Adjunctive Aripiprazole, Olanzapine, or Quetiapine for Major Depressive Disorder: An Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed

Abstract

Objective: To describe the efficacy and safety of adjunctive aripiprazole, olanzapine, and quetiapine for major depressive disorder. Data sources: Published registration study reports, supplemented by clinical trial synopses as disclosed by manufacturers and product labeling. Study selection: All available reports of studies were identified. Data extraction: Descriptions of the principal results and calculation of number needed to treat (NNT) for response and remission and number needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated. Data synthesis: Three registration studies of adjunctive aripiprazole, 5 for olanzapine-fluoxetine combination, and 2 for quetiapine extended-release reveal NNT for response and remission to range from 7 to 14 and 7 to 13, respectively, for adjunctive antipsychotic versus antidepressant monotherapy, depending on the antipsychotic and/or dose. Adverse event profiles for the 3 different adjunctive antipsychotics are more diverse, with adjunctive aripiprazole more strongly associated with akathisia (NNH, 6), adjunctive olanzapine with weight gain (NNH, 3), and adjunctive quetiapine with somnolence (NNH, 5 for 300 mg/d and NNH, 6 for 150 mg/d). Conclusions: Number needed to treat and NNH can be used to quantify efficacy and tolerability outcomes and help place various therapeutic options into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and the patient the trade-offs between obtaining potential benefits versus harms. In the case of the adjunctive second-generation antipsychotics approved for treating major depressive disorder, these trade-offs vary greatly among the choices available and require careful, individualized, patient-centered clinical decision making.

Keywords:

• antipsychotic
• aripiprazole
• clinical trials
• major depressive disorder
• likelihood to be helped or harmed
• number needed to harm
• number needed to treat
• olanzapine
• quetiapine