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evident
Original paper
2007NEJMPsychiatry

STEP-BD

Effectiveness of adjunctive antidepressant treatment for bipolar depression

RCTBipolar depression

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Overview

Adjunctive antidepressants did not improve durable recovery in bipolar depression versus mood stabilizer plus placebo, and switch rates were similar.

Clinical takeaway

Adding a standard antidepressant to a mood stabilizer did not increase durable recovery and did not increase treatment-emergent affective switch compared with a mood stabilizer plus placebo.

Key result

Durable recovery occurred in 42 of 179 (23.5%) with adjunctive antidepressant vs 51 of 187 (27.3%) with placebo (P=0.40).

Practice impact

Do not add an antidepressant to a mood stabilizer expecting a durable-recovery benefit in bipolar depression.

Evidence

Study design

Double-blind, placebo-controlled trial randomly assigning subjects with bipolar depression to up to 26 weeks of a mood stabilizer plus adjunctive antidepressant or a mood stabilizer plus matching placebo.

Enrollment

366

Follow-up

Up to 26 weeks of treatment.

Geography

Not listed

Clinical question

Does adjunctive antidepressant therapy reduce symptoms of bipolar depression without increasing the risk of mania?

Population

  • Subjects with bipolar depression treated under conditions generalizable to routine clinical care.

Intervention

Mood stabilizer plus adjunctive standard antidepressant therapy for up to 26 weeks.

Comparator

Mood stabilizer plus matching placebo.

Primary outcome

Percentage of subjects meeting the criterion for a durable recovery (8 consecutive weeks of euthymia).

Durable recovery occurred in 42 of 179 (23.5%) with a mood stabilizer plus adjunctive antidepressant vs 51 of 187 (27.3%) with a mood stabilizer plus placebo (P=0.40).

p=0.40

Key results

  • Durable recovery: 42 of 179 (23.5%) with a mood stabilizer plus adjunctive antidepressant vs 51 of 187 (27.3%) with a mood stabilizer plus matching placebo (P=0.40).
  • Modest nonsignificant trends favoring mood stabilizer plus placebo were observed across secondary effectiveness outcomes.
  • Rates of treatment-emergent affective switch (mania or hypomania early in treatment) were similar in the two groups.

Harms

  • Rates of treatment-emergent affective switch were similar in the two groups; the abstract does not report numeric switch rates.

Clinical Use

Practice impact

  • Do not add a standard antidepressant to a mood stabilizer for bipolar depression expecting more durable recovery than a mood stabilizer alone.

Applicability

  • Most applicable to patients with bipolar depression treated with a mood stabilizer plus antidepressant or placebo for up to 26 weeks under conditions generalizable to routine care.

Limitations

  • The abstract does not name the antidepressants or mood stabilizers used.
  • The authors note that longer-term outcome studies are needed to fully assess benefits and risks.
  • No confidence interval is reported for the primary comparison.

Common misinterpretations

  • This is a negative efficacy trial, not evidence that antidepressants cause more mania here; switch rates were similar.
  • Do not read the modest secondary trends as a benefit of placebo or a harm of antidepressants; the abstract calls them nonsignificant.

Related evidence

STAR*D - Context

Citation

Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):1711-1722. doi:10.1056/NEJMoa064135

The use of adjunctive, standard antidepressant medication, as compared with the use of mood stabilizers, was not associated with increased efficacy or with increased risk of treatment-emergent affective switch.