Introduction: Meta-analyses can provide a clear presentation of individual and pooled trial data, but they are limited by the quality of the original RCTs. 105 RCTs and four meta-analyses have failed to provide a clear answer to the question of whether selective serotonin reuptake inhibitors (SSRIs) or tricyclic/heterocyclic antidepressants should be used as first line treatment for depression in primary care settings. Systematic reviews, by illustrating the limitations of trials, can provide information of greater value.
Objective: To conduct a systematic review and meta-analysis of trials comparing SSRIs and tricyclic antidepressants for the treatment of depression in primary care.
Methods: All randomised controlled trials reported in previous meta-analyses comparing SSRIs and tricyclic antidepressants were used. In addition, a Medline and Index Medicus search was performed. Two journals were also handsearched: International Clinical Psychopharmacology and Acta Psychiatrica Scandinavica.
Results: The key findings of the systematic review are that the majority of trials are small, fail to conduct intention to treat analyses, are based in secondary care where only a minority of patients are treated, use observer rated assessments of depressive symptoms which are open to observer bias, and fail to give economic evaluations. A meta-analysis using drop outs from treatment showed that overall the SSRIs had a modest advantage over tricyclics and heterocyclics (Risk Ratio 0.90; (95% CI: 0.86-0.97)). As hypothesised, this effect was strongest when older tricyclics were used as the comparison group, probably due to their more prominent side effects (RR 0.88; 95% CI: 0.82-0.95). When compared with newer tricyclics or heterocyclics no significant advantage for the SSRIs could be found (RR=0.92; (95% CI: 0.82-1.04) for new tricyclics, and RR 1.02; (95% CI: 0.83-1.25) for heterocyclics).
Discussion: The poor quality of many trials and these still equivocal results, based on drop out not clinical recovery, indicate a need for a large RCT based in primary care, and using a newer tricyclic as the comparison drug.