Effect of Brexpiprazole on Prolactin: An Analysis of Short- and Long-Term Studies in Schizophrenia

BACKGROUND: Hyperprolactinemia is an undesirable effect of most antipsychotics because of D(2)-receptor blockade. We assessed the effect of the D(2)-receptor partial agonist brexpiprazole on prolactin, based on pooled data from three 6-week, randomized, placebo-controlled studies and two open-label extension studies in patients with schizophrenia. METHODS: In the short-term studies, patients received 0.25, 1, 2, 4 mg brexpiprazole or placebo; or flexible-dose brexpiprazole (2–4 mg/d), placebo, or active reference. The extension studies were 52-week, flexible-dose (1–4 mg/d) studies. We studied changes from baseline and shifts in prolactin status in patients with normal or elevated prolactin levels at baseline, and prolactin-related treatment-emergent adverse events (TEAEs). RESULTS: Median changes from baseline to week 6 in brexpiprazole-treated patients in short-term studies were as follows: 3.63 ng/mL (females), 0.26 ng/mL (males); placebo: −2.15 ng/mL (females), −1.08 ng/mL (males). Median changes from baseline to week 52 in long-term studies were 0.60 ng/mL (females) and 0.18 ng/mL (males). Prolactin levels in patients with baseline values greater than 1× upper limit of normal tended to decrease over time regardless of previous treatment. The proportions of brexpiprazole-treated patients with greater than 3× upper limit of normal postbaseline prolactin values in short-term studies were as follows: 1.5% (females), 1.6% (males); placebo: 3.6% (females), 3.4% (males). Corresponding figures in long-term studies were 5.3% (females) and 2.0% (males). In short-term studies, the incidence of prolactin-related TEAEs was 1.8% for brexpiprazole and 0.6% for placebo. In long-term studies, the incidence of prolactin-related TEAEs was 1.7%. CONCLUSIONS: Small changes in prolactin levels, low proportions of patients with postbaseline elevated prolactin values, and low incidence of prolactin-related TEAEs were observed after treatment with brexpiprazole.