The Utility of Low-Dose Aripiprazole for the Treatment of Bipolar II and Bipolar NOS Depression

J Clin Psychopharmacol. 2017 Feb;37(1):99-101. doi: 10.1097/JCP.0000000000000636.


Background: Despite initial reports of efficacy in bipolar depression, multicenter trials did not show aripiprazole to be better than placebo, possibly because the doses used were too high, leading to lower efficacy and high dropout rates. This study evaluated the effects of low-dose aripiprazole. Extensive clinical experience has suggested that doses beyond 5 mg are rarely efficacious.

Methods: Data were gathered from patients with bipolar II or bipolar not otherwise specified depression using a retrospective chart review. Efficacy was assessed with the Clinical Global Impression-Improvement score. Patients who had at least 2 trials of aripiprazole were included in a retrospective off-on-off-on experimental design. All patients were on other medications when aripiprazole was started. Patients were treated with doses of 1 to 5 mg.

Findings: On average, patients were rated improved or very much improved compared with baseline. Sixteen of 211 patients worsened or experienced no change. Forty-four patients (21%) discontinued due to adverse effects. The group of patients who underwent off-on-off-on trials experienced statistically significant improvement when they started and restarted aripiprazole, and statistically significant worsening when they discontinued it.

Conclusions: When treating bipolar II or bipolar not otherwise specified depression, low doses of aripiprazole, 5 mg or less, may be more effective and better tolerated than higher ones. Clinicians should start treatment with a very low dose and give patients time to respond.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / pharmacology*
  • Aripiprazole / administration & dosage*
  • Aripiprazole / pharmacology*
  • Bipolar Disorder / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Young Adult


  • Antipsychotic Agents
  • Aripiprazole