REVIEW OF: Zhuo C et al, Front Psychiatry 2021;12:681418

STUDY TYPE: Randomized, double-blind trial with an active control

Hyperprolactinemia, a common problem on antipsychotics, can cause multiple issues, including sexual dysfunction and gynecomastia. It is a particular problem in treatment-resistant schizophrenia (TRS), as these patients often need higher antipsychotic doses that are more likely to elevate prolactin. Dopamine agonists like bromocriptine can reverse the effect, as can low doses of the dopamine partial agonist aripiprazole (that’s right, this antipsychotic actually treats hyperprolactinemia)—but beyond that, there is limited evidence for other treatment options. Vitamin B6 showed potential in earlier research, and this study tested that treatment in a large controlled trial.

This trial, run in China, tested high-dose vitamin B6 against an active control (low-dose aripiprazole) in 200 men ages 20–40 with TRS and hyperprolactinemia. Patients received either aripiprazole 5 mg twice daily or vitamin B6 300 mg twice daily, in addition to their current antipsychotic, for 16 weeks. Hyperprolactinemia was defined as a prolactin level > 25 µg/L, the usual cutoff for this diagnosis. Prolactin levels, psychotic symptoms, and cognition were assessed at baseline and every four weeks after study initiation. A total of 97% of subjects finished the trial.

Patients randomized to vitamin B6 were much younger, had higher levels of education, and had significantly higher prolactin levels at baseline (95.5 vs 89.1 µg/L) than the aripiprazole group. After 16 weeks, the vitamin B6 group showed a greater reduction in prolactin levels compared to the aripiprazole group (68.1% vs 37.4%). Both groups showed steep reductions in prolactin levels from baseline to week four, but the efficacy of aripiprazole plateaued after week eight, whereas vitamin B6 further reduced prolactin levels through week 16. Also, after 16 weeks, the vitamin B6 group showed a greater reduction in psychotic symptoms (17.8% vs 12.0%) and improvement in cognition (10% vs -5.4%) compared with the aripiprazole group, respectively. Vitamin B6 was well tolerated, with fewer side effects than in the aripiprazole group. Vitamin B6 also had favorable metabolic effects, as it did not increase blood glucose or lipids.

Limitations of the study include the fact that all subjects were male and had TRS. Therefore, the generalizability of findings to other patients and phases of illness is limited.

TCPR’S TAKE
Vitamin B6 may be a viable treatment option for antipsychotic-induced hyperprolactinemia, at least in TRS.