30 years I have been doing this, I have never seen a more insulting, factually devoid presentation in my entire career,” Mr. McKenna said, according to court transcripts. “On the strength of this evidence, they want you to award them $10 million. Welcome to America. Welcome to the personal injury machine, the personal injury industrial complex.”

After less than 30 minutes of deliberation, jurors returned a 12-0 verdict in favor of the physician.

However, Mr. McKenna, from Huntington Beach, Calif., described the case very differently to his staff in a celebration video, which he never expected to become public.

In the video, posted on Twitter and Instagram, Mr. McKenna bragged about how his legal team convinced jurors to doubt the patient’s official cause of death. He said the lawsuit involved a guy “that was probably negligently killed, but we kind of made it look like other people did it.”

“We actually had a death certificate that said he died the very way the plaintiff said he died, and we had to say, ‘No, you really shouldn’t believe what that death certificate says, or the coroner from the Orange County coroner’s office ... who says that it’s right,’” Mr. McKenna said in the video.

The 26-minute verdict was the fastest he’s ever received, Mr. McKenna says in the video, encouraging his partner to ring the firm’s victory bell.

“Overcoming all of those hurdles, we managed to sock three lawyers in the face,” Mr. McKenna said, referring to the plaintiffs’ lawyers. 

The video of Mr. McKenna’s remarks is now in wide circulation after having been posted to online attorney forums, Instagram, where it’s been viewed more than 8,000 times, and Twitter, where views have reached over 3,000.

Jorge Ledezma, an Orange County, Calif., attorney who represented the patient’s family in the case, said the remarks make it appear as if Mr. McKenna tricked the jury.

“It was a drastic change from the comments he made to the jury during his closing arguments,” Mr. Ledezma said. “But the video is more important for what he doesn’t say. He doesn’t say his client did everything properly. He doesn’t say our case didn’t have any merit. He doesn’t say his client was a good doctor. Clearly, what he told the jury and what he believes are the exact opposite of each other.”

Mr. McKenna did not return multiple messages seeking comment for this story. In a statement to the LA Times, Mr. McKenna said his remarks were “intended purely as an internal briefing to our staff, using shorthand phrases which might understandably cause confusion for a lay audience unfamiliar with the case at hand, and the law in general.”

“I have expressed my apologies to my client, opposing counsel, and both the medical and legal communities,” Mr. McKenna said in the statement to the LA Times. “However, nothing about my remarks should call into question our very transparent trial strategy or the jury’s verdict in favor of my client.”
 

What happened to the patient?

Enrique Garcia Sanchez, 49, arrived at the critical care unit at South Coast Global Medical Center in Santa Ana, Calif., on Nov. 5, 2017, complaining of abdominal pain. He was diagnosed with acute pancreatitis, acute hypokalemia, and alcohol abuse, and transferred to the ICU, according to the family’s legal complaint.

Mr. Sanchez had a positive D-Dimer test, indicating a probable blood clot, and he appeared to be experiencing septic shock caused by pancreatitis, according to the complaint. By Nov. 17, Mr. Sanchez was suffering from respiratory failure and severe hypoxemia, and as a result, he was sedated. In addition, his abdomen was described as distended with decreased bowel sounds, according to court documents.

On. Nov. 18, a gastrointestinal specialist was consulted because of Mr. Sanchez’s prolonged intubation and oropharyngeal dysphagia, according to the lawsuit. On Nov. 21, air was leaking from Mr. Sanchez’s breathing tube with diffuse infiltration noted on the right side, and pneumonia.

Mr. Sanchez was eventually unable to swallow, and the gastroenterologist inserted a percutaneous endoscopic gastrostomy (PEG) tube, according to court records. 

Mr. Sanchez’s condition worsened, and he developed respiratory distress, hypotension, and weakness during dialysis. On Dec. 9, 2017, physicians noted he had a bacterial infection, and he was later intubated on vent support because of progressive respiratory failure. Additionally, an internist reported that “fecal material” was observed per the PEG tube. Mr. Sanchez’s white blood cell count continued to rise, and his condition deteriorated. Mr. Sanchez died on Dec. 31, 2017.

A death certificate concluded that Mr. Sanchez died from complications of a PEG tube that perforated his colon, according to Mr. Ledezma. The plaintiffs’ legal team argued the gastroenterologist breached the standard of care by failing to ensure the tube was placed properly and failing to remedy the error after leakage was noted. 

“Mr. Garcia died because of a misplaced PEG tube that perforated the colon, resulting in peritonitis and sepsis,” attorney Jose Robles said during his closing arguments. “Mr. Garcia had ascites, a contraindication for PEG tube placement. He had ileus, a contraindication for PEG tube placement. The standard of care requires that [the gastroenterologist] conduct a proper workup to confirm that a PEG tube placement can be done appropriately and safely.”

Mr. McKenna argued the gastroenterologist was not at fault for the patient’s death, and that complications from his pancreatitis ultimately killed him. During the trial, physicians who cared for Mr. Sanchez testified the patient had a less than 50% chance of survival.

“What he had was end-stage catastrophic [pancreatitis] that was affecting his organ system and aspiration pneumonia that made it impossible for him to try to breathe on his own,” Mr. McKenna said during closing arguments. “The man ... had a catastrophic injury that ate most of his pancreas. That is not a survivable event.”
 

Attorney faces backlash from legal community

Since his celebratory remarks were posted online, Mr. McKenna has faced much backlash, particularly from the legal community.

@mgvolada tweeted, “As an attorney I am revolted and I hope sanctions follow ... this is why people hate attorneys.”

@stevewieland, who identified himself as a trial lawyer, wrote he would not feel good about winning such a case.

“No wonder we get no love from the public,” he tweeted.

“Let’s see how the Court of Appeals thinks about your braggadocio and how this makes lawyers appear to the public,” tweeted @Stephen60134955, a self-identified attorney.

Mr. McKenna’s license remains active and in good standing with no disciplinary actions, according to the State Bar of California website.

Mr. Ledezma has filed a motion for a new trial, and a hearing on the motion is scheduled for Aug. 4, 2022. The motion was filed primarily because of issues during the trial, what Mr. Ledezma described as “inflammatory closing arguments,” and in small part, Mr. McKenna’s video remarks, he said.

If the motion is denied, the plaintiffs will move forward with an appeal, he said.

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

During the closing arguments in a $10 million malpractice trial, attorney Robert McKenna III told jurors the claims against his client, a gastroenterologist, were baseless and equivalent to “extortion.” The patient’s family blamed the gastroenterologist for their father’s death, alleging the doctor perforated his colon during insertion of a feeding tube. 

“I take pride in what I do, and I’ve got to tell you, in the 30 years I have been doing this, I have never seen a more insulting, factually devoid presentation in my entire career,” Mr. McKenna said, according to court transcripts. “On the strength of this evidence, they want you to award them $10 million. Welcome to America. Welcome to the personal injury machine, the personal injury industrial complex.”

After less than 30 minutes of deliberation, jurors returned a 12-0 verdict in favor of the physician.

However, Mr. McKenna, from Huntington Beach, Calif., described the case very differently to his staff in a celebration video, which he never expected to become public.

In the video, posted on Twitter and Instagram, Mr. McKenna bragged about how his legal team convinced jurors to doubt the patient’s official cause of death. He said the lawsuit involved a guy “that was probably negligently killed, but we kind of made it look like other people did it.”

“We actually had a death certificate that said he died the very way the plaintiff said he died, and we had to say, ‘No, you really shouldn’t believe what that death certificate says, or the coroner from the Orange County coroner’s office ... who says that it’s right,’” Mr. McKenna said in the video.

The 26-minute verdict was the fastest he’s ever received, Mr. McKenna says in the video, encouraging his partner to ring the firm’s victory bell.

“Overcoming all of those hurdles, we managed to sock three lawyers in the face,” Mr. McKenna said, referring to the plaintiffs’ lawyers. 

The video of Mr. McKenna’s remarks is now in wide circulation after having been posted to online attorney forums, Instagram, where it’s been viewed more than 8,000 times, and Twitter, where views have reached over 3,000.

Jorge Ledezma, an Orange County, Calif., attorney who represented the patient’s family in the case, said the remarks make it appear as if Mr. McKenna tricked the jury.

“It was a drastic change from the comments he made to the jury during his closing arguments,” Mr. Ledezma said. “But the video is more important for what he doesn’t say. He doesn’t say his client did everything properly. He doesn’t say our case didn’t have any merit. He doesn’t say his client was a good doctor. Clearly, what he told the jury and what he believes are the exact opposite of each other.”

Mr. McKenna did not return multiple messages seeking comment for this story. In a statement to the LA Times, Mr. McKenna said his remarks were “intended purely as an internal briefing to our staff, using shorthand phrases which might understandably cause confusion for a lay audience unfamiliar with the case at hand, and the law in general.”

“I have expressed my apologies to my client, opposing counsel, and both the medical and legal communities,” Mr. McKenna said in the statement to the LA Times. “However, nothing about my remarks should call into question our very transparent trial strategy or the jury’s verdict in favor of my client.”
 

What happened to the patient?

Enrique Garcia Sanchez, 49, arrived at the critical care unit at South Coast Global Medical Center in Santa Ana, Calif., on Nov. 5, 2017, complaining of abdominal pain. He was diagnosed with acute pancreatitis, acute hypokalemia, and alcohol abuse, and transferred to the ICU, according to the family’s legal complaint.

Mr. Sanchez had a positive D-Dimer test, indicating a probable blood clot, and he appeared to be experiencing septic shock caused by pancreatitis, according to the complaint. By Nov. 17, Mr. Sanchez was suffering from respiratory failure and severe hypoxemia, and as a result, he was sedated. In addition, his abdomen was described as distended with decreased bowel sounds, according to court documents.

On. Nov. 18, a gastrointestinal specialist was consulted because of Mr. Sanchez’s prolonged intubation and oropharyngeal dysphagia, according to the lawsuit. On Nov. 21, air was leaking from Mr. Sanchez’s breathing tube with diffuse infiltration noted on the right side, and pneumonia.

Mr. Sanchez was eventually unable to swallow, and the gastroenterologist inserted a percutaneous endoscopic gastrostomy (PEG) tube, according to court records. 

Mr. Sanchez’s condition worsened, and he developed respiratory distress, hypotension, and weakness during dialysis. On Dec. 9, 2017, physicians noted he had a bacterial infection, and he was later intubated on vent support because of progressive respiratory failure. Additionally, an internist reported that “fecal material” was observed per the PEG tube. Mr. Sanchez’s white blood cell count continued to rise, and his condition deteriorated. Mr. Sanchez died on Dec. 31, 2017.

A death certificate concluded that Mr. Sanchez died from complications of a PEG tube that perforated his colon, according to Mr. Ledezma. The plaintiffs’ legal team argued the gastroenterologist breached the standard of care by failing to ensure the tube was placed properly and failing to remedy the error after leakage was noted. 

“Mr. Garcia died because of a misplaced PEG tube that perforated the colon, resulting in peritonitis and sepsis,” attorney Jose Robles said during his closing arguments. “Mr. Garcia had ascites, a contraindication for PEG tube placement. He had ileus, a contraindication for PEG tube placement. The standard of care requires that [the gastroenterologist] conduct a proper workup to confirm that a PEG tube placement can be done appropriately and safely.”

Mr. McKenna argued the gastroenterologist was not at fault for the patient’s death, and that complications from his pancreatitis ultimately killed him. During the trial, physicians who cared for Mr. Sanchez testified the patient had a less than 50% chance of survival.

“What he had was end-stage catastrophic [pancreatitis] that was affecting his organ system and aspiration pneumonia that made it impossible for him to try to breathe on his own,” Mr. McKenna said during closing arguments. “The man ... had a catastrophic injury that ate most of his pancreas. That is not a survivable event.”
 

Attorney faces backlash from legal community

Since his celebratory remarks were posted online, Mr. McKenna has faced much backlash, particularly from the legal community.

@mgvolada tweeted, “As an attorney I am revolted and I hope sanctions follow ... this is why people hate attorneys.”

@stevewieland, who identified himself as a trial lawyer, wrote he would not feel good about winning such a case.

“No wonder we get no love from the public,” he tweeted.

“Let’s see how the Court of Appeals thinks about your braggadocio and how this makes lawyers appear to the public,” tweeted @Stephen60134955, a self-identified attorney.

Mr. McKenna’s license remains active and in good standing with no disciplinary actions, according to the State Bar of California website.

Mr. Ledezma has filed a motion for a new trial, and a hearing on the motion is scheduled for Aug. 4, 2022. The motion was filed primarily because of issues during the trial, what Mr. Ledezma described as “inflammatory closing arguments,” and in small part, Mr. McKenna’s video remarks, he said.

If the motion is denied, the plaintiffs will move forward with an appeal, he said.

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

During the closing arguments in a $10 million malpractice trial, attorney Robert McKenna III told jurors the claims against his client, a gastroenterologist, were baseless and equivalent to “extortion.” The patient’s family blamed the gastroenterologist for their father’s death, alleging the doctor perforated his colon during insertion of a feeding tube. 

“I take pride in what I do, and I’ve got to tell you, in the 30 years I have been doing this, I have never seen a more insulting, factually devoid presentation in my entire career,” Mr. McKenna said, according to court transcripts. “On the strength of this evidence, they want you to award them $10 million. Welcome to America. Welcome to the personal injury machine, the personal injury industrial complex.”

After less than 30 minutes of deliberation, jurors returned a 12-0 verdict in favor of the physician.

However, Mr. McKenna, from Huntington Beach, Calif., described the case very differently to his staff in a celebration video, which he never expected to become public.

In the video, posted on Twitter and Instagram, Mr. McKenna bragged about how his legal team convinced jurors to doubt the patient’s official cause of death. He said the lawsuit involved a guy “that was probably negligently killed, but we kind of made it look like other people did it.”

“We actually had a death certificate that said he died the very way the plaintiff said he died, and we had to say, ‘No, you really shouldn’t believe what that death certificate says, or the coroner from the Orange County coroner’s office ... who says that it’s right,’” Mr. McKenna said in the video.

The 26-minute verdict was the fastest he’s ever received, Mr. McKenna says in the video, encouraging his partner to ring the firm’s victory bell.

“Overcoming all of those hurdles, we managed to sock three lawyers in the face,” Mr. McKenna said, referring to the plaintiffs’ lawyers. 

The video of Mr. McKenna’s remarks is now in wide circulation after having been posted to online attorney forums, Instagram, where it’s been viewed more than 8,000 times, and Twitter, where views have reached over 3,000.

Jorge Ledezma, an Orange County, Calif., attorney who represented the patient’s family in the case, said the remarks make it appear as if Mr. McKenna tricked the jury.

“It was a drastic change from the comments he made to the jury during his closing arguments,” Mr. Ledezma said. “But the video is more important for what he doesn’t say. He doesn’t say his client did everything properly. He doesn’t say our case didn’t have any merit. He doesn’t say his client was a good doctor. Clearly, what he told the jury and what he believes are the exact opposite of each other.”

Mr. McKenna did not return multiple messages seeking comment for this story. In a statement to the LA Times, Mr. McKenna said his remarks were “intended purely as an internal briefing to our staff, using shorthand phrases which might understandably cause confusion for a lay audience unfamiliar with the case at hand, and the law in general.”

“I have expressed my apologies to my client, opposing counsel, and both the medical and legal communities,” Mr. McKenna said in the statement to the LA Times. “However, nothing about my remarks should call into question our very transparent trial strategy or the jury’s verdict in favor of my client.”
 

What happened to the patient?

Enrique Garcia Sanchez, 49, arrived at the critical care unit at South Coast Global Medical Center in Santa Ana, Calif., on Nov. 5, 2017, complaining of abdominal pain. He was diagnosed with acute pancreatitis, acute hypokalemia, and alcohol abuse, and transferred to the ICU, according to the family’s legal complaint.

Mr. Sanchez had a positive D-Dimer test, indicating a probable blood clot, and he appeared to be experiencing septic shock caused by pancreatitis, according to the complaint. By Nov. 17, Mr. Sanchez was suffering from respiratory failure and severe hypoxemia, and as a result, he was sedated. In addition, his abdomen was described as distended with decreased bowel sounds, according to court documents.

On. Nov. 18, a gastrointestinal specialist was consulted because of Mr. Sanchez’s prolonged intubation and oropharyngeal dysphagia, according to the lawsuit. On Nov. 21, air was leaking from Mr. Sanchez’s breathing tube with diffuse infiltration noted on the right side, and pneumonia.

Mr. Sanchez was eventually unable to swallow, and the gastroenterologist inserted a percutaneous endoscopic gastrostomy (PEG) tube, according to court records. 

Mr. Sanchez’s condition worsened, and he developed respiratory distress, hypotension, and weakness during dialysis. On Dec. 9, 2017, physicians noted he had a bacterial infection, and he was later intubated on vent support because of progressive respiratory failure. Additionally, an internist reported that “fecal material” was observed per the PEG tube. Mr. Sanchez’s white blood cell count continued to rise, and his condition deteriorated. Mr. Sanchez died on Dec. 31, 2017.

A death certificate concluded that Mr. Sanchez died from complications of a PEG tube that perforated his colon, according to Mr. Ledezma. The plaintiffs’ legal team argued the gastroenterologist breached the standard of care by failing to ensure the tube was placed properly and failing to remedy the error after leakage was noted. 

“Mr. Garcia died because of a misplaced PEG tube that perforated the colon, resulting in peritonitis and sepsis,” attorney Jose Robles said during his closing arguments. “Mr. Garcia had ascites, a contraindication for PEG tube placement. He had ileus, a contraindication for PEG tube placement. The standard of care requires that [the gastroenterologist] conduct a proper workup to confirm that a PEG tube placement can be done appropriately and safely.”

Mr. McKenna argued the gastroenterologist was not at fault for the patient’s death, and that complications from his pancreatitis ultimately killed him. During the trial, physicians who cared for Mr. Sanchez testified the patient had a less than 50% chance of survival.

“What he had was end-stage catastrophic [pancreatitis] that was affecting his organ system and aspiration pneumonia that made it impossible for him to try to breathe on his own,” Mr. McKenna said during closing arguments. “The man ... had a catastrophic injury that ate most of his pancreas. That is not a survivable event.”
 

Attorney faces backlash from legal community

Since his celebratory remarks were posted online, Mr. McKenna has faced much backlash, particularly from the legal community.

@mgvolada tweeted, “As an attorney I am revolted and I hope sanctions follow ... this is why people hate attorneys.”

@stevewieland, who identified himself as a trial lawyer, wrote he would not feel good about winning such a case.

“No wonder we get no love from the public,” he tweeted.

“Let’s see how the Court of Appeals thinks about your braggadocio and how this makes lawyers appear to the public,” tweeted @Stephen60134955, a self-identified attorney.

Mr. McKenna’s license remains active and in good standing with no disciplinary actions, according to the State Bar of California website.

Mr. Ledezma has filed a motion for a new trial, and a hearing on the motion is scheduled for Aug. 4, 2022. The motion was filed primarily because of issues during the trial, what Mr. Ledezma described as “inflammatory closing arguments,” and in small part, Mr. McKenna’s video remarks, he said.

If the motion is denied, the plaintiffs will move forward with an appeal, he said.

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

On the basis of the history, examination, and investigations, retinal migraine was diagnosed according to the International Classification of Headache Disorders, third edition (1.2 migraine with aura; 1.2.4 retinal migraine). This classification system describes retinal migraine as a subtype of migraine with aura. 

Retinal migraine (also called ophthalmic or ocular migraine) is relatively rare but is sometimes a cause of transient monocular blindness in young adults. It manifests as recurrent attacks of unilateral visual disturbance (positive symptoms) or blindness (negative symptoms) lasting from minutes to 1 hour, associated with minimal or no headache. 

Some patients describe a positive visual symptom/disturbance in a mosaic pattern of scotomata that gradually enlarge, producing total or near-total unilateral visual loss. Precipitating factors may include emotional stress, hypertension, and hormonal contraceptive pills, as well as exercise, high altitude, dehydration, smoking, hypoglycemia, and hyperthermia.

Retinal migraine is believed to result from transient vasospasm of the choroidal or retinal arteries. A history of recurrent attacks of transient monocular visual disturbance or blindness, with or without a headache and without other neurologic symptoms, can suggest retinal migraine. A personal or family history of migraine can confirm the diagnosis.

Ruling out eye disease or vascular causes, especially when risk factors for arteriosclerosis exist, is important; that is, the condition must be differentiated from ocular or vascular causes of transient monocular blindness, mainly carotid artery disease. 

Carotid duplex ultrasonography, transcranial Doppler ultrasonography, magnetic resonance angiography, or CT angiography of the brain may be helpful. Fluorescein or cerebral angiography is rarely necessary. A hypercoagulability workup and evaluation of the erythrocyte sedimentation rate may be useful in excluding other coagulation disorders associated with retinal vasculopathy.

Regarding management, calcium-channel blockers have shown some efficacy. Even in patients with low blood pressure, nifedipine 10-20 mg/d is generally tolerated. From the available literature on treatment of this condition, it is recommended that triptans, ergots, and beta-blockers be used with caution or avoided in patients with retinal migraine owing to the potential for exacerbating vasoconstriction of the retinal artery. Transient vision loss in retinal migraine has been associated with future onset of permanent vision loss from occlusive conditions such as central retinal artery occlusion and branch retinal artery occlusion.

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the history, examination, and investigations, retinal migraine was diagnosed according to the International Classification of Headache Disorders, third edition (1.2 migraine with aura; 1.2.4 retinal migraine). This classification system describes retinal migraine as a subtype of migraine with aura. 

Retinal migraine (also called ophthalmic or ocular migraine) is relatively rare but is sometimes a cause of transient monocular blindness in young adults. It manifests as recurrent attacks of unilateral visual disturbance (positive symptoms) or blindness (negative symptoms) lasting from minutes to 1 hour, associated with minimal or no headache. 

Some patients describe a positive visual symptom/disturbance in a mosaic pattern of scotomata that gradually enlarge, producing total or near-total unilateral visual loss. Precipitating factors may include emotional stress, hypertension, and hormonal contraceptive pills, as well as exercise, high altitude, dehydration, smoking, hypoglycemia, and hyperthermia.

Retinal migraine is believed to result from transient vasospasm of the choroidal or retinal arteries. A history of recurrent attacks of transient monocular visual disturbance or blindness, with or without a headache and without other neurologic symptoms, can suggest retinal migraine. A personal or family history of migraine can confirm the diagnosis.

Ruling out eye disease or vascular causes, especially when risk factors for arteriosclerosis exist, is important; that is, the condition must be differentiated from ocular or vascular causes of transient monocular blindness, mainly carotid artery disease. 

Carotid duplex ultrasonography, transcranial Doppler ultrasonography, magnetic resonance angiography, or CT angiography of the brain may be helpful. Fluorescein or cerebral angiography is rarely necessary. A hypercoagulability workup and evaluation of the erythrocyte sedimentation rate may be useful in excluding other coagulation disorders associated with retinal vasculopathy.

Regarding management, calcium-channel blockers have shown some efficacy. Even in patients with low blood pressure, nifedipine 10-20 mg/d is generally tolerated. From the available literature on treatment of this condition, it is recommended that triptans, ergots, and beta-blockers be used with caution or avoided in patients with retinal migraine owing to the potential for exacerbating vasoconstriction of the retinal artery. Transient vision loss in retinal migraine has been associated with future onset of permanent vision loss from occlusive conditions such as central retinal artery occlusion and branch retinal artery occlusion.

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the history, examination, and investigations, retinal migraine was diagnosed according to the International Classification of Headache Disorders, third edition (1.2 migraine with aura; 1.2.4 retinal migraine). This classification system describes retinal migraine as a subtype of migraine with aura. 

Retinal migraine (also called ophthalmic or ocular migraine) is relatively rare but is sometimes a cause of transient monocular blindness in young adults. It manifests as recurrent attacks of unilateral visual disturbance (positive symptoms) or blindness (negative symptoms) lasting from minutes to 1 hour, associated with minimal or no headache. 

Some patients describe a positive visual symptom/disturbance in a mosaic pattern of scotomata that gradually enlarge, producing total or near-total unilateral visual loss. Precipitating factors may include emotional stress, hypertension, and hormonal contraceptive pills, as well as exercise, high altitude, dehydration, smoking, hypoglycemia, and hyperthermia.

Retinal migraine is believed to result from transient vasospasm of the choroidal or retinal arteries. A history of recurrent attacks of transient monocular visual disturbance or blindness, with or without a headache and without other neurologic symptoms, can suggest retinal migraine. A personal or family history of migraine can confirm the diagnosis.

Ruling out eye disease or vascular causes, especially when risk factors for arteriosclerosis exist, is important; that is, the condition must be differentiated from ocular or vascular causes of transient monocular blindness, mainly carotid artery disease. 

Carotid duplex ultrasonography, transcranial Doppler ultrasonography, magnetic resonance angiography, or CT angiography of the brain may be helpful. Fluorescein or cerebral angiography is rarely necessary. A hypercoagulability workup and evaluation of the erythrocyte sedimentation rate may be useful in excluding other coagulation disorders associated with retinal vasculopathy.

Regarding management, calcium-channel blockers have shown some efficacy. Even in patients with low blood pressure, nifedipine 10-20 mg/d is generally tolerated. From the available literature on treatment of this condition, it is recommended that triptans, ergots, and beta-blockers be used with caution or avoided in patients with retinal migraine owing to the potential for exacerbating vasoconstriction of the retinal artery. Transient vision loss in retinal migraine has been associated with future onset of permanent vision loss from occlusive conditions such as central retinal artery occlusion and branch retinal artery occlusion.

Jasmin Harpe, MD, MPH, Headache Fellow, Department of Neurology, Harvard University, John R. Graham Headache Center, Mass General Brigham, Boston, MA

Jasmin Harpe, MD, MPH, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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