Michele M. Larzelere, PhD Ernest James III, MD Michael Arcuri, MD Department of Family Medicine, Louisiana State University Health Sciences Center, New Orleans mlarze@lsuhsc.edu
The authors reported no potential conflict of interest relevant to this article.
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.
