Safety and Efficacy of High-Dose Vitamin B6 as an Adjunctive Treatment for Antipsychotic-Induced Hyperprolactinemia in Male Patients With Treatment-Resistant Schizophrenia

Abstract

This study aimed to investigate the safety and efficacy of high-dose vitamin B6 (vB6) as an adjunct treatment for antipsychotic-induced hyperprolactinemia (AIHP) in male patients with treatment-resistant schizophrenia (TRS). In this randomized double-blinded controlled study, patients were randomized (1:1) into a control group given aripiprazole (ARI; 10 mg/day; n = 100) or an intervention group given vB6 (300 mg/12 h for 16 weeks; n = 100). Prolactin levels, psychotic symptoms [Positive and Negative Syndrome Scale (PANSS)], cognitive function [MATRICS Consensus Cognitive Battery (MCCB)], liver function, kidney function, growth hormone level, micronutrient levels, blood lipids, and adverse secondary effects (ASEs)[Treatment Emergent Symptom Scale (TESS) and Barnes-Akathisia scale] were monitored. After a 16-week treatment period, the vB6 group showed a 68.1% reduction in serum prolactin levels (from 95.52 ± 6.30 μg/L to 30.43 ± 18.65 μg/L) while the ARI group showed only a 37.4% reduction (from 89.07 ± 3.59 μg/L to 55.78 ± 7.39 μg/L). During weeks 1–4, both treatments reduced prolactin similarly. Subsequently, the ARI effect plateaued, while the vB6 effect remained robust. The vB6 group showed better alleviation of psychotic symptoms and cognitive impairment. No serious ASEs were observed; ASEs were more frequent in the ARI group. AIHP reduction efficacy of vB6 was associated with baseline prolactin and triglyceride levels, total vB6 dosage, and education level. In conclusion, compared with the ARI group, TRS patients given vB6 showed better attenuation of AIHP, lower ASE scores, and greater improvements in clinical symptoms and cognitive impairments. These results support further consideration of vB6 as a putative treatment for AIHP.Trial Registration: ChiCTR1800014755

Pharmacological treatment strategies for antipsychotic-induced hyperprolactinemia: a systematic review and network meta-analysis

“…Due to the inconsistent curative effect and considering the adverse effect of high-dose vitamin B6, few studies were conducted to evaluate the potential efficacy. However, vitamin B6 is supposed that it works by promoting dopamine production and then activates dopamine receptors to reduce the secretion of pituitary prolactin [ 51 ], and the side-effects of high-dose vitamin B6 are fewer than expected [ 52 ], re-attempts of it are conducted recently and the results indicated that it could improve the AP-induced HPRL with few side-effects [ 30 , 53 ]. In our study, the results of NMA showed that this option might be a very effective method for the patients with AP-induced HPRL and provide a moderate certainly evidence.…”

“…In our study, the results of NMA showed that this option might be a very effective method for the patients with AP-induced HPRL and provide a moderate certainly evidence. However, there was only one study about it, this moderate evidence needed to be further researched in the future [ 30 ].…”

“…Several pharmacological strategies that can improve the AP-induced HPRL, such as adding adjunctive aripiprazole (ARI) [ 9 – 11 ], switching to another antipsychotic (e.g., ARI, quetiapine, olanzapine, clozapine, blonanserin, and brexpiprazole) [ 12 – 20 ], adding dopamine agonists (DA, e.g., cabergoline, bromocriptine) [ 21 – 23 ], adding metformin (MET) [ 24 ], or adding the Peony-Glycyrrhiza decoction (PGD) and other traditional herb treatments [ 25 – 29 ]. One recent study also suggested a potential option for adjunctive high-dose vitamin B6 [ 30 ]. The most important issue associated with those strategies is the risk of worsening psychopathology of psychosis, which is particularly high in the strategies of switching to another antipsychotic or adding dopamine agonist [ 31 ].…”