Review of: Zheng W et al, General Psychiatry 2019;32(5):e100091

Antipsychotic-induced hyperprolactinemia is a common adverse reaction contributing to treatment non-adherence. Male patients are embarrassed by the resulting breast enlargement, and female patients experience amenorrhea, infertility, and reduced bone density. We can bring prolactin levels down by decreasing the antipsychotic dose, switching to a different antipsychotic, or adding a dopamine agonist (eg, cabergoline), but these interventions put patients at risk of relapse.

Most antipsychotic medications cause hyperprolactinemia, though the risk is higher with first-generation agents and risperidone. Aripiprazole was the first antipsychotic approved with partial dopamine agonist activity, which may underlie its tendency to reduce, rather than raise, prolactin. Numerous case reports have found that adjunctive aripiprazole use reduces prolactin levels in antipsychotic-treated patients.

The authors conducted a meta-analysis of randomized controlled trials of patients with first-episode schizophrenia who received risperidone, olanzapine, or amisulpride (not approved as an antipsychotic in the US) with either adjunctive aripiprazole or placebo, and they compared patients’ serum prolactin levels. The final analysis included five randomized controlled trials with a total of 400 patients and a mean treatment duration of 11 weeks. A secondary outcome focused on improvement in psychosis as measured with the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS). The mean dose of aripiprazole was 7.5 mg/day (range 2.5–10 mg/day) in the four studies that included dosage.

Prolactin levels in patients receiving aripiprazole in addition to an antipsychotic were significantly lower, with a mean difference of 50 ng/mL. An additional benefit was that patients taking adjunctive aripiprazole experienced significant improvement in PANSS negative symptoms, though not in positive symptoms. The rate of side effects, including extrapyramidal side effects (EPS), in the patients on adjunctive aripiprazole was no higher than in the patients receiving placebo.

CHPR’s Take
Addition of a small to moderate dose of aripiprazole significantly lowers prolactin levels in patients with antipsychotic-induced hyperprolactinemia, without contributing to side effects including EPS. An added benefit is that negative symptoms may improve with this intervention. It remains to be seen if other newer antipsychotics with partial agonism activity (eg, brexpiprazole, cariprazine, lumateperone) will show similar effects.