REVIEW OF: Bschor T, Kern H, Henssler J, Baethge C. Switching the antidepressant after nonresponse in adults with major depression: A systemic literature search and metaanalysis. J Clin Psychiatry 2016. doi:10.4088/JCP.16r10749. [Epub ahead of print]
STUDY TYPE: Meta-analysis
Clinical trials have shown that the response rate of major depression to a course of antidepressants is 50% to 70%. After a non-response, what should we do? Increase the dose? Switch to another medication? Augment with a different one? Unfortunately, we have remarkably little to guide us in the way of empirical studies. The largest “real-world” study of antidepressants, the oft-cited STAR*D trial, enrolled plenty of patients and compared various strategies. Unfortunately, that study was not very informative, because there was no placebo group, and patients were not fully randomized to group assignments.
The authors of this meta-analysis sought evidence to answer a specific question: Is it better to stay the course with the original antidepressant, or is it better to switch? They searched the literature for studies that enrolled patients with major depressive disorder who did not respond to at least a 2-week trial of an antidepressant. These patients were then randomly assigned to either continuation of the same medication or a switch to a different one. They found eight relevant studies, and combining them, 783 patients were randomized to continuation arms while 844 were assigned to switching arms. Some of the studies blinded participants to their treatment, but others did not; the followup lasted from 4 to 12 weeks, depending on the study.
The studies spanned a long time period, with the oldest published in 2001 and the most recent in 2014. Medications compared included the following (listed in order of continuation medication, switched-to medication): fluoxetine, mianserin; nortriptyline, fluoxetine; venlafaxine, fluoxetine; escitalopram, duloxetine (two studies); various SSRIs, duloxetine; various SSRIs, mirtazapine; desipramine or citalopram, desipramine or citalopram.
RESULTS: There were no statistically significant differences between patients who continued vs those who switched medications. This was true both for the primary outcome of change in depression scale score and for the secondary outcomes of response rate and remission rate.
TCPR’S TAKE: This is the largest and best study yet looking at whether it’s better to switch antidepressants or stay the course, and the implication is that there is no advantage to switching.
PRACTICE IMPLICATIONS: When patients do not respond to an antidepressant, you may be tempted to switch to another one and then rotate through your list of favorites. But given the surprising finding that switching antidepressants incurs no discernible benefit, you may want to instead consider augmentation strategies or a psychotherapy referral.
Meditation: An Effective Treatment for Depression?
REVIEW OF: Sharma A, Barrett M, Cucchiara A, Gooneratne N, Thase M. A breathing-based meditation intervention for patients with major depressive disorder following inadequate response to antidepressants: A randomized pilot study. J Clin Psychiatry 2016 Nov 22. doi:10.4088/JCP.16m10819. [Epub ahead of print]
STUDY TYPE: Randomized, rater-blind, waitlist-controlled study
Complementary and alternative medicine is gradually becoming more mainstream, and we covered some of these treatments in a recent issue of TCPR, but we didn’t cover yoga and meditation. Sudarshan Kriya yoga (SKY) is a meditation technique that combines yoga poses, sitting meditation, and breathing exercises. Past small studies have shown that SKY is effective for dysthymic disorder, depression due to alcohol dependence, and major depressive disorder in inpatients. In this trial, 25 adult outpatients with depression were recruited from the University of Pennsylvania Mood and Anxiety Disorders Treatment and Research Program. These patients had been on antidepressants for at least 8 weeks without a response. They were randomly assigned to either the SKY active (n = 13) or waitlist control (n = 12) group. The study lasted 8 weeks and consisted of 2 phases. Phase 1 (week 1) included six 3.5-hour sessions of the SKY program. Phase 2 (weeks 2–8) consisted of weekly follow-up sessions (of 3.5 hours) and daily at-home practice sessions of 20–25 minutes. While 3.5 hours of yoga might sound like a lot, only a small portion of the sessions involved yoga postures; these sessions included rhythmic breathing exercises, sitting meditation, and stress education. Clinical raters conducted 3 assessments: baseline, at the 1-month visit, and at the 2-month visit. The primary outcome was change in patients’ HDRS-17 scores from the baseline to the 2-month visit.
RESULTS: Patients in the SKY active group had a mean reduction in their HDRS-17 score of 9.77 points, whereas the waitlist control group had a small increase in their score of 0.50 points (p = 0.032). SKY patients also showed greater improvement on two secondary outcomes: the Beck Depression Inventory and the Beck Anxiety Inventory. No patient in the SKY group reported any adverse reactions.
TCPR’S TAKE: The study was limited by the small sample size and by the lack of an active comparator control group. In addition, the treatment was pretty resource-intensive— it’s unlikely that most patients will be able to find a program offering 3.5 hours of yoga and meditation per day for 6 days, much less be able to afford it, either in terms of time or money. Nonetheless, given that several other small studies have endorsed the SKY approach for depression and other conditions, it looks like SKY meditation has some promise as an augmenting treatment for patients with treatment resistant major depressive disorder.
PRACTICE IMPLICATIONS: This is a promising preliminary study, and we look forward to larger ones in the future that hopefully will replicate these results. In the meantime, namaste!