Body Mass Index (BMI) and Metabolic Changes Following Switch to Aripiprazole From Olanzapine, Risperidone and Quetiapine
Condition: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Mood Disorders
MeSH terms: Schizophrenia; Psychotic Disorders; Mood Disorders
Study type: Observational

Summary: 
      Weight gain is a serious, common side effect of many antipsychotic medications. On average,
      the highest amounts of weight gain are found to occur in people taking clozaril and
      olanzapine, but with significant weight gain occuring in those on the other atypical
      antipsychotics as well.

      We, the researchers at the University of North Carolina, propose an open-label observational,
      pilot study of the changes in weight, BMI, body composition, and lipids, glucose, insulin and
      other metabolic parameters occurring in subjects as they switch from treatment with
      olanzapine, risperidone or quetiapine to aripiprazole. This medication switch will be
      determined prior to their entering this study by their treating psychiatrist. We also will
      determine resting energy expenditure (REE) and respiratory quotient (RQ) as measured by
      metabolic cart to determine if either energy expenditure or the propensity to store energy as
      fat may be involved in any changes to weight that are detected. Food intake, hunger, and
      physical activity will also be assessed.
    

Detailed description: 
      Weight gain is a serious, common side effect of many antipsychotic medications. It is a
      frequent cause of poor adherence to antipsychotic medications and a major contributor to
      medical problems including Syndrome X, various cancers, osteoarthritis and sleep apnea.
      Syndrome X, also called the Metabolic Syndrome, is a constellation of abnormalities of
      metabolism that confer a high risk of coronary heart disease. Syndrome X includes glucose
      intolerance, dyslipidemia, hypertension, and central obesity. Long-term patients on
      antipsychotic medications have markedly increased rates of Syndrome X that are consistent
      with increased cardiovascular morbidity and decreased life expectancy.

      A recent meta-analysis estimated weight gain at 10 weeks of treatment for a variety of
      antipsychotics and found that clozapine had the highest average weight gain (4.45 kg),
      followed by olanzapine (4.15 kg), quetiapine (2.2 kg), risperidone (2.18 kg), and ziprasidone
      (0.04 kg) . For some drugs weight gain continues over many months, with the time to plateau
      being directly related to the initial degree of weight gain. Early data for the most recently
      approved antipsychotic, aripiprazole, shows it to be weight neutral but the characteristics
      of its effects on weight are still to be determined. A recent publication of 224 subjects
      switching by three different switching strategies from haloperidol, thioridazine, risperidone
      or olanzapine to aripiprazole found weight loss of between 1.3 and 1.7 kg after 8 weeks on
      aripiprazole. Cholesterol levels improved in subjects switching from olanzapine to
      aripiprazole.

      Atypical antipsychotic medications that can improve the factors associated with Syndrome X
      could offer a very attractive alternative for patients who have already developed this
      constellation of symptoms during treatment with other antipsychotics. It is not known if a
      switch to aripiprazole from an atypical antipsychotic medication that has caused excessive
      weight gain and/or abnormalities of glucose, lipids or blood pressure will result in
      significant improvement in these factors or simply halt worsening. If worsening is only
      halted, then switch from a weight-inducing drug to aripiprazole should be done early. If
      factors associated with Syndrome X can be reversed, then switch to aripiprazole would be very
      beneficial even after abnormalities have developed.

      We propose an open-label pilot study of the changes in weight, BMI, body composition, and
      lipids, glucose, insulin and other metabolic parameters occurring in subjects as they switch
      from treatment with olanzapine, risperidone or quetiapine to aripiprazole. We also will
      determine resting energy expenditure (REE) and respiratory quotient (RQ) as measured by
      metabolic cart to determine if either energy expenditure or the propensity to store energy as
      fat may be involved in any changes to weight that are detected. Food intake, hunger, and
      physical activity will also be assessed.

      Recruited subjects will enter a screening phase where patient eligibility is determined
      through assessments of psychiatric and physical health, including physical examination, blood
      tests and urine drug screen. Subjects not meeting eligibility criteria will be discontinued.

      Thirty subjects will be enrolled into this open label study. At entry into the study,
      anthropometric measures (wt, ht, waist, hip), body composition, respiratory quotient (RQ),
      resting energy expenditure (REE), and measures of food intake, hunger, and physical activity
      will be assessed. Additionally, the Positive and Negative Symptom Scale (PANSS) will be used
      to assess clinical status and all women will have a blood pregnancy test as required prior to
      having a DXA scan. Following completion of these assessments, subjects will begin a two week
      cross-taper from their current antipsychotic to aripiprazole. Psychiatric symptoms, weight,
      medical status and medication query will be reassessed after 2, 4, 8 and 12 weeks. RQ and
      hunger will be reassessed at the 4 week time point. Fasting bloodwork, pregnancy test, urine
      drug screen, vital signs, and all baseline assessments will be repeated at the 12 week time
      point or at early termination. During the study, dosage of aripiprazole will be tailored to
      each subject's need based on symptoms and side effects, and will remain at or below the
      maximum recommended dosage.
    

Intervention name(s): Aripiprazole
Intervention type(s): Drug
Other intervention name(s): Abilify
Intervention MeSH terms: Aripiprazole
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Psychiatry outpatient clinic
      
Biospecimen description: 
      serum collected at baseline and end of study to be assayed in the future for related
      metabolic tests which are not specified at this time.
    
Keywords: schizophrenia; BMI; weight; aripiprazole; antipsychotic; Mood Disorders with psychotic features