Aripiprazole as an Adjunct to Atypical Antipsychotics for Weight Reduction and Improvement in Metabolic Profile
Condition: Antipsychotics Weight Gain
MeSH terms: Body Weight; Weight Gain; Weight Loss
Study type: Interventional
Phase: Phase 4

Summary: 
      This is an open label study to prospectively evaluate the effect of adjunct use of
      Aripiprazole, as an agent to improve metabolic profile and induce weight loss in patients
      established on atypical antipsychotics (Olanzapine, Clozapine and Risperidone).
    

Detailed description: 
      The metabolic syndrome (MetS) is a well described cluster of interrelated risk factors for
      developing cardiovascular disease and type 2 diabetes. The main components of MetS are
      central obesity, hypertension, hyperglycaemia and dyslipidaemia. Individuals with MetS are
      two to three times more likely to have a heart attack or stroke and five times more likely to
      develop type 2 diabetes than those without. Metabolic abnormalities have often been
      identified in individuals with schizophrenia. Since the introduction of second generation
      antipsychotics, evidence has accumulated of their link with metabolic abnormalities. An
      abnormality in glucose metabolism, particularly diabetes mellitus (DM), has received the most
      attention. Other conditions such as cardiovascular morbidity, abnormal lipid metabolism and
      obesity also have a serious impact on the physical health of individuals with schizophrenia.
      Several pharmacological strategies are under investigation for countering the metabolic side
      effects, of which antipsychotic Aripiprazole has shown good evidence, when switched to as
      monotherapy, and also as an adjunct .

      The study is planned as an open label study. An open label exploratory design will help test
      the hypothesis that use of adjunct Aripiprazole can help with reducing weight gain on
      atypical antipsychotics, and improve metabolic parameters. The number of patients in each arm
      is designed to yield an 80% power to detect significant differences in weight from baseline
      at P<0.05. There is no randomisation, blinding or placebo control, as this study is planned
      to test the initial hypothesis, which can inform further RCT's, if results are encouraging.

      Participants will initially be screened to ensure that they fulfil the inclusion criterion,
      and eligible participants will be entered into the 12 week study, where they will be
      prescribed 5 mg Aripiprazole per day, in addition to their routine atypical antipsychotic.
      The typical dose range of the routine atypical antipsychotics are clozapine 200-450 mg,
      olanzapine 5-20mg and risperidone 2-16mg respectively. During the 12 week study, the dose of
      the antipsychotic and Aripiprazole should stay unchanged. If the clinical situation warrants
      a change in dose of antipsychotic or switch of antipsychotic, the participant will be
      withdrawn from the study. Atypical antipsychotic other than the ones under investigation will
      be prohibited, as well as medications or supplements for weight loss or weight gain, or
      medications known to have substantial propensity for weight changes. Benzodiazepines,
      anticholinergics, sleep aides will generally be allowed. Antidepressants and mood stabilisers
      at a stable dose, which patients were receiving prior to the study, will be allowed. Patients
      at high risk of suicide or self-harm as assessed by the study investigator, will be withdrawn
      from the study, as well as those with significant side effects from adjunct Aripiprazole.

      The primary objective of the study is to assess mean change of weight from the baseline after
      use of adjunct Aripiprazole. The secondary endpoints include changes in metabolic parameters
      (waist circumference, fasting blood glucose, HbA1c, total, HDL and LDL cholesterol
      levels).Safety and tolerability will be measured by Simpson Angus Scale (SAS total score),
      Side Effects Checklist, Barnes Akathisia Scale (BAS), Abnormal Involuntary Movement Scale
      (AIMS), adverse events or serious adverse events reports.

      The study will also evaluate neurocognition via a brief battery of 2 tests - the digit
      sequencing and symbol coding. These 2 tasks have been shown in a previous study to explain
      76% of the variance of global neurocognition in a large sample of patients with
      schizophrenia. In our local sample, it was similarly shown that these 2 tasks are valid,
      representing 72% of the variance in global neurocognition in schizophrenia (unpublished
      results). The avoidance of a language component in these 2 tasks is a significant strength in
      choice of cognitive tasks as has been previously shown that the local population tend to
      underperform on language-based cognitive tasks.
    

Intervention name(s): Aripiprazole
Intervention type(s): Drug
Intervention description(s): Aripiprazole 5 mg every morning will be prescribed for 12 weeks
Intervention MeSH terms: Aripiprazole
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment