Berberine as Adjuvant Treatment for Schizophrenia Patients
Condition: Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Metabolic Syndrome x
MeSH terms: Metabolic Syndrome; Syndrome; Schizophrenia; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      One double-blind, randomized, placebo-controlled trial is designed to examine whether
      berberine added to current antipsychotic drugs could produce significantly greater efficacy
      in reducing atypical antipsychotic-induced metabolic syndrome. To achieve this objective, 120
      patients with schizophrenia spectrum disorders (SSD) who have developed metabolic syndrome
      will be recruited and randomly assigned to receive additional treatment with placebo (n = 60)
      or berberine (n = 60, 0.6 g/day, 0.3 g, b.i.d.) for 12 weeks. The primary outcome is changes
      in net weight gain; other outcomes include body mass index (BMI), waist circumference (WC),
      blood pressure, triglycerides (TG), total cholesterol, high-density lipoprotein (HDL), and
      low-density lipoprotein (LDL), fasting glucose, glycated haemoglobin (HbA1c).
    

Detailed description: 
      Schizophrenia is a severe mental illness that affects about 1% of the worldwide population.
      Most patients develop a chronic course with frequent relapses and exacerbation of symptoms
      and required to have long-term treatment. Although antipsychotic therapy is the mainstay of
      the management of schizophrenia, the treatment outcomes are often unsatisfactory, largely due
      to adverse drug reactions. Metabolic syndrome is a highly prevalent side effect incurred in
      antipsychotic therapy, with a prevalence of 35% in patients with severe mental illness in
      Hong Kong. No effective therapies are available in treating antipsychotic-induced metabolic
      syndrome, although some antidiabetic medications may have limited benefits in controlling
      weight gain and increased glucose level.

      Berberine is a natural plant alkaloid isolated from the Chinese herb, Coptis chinensis
      (Huang-Lian), which is traditionally used for diarrhea caused by bacterial and viral
      infections in clinical practice. Several lines of evidence suggest that berberine has body
      weight-lowering, anti-diabetic, and anti-hyperlipidemic effects. One recent study has further
      shown that the addition of berberine significantly prevented olanzapine (OLZ)-Induced weight
      gain in rats and modulated the expression of multiple key genes that control energy
      expenditure.

      In addition to the peripheral effects, berberine also broadly modulates brain biogenic amines
      and related receptors that are involved in the pathogenesis of antipsychotic-induced
      metabolic syndrome. This suggests that it may be suitable for the treatment of
      antipsychotic-induced metabolic disturbance.

      Over the past decade, a number of studies have demonstrated comparable efficacy of berberine
      as mono- and combination therapy in reducing metabolic symptoms, without serious side effect.
      The efficacy of berberine also has been well confirmed in patients with gastrointestinal,
      liver, heart, and ovary disease as well as in renal-transplant recipients and healthy
      volunteers. It is well tolerated and only minor digestive reactions were observed, mainly
      nausea, diarrhea, constipation, abdominal distension and pain.

      The results obtained from the clinical and animal studies of the group strongly suggest the
      promising effects of berberine against OLZ-induced weight gain, without changing
      pharmacokinetic and pharmacodynamics profile of OLZ at peripheral and central levels. This
      warrants further evaluation in a larger randomized controlled trial.

      The working hypothesis of the proposed study is that berberine as an adjuvant can control
      weight gain and other metabolic symptoms associated with antipsychotic therapy. To test this
      hypothesis, a 12-week, double-blind, randomized, placebo-controlled trial will be conducted
      in patients with schizophrenia spectrum disorders (SSD) to determine whether berberine
      adjunctive treatment could limit weight gain and improve other anthropometric and metabolic
      measures in patients with SSD who have developed metabolic syndrome.
    

Intervention name(s): Berberine; Placebos; Antipsychotic Agents
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Berberine tablets, 0.3g every time, two times daily; Placebo tablets, 0.3g every time, two times daily; Antipsychotic agents prescribed at the discretion of the patients' psychiatrists with respect to patients' conditions. Concomitant use of other psychotropic drugs, including antidepressants, anxiolytics, and mood stabilizers for mood disorders, benzodiazepines and non-benzodiazepines for insomnia, and anticholinergics for extrapyramidal symptoms, was allowed as usual. For those who were under anti-hyperlipidemic, antihypertensive and anti-diabetic treatment, they were allowed to continue their current medications throughout the study.
Other intervention name(s): Placebo
Intervention MeSH terms: Antipsychotic Agents
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Berberine; Metabolic Syndrome; Chinese medicine; Herbal medicine