Twenty-five studies with a total of 1,377 patients were included in the analyses.
No eligible studies on sertraline in in-patients were identified.
Overall, TCAs were significantly more effective than the SSRIs (effect size, ES -0.23, 95% confidence interval, CI: -0.40, -0.05, p=0.011). The studies showed significant heterogeneity (Q=57.3529, d.f.=24, p=0.0001). Sensitivity analyses using 5 of the larger studies (with greater than 100 patients) and those providing complete data (15 studies) reduced the advantage of TCAs to a non significant trend (p<0.10). When TCAs were grouped into those with dual action on 5-hydroxytryptamine and noradrenaline re-uptake (clomipramine and amitriptyline), and those with predominantly noradrenaline re-uptake, (imipramine, desipramine and maprotiline) only the dual action TCAs had greater efficacy than the SSRIs (ES -0.30, 95% CI: -0.54, -0.05, p=0.017). When TCAs were considered individually, only amitriptyline was significantly more effective than the SSRIs (ES -0.37, 95% CI: -0.67, -0.07, p=0.015). When considering the SSRIs separately, there was a significant advantage to the TCAs over paroxetine (ES -0.44, 95% CI: -0.78, -0.11, p=0.009), but not to fluvoxamine or fluoxetine.
Tolerability results (22 studies) indicated that more patients discontinued treatment on TCAs than on SSRIs (29 versus 25.5%; not significant). However, significantly more patients stopped treatment due to adverse effects with TCAs than with SSRIs (14.2 versus 9.1%; relative risk 0.66, 95% CI: 0.50, 0.87, p=0.003). However, there was no significant difference in discontinuations due to treatment failure: 10% with TCAs versus 11.6% with SSRIs. Analysis according to the size of the study, type of TCA, and type of SSRI showed the same pattern of results.