Berberine for the management of antipsychotic-associated metabolic syndrome in patients with chronic schizophrenia : a literature review and a randomised controlled trial

Abstract

Schizophrenia spectrum disorders (SSDs) are a cluster of psychiatric disorders that often require to have a prolonged treatment. Treatment with antipsychotics is extensively applied for SSDs, but weight gain and metabolic syndrome (MetS) are often seen in atypical antipsychotic therapy. Berberine, a low-cost and over-the-counter (OTC) drug, may have potential in controlling weight gain and MetS. The aim of this double-blind, randomised, placebo-controlled trial was to study the efficacy and safety of berberine as an adjuvant in dealing with antipsychotic-associated weight gain and MetS.

A total of 113 subjects with SSDs and MetS developed were randomly allocated to the berberine (600 mg/day, n=58) or placebo (n=55) groups in a 1:1 ratio for 12 weeks. Net weight gain from baseline was studied as the primary outcome. Secondary outcomes included waist circumference (WC), body mass index (BMI), blood pressure (BP), serum glucose and lipid profiles, changes in psychotic symptoms by Positive and Negative Syndrome Scale (PANSS), and changes in antipsychotic-induced movement symptoms by the abbreviated version of Extrapyramidal Symptom Rating Scale (ESRS-A).

Study outcomes were evaluated on the basis of the intention-to-treat analysis. A linear mixed-effect model was employed in order to examine the primary and secondary outcomes over time between the two groups: change in weight gain, BMI and WC from baseline, BP, biochemical variables, and PANSS scores. Wilcoxon rank-sum test was applied to detect significance in the ESRS-A scores. Continuous baseline variables were compared by Student t-test. Categorical baseline variables and incidence of adverse events were examined using Chi-square (2) test or Fisher exact test.

The berberine group showed a significantly greater reduction in weight gain, compared with the placebo group, at 9 weeks (treatment difference=-0.75 kg, 95% CI=-1.42, -0.07, p=0.031) and 12 weeks (treatment difference=-1.08 kg, 95% CI=-1.76, -0.40, p=0.002). Patients receiving berberine also showed statistically significant improvements in endpoint in BMI (treatment difference=-0.41 kg/m2, 95% CI=-0.65, -0.17, p=0.001), diastolic BP (treatment difference=-3.47 mmHg, 95% CI=-6.36, -0.59, p=0.019), total cholesterol (treatment difference=-0.58 mmol/L, 95% CI=-0.74, -0.41, p<0.0001), low-density lipoprotein (LDL: treatment difference=-0.52 mmol/L, 95% CI=-0.68, -0.35 p<0.0001), and glycated haemoglobin (HbA1c: treatment difference=-0.09%, 95% CI=-0.18, -0.00, p=0.050). The severity of psychotic and movement symptoms was unchanged in the two groups over the course of the treatment. The berberine-treated group had less incidence of drowsiness than the placebo group (19.0% versus 41.8%, p=0.008), while no serious adverse events were reported.

These findings suggest that berberine appears to be an effective and safe therapy for antipsychotic-associated weight gain and MetS, without exacerbating psychotic and movement symptoms and generating adverse side effects. Berberine owns the potential to serve as an adjuvant to control antipsychotic-associated weight gain and MetS.