Mehmet E. Dokucu, MD, PhD Associate Professor Department of Psychiatry and Behavioral Sciences Northwestern University Feinberg School of Medicine Chicago, Illinois
Philip G. Janicak, MD Adjunct Professor Department of Psychiatry and Behavioral Sciences Northwestern University Feinberg School of Medicine Chicago, Illinois
Disclosures Dr. Dokucu reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products. Dr. Janicak is a speaker for Otsuka PsychU program and TMS Health Solutions.
A meta-analysis of 7 clinical trials (N = 3,808) comparing St. John’s Wort with various selective serotonin reuptake inhibitors (SSRIs) reported comparable rates of response (pooled relative risk .983, 95% CI .924 to 1.042; P < .001) and remission (pooled relative risk 1.013, 95% CI .892 to 1.134; P < .001).9 Further, there were significantly lower discontinuation/dropout rates (pooled odds ratio .587, 95% CI .478 to 0.697; P < .001) for St. John’s Wort compared with the SSRIs.
Existing evidence on the long-term efficacy and safety is limited (studies ranged from 4 to 12 weeks), as is evidence for patients with more severe depression or high suicidality.
Serious drug interactions include the potential for serotonin syndrome when St. John’s Wort is combined with certain antidepressants, compromised efficacy of benzodiazepines and standard antidepressants, and severe skin reactions to sun exposure. In addition, St. John’s Wort may not be safe to use during pregnancy or while breastfeeding. Because potential drug interactions can be serious and individuals often self-prescribe this agent, it is important to ask patients about their use of St. John’s Wort, and to be vigilant for such potential adverse interactions.
Probiotics.These agents produce neuroactive substances that act on the brain/gut axis. Preliminary evidence suggests that these “psychobiotics” confer mental health benefits.10-12 Relative to other approaches, their low-risk profile make them an attractive option for some patients.
Anti-inflammatory/immune system therapies
Inflammation is linked to various medical and brain disorders. For example, patients with depression often demonstrate increased levels of peripheral blood inflammatory biomarkers (such as C-reactive protein and interleukin-6 and -17) that are known to alter norepinephrine, neuroendocrine (eg, the hypothalamic-pituitary-adrenal axis), and microglia function in addition to neuroplasticity. Thus, targeting inflammation may facilitate the development of novel antidepressants. In addition, these agents may benefit depression associated with comorbid autoimmune disorders, such as psoriasis or rheumatoid arthritis. A systematic review and meta-analysis of 36 RCTs (N = 10,000) found 5 out of 6 anti-inflammatory agents improved depression.13,14 In general, reported disadvantages of anti-inflammatories/immunosuppressants include the potential to block the antidepressant effect of some agents, the risk of opportunistic infections, and an increased risk of suicide.
