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"Augmentation" of antidepressant treatment offers little benefit
Clinical Question
Is augmentation treatment effective for patients with treatment-resistant depression?
Bottom line
The available evidence that treatment-resistant depression—depression unresponsive to 2 different treatments of adequate dose and length—responds well to augmentation treatment (ie, adding psychotherapy, lithium, or aripiprazole [Abilify] to current treatment) is weak. The available evidence shows no benefit with lithium and small benefit with psychotherapy or aripiprazole. 1a-
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Government
Setting: Various (meta-analysis)
Synopsis
The authors searched 2 databases (but not the Cochrane Library) for randomized studies of augmentation treatment for patients who did not respond to at least 2 courses of treatment for major depressive disorder.Two authors selected studies for inclusion and independently extracted the data. Most of the 28 studies of 5461 patients had low to moderate risk of bias (ie, were of medium to high quality) and included both drug treatment and psychological therapies. Instead of comparing directly across treatments (that is, the benefit in one group vs the other), the authors compared the before-after change in results within each group. In 3 low-quality studies, psychological treatment showed a moderate benefit. In 4 studies of aripiprazole, there was a small likelihood of benefit after short-term treatment (effect size = 1.33; 95% CI 1.23 - 1.44) as compared with placebo. Lithium produced an effect size similar to placebo.
Reviewer
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA
Comments
Augmentation still has its place
As a psychiatrist since 1992 seeing patients with treatment resistant depression, I prefer monotherapy when it works, but I have seen patients who have failed ten or more medications and even ECT respond to augmentation with lithium, Cytomel, aripiprazole, brexpiprazole, olanzapine, modafinil, stimulants. I think there was more robust evidence for augmentation when using tricyclics or MAOIs and I have certainly seen patients not respond to augmentation when they were on an SSRI or SNRI (but to confound matters some do respond). One needs to look for occult reasons for treatment resistance (substance abuse, endocrine disease, other illness, noncompliance) and consider switching if there is no response to an adequate dose of a medication in a reasonable time frame. Sometimes there is a partial response and then one consults with the patient about either increasing the dose (often you get results in a week) or augmenting. Augmenting can also be a useful strategy when you're giving the drug the benefit of the doubt by giving it for another two weeks before you switch. I have taken patients off the augmenting drug only to have them relapse in depression and the augmenting drug by itself often didn't work, so there is something to augmentation. It is good to see RCTs but don't completely rule out augmentation.