Sixteen studies (1,104 participants in total) were included in the pooled analysis of antidepressant efficacy: there were 4 studies of TCAs, 8 of SSRIs, 2 of ATYP antidepressants, and 2 of placebo.
Thirty-nine studies (1,274 participants in total) were included in the pooled analysis of tolerability (adverse effects): there were 8 studies of TCAs, 11 of SSRIs, 4 of RIMAs, 12 of ATYP antidepressants, and 4 of placebo.
Sixty-three studies (3,180 participants in total) were included in the pooled analysis of drop-out rates: there were 19 studies of TCAs, 19 of SSRIs, 3 of RIMAs, 16 of ATYP antidepressants, and 6 of placebo.
The majority of analyses had significant homogeneity (P<0.05), meaning that the studies aggregated were considered heterogeneous. Only 3 of the analyses were homogeneous: ATYP-efficacy assessment, TCA-efficacy assessment and placebo-efficacy assessment.
Efficacy and tolerability.
ATYP antidepressants: 33.4% (95% confidence interval, CI: 5.2, 61.7) of the participants responded to treatment. Adverse effects were reported in 37.5% (95% CI: 29.1, 45.9) of users, and 11.2% (95% CI: 6.9, 45.6) of the patients dropped out of the trials.
RIMAs: efficacy results for patients prescribed RIMAs, based upon the percentage of responders, were unavailable because they were not reported according to the categorical definition. Adverse effects were reported in 57.7% (95% CI: 35.7, 79.7) of RIMA users and the drop-out rate was 27.1% (95% CI: -1.2, 55.5).
SSRIs: 57.7% (95% CI: 45.5, 69.8) of the participants responded to treatment. Adverse effects were reported in 59.1% (95% CI: 44.2, 74.0) of SSRI users and the drop-out rate was 18.5% (95% CI: 14.3, 22.8).
TCAs: 63.1% (95% CI: 57.4, 76.7) of the participants responded to treatment. Adverse effects were reported in 60.3% (95% CI: 31.3, 89.2) of TCA users and the drop-out rate was 23.2% (95% CI: 17.0, 29.4).
Placebo: 27.2% (95% CI: 22.1, 32.2) of the participants responded to placebo. Adverse effects were reported in 39.6% (95% CI: 6.9, 72.4) of placebo takers and the drop-out rate was 25.6% (95% CI: 11.5, 39.7).
Comparative analyses: SSRIs were shown to have superior efficacy to ATYP antidepressants. The pooled difference (ATYP minus SSRI) in efficacy was -36.9% (95% CI: -65.4, -8.4, p=0.01). No other antidepressant class was shown to be superior with respect to efficacy, safety, or drop-outs. ATYP antidepressants were not shown to be superior to placebo.
Sensitivity analysis: when only high-quality studies were included in the analyses, no significant differences were observed. When only out-patients were included in the analyses, the results appeared similar to those incorporating both in- and out-patients. The authors did not report whether any of the differences were significant.