REVIEW OF: Hu Y et al, Psychiatry Res 2024;337:115926

STUDY TYPE: Systematic review and meta-analysis

A common clinical scenario involves a patient with major depression who responds well to antidepressant treatment and then wonders when they might safely stop their medication. Current guidelines suggest continuing for 4–12 months after remission, but there’s no clear answer. The authors of this meta-analysis point out that most clinical trials don’t directly compare different lengths of treatment to assess how duration impacts relapse risk. 

Accordingly, they analyzed 35 RCTs of antidepressant therapy that used a “discontinuation design.” In these trials, patients who had responded to antidepressants were randomly assigned to either continue treatment or switch to placebo. The main question: What happens to relapse rates after discontinuation at different time points—1, 3, 6, and 12 months? The studies included 9,312 patients who had responded to acute and/or maintenance treatment. The acute treatment phase in these trials ranged from 6 to 13 weeks, and the maintenance phase ranged from 0 to 26 weeks. 

By 6 months after stopping antidepressants, about 35% of patients had relapsed if they were switched to placebo, compared to 17% who stayed on medication. After 12 months, the relapse rates were higher for discontinuers, at 45% vs 21% for continuers. Patients who had received treatment for fewer than three months were at a much greater risk of relapse. After three months of treatment, relapse risk dropped, but treatment beyond six months didn’t significantly lower the relapse rate.

The researchers also found that younger patients were more prone to relapse. Interestingly, there wasn’t much difference in relapse rates based on which type of antidepressant was used. Also, tapering off antidepressants resulted in a slightly lower relapse rate (32%) compared to stopping abruptly (39%). (See also “How to Stop a Psychiatric Med” in the November/December 2024 TCPR.)

CARLAT TAKE
This study supports keeping patients on antidepressants for at least six months after remission. Staying on meds for longer than six months doesn’t seem to offer much additional protection. And as always, tapering is key—stopping abruptly increases the risk of relapse. When we compare this to the APA guidelines, the findings align fairly well. The APA recommends a continuation phase of four to nine months after acute remission to prevent relapse. For patients with three or more episodes or chronic, recurrent depression, the APA advises indefinite maintenance therapy. This study doesn’t challenge those recommendations but suggests that for some patients, extending treatment beyond six months might not be necessary.