Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial

J Clin Psychopharmacol. 2018 Aug;38(4):317-326. doi: 10.1097/JCP.0000000000000898.


Purpose/background: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes.

Methods/procedures: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored.

Findings/results: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain.

Implications/conclusions: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amenorrhea / chemically induced
  • Amenorrhea / prevention & control
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Aripiprazole / administration & dosage
  • Aripiprazole / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination / methods*
  • Female
  • Galactorrhea / chemically induced
  • Galactorrhea / prevention & control
  • Humans
  • Medication Adherence
  • Oligomenorrhea / chemically induced
  • Oligomenorrhea / prevention & control
  • Premenopause / drug effects*
  • Prolactin / blood*
  • Psychotic Disorders / drug therapy*
  • Quality of Life


  • Antipsychotic Agents
  • Aripiprazole
  • Prolactin