Skip to content

Sachs et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. New England Journal of Medicine. 2007;356:1711–1722. PMID 17392295

One-paragraph summary

STEP-BD used a double-blind, placebo-controlled effectiveness design to test whether adding a standard antidepressant to mood-stabilizing treatment improved bipolar depression without increasing mania or hypomania. Participants received up to 26 weeks of adjunctive antidepressant or matching placebo. The primary endpoint was stringent: eight consecutive euthymic weeks. Durable recovery occurred in 42/179 (23.5%) participants assigned antidepressant and 51/187 (27.3%) assigned placebo, P=.40; secondary outcomes also showed no significant antidepressant advantage, and treatment-emergent affective-switch rates were similar (Sachs 2007, PMID 17392295).

Key findings

  • Durable recovery: 23.5% with adjunctive antidepressant versus 27.3% with placebo, P=.40.
  • The direction of the primary estimate did not favor antidepressant treatment.
  • Modest nonsignificant trends across secondary outcomes favored mood stabilizer plus placebo.
  • Acute treatment-emergent mania/hypomania did not occur more often with the tested adjunctive antidepressant strategy.
  • The trial tested adjunctive treatment under effectiveness-oriented conditions, not antidepressant monotherapy.

Limitations

  • The result applies to the antidepressants and mood-stabilizing context studied; it is not a class-wide monotherapy trial.
  • Up to 26 weeks is insufficient to establish or exclude multi-year cycle acceleration.
  • Affective switch and durable recovery are distinct outcomes; similar switch risk did not compensate for absent efficacy.
  • The abstract does not provide drug-specific subgroup effect estimates.
  • Participants able to enter a randomized effectiveness study may differ from people with severe mixed activation or immediate safety risk.

Why it matters

This trial changed the default evidentiary claim from “antidepressants probably help if protected by a mood stabilizer” to “common adjunctive antidepressants did not improve durable recovery in this strategy.” It also demonstrated that efficacy and switch must be reported together: a treatment can show no switch excess and still lack clinical utility. The paper anchors the modern antidepressant controversy and is a critical counterweight to older small positive trials.

Cited by wiki pages

  • The antidepressant controversy