Herbal medicine for antipsychotic-induced hyperprolactinemia in women with schizophrenia : a randomized controlled trial

Abstract

Schizophrenia is a complicated mental disorder that remains incurable. Current psychotic medications have limited therapeutic benefits, and the severe adverse drug reactions (ADRs) are obstacles to medication adherence. Hyperprolactinemia (hyperPRL) is one of the inevitable ADRs induced in psychotic medication treatments, and it introduces substantial health impacts. Previous studies have shown the potential of an herbal preparation called Peony-Glycyrrhiza Decoction (PGD) in treating antipsychotic-induced hyperPRL. This double-blind randomised placebo-controlled study aimed to re-evaluate the efficacy of PGD against antipsychotic-induced hyperPRL. Ninety-nine schizophrenic women who were under antipsychotic therapy and experiencing symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/day) for 16 weeks. The primary outcome was the changes in the total score of the Prolactin-Related Adverse Event Questionnaire (PRAEQ) from baseline to week 8 and week 16, while the secondary outcomes included the clinical improvement in hyperPRL symptoms, psychosis, abnormal involuntary movements measured using related instruments; and blood levels of prolactin (PRL), related pituitary and sex hormones, all measured at the same time points. Treatment outcomes were evaluated based on the intention-to-treat analysis. A linear mixed effects model was applied to compare the treatment outcomes over time between two groups. Bonferroni t-test was further used for multiple pairwise comparisons to detect between-group differences. Student t-test was used to compare continuous baseline variables, serum hormone levels between the two groups at each measured time point. Categorical data were examined using χ2 test. PGD treatment produced a significantly greater reduction of PRAEQ score at endpoint compared to placebo, but the severity of psychosis and abnormal involuntary movements was unchanged. The proportion of patients showing a clinically meaningful improvement in hyperPRL symptoms was markedly greater with PGD than placebo at week 8 (49.0% vs. 24.0%, P = 0.039). PGD-treated group had significantly lower free testosterone and higher follicle-stimulating hormone (FSH) levels than the placebo group at both post-treatment time points, but PRL levels were similar in the two groups. These results demonstrate again that PGD appear to be a safe and effective therapy for antipsychotic-related hyperPRL, without exacerbating psychosis and abnormal involuntary movements. Its anti-hyperPRL effect may be associated with the normalisation of related sex hormone dysfunction, rather than the direct suppression of elevated PRL. Nevertheless, taking into account of limitations including high discontinuation rate at endpoint, unclear relationships with different antipsychotic medications at various dosage, lack of global standard for PGD manufacture, and potential adverse effects of excessive liquorice consumption, caution should be taken when different PGD products are used in clinical practice.