• antidepressants;
  • drug combinations;
  • depression;
  • resistant depression;
  • drug interactions;
  • surveys;
  • algorithms

Objective:  To review the current literature on the use of combinations of antidepressive agents.

Method:  Literature searches were undertaken and reviewed on the use of combinations of antidepressants.

Results:  Data sources included surveys, analyses of prescription records, decision algorithms, clinical reports, and studies comparing the monotherapy with combination therapy. More recent surveys recommend combining different selective serotonin reuptake inhibitors (SSRIs), an SSRI plus bupropion or dual action antidepressants plus an SSRI. Decision algorithms recommend an SSRI plus tricyclic antidepressant (TCA) and more recently bupropion plus venlafaxine or mirtazapine. Few controlled clinical trials comparing the combined therapy with monotherapy have been conducted. Beneficial effects have been reported with combinations of TCAs plus mianserin or SSRIs plus mirtazapine.

Conclusion:  Adding or combining antidepressant medications has advantages for the speed of onset and maintaining the existing response. More rigorous clinical trials comparing combination therapy with monotherapy and for the development of rational treatment guidelines are required.