Investigation of Body Mass Index, Body Composition, Resting Energy Expenditure, Respiratory Quotient and Metabolic Changes Following a Switch From Olanzapine, Quetiapine or Risperidone to Aripiprazole

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.