Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial

Am J Psychiatry. 2007 Sep;164(9):1404-10. doi: 10.1176/appi.ajp.2007.06071075.


Objective: Hyperprolactinemia and associated side effects often occur with antipsychotics. The authors investigated the effect of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in patients with schizophrenia maintained with haloperidol.

Method: Fifty-six patients with hyperprolactinemia taking haloperidol were enrolled. Haloperidol dose was fixed; aripiprazole was dosed at 15 mg/day for the first 4 weeks, then 30 mg/day for the following 4 weeks. Serum prolactin, haloperidol, and aripiprazole levels were measured. Symptoms and side effects were assessed with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms, Clinical Global Impression symptom scale, Simpson-Angus Rating Scale, and Barnes Akathisia Rating Scale at weeks 1, 2, 4, 6, and 8.

Results: Prolactin levels of patients receiving aripiprazole significantly decreased over time, demonstrating a significant time effect and a time-by-group interaction. In the aripiprazole group, 88.5% of patients at week 8 had prolactin levels normalize compared to 3.6% of patients receiving placebo. Among 11 female patients with menstrual disturbances randomly assigned to aripiprazole, seven patients regained menstruation during the study, whereas none receiving placebo did. Plasma levels of haloperidol were not significantly altered. No significant time effect and time-by-group interactions on BPRS, Scale for the Assessment of Negative Symptoms, and Simpson-Angus Rating Scale scores were noted.

Conclusions: Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D(2) receptors than haloperidol, which is the likely cause of this observation.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use*
  • Aripiprazole
  • Brief Psychiatric Rating Scale
  • Dopamine Antagonists / adverse effects
  • Dopamine Antagonists / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Haloperidol / adverse effects
  • Haloperidol / therapeutic use
  • Humans
  • Hyperprolactinemia / chemically induced*
  • Hyperprolactinemia / drug therapy*
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Placebos
  • Quinolones / therapeutic use*
  • Receptors, Dopamine D2 / agonists
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology
  • Sex Factors
  • Treatment Outcome


  • Antipsychotic Agents
  • Dopamine Antagonists
  • Piperazines
  • Placebos
  • Quinolones
  • Receptors, Dopamine D2
  • Aripiprazole
  • Haloperidol