The Journal of Family Practice

Team-based care lowers BP in hypertensive patients

A systematic review evaluated 80 trials (total N not defined), which included randomized controlled trials (RCTs) and quasi-experimental trials, to compare blood pressure control in hypertensive patients who received team-based care with that of patients who received usual care.¹

Team-based care was defined as adding new staff or changing the roles of existing staff to provide process support and share responsibility for hypertension care with a primary care provider. Examples included using staff to help with medication management, active patient follow-up, adherence, and self-management support. The mean duration of the interventions was 12 months.

The intervention group showed greater reductions in SBP (44 trials; 5.4 mm Hg; interquartile interval [IQI]=2.0-7.2) and DBP (38 trials; 1.8 mm Hg; IQI=0.7-3.2) compared with usual care.

Free medication, care involving nurses, pharmacists lead to lower BP

Another meta-analysis examined 37 RCTs (total N not provided) comparing blood pressure control in hypertensive patients who received team-based care with patients who received usual care.² The meta-analysis divided the studies by specific types of team-based interventions and analyzed the effect of each type on blood pressure control. It also analyzed studies based on what kind of health care professionals were involved in the intervention.

Team-based care appears to lower systolic blood pressure by 5 to 11 mm Hg and diastolic blood pressure by 2 to 6 mm Hg in patients with hypertension.

The largest absolute changes in both SBP and DBP were observed with the following interventions, compared with the control group: free medication (3 trials; SBP reduction (SBPR)=−11 mm Hg; interquartile range [IQR]=−15 to −9.1; DBP reduction [DBPR]=−6.4 mm Hg; IQR=−8.7 to −3.9); pharmacist recommending medication to physician (15 trials; SBPR=−9.3 mm Hg; IQR=−15 to −5.0; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); education about BP medications (23 trials; SBPR=−8.8 mm Hg; IQR=−12 to −4.3; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); and pharmacist-performed intervention (22 trials; SBPR=−8.4 mm Hg; IQR=−12 to −4; DBPR=−3.3 mm Hg; IQR=−6.9 to −0.90).

Patients who underwent team-based care interventions had greater SBP control (defined as <140, or <130 in patients with diabetes mellitus or chronic kidney disease) than the control group in trials involving nurses (8 trials; odds ratio [OR]=1.7; 95% confidence interval [CI], 1.5-1.9), trials conducted in community pharmacies (5 trials; OR=2.9; 95% CI, 1.8-4.6), and trials incorporating pharmacists into primary care clinics (9 trials; OR=2.2; 95% CI, 1.8-2.7).

Team-based care improves lipid control

An RCT of 6963 patients with type 2 diabetes mellitus in 9 clinics examined the proportion of patients receiving team-based care that achieved a target low-density lipoprotein (LDL) of ≤100 mg/dL compared with patients receiving usual care.³

Clinics were randomized to participate in team-based care (defined as a physician-pharmacist team in which the pharmacist reviewed the medical charts of patients with elevated LDL and then developed individualized, evidence-based treatment recommendations) or usual care, which involved access to a disease management program providing automated quality reporting, benchmarking, and care opportunity decision support.

Over 2 years, the team-based care model had significantly more patients with a lower LDL, more patients at LDL goal, and more patients on lipid-lowering medication (TABLE³).

Team-based care lowers BP in hypertensive patients

A systematic review evaluated 80 trials (total N not defined), which included randomized controlled trials (RCTs) and quasi-experimental trials, to compare blood pressure control in hypertensive patients who received team-based care with that of patients who received usual care.¹

Team-based care was defined as adding new staff or changing the roles of existing staff to provide process support and share responsibility for hypertension care with a primary care provider. Examples included using staff to help with medication management, active patient follow-up, adherence, and self-management support. The mean duration of the interventions was 12 months.

The intervention group showed greater reductions in SBP (44 trials; 5.4 mm Hg; interquartile interval [IQI]=2.0-7.2) and DBP (38 trials; 1.8 mm Hg; IQI=0.7-3.2) compared with usual care.

Free medication, care involving nurses, pharmacists lead to lower BP

Another meta-analysis examined 37 RCTs (total N not provided) comparing blood pressure control in hypertensive patients who received team-based care with patients who received usual care.² The meta-analysis divided the studies by specific types of team-based interventions and analyzed the effect of each type on blood pressure control. It also analyzed studies based on what kind of health care professionals were involved in the intervention.

Team-based care appears to lower systolic blood pressure by 5 to 11 mm Hg and diastolic blood pressure by 2 to 6 mm Hg in patients with hypertension.

The largest absolute changes in both SBP and DBP were observed with the following interventions, compared with the control group: free medication (3 trials; SBP reduction (SBPR)=−11 mm Hg; interquartile range [IQR]=−15 to −9.1; DBP reduction [DBPR]=−6.4 mm Hg; IQR=−8.7 to −3.9); pharmacist recommending medication to physician (15 trials; SBPR=−9.3 mm Hg; IQR=−15 to −5.0; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); education about BP medications (23 trials; SBPR=−8.8 mm Hg; IQR=−12 to −4.3; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); and pharmacist-performed intervention (22 trials; SBPR=−8.4 mm Hg; IQR=−12 to −4; DBPR=−3.3 mm Hg; IQR=−6.9 to −0.90).

Patients who underwent team-based care interventions had greater SBP control (defined as <140, or <130 in patients with diabetes mellitus or chronic kidney disease) than the control group in trials involving nurses (8 trials; odds ratio [OR]=1.7; 95% confidence interval [CI], 1.5-1.9), trials conducted in community pharmacies (5 trials; OR=2.9; 95% CI, 1.8-4.6), and trials incorporating pharmacists into primary care clinics (9 trials; OR=2.2; 95% CI, 1.8-2.7).

Team-based care improves lipid control

An RCT of 6963 patients with type 2 diabetes mellitus in 9 clinics examined the proportion of patients receiving team-based care that achieved a target low-density lipoprotein (LDL) of ≤100 mg/dL compared with patients receiving usual care.³

Clinics were randomized to participate in team-based care (defined as a physician-pharmacist team in which the pharmacist reviewed the medical charts of patients with elevated LDL and then developed individualized, evidence-based treatment recommendations) or usual care, which involved access to a disease management program providing automated quality reporting, benchmarking, and care opportunity decision support.

Over 2 years, the team-based care model had significantly more patients with a lower LDL, more patients at LDL goal, and more patients on lipid-lowering medication (TABLE³).

Team-based care lowers BP in hypertensive patients

A systematic review evaluated 80 trials (total N not defined), which included randomized controlled trials (RCTs) and quasi-experimental trials, to compare blood pressure control in hypertensive patients who received team-based care with that of patients who received usual care.¹

Team-based care was defined as adding new staff or changing the roles of existing staff to provide process support and share responsibility for hypertension care with a primary care provider. Examples included using staff to help with medication management, active patient follow-up, adherence, and self-management support. The mean duration of the interventions was 12 months.

The intervention group showed greater reductions in SBP (44 trials; 5.4 mm Hg; interquartile interval [IQI]=2.0-7.2) and DBP (38 trials; 1.8 mm Hg; IQI=0.7-3.2) compared with usual care.

Free medication, care involving nurses, pharmacists lead to lower BP

Another meta-analysis examined 37 RCTs (total N not provided) comparing blood pressure control in hypertensive patients who received team-based care with patients who received usual care.² The meta-analysis divided the studies by specific types of team-based interventions and analyzed the effect of each type on blood pressure control. It also analyzed studies based on what kind of health care professionals were involved in the intervention.

Team-based care appears to lower systolic blood pressure by 5 to 11 mm Hg and diastolic blood pressure by 2 to 6 mm Hg in patients with hypertension.

The largest absolute changes in both SBP and DBP were observed with the following interventions, compared with the control group: free medication (3 trials; SBP reduction (SBPR)=−11 mm Hg; interquartile range [IQR]=−15 to −9.1; DBP reduction [DBPR]=−6.4 mm Hg; IQR=−8.7 to −3.9); pharmacist recommending medication to physician (15 trials; SBPR=−9.3 mm Hg; IQR=−15 to −5.0; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); education about BP medications (23 trials; SBPR=−8.8 mm Hg; IQR=−12 to −4.3; DBPR=−3.6 mm Hg; IQR=−7.0 to −1.0); and pharmacist-performed intervention (22 trials; SBPR=−8.4 mm Hg; IQR=−12 to −4; DBPR=−3.3 mm Hg; IQR=−6.9 to −0.90).

Patients who underwent team-based care interventions had greater SBP control (defined as <140, or <130 in patients with diabetes mellitus or chronic kidney disease) than the control group in trials involving nurses (8 trials; odds ratio [OR]=1.7; 95% confidence interval [CI], 1.5-1.9), trials conducted in community pharmacies (5 trials; OR=2.9; 95% CI, 1.8-4.6), and trials incorporating pharmacists into primary care clinics (9 trials; OR=2.2; 95% CI, 1.8-2.7).

Team-based care improves lipid control

An RCT of 6963 patients with type 2 diabetes mellitus in 9 clinics examined the proportion of patients receiving team-based care that achieved a target low-density lipoprotein (LDL) of ≤100 mg/dL compared with patients receiving usual care.³

Clinics were randomized to participate in team-based care (defined as a physician-pharmacist team in which the pharmacist reviewed the medical charts of patients with elevated LDL and then developed individualized, evidence-based treatment recommendations) or usual care, which involved access to a disease management program providing automated quality reporting, benchmarking, and care opportunity decision support.

Over 2 years, the team-based care model had significantly more patients with a lower LDL, more patients at LDL goal, and more patients on lipid-lowering medication (TABLE³).

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.¹ They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia²), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.³ A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.³ Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.¹ Lead causes severe neurotoxicity,⁴ cadmium can cause organ damage,⁵ and inhaled nickel causes an inflammatory reaction in the lungs.⁶

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD
Louisville, Ky

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.¹ They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia²), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.³ A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.³ Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.¹ Lead causes severe neurotoxicity,⁴ cadmium can cause organ damage,⁵ and inhaled nickel causes an inflammatory reaction in the lungs.⁶

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD
Louisville, Ky

Electronic cigarettes (e-cigarettes) have become popular in the United States over the past decade.¹ They have been widely marketed as an alternative to tobacco and as a way to quit smoking.

While the negative effects of smoking tobacco are well known (having as few as one to 4 cigarettes a day triples the risk of coronary artery disease and pulmonary neoplasia²), the potential risks of e-cigarettes are not as well known. There has been limited regulation and insufficient research into the harmful effects of inhaling their vapor.

The potentially harmful compounds within e-cigarette vapors include both organic and inorganic toxins.³ A study of the contents of numerous e-cigarette refills found formaldehyde and acrolein, along with several hydrocarbons.³ Lead, cadmium, and nickel were also found in e-cigarette refills and their inhaled vapors.¹ Lead causes severe neurotoxicity,⁴ cadmium can cause organ damage,⁵ and inhaled nickel causes an inflammatory reaction in the lungs.⁶

The risk-to-benefit ratio of e-cigarettes as a means of tobacco cessation and the health consequences of breathing their vapors cannot be established until research is completed. What we do know is that the nicotine in e-cigarette vapors maintains continued addiction.

It’s up to us as physicians to educate our patients about the potential harm of e-cigarette chemical toxicity and encourage cessation of both tobacco products and e-cigarettes.

Kavitha Srinivasan, MD
Lee Smith, BA
Manasa Enja, MD
Steven Lippmann, MD
Louisville, Ky

My new patient had just left his family doctor after 15 years. When I asked why, he said, “The doctor came into the room, looked at my chart, and told me I needed to lose weight, lower my cholesterol, and stop smoking. I looked at the 300-pound doctor who smelled of smoke and said, ‘Really?’ ”

How can we empower our patients to make healthy choices when we don’t always make these choices ourselves? Here’s one possibility: Invite them to join us in the struggle.

As physicians, we should walk the walk and show our patients that we’re right there in the trenches with them when it comes to making healthy choices.

Last year, my practice created “Run 5K or Walk 1 Mile With Your Doctor” as a way to encourage both patients and medical professionals to get healthy. We also invited patients to join us in a walking/running club to prepare for the event. More than 200 people showed up, including physician assistants, nurses, nurse practitioners, medical assistants, respiratory therapists, family doctors, internists, office staff, cardiologists, orthopedists, and patients. In addition to raising heart rates, we also raised $7000 for the American Heart Association (AHA). This year we plan to merge the event with the annual AHA walk in September. I encourage all health care professionals to do the same.

As physicians, we can’t just talk the talk in the examining room. We should also walk the walk and show our patients that we’re right there in the trenches with them.

Elizabeth Khan, MD
Allentown, Pa

My new patient had just left his family doctor after 15 years. When I asked why, he said, “The doctor came into the room, looked at my chart, and told me I needed to lose weight, lower my cholesterol, and stop smoking. I looked at the 300-pound doctor who smelled of smoke and said, ‘Really?’ ”

How can we empower our patients to make healthy choices when we don’t always make these choices ourselves? Here’s one possibility: Invite them to join us in the struggle.

As physicians, we should walk the walk and show our patients that we’re right there in the trenches with them when it comes to making healthy choices.

Last year, my practice created “Run 5K or Walk 1 Mile With Your Doctor” as a way to encourage both patients and medical professionals to get healthy. We also invited patients to join us in a walking/running club to prepare for the event. More than 200 people showed up, including physician assistants, nurses, nurse practitioners, medical assistants, respiratory therapists, family doctors, internists, office staff, cardiologists, orthopedists, and patients. In addition to raising heart rates, we also raised $7000 for the American Heart Association (AHA). This year we plan to merge the event with the annual AHA walk in September. I encourage all health care professionals to do the same.

As physicians, we can’t just talk the talk in the examining room. We should also walk the walk and show our patients that we’re right there in the trenches with them.

Elizabeth Khan, MD
Allentown, Pa

My new patient had just left his family doctor after 15 years. When I asked why, he said, “The doctor came into the room, looked at my chart, and told me I needed to lose weight, lower my cholesterol, and stop smoking. I looked at the 300-pound doctor who smelled of smoke and said, ‘Really?’ ”

How can we empower our patients to make healthy choices when we don’t always make these choices ourselves? Here’s one possibility: Invite them to join us in the struggle.

As physicians, we should walk the walk and show our patients that we’re right there in the trenches with them when it comes to making healthy choices.

Last year, my practice created “Run 5K or Walk 1 Mile With Your Doctor” as a way to encourage both patients and medical professionals to get healthy. We also invited patients to join us in a walking/running club to prepare for the event. More than 200 people showed up, including physician assistants, nurses, nurse practitioners, medical assistants, respiratory therapists, family doctors, internists, office staff, cardiologists, orthopedists, and patients. In addition to raising heart rates, we also raised $7000 for the American Heart Association (AHA). This year we plan to merge the event with the annual AHA walk in September. I encourage all health care professionals to do the same.

As physicians, we can’t just talk the talk in the examining room. We should also walk the walk and show our patients that we’re right there in the trenches with them.

Elizabeth Khan, MD
Allentown, Pa

CASE 1 › Steve J, age 43, comes to your clinic looking uncharacteristically glum. He was recently downsized from his job and misses his former colleagues. His job loss has caused a financial strain for his family, and he admits to crying in the shower when he thinks about how his life has turned out. Mr. J tells you that he’s gotten a part-time job, but he’s already called in sick several times. On those sick days he “stayed in bed all day and slept.” He says that when he does go to work, he rarely interacts with his coworkers and his concentration is poor. He tells you he wakes up early in the morning on most days and cannot return to sleep, despite being “tired all the time.” He denies suicidal ideation. Mr. J has never felt this way before, which is what prompted his visit today, but he thinks it is “weak to take a pill to feel better.”

What nonpharmacologic options can you offer him?

CASE 2 › Kerri S is a 27-year-old mother of 2 who comes to your clinic to establish care. She tells you about a recent recurrence of depressed mood, which she feels is due to the stress of moving to the area. She is experiencing sleep-onset insomnia and concentration lapses. Her appetite is poor (self-reported 8-lb weight loss in 2 months) and she lacks the motivation to engage in her daily activities, saying, “I wouldn’t even get out of bed if my kids didn’t need me.” She notes that she is constantly irritable and has completely lost her sex drive. Unlike her prior depressive episode, she has not had any suicidal thoughts. Mrs. S was previously successfully treated with paroxetine, 20 mg/d, but she is not interested in restarting her medication because she is still breastfeeding her toddler.

Are there evidence-based options for her care that do not include medication?

Major depressive disorder (MDD) is widespread and often disabling, affecting nearly 8% of people ages 12 and older at any given time.¹ Thus, it’s crucial to be familiar with the diverse array of evidence-based treatment options from which patients can choose. Although medications are an essential treatment option for patients with severe depression, their value for patients with mild to moderate depression is often limited.² In addition, when antidepressants aren’t combined with psychosocial interventions, discontinuing them is associated with relapse.³

Fortunately, research has found that certain nonpharmacologic interventions—including psychotherapies, somatic therapies, and dietary supplements—can have either therapeutic or adjunctive benefits for treating depression, and can be provided in ways that are time- and cost-effective. This article reviews the evidence supporting several options in each of these treatment categories.

Evidence backs several types of psychotherapy

Several recent meta-analyses suggest that a variety of psychotherapeutic treatments may hold promise for your patients with depression.^4,5 When analyses were limited to larger studies in order to decrease the risk of bias, cognitive behavioral therapy (CBT), interpersonal therapy (IPT), and problem-solving therapy (PST) all resulted in moderate to large improvement in depressive symptoms when compared to wait-list controls.⁴ These findings were echoed in a recent systematic review/meta-analysis that focused on depressed primary care patients. Linde et al⁵ found that the number needed to treat (NNT) to achieve one response (≥50% reduction in score on a depression scale) using any type of psychotherapy was 10, and the NNT to achieve one remission (scoring below a predefined score on a depression scale) was 15.

Psychotherapy can be effective when provided in individual and group settings,⁶ as well as via telephone, the Internet, or software programs.⁷ (For a list of self-help, computerized, and Internet-based resources, see TABLE W1 below.)

CBT has been studied for several decades and there’s strong evidence for its efficacy.⁶ Recent investigations have suggested that CBT delivered in less resource-intensive modes (such as via computer program, Internet, telephone, or videoconferencing) can be as effective as face-to-face CBT.^6,8 CBT has been shown to be helpful for a wide range of patients,⁶ improves outcomes over standard primary care treatment,⁹ and provides a useful adjunct to medication in treatment-resistant severe depression.¹⁰

Behavioral activation (BA), which generally is included as a component of CBT, has received support as an independent treatment, and may produce therapeutic results similar to CBT¹¹ and PST (which we’ll discuss in a bit).¹² The core components of BA are scheduling pleasant activities and increasing the patient’s positive interactions with his or her environment by decreasing avoidance, withdrawal, and inactivity.¹¹ Compared to CBT, BA is easier for clinicians to learn and incorporate into primary care visits, and it may be especially useful as an adjunctive or first-step intervention in outpatient clinics.¹¹ Like CBT, BA can be effective in diverse patient groups^13,14 and can be provided using novel delivery modes, such as via the Internet.¹⁵

Compared to cognitive behavioral therapy, behavioral activation is easier for clinicians to learn and incorporate into primary care visits.

IPT is a supportive, structured, brief therapy (12-16 visits) that focuses on helping patients identify and solve current situation- and relationship-based problems that stem from or contribute to their depression.¹⁶ Enhancing the patient’s interpersonal communication—including improving social skills, assertiveness, and appropriate expression of anger—is typically a component of IPT. Like CBT, IPT has been found to be effective for treating depression when administered in person, in group therapy, or via the phone or Internet, and across a broad age range.^17-19

PST involves teaching patients a structured problem-solving process to decrease interpersonal strain and improve positive life experiences.²⁰ Patients are taught to define their problem, generate and evaluate multiple solutions for it, implement a plan for the solution, and evaluate the results. In addition to being used to successfully treat adults,^4,5 PST has been adapted effectively to treat adolescents¹⁶ and older adults.¹⁸

Somatic therapies are also an option

Exercise has long been considered a possible depression treatment due to its activity on endorphin, monoamine, and cortisol levels and via increased social and general activity. A 2013 Cochrane review of 39 randomized control trials (RCTs; N=2326) assessed whether exercise was effective for treating depression in adults.²¹ Thirty-five trials found a moderate effect size when specifically comparing exercise to no treatment or control interventions. The effect size was reduced, however, when analyses were restricted to trials with the highest methodological quality. There was no statistically significant difference when exercise was compared to pharmacologic treatment or psychotherapy.

Although the amount of research is meager, small but statistically significant improvements have also been found for older adults²² and children/adolescents.²³ There is no consensus on the type, frequency, or intensity of exercise needed to achieve benefit. However, because nearly all studies for all age groups have found that exercise has no adverse psychological effects and substantial positive physical effects, exercise should be recommended to all patients with depression unless contraindicated.

Yoga (both exercise-based and meditation-based) has been evaluated both as a sole treatment and as an adjunctive treatment for depression. Several studies have supported the impact of yoga, particularly in pregnant women,²⁴ although the evidence for its efficacy is inconsistent, with yoga frequently failing to improve upon the outcome of waitlist control.²⁵ The evidence for meditation and mindfulness is more consistently positive, with these interventions equaling or exceeding “treatment as usual,” other psychotherapies, and antidepressants in numerous RCTs.²⁵

Electroconvulsive therapy (ECT) has a substantial evidence base supporting its efficacy.²⁶ ECT has been used for decades, although stigma, cardiac and memory risks, and risks of anesthesia often limit its use. Benefits of ECT include a rapid response relative to pharmacotherapy (>50% of patients respond by the end of the first week of ECT)²⁷ and a strong response in older patients.²⁸

More than half of patients receiving electroconvulsive therapy respond to treatment by the end of the first week.

In repetitive transcranial magnetic stimulation (rTMS), electromagnetic coils are placed on a patient’s head to deliver electromagnetic pulses that stimulate areas of the brain that regulate mood. Although rTMS is not widely available, a growing body of evidence supports its use for treating depression, including a meta-analysis of 34 RCTs that included 1383 patients.²⁹ A multisite RCT (N=190) that was not industry-funded reported a 15% response rate and 60% maintenance of remission at 3 months (NNT=12).³⁰ Although ECT is more effective than rTMS, rTMS appears useful for treatment-resistant depression, and can be used as an adjunctive treatment.^29,31

Dietary supplements may be best used as adjuncts

St. John’s wort (Hypericum perforatum), which contains 2 bioactive ingredients (hyperforin and hypericin), has been effectively used to treat depression.³² A 2008 Cochrane review that was limited to high-quality trials involving patients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for depression identified 29 trials (N=5489), of which 18 involved comparisons with placebo and 17 with standard antidepressants.³³ Patients’ depression was rated mild to moderate in 19 studies and moderate to severe in 9 studies. Trials examined 4 to 12 weeks of treatment with Hypericum extracts. This study (and several published since) provides strong clinical evidence supporting the efficacy of St. John’s wort for mild to moderate depression. There is insufficient evidence for its use for severe major depression.³³TABLE 1 contains dosing information for St. John’s wort and other supplements used to treat depression.^34-36 

S-adenosyl-L-methionine (SAMe). In a 2003 systematic review,³⁷ 1600 mg/d of oral SAMe was found to significantly benefit patients with depression in 4 of 5 studies, as did parenteral SAMe (7 of 7 trials). Another review of 48 studies found SAMe was safe and effective for depression.³⁸ SAMe has been proposed for use alone or in combination with an antidepressant.

Low folate levels have been associated with a less robust response to antidepressants in patients with major depressive disorder.

Folate and folic acid. Low folate levels have been associated with a less robust response to antidepressants in patients with MDD,³⁹ and higher folate levels appear to be associated with better antidepressant response.⁴⁰ A 2003 Cochrane review suggested folate might have a role in treating depression.³⁹ A 2009 study found folate supplementation could reduce depressive symptoms for patients with normal baseline folate levels as well as those with low levels.⁴¹ Although the evidence is equivocal, folate augmentation may enhance antidepressant efficacy or improve response/remission rates.^41,42

It seems reasonable to check folate levels in depressed patients, and address deficiencies by instructing patients to increase their dietary intake of folate or to take supplements. Augmenting antidepressants with folate appears to be low-risk and possibly helpful in maintaining remission.

Omega-3 fatty acids. There is substantial evidence that omega-3 fatty acids can prevent and treat depression.^43,44 Recent meta-analyses support the use of omega-3 fatty acids as monotherapy and augmentation, but only formulations that contain a high eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) ratio (EPA/DHA 2:1).^45,46 Omega-3 supplementation has been used with positive results in older adults, children,⁴⁷ pregnant women,⁴⁸ and women with postpartum depression.⁴⁹ Although initial research into omega-3 treatment of depression appears promising, augmentation of standard antidepressant therapy may be a good conservative option.

Use a validated tool to monitor response to treatment

You can enhance outcomes for your patients with depression if you schedule routine follow-up visits with them to gauge adherence to recommendations, monitor response to treatment, and increase the intensity of care when response is inadequate.⁵⁰ The most important aspect of monitoring response is to use a standardized instrument that quantifies symptoms at every visit.

The PHQ-9—which is free—has been validated for depression screening and monitoring of treatment response in primary care patients.

The Patient Health Questionnaire 9-item depression assessment (PHQ-9)—which is free—has been validated for depression screening and monitoring of treatment response in primary care patients.⁵¹ A decrease of 5 points on the PHQ-9 is the minimum considered to be clinically significant.⁵² Other well-validated, although lengthier, self-report depression assessment and monitoring instruments include the Beck Depression Inventory-revised and the Zung Depression Scale.

CASE 1 › Mr. J is not enjoying his new job or engaging with new coworkers to replace the positive social experiences he had at his previous job. Together, you set a goal of increasing social involvement by having him make plans to see at least one friend per weekend. Because he indicates that he is unlikely to follow through with a therapy referral, you encourage him to try an online CBT program, start an exercise regimen, or take a SAMe supplement. Mr. Jackson agrees to try the CBT and exercise (moderate intensity, 30 minutes 3-4 times per week), but does not want to take SAMe. He agrees to an assessment of his folate levels, which are normal.

Mr. J starts the online CBT program, which reinforces the exercise and social activity prescription you provided. He establishes a regular exercise routine with a good friend. After one month, his mood has started to improve and he has added regular participation in a hobby (woodworking), as well as volunteer work, which he finds fulfilling. You plan to continue monitoring his depression and his adherence to the treatment plan.

CASE 2 › The recent move has decreased Mrs. S’s interactions with family and long-time friends. Because she had previously expressed interest in exercise, you encourage her to join a local “Mommy and Me” exercise and support group for mothers of toddlers. She is willing to participate in psychotherapy, so you provide a referral to a local therapist with expertise in IPT. You also discuss with Mrs. S the possible benefits of omega-3 fatty acid supplementation, which appears to be safe during breastfeeding.³⁴

Mrs. S begins therapy and exercise classes, but can’t motivate herself to continue either of these activities. She becomes discouraged because she’s unable to easily find an omega-3 fatty acid supplement with the ratio you specified (EPA/DHA 2:1). When you see her 2 weeks later, her depression has worsened.

Because you are concerned her suicidality will return, you revisit the pros and cons of taking an antidepressant. Although small amounts of antidepressants can be passed from mother to infant via breastmilk, the amount varies by specific medication, as do the potential risks. Mrs. S decides to resume taking paroxetine 20 mg/d and eventually, once her motivation improves, she’s able to add psychotherapy and exercise to her maintenance/relapse prevention regimen. After you discuss with her the possibility that B vitamin supplementation may assist in maintenance of remission, she adds L-methylfolate 7.5 mg/day to her regimen.

CORRESPONDENCE 
Michele M. Larzelere, PhD; LSUHSC Department of Family Medicine; 200 W. Esplanade Avenue, Suite 409; Kenner, LA 70065; mlarze@lsuhsc.edu

CASE 1 › Steve J, age 43, comes to your clinic looking uncharacteristically glum. He was recently downsized from his job and misses his former colleagues. His job loss has caused a financial strain for his family, and he admits to crying in the shower when he thinks about how his life has turned out. Mr. J tells you that he’s gotten a part-time job, but he’s already called in sick several times. On those sick days he “stayed in bed all day and slept.” He says that when he does go to work, he rarely interacts with his coworkers and his concentration is poor. He tells you he wakes up early in the morning on most days and cannot return to sleep, despite being “tired all the time.” He denies suicidal ideation. Mr. J has never felt this way before, which is what prompted his visit today, but he thinks it is “weak to take a pill to feel better.”

What nonpharmacologic options can you offer him?

CASE 2 › Kerri S is a 27-year-old mother of 2 who comes to your clinic to establish care. She tells you about a recent recurrence of depressed mood, which she feels is due to the stress of moving to the area. She is experiencing sleep-onset insomnia and concentration lapses. Her appetite is poor (self-reported 8-lb weight loss in 2 months) and she lacks the motivation to engage in her daily activities, saying, “I wouldn’t even get out of bed if my kids didn’t need me.” She notes that she is constantly irritable and has completely lost her sex drive. Unlike her prior depressive episode, she has not had any suicidal thoughts. Mrs. S was previously successfully treated with paroxetine, 20 mg/d, but she is not interested in restarting her medication because she is still breastfeeding her toddler.

Are there evidence-based options for her care that do not include medication?

Major depressive disorder (MDD) is widespread and often disabling, affecting nearly 8% of people ages 12 and older at any given time.¹ Thus, it’s crucial to be familiar with the diverse array of evidence-based treatment options from which patients can choose. Although medications are an essential treatment option for patients with severe depression, their value for patients with mild to moderate depression is often limited.² In addition, when antidepressants aren’t combined with psychosocial interventions, discontinuing them is associated with relapse.³

Fortunately, research has found that certain nonpharmacologic interventions—including psychotherapies, somatic therapies, and dietary supplements—can have either therapeutic or adjunctive benefits for treating depression, and can be provided in ways that are time- and cost-effective. This article reviews the evidence supporting several options in each of these treatment categories.

Evidence backs several types of psychotherapy

Several recent meta-analyses suggest that a variety of psychotherapeutic treatments may hold promise for your patients with depression.^4,5 When analyses were limited to larger studies in order to decrease the risk of bias, cognitive behavioral therapy (CBT), interpersonal therapy (IPT), and problem-solving therapy (PST) all resulted in moderate to large improvement in depressive symptoms when compared to wait-list controls.⁴ These findings were echoed in a recent systematic review/meta-analysis that focused on depressed primary care patients. Linde et al⁵ found that the number needed to treat (NNT) to achieve one response (≥50% reduction in score on a depression scale) using any type of psychotherapy was 10, and the NNT to achieve one remission (scoring below a predefined score on a depression scale) was 15.

Psychotherapy can be effective when provided in individual and group settings,⁶ as well as via telephone, the Internet, or software programs.⁷ (For a list of self-help, computerized, and Internet-based resources, see TABLE W1 below.)

CBT has been studied for several decades and there’s strong evidence for its efficacy.⁶ Recent investigations have suggested that CBT delivered in less resource-intensive modes (such as via computer program, Internet, telephone, or videoconferencing) can be as effective as face-to-face CBT.^6,8 CBT has been shown to be helpful for a wide range of patients,⁶ improves outcomes over standard primary care treatment,⁹ and provides a useful adjunct to medication in treatment-resistant severe depression.¹⁰

Behavioral activation (BA), which generally is included as a component of CBT, has received support as an independent treatment, and may produce therapeutic results similar to CBT¹¹ and PST (which we’ll discuss in a bit).¹² The core components of BA are scheduling pleasant activities and increasing the patient’s positive interactions with his or her environment by decreasing avoidance, withdrawal, and inactivity.¹¹ Compared to CBT, BA is easier for clinicians to learn and incorporate into primary care visits, and it may be especially useful as an adjunctive or first-step intervention in outpatient clinics.¹¹ Like CBT, BA can be effective in diverse patient groups^13,14 and can be provided using novel delivery modes, such as via the Internet.¹⁵

Compared to cognitive behavioral therapy, behavioral activation is easier for clinicians to learn and incorporate into primary care visits.

IPT is a supportive, structured, brief therapy (12-16 visits) that focuses on helping patients identify and solve current situation- and relationship-based problems that stem from or contribute to their depression.¹⁶ Enhancing the patient’s interpersonal communication—including improving social skills, assertiveness, and appropriate expression of anger—is typically a component of IPT. Like CBT, IPT has been found to be effective for treating depression when administered in person, in group therapy, or via the phone or Internet, and across a broad age range.^17-19

PST involves teaching patients a structured problem-solving process to decrease interpersonal strain and improve positive life experiences.²⁰ Patients are taught to define their problem, generate and evaluate multiple solutions for it, implement a plan for the solution, and evaluate the results. In addition to being used to successfully treat adults,^4,5 PST has been adapted effectively to treat adolescents¹⁶ and older adults.¹⁸

Somatic therapies are also an option

Exercise has long been considered a possible depression treatment due to its activity on endorphin, monoamine, and cortisol levels and via increased social and general activity. A 2013 Cochrane review of 39 randomized control trials (RCTs; N=2326) assessed whether exercise was effective for treating depression in adults.²¹ Thirty-five trials found a moderate effect size when specifically comparing exercise to no treatment or control interventions. The effect size was reduced, however, when analyses were restricted to trials with the highest methodological quality. There was no statistically significant difference when exercise was compared to pharmacologic treatment or psychotherapy.

Although the amount of research is meager, small but statistically significant improvements have also been found for older adults²² and children/adolescents.²³ There is no consensus on the type, frequency, or intensity of exercise needed to achieve benefit. However, because nearly all studies for all age groups have found that exercise has no adverse psychological effects and substantial positive physical effects, exercise should be recommended to all patients with depression unless contraindicated.

Yoga (both exercise-based and meditation-based) has been evaluated both as a sole treatment and as an adjunctive treatment for depression. Several studies have supported the impact of yoga, particularly in pregnant women,²⁴ although the evidence for its efficacy is inconsistent, with yoga frequently failing to improve upon the outcome of waitlist control.²⁵ The evidence for meditation and mindfulness is more consistently positive, with these interventions equaling or exceeding “treatment as usual,” other psychotherapies, and antidepressants in numerous RCTs.²⁵

Electroconvulsive therapy (ECT) has a substantial evidence base supporting its efficacy.²⁶ ECT has been used for decades, although stigma, cardiac and memory risks, and risks of anesthesia often limit its use. Benefits of ECT include a rapid response relative to pharmacotherapy (>50% of patients respond by the end of the first week of ECT)²⁷ and a strong response in older patients.²⁸

More than half of patients receiving electroconvulsive therapy respond to treatment by the end of the first week.

In repetitive transcranial magnetic stimulation (rTMS), electromagnetic coils are placed on a patient’s head to deliver electromagnetic pulses that stimulate areas of the brain that regulate mood. Although rTMS is not widely available, a growing body of evidence supports its use for treating depression, including a meta-analysis of 34 RCTs that included 1383 patients.²⁹ A multisite RCT (N=190) that was not industry-funded reported a 15% response rate and 60% maintenance of remission at 3 months (NNT=12).³⁰ Although ECT is more effective than rTMS, rTMS appears useful for treatment-resistant depression, and can be used as an adjunctive treatment.^29,31

Dietary supplements may be best used as adjuncts

St. John’s wort (Hypericum perforatum), which contains 2 bioactive ingredients (hyperforin and hypericin), has been effectively used to treat depression.³² A 2008 Cochrane review that was limited to high-quality trials involving patients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for depression identified 29 trials (N=5489), of which 18 involved comparisons with placebo and 17 with standard antidepressants.³³ Patients’ depression was rated mild to moderate in 19 studies and moderate to severe in 9 studies. Trials examined 4 to 12 weeks of treatment with Hypericum extracts. This study (and several published since) provides strong clinical evidence supporting the efficacy of St. John’s wort for mild to moderate depression. There is insufficient evidence for its use for severe major depression.³³TABLE 1 contains dosing information for St. John’s wort and other supplements used to treat depression.^34-36 

S-adenosyl-L-methionine (SAMe). In a 2003 systematic review,³⁷ 1600 mg/d of oral SAMe was found to significantly benefit patients with depression in 4 of 5 studies, as did parenteral SAMe (7 of 7 trials). Another review of 48 studies found SAMe was safe and effective for depression.³⁸ SAMe has been proposed for use alone or in combination with an antidepressant.

Low folate levels have been associated with a less robust response to antidepressants in patients with major depressive disorder.

Folate and folic acid. Low folate levels have been associated with a less robust response to antidepressants in patients with MDD,³⁹ and higher folate levels appear to be associated with better antidepressant response.⁴⁰ A 2003 Cochrane review suggested folate might have a role in treating depression.³⁹ A 2009 study found folate supplementation could reduce depressive symptoms for patients with normal baseline folate levels as well as those with low levels.⁴¹ Although the evidence is equivocal, folate augmentation may enhance antidepressant efficacy or improve response/remission rates.^41,42

It seems reasonable to check folate levels in depressed patients, and address deficiencies by instructing patients to increase their dietary intake of folate or to take supplements. Augmenting antidepressants with folate appears to be low-risk and possibly helpful in maintaining remission.

Omega-3 fatty acids. There is substantial evidence that omega-3 fatty acids can prevent and treat depression.^43,44 Recent meta-analyses support the use of omega-3 fatty acids as monotherapy and augmentation, but only formulations that contain a high eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) ratio (EPA/DHA 2:1).^45,46 Omega-3 supplementation has been used with positive results in older adults, children,⁴⁷ pregnant women,⁴⁸ and women with postpartum depression.⁴⁹ Although initial research into omega-3 treatment of depression appears promising, augmentation of standard antidepressant therapy may be a good conservative option.

Use a validated tool to monitor response to treatment

You can enhance outcomes for your patients with depression if you schedule routine follow-up visits with them to gauge adherence to recommendations, monitor response to treatment, and increase the intensity of care when response is inadequate.⁵⁰ The most important aspect of monitoring response is to use a standardized instrument that quantifies symptoms at every visit.

The PHQ-9—which is free—has been validated for depression screening and monitoring of treatment response in primary care patients.

The Patient Health Questionnaire 9-item depression assessment (PHQ-9)—which is free—has been validated for depression screening and monitoring of treatment response in primary care patients.⁵¹ A decrease of 5 points on the PHQ-9 is the minimum considered to be clinically significant.⁵² Other well-validated, although lengthier, self-report depression assessment and monitoring instruments include the Beck Depression Inventory-revised and the Zung Depression Scale.

CASE 1 › Mr. J is not enjoying his new job or engaging with new coworkers to replace the positive social experiences he had at his previous job. Together, you set a goal of increasing social involvement by having him make plans to see at least one friend per weekend. Because he indicates that he is unlikely to follow through with a therapy referral, you encourage him to try an online CBT program, start an exercise regimen, or take a SAMe supplement. Mr. Jackson agrees to try the CBT and exercise (moderate intensity, 30 minutes 3-4 times per week), but does not want to take SAMe. He agrees to an assessment of his folate levels, which are normal.

Mr. J starts the online CBT program, which reinforces the exercise and social activity prescription you provided. He establishes a regular exercise routine with a good friend. After one month, his mood has started to improve and he has added regular participation in a hobby (woodworking), as well as volunteer work, which he finds fulfilling. You plan to continue monitoring his depression and his adherence to the treatment plan.

CASE 2 › The recent move has decreased Mrs. S’s interactions with family and long-time friends. Because she had previously expressed interest in exercise, you encourage her to join a local “Mommy and Me” exercise and support group for mothers of toddlers. She is willing to participate in psychotherapy, so you provide a referral to a local therapist with expertise in IPT. You also discuss with Mrs. S the possible benefits of omega-3 fatty acid supplementation, which appears to be safe during breastfeeding.³⁴

Mrs. S begins therapy and exercise classes, but can’t motivate herself to continue either of these activities. She becomes discouraged because she’s unable to easily find an omega-3 fatty acid supplement with the ratio you specified (EPA/DHA 2:1). When you see her 2 weeks later, her depression has worsened.

Because you are concerned her suicidality will return, you revisit the pros and cons of taking an antidepressant. Although small amounts of antidepressants can be passed from mother to infant via breastmilk, the amount varies by specific medication, as do the potential risks. Mrs. S decides to resume taking paroxetine 20 mg/d and eventually, once her motivation improves, she’s able to add psychotherapy and exercise to her maintenance/relapse prevention regimen. After you discuss with her the possibility that B vitamin supplementation may assist in maintenance of remission, she adds L-methylfolate 7.5 mg/day to her regimen.

CORRESPONDENCE 
Michele M. Larzelere, PhD; LSUHSC Department of Family Medicine; 200 W. Esplanade Avenue, Suite 409; Kenner, LA 70065; mlarze@lsuhsc.edu

CASE 1 › Steve J, age 43, comes to your clinic looking uncharacteristically glum. He was recently downsized from his job and misses his former colleagues. His job loss has caused a financial strain for his family, and he admits to crying in the shower when he thinks about how his life has turned out. Mr. J tells you that he’s gotten a part-time job, but he’s already called in sick several times. On those sick days he “stayed in bed all day and slept.” He says that when he does go to work, he rarely interacts with his coworkers and his concentration is poor. He tells you he wakes up early in the morning on most days and cannot return to sleep, despite being “tired all the time.” He denies suicidal ideation. Mr. J has never felt this way before, which is what prompted his visit today, but he thinks it is “weak to take a pill to feel better.”

What nonpharmacologic options can you offer him?

CASE 2 › Kerri S is a 27-year-old mother of 2 who comes to your clinic to establish care. She tells you about a recent recurrence of depressed mood, which she feels is due to the stress of moving to the area. She is experiencing sleep-onset insomnia and concentration lapses. Her appetite is poor (self-reported 8-lb weight loss in 2 months) and she lacks the motivation to engage in her daily activities, saying, “I wouldn’t even get out of bed if my kids didn’t need me.” She notes that she is constantly irritable and has completely lost her sex drive. Unlike her prior depressive episode, she has not had any suicidal thoughts. Mrs. S was previously successfully treated with paroxetine, 20 mg/d, but she is not interested in restarting her medication because she is still breastfeeding her toddler.

Are there evidence-based options for her care that do not include medication?

Major depressive disorder (MDD) is widespread and often disabling, affecting nearly 8% of people ages 12 and older at any given time.¹ Thus, it’s crucial to be familiar with the diverse array of evidence-based treatment options from which patients can choose. Although medications are an essential treatment option for patients with severe depression, their value for patients with mild to moderate depression is often limited.² In addition, when antidepressants aren’t combined with psychosocial interventions, discontinuing them is associated with relapse.³

Fortunately, research has found that certain nonpharmacologic interventions—including psychotherapies, somatic therapies, and dietary supplements—can have either therapeutic or adjunctive benefits for treating depression, and can be provided in ways that are time- and cost-effective. This article reviews the evidence supporting several options in each of these treatment categories.

Evidence backs several types of psychotherapy

Several recent meta-analyses suggest that a variety of psychotherapeutic treatments may hold promise for your patients with depression.^4,5 When analyses were limited to larger studies in order to decrease the risk of bias, cognitive behavioral therapy (CBT), interpersonal therapy (IPT), and problem-solving therapy (PST) all resulted in moderate to large improvement in depressive symptoms when compared to wait-list controls.⁴ These findings were echoed in a recent systematic review/meta-analysis that focused on depressed primary care patients. Linde et al⁵ found that the number needed to treat (NNT) to achieve one response (≥50% reduction in score on a depression scale) using any type of psychotherapy was 10, and the NNT to achieve one remission (scoring below a predefined score on a depression scale) was 15.

Psychotherapy can be effective when provided in individual and group settings,⁶ as well as via telephone, the Internet, or software programs.⁷ (For a list of self-help, computerized, and Internet-based resources, see TABLE W1 below.)

CBT has been studied for several decades and there’s strong evidence for its efficacy.⁶ Recent investigations have suggested that CBT delivered in less resource-intensive modes (such as via computer program, Internet, telephone, or videoconferencing) can be as effective as face-to-face CBT.^6,8 CBT has been shown to be helpful for a wide range of patients,⁶ improves outcomes over standard primary care treatment,⁹ and provides a useful adjunct to medication in treatment-resistant severe depression.¹⁰

Behavioral activation (BA), which generally is included as a component of CBT, has received support as an independent treatment, and may produce therapeutic results similar to CBT¹¹ and PST (which we’ll discuss in a bit).¹² The core components of BA are scheduling pleasant activities and increasing the patient’s positive interactions with his or her environment by decreasing avoidance, withdrawal, and inactivity.¹¹ Compared to CBT, BA is easier for clinicians to learn and incorporate into primary care visits, and it may be especially useful as an adjunctive or first-step intervention in outpatient clinics.¹¹ Like CBT, BA can be effective in diverse patient groups^13,14 and can be provided using novel delivery modes, such as via the Internet.¹⁵

Compared to cognitive behavioral therapy, behavioral activation is easier for clinicians to learn and incorporate into primary care visits.

IPT is a supportive, structured, brief therapy (12-16 visits) that focuses on helping patients identify and solve current situation- and relationship-based problems that stem from or contribute to their depression.¹⁶ Enhancing the patient’s interpersonal communication—including improving social skills, assertiveness, and appropriate expression of anger—is typically a component of IPT. Like CBT, IPT has been found to be effective for treating depression when administered in person, in group therapy, or via the phone or Internet, and across a broad age range.^17-19

PST involves teaching patients a structured problem-solving process to decrease interpersonal strain and improve positive life experiences.²⁰ Patients are taught to define their problem, generate and evaluate multiple solutions for it, implement a plan for the solution, and evaluate the results. In addition to being used to successfully treat adults,^4,5 PST has been adapted effectively to treat adolescents¹⁶ and older adults.¹⁸

Somatic therapies are also an option

Exercise has long been considered a possible depression treatment due to its activity on endorphin, monoamine, and cortisol levels and via increased social and general activity. A 2013 Cochrane review of 39 randomized control trials (RCTs; N=2326) assessed whether exercise was effective for treating depression in adults.²¹ Thirty-five trials found a moderate effect size when specifically comparing exercise to no treatment or control interventions. The effect size was reduced, however, when analyses were restricted to trials with the highest methodological quality. There was no statistically significant difference when exercise was compared to pharmacologic treatment or psychotherapy.

Although the amount of research is meager, small but statistically significant improvements have also been found for older adults²² and children/adolescents.²³ There is no consensus on the type, frequency, or intensity of exercise needed to achieve benefit. However, because nearly all studies for all age groups have found that exercise has no adverse psychological effects and substantial positive physical effects, exercise should be recommended to all patients with depression unless contraindicated.

Yoga (both exercise-based and meditation-based) has been evaluated both as a sole treatment and as an adjunctive treatment for depression. Several studies have supported the impact of yoga, particularly in pregnant women,²⁴ although the evidence for its efficacy is inconsistent, with yoga frequently failing to improve upon the outcome of waitlist control.²⁵ The evidence for meditation and mindfulness is more consistently positive, with these interventions equaling or exceeding “treatment as usual,” other psychotherapies, and antidepressants in numerous RCTs.²⁵

Electroconvulsive therapy (ECT) has a substantial evidence base supporting its efficacy.²⁶ ECT has been used for decades, although stigma, cardiac and memory risks, and risks of anesthesia often limit its use. Benefits of ECT include a rapid response relative to pharmacotherapy (>50% of patients respond by the end of the first week of ECT)²⁷ and a strong response in older patients.²⁸

More than half of patients receiving electroconvulsive therapy respond to treatment by the end of the first week.

In repetitive transcranial magnetic stimulation (rTMS), electromagnetic coils are placed on a patient’s head to deliver electromagnetic pulses that stimulate areas of the brain that regulate mood. Although rTMS is not widely available, a growing body of evidence supports its use for treating depression, including a meta-analysis of 34 RCTs that included 1383 patients.²⁹ A multisite RCT (N=190) that was not industry-funded reported a 15% response rate and 60% maintenance of remission at 3 months (NNT=12).³⁰ Although ECT is more effective than rTMS, rTMS appears useful for treatment-resistant depression, and can be used as an adjunctive treatment.^29,31

Dietary supplements may be best used as adjuncts

St. John’s wort (Hypericum perforatum), which contains 2 bioactive ingredients (hyperforin and hypericin), has been effectively used to treat depression.³² A 2008 Cochrane review that was limited to high-quality trials involving patients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for depression identified 29 trials (N=5489), of which 18 involved comparisons with placebo and 17 with standard antidepressants.³³ Patients’ depression was rated mild to moderate in 19 studies and moderate to severe in 9 studies. Trials examined 4 to 12 weeks of treatment with Hypericum extracts. This study (and several published since) provides strong clinical evidence supporting the efficacy of St. John’s wort for mild to moderate depression. There is insufficient evidence for its use for severe major depression.³³TABLE 1 contains dosing information for St. John’s wort and other supplements used to treat depression.^34-36 

S-adenosyl-L-methionine (SAMe). In a 2003 systematic review,³⁷ 1600 mg/d of oral SAMe was found to significantly benefit patients with depression in 4 of 5 studies, as did parenteral SAMe (7 of 7 trials). Another review of 48 studies found SAMe was safe and effective for depression.³⁸ SAMe has been proposed for use alone or in combination with an antidepressant.

Low folate levels have been associated with a less robust response to antidepressants in patients with major depressive disorder.

Folate and folic acid. Low folate levels have been associated with a less robust response to antidepressants in patients with MDD,³⁹ and higher folate levels appear to be associated with better antidepressant response.⁴⁰ A 2003 Cochrane review suggested folate might have a role in treating depression.³⁹ A 2009 study found folate supplementation could reduce depressive symptoms for patients with normal baseline folate levels as well as those with low levels.⁴¹ Although the evidence is equivocal, folate augmentation may enhance antidepressant efficacy or improve response/remission rates.^41,42

It seems reasonable to check folate levels in depressed patients, and address deficiencies by instructing patients to increase their dietary intake of folate or to take supplements. Augmenting antidepressants with folate appears to be low-risk and possibly helpful in maintaining remission.

Omega-3 fatty acids. There is substantial evidence that omega-3 fatty acids can prevent and treat depression.^43,44 Recent meta-analyses support the use of omega-3 fatty acids as monotherapy and augmentation, but only formulations that contain a high eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) ratio (EPA/DHA 2:1).^45,46 Omega-3 supplementation has been used with positive results in older adults, children,⁴⁷ pregnant women,⁴⁸ and women with postpartum depression.⁴⁹ Although initial research into omega-3 treatment of depression appears promising, augmentation of standard antidepressant therapy may be a good conservative option.

Use a validated tool to monitor response to treatment

You can enhance outcomes for your patients with depression if you schedule routine follow-up visits with them to gauge adherence to recommendations, monitor response to treatment, and increase the intensity of care when response is inadequate.⁵⁰ The most important aspect of monitoring response is to use a standardized instrument that quantifies symptoms at every visit.

The PHQ-9—which is free—has been validated for depression screening and monitoring of treatment response in primary care patients.

The Patient Health Questionnaire 9-item depression assessment (PHQ-9)—which is free—has been validated for depression screening and monitoring of treatment response in primary care patients.⁵¹ A decrease of 5 points on the PHQ-9 is the minimum considered to be clinically significant.⁵² Other well-validated, although lengthier, self-report depression assessment and monitoring instruments include the Beck Depression Inventory-revised and the Zung Depression Scale.

CASE 1 › Mr. J is not enjoying his new job or engaging with new coworkers to replace the positive social experiences he had at his previous job. Together, you set a goal of increasing social involvement by having him make plans to see at least one friend per weekend. Because he indicates that he is unlikely to follow through with a therapy referral, you encourage him to try an online CBT program, start an exercise regimen, or take a SAMe supplement. Mr. Jackson agrees to try the CBT and exercise (moderate intensity, 30 minutes 3-4 times per week), but does not want to take SAMe. He agrees to an assessment of his folate levels, which are normal.

Mr. J starts the online CBT program, which reinforces the exercise and social activity prescription you provided. He establishes a regular exercise routine with a good friend. After one month, his mood has started to improve and he has added regular participation in a hobby (woodworking), as well as volunteer work, which he finds fulfilling. You plan to continue monitoring his depression and his adherence to the treatment plan.

CASE 2 › The recent move has decreased Mrs. S’s interactions with family and long-time friends. Because she had previously expressed interest in exercise, you encourage her to join a local “Mommy and Me” exercise and support group for mothers of toddlers. She is willing to participate in psychotherapy, so you provide a referral to a local therapist with expertise in IPT. You also discuss with Mrs. S the possible benefits of omega-3 fatty acid supplementation, which appears to be safe during breastfeeding.³⁴

Mrs. S begins therapy and exercise classes, but can’t motivate herself to continue either of these activities. She becomes discouraged because she’s unable to easily find an omega-3 fatty acid supplement with the ratio you specified (EPA/DHA 2:1). When you see her 2 weeks later, her depression has worsened.

Because you are concerned her suicidality will return, you revisit the pros and cons of taking an antidepressant. Although small amounts of antidepressants can be passed from mother to infant via breastmilk, the amount varies by specific medication, as do the potential risks. Mrs. S decides to resume taking paroxetine 20 mg/d and eventually, once her motivation improves, she’s able to add psychotherapy and exercise to her maintenance/relapse prevention regimen. After you discuss with her the possibility that B vitamin supplementation may assist in maintenance of remission, she adds L-methylfolate 7.5 mg/day to her regimen.

CORRESPONDENCE 
Michele M. Larzelere, PhD; LSUHSC Department of Family Medicine; 200 W. Esplanade Avenue, Suite 409; Kenner, LA 70065; mlarze@lsuhsc.edu

The number of women using long-acting reversible contraception (LARC) in the United States has been increasing, with current use accounting for approximately 18% of reversible contraception, according to the National Survey of Family Growth.^1,2 LARC includes any method of contraception that lasts ≥3 years, is easily reversed, and does not rely on the user to maintain efficacy. Five LARC devices are available in the United States: 4 intrauterine devices (IUDs) and one subdermal implant.

The number of women using LARC is surprisingly low, given that it is considered a first-line contraceptive method for most women and adolescents,³ and when compared with other forms of reversible contraception, is more efficacious,^4-6 has higher satisfaction rates,^7-9 and higher rates of continuation.⁹ In fact, the Contraceptive CHOICE Project—a St. Louis community-based research program promoting and enabling access to reversible contraceptive methods—has shown that when appropriate counseling is provided and cost barriers are removed, up to 79% of women choose LARC as their preferred method of contraception.¹⁰

CASES › Jenny, who is 16 years old, comes to your office with her mother to discuss contraceptive options. She is nulliparous, has regular menses, and, aside from a body mass index (BMI) of 28, has no medical problems. Her mother is concerned about Jenny becoming pregnant while she is still in high school.

Maria D, a 32-year-old G2P1, comes in for a prenatal visit with her husband. She tells you that after delivery she is interested in a long-acting contraceptive, but is planning on breastfeeding and does not want anything to interfere with that.

What LARC options do these and other patients have?

The 4 IUDs and one implant approved for use are all viable options depending on a patient’s preference and comorbidities (TABLE 1).^3-9,11-15 The copper IUD is the oldest method of LARC available and the only one that is nonhormonal. It is approved by the Food and Drug Administration (FDA) for use up to 10 years,¹¹ but studies support its effectiveness for up to 12 years.¹⁶

Overweight and obese women enrolled in the Contraceptive CHOICE Project did not experience reduced contraceptive efficacy when using the implant when compared with normal-weight women.

The remaining IUDs (Skyla, Liletta, Mirena) contain varying amounts of the progestin levonorgestrel (LNG), released by each device at a slightly different rate that declines over time. Skyla releases a significantly lower dose of hormone than Liletta or Mirena.^12-14 Skyla and Liletta are FDA-approved for up to 3 years of use,^12,13 and Liletta is currently undergoing trials to gain approval for use up to 5 years. Mirena is FDA-approved for use up to 5 years,¹⁴ but studies have shown that it can be effective for 7 years.^4,16

The only implant available in the US is Nexplanon, a plastic rod containing 68 mg of etonorgestrel. It is inserted subdermally and is FDA-approved for use up to 3 years.¹⁵

Through systemic hormonal effects, the primary mechanism of action of the implant is prevention of ovulation. Additionally, the implant has been shown to inhibit endometrial proliferation and cervical mucus thickening, both of which may contribute to the implant’s overall effectiveness.¹⁷ In contrast, both the copper IUD and the LNG-IUDs work primarily by preventing fertilization. The LNG-IUDs also exhibit local hormonal effects (endometrial atrophy and thickened cervical mucus) that contribute to their effectiveness.¹⁷

Who is eligible for LARC?

LARC is suitable for the vast majority of women of reproductive age. For most multiparous women ≥20 years, all LARC devices are classified as category 1 (use without restriction) in the Centers for Disease Control and Prevention’s (CDC) US Medical Eligibility Criteria (US MEC).³ For women <20 years, the implant is also considered category 1, but IUDs in this age group are classified as category 2 (recommended with the caution that advantages usually outweigh risks) because of concerns about an increased risk of IUD expulsion and the increased prevalence of sexually transmitted infections (STIs) in adolescents.³ Contraindications to use of LARC vary depending on the method chosen (TABLE 1).³

There has been concern about the efficacy of implants in overweight women because the original trials of subdermal implants excluded women >130% of ideal body weight. However, according to the Contraceptive CHOICE Project, overweight and obese women enrolled in its program did not experience reduced contraceptive efficacy when using the implant when compared with normal-weight women.¹⁸

When can LARC devices be inserted?

LARC device insertion is possible at any time during the menstrual cycle. An algorithm to guide initiation of LARC is available through the Reproductive Health Access Project’s Web site at http://www.reproductiveaccess.org/wp-content/uploads/2014/12/quickstart_algorithm.pdf.

Rule out pregnancy before placing any LARC device. The copper IUD can be inserted at any time during the menstrual cycle without the need for back-up contraception.^11,19 In contrast, for LNG-IUDs, back-up contraception is recommended for 7 days unless the insertion is done during the first 7 days of the menstrual cycle.^12-14,19

For the implant, recommendations about when to insert are based on a woman’s previous method of contraception (TABLE 2).¹⁵ If insertion is done at a time other than when recommended, advise patients to use barrier protection for 7 days after insertion.^4,15,19

Other issues often arise and cause concern about whether and when a LARC device can be inserted, including the possibility of undiagnosed STI, time elapsed since delivery, and advisability of use when breastfeeding.

Sexually transmitted infections and IUDs

Whether or not a woman chooses to receive an IUD, follow routine CDC guidelines in determining if a patient is a candidate for STI screening.²⁰ If a woman wants an IUD and routine screening is recommended, you can perform screening on the day of IUD insertion.^4,19 For women with an IUD already in place who are diagnosed with an STI, treat the infection while leaving the IUD in place.¹⁹ For women with a known or suspected STI who do not have an IUD already, treat the STI before inserting the IUD. The American Congress of Obstetricians and Gynecologists (ACOG) advises postponing insertion of an IUD until a negative STI test result is obtained 3 to 4 weeks after treatment completion.⁴

Breastfeeding concerns and timing of insertion postpartum

The US MEC classifies insertion of the copper IUD as category 1 for all postpartum women, regardless of breastfeeding status, if placed >4 weeks postpartum or immediately postpartum (defined as within 10 minutes of the delivery of the placenta). IUD placement is category 2 (recommended with the caution that advantages usually outweigh risks) if placed ≥10 minutes after placental delivery (until 4 weeks postpartum) because of an increased risk of expulsion.³

The US MEC also considers use of the implant and LNG-IUDs in breastfeeding women as category 1 if the device is placed at ≥4 weeks postpartum. Insertion at <4 weeks postpartum is considered category 2 because of concerns for decreased breast milk supply.³ However, studies on whether progestin-containing LARC devices affect breastfeeding have yielded varying results. In one randomized controlled trial (RCT) of 69 breastfeeding women using the implant, breastfeeding duration and milk production were not dependent on the timing of insertion after delivery.²¹ Another RCT of 96 women using LNG-IUDs showed fewer women continued to breastfeed at 6 months when their LNG-IUD was inserted immediately postpartum, compared with waiting 6 weeks.²²

In addition to a concern about breast milk supply, breastfeeding women have a higher risk for uterine perforation from IUDs, especially during the first 36 weeks after delivery.²³

The failure rate of long-acting reversible contraception is equal to, or lower than, that of female sterilization and is significantly lower than that of oral contraceptives.

Several studies have shown that there is a lower repeat pregnancy rate among women who receive immediate postpartum LARC placement.²⁴ However, even if IUD insertion is performed immediately postpartum, there is a higher expulsion rate than when the IUD is inserted ≥4 weeks postpartum. The expulsion rates for insertion <10 minutes after vaginal delivery range from 9.5% to 15% for the copper IUD to as high as 24% for the LNG-IUDs. Expulsion rates for all IUDs are slightly lower for cesarean delivery.^4,25,26 ACOG supports immediate post-placental placement for women with barriers to postpartum care or limited access to contraception.⁴

How can I help my patients make an informed choice?

Provide counseling on efficacy, common adverse effects, risks, and complications.

Efficacy is high

The failure rate of LARC is equal to, or lower than, that of female sterilization and is significantly lower than that of oral contraceptives (TABLE 1).^4-6 Not only are LARC devices extremely effective, they have a higher rate of satisfaction than any other reversible contraceptive (TABLE 1).^7,8

Common adverse effects

The most common adverse effect seen with all LARC devices is an alteration in menstrual bleeding, and a frequent adverse effect with IUDs is pain. Vaginitis is less common and can be seen with any of the devices. The progestin-containing LARC devices are associated with hormonal effects: vaginitis, headache, weight gain, acne, breast pain, hair loss, and emotional lability.^12-15

Copper IUD. Many women using the copper IUD experience either a transient increase in menstrual bleeding lasting for a few months or inter-menstrual bleeding that tends to continue for the duration of use.^4,17 However, according to data from the Contraceptive CHOICE Project, the most common reason cited for early discontinuation of the copper IUD is pain and cramping.⁹

LNG-IUDs. Like the copper IUD, many users of LNG-IUDs experience an initial increase in menstrual bleeding. However, unlike the other LARC devices, 20% to 33% of Mirena users are likely to experience amenorrhea after one year of use and 70% at 2 years.^4,14 According to package inserts, amenorrhea after 3 years is less common with both Skyla (12%) and Liletta (38%).^12,13 As with the copper IUD, based on data from the Contraceptive CHOICE Project, the most common reason cited for early discontinuation of LNG-IUDs is pain and cramping.⁹

Subdermal implant. Changes in menses in women using the subdermal implant range from amenorrhea (22%) to prolonged bleeding (18%).^15,17 Although it is difficult to predict which pattern a particular woman will experience, heavier women are more likely to have heavier bleeding patterns, and initial bleeding patterns are predictive of future ones.⁴ The most common reason women choose to discontinue use of the implant is abnormal bleeding.^4,9,27,28

Newer IUDs do not increase risk of STIs

Many patients and clinicians erroneously believe that IUDs increase the risk of STIs and therefore assume that patients with a history of STI are not appropriate candidates for an IUD.²⁹ There is a slightly increased risk of pelvic inflammatory disease (PID) in the first 21 days after insertion of an IUD. However, in contrast to older IUDs, currently available IUDs do not increase the general risk for STIs.^17,30

Risk of infertility is nil

There is no risk of infertility from use of currently available LARCs. For those who want to become pregnant, fertility typically returns immediately after removal of the device, regardless of which method of LARC is used.^11-15,30

Complications of IUD insertion

Uterine perforation. Uterine perforation occurs in 0.8 to 2.1 per 1000 women, usually at the time of IUD placement. If IUD strings are not visible during a speculum examination, locate the IUD with ultrasound.^4,17,30 If the IUD is in the abdomen, refer to a gynecologist for laparoscopic removal and select another form of contraception for use in the interim.³⁰

Expulsion. Rates of expulsion are low, occurring in less than 10% of women^4,17 and are not affected by parity or BMI.³¹ Expulsion rates are higher when the IUD is inserted immediately postpartum.^4,25,26 Adolescents also have a 2-fold higher risk of uterine expulsion than older women.³¹

Ectopic pregnancy. Although a woman’s overall risk of ectopic pregnancy is not increased by using an IUD,⁴ it is true that if a woman becomes pregnant with an IUD in place, the pregnancy is more likely to be ectopic. Thus, if pregnancy is confirmed in a woman with an IUD in place, rule out ectopic pregnancy.

The most common reason for early discontinuation of IUDs is pain and cramping.

The FDA and the World Health Organization recommend that if an intrauterine pregnancy is confirmed with an IUD in place and the strings are visible, the IUD should be removed.⁴ Although removing the IUD increases the risk of spontaneous abortion (SAB) as compared with pregnancies without an IUD in place, the risk of SAB is still lower than if the IUD is left in place.⁴ Additional risks of continuing a pregnancy with an IUD in place include increased risks of preterm labor, chorioamnionitis, and septic abortion.^4,30

Complications of subdermal implant insertion

After insertion of the implant, women usually experience temporary bruising and soreness at the insertion site. Less than 1% of women develop an infection or hematoma.¹⁷ There is a low risk of nerve damage if the implant is inserted too deeply.¹⁵ Removal of the subdermal implant is recommended if pregnancy occurs.¹⁵

For those who want to become pregnant, fertility typically returns immediately after removal of the device, regardless of which form of long-acting reversible contraception is used.

CASE DECISIONS › Jenny has been using oral contraceptive pills, but not regularly. You suggest that LARC may be a better option and counsel her that if she does choose an IUD or the implant, it is likely that her menses will change. You provide information and reassurance that LARC is safe to use in adolescents. Jenny says she would like to try an implant. Six months later, Jenny returns and says the implant is working well. She has some irregular bleeding, but it is not bothersome.

You review with Ms. D the types of LARC devices available and reassure her that all are safe to use once breastfeeding is established. Ms. D says she would like to use an IUD and elects to wait until her postpartum visit to have an IUD inserted. Ms. D returns 6 months after IUD insertion; breastfeeding is going well, and she has not had any menstrual bleeding since delivery.

CORRESPONDENCE 
Karyn Kolman, MD, 2800 East Ajo Way, Room 3006, Tucson, AZ 85713; karyn.kolman@bannerhealth.com