[Second-step strategies in antidepressant pharmacotherapy : Results of current meta-analyses].

Background: Antidepressant pharmacotherapy often does not result in the desired effect despite adequate duration and dose. Better evidence on second-step strategies is needed.

Objective: Overview of the current evidence for various pharmacological second-step strategies after nonresponse to antidepressant monotherapy.

Material and methods: Summary of recent systematic reviews with meta-analyses of the group of authors on pharmacological second-step treatment.

Results: A meta-analysis showed no advantage of switching to a second antidepressant compared with continuing the previously ineffective monotherapy. Another two meta-analyses showed no benefit of increasing the dose of selective serotonin reuptake inhibitors (SSRI). For serotonin and noradrenaline reuptake inhibitors (SNRI) and tricyclic antidepressants (TCA) in each case a meta-analysis showed no clear advantage of increasing the dose. Another two meta-analyses showed a superiority of a combination therapy consisting of a reuptake inhibitor (SSRI, SNRI, TCA) with a presynaptic alpha‑2 autoreceptor antagonist (e.g., mirtazapine) compared with an antidepressant monotherapy.

Conclusion: In accordance with the recommendations of the German national treatment guideline, in the event of nonresponse to antidepressant monotherapy, the combination of two antidepressants is preferable to repeated switching of the antidepressant.