Is combination pharmacotherapy effective for patients with acute depression?
A systematic review and meta-analysis found that these combinations were superior to monotherapy and had comparable tolerability.
PRACTICE CHANGER
Use a combination of a presynaptic α2-autoreceptor antagonist (eg, mirtazapine or trazodone) and a monoamine reuptake inhibitor (eg, selective serotonin reuptake inhibitor [SSRI], serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) to treat acute depression in adult patients.
STRENGTH OF RECOMMENDATION
A: Based on a single systematic review with meta-analysis.1
Henssler J, Alexander D, Schwarzer G, et al. Combining antidepressants vs antidepressant monotherapy for treatment of patients with acute depression: a systematic review and meta-analysis. JAMA Psychiatry. 2022;79:300-312. doi: 10.1001/jamapsychiatry.2021.4313
WHAT’S NEW
One combination proved more effective than others
Current clinical guidelines indicate the suitability of trialing pharmacologic monotherapy during the acute phase of depression treatment prior to initiating an adjunctive medication.9 All classes of medication investigated in this meta-analysis are generally regarded as first-line therapies, although they are rarely started in combination. This study’s findings suggest that combination pharmacotherapy, especially with a presynaptic α2-autoreceptor antagonist (eg, mirtazapine, trazodone) and a monoamine reuptake inhibitor (eg, an SSRI, SNRI, or a TCA), is superior to monotherapy, both at the time of treatment initiation and in patients with previous inadequate pharmacologic response.
CAVEATS
Potential limitations due to publication bias
Concerns about publication bias and significant study heterogeneity may limit the generalizability of these findings. However, conclusions were robust in a subgroup analysis that was restricted to publications with low risk for bias.
CHALLENGES TO IMPLEMENTATION
None to report
There are no major challenges to implementing this combination treatment. Importantly, there were no differences in tolerability between monotherapy and combination treatment.
