Antidepressant data show only small improvement over placebo, meta-analysis finds
A recent analysis looked at 232 randomized, double-blind, placebo-controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016.
The mean effect of antidepressants for patients with major depressive disorder is only a small improvement over placebo, a recent study found.
Researchers analyzed individual participant data from 232 randomized, double-blind, placebo-controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016. The trials included 73,388 adult and child participants. The researchers characterized individual participant-level response distribution to acute monotherapy for major depressive disorder. They converted responses to Hamilton Rating Scale for Depression-equivalent scores where other measures were used to assess efficacy. Results were published Aug. 2 by The BMJ.
The random effects mean difference between drug and placebo favored the drugs (1.75 points, 95% CI, 1.63 to 1.86). Differences between drug and placebo increased significantly (P<0.001) with greater baseline severity of depression. After controlling for participant characteristics at baseline, no trends in treatment effect or placebo response over time were observed. The best-fitting model of response distributions was three normal distributions, with mean improvements from baseline to end of treatment of 16.0 (large), 8.9 (nonspecific), and 1.7 points (minimal). Participants who received a drug were more likely to have a large response (24.5% vs. 9.6%) and were less likely to have a minimal response (12.2.% vs. 21.5%), suggesting that about 15% of participants had a substantial effect beyond that of placebo.
The database did not include details of study design, such as inclusion and exclusion criteria, the study authors noted. They added that more demographic information, evaluation of blinding, individual length of treatment, and item-level data were not available.
“Patients with depression are likely to improve substantially from acute treatment of their depression with drug or placebo. Although the mean effect of antidepressants is only a small improvement over placebo, the effect of active drug seems to increase the probability that any patient will benefit substantially from treatment by about 15%,” the authors wrote. “Further research is needed to identify the subset of patients who are likely to require antidepressants for substantial improvement.”