Weight gain is a well-known side effect of many medical treatments for psychiatric illness, including antipsychotics, antidepressants, and mood stabilizers.1 The amount of and mechanisms for weight gain differ in the various drug classes, but in general weight gain generates substantial concern.
Efforts to understand and manage treatment-associated weight gain stem from its association with medication noncompliance and discontinuation,2 as well as clinically relevant health outcomes associated with excess weight and obesity.3 Research has focused particularly on the atypical antipsychotics, often prescribed to individuals with schizophrenia or treatment-resistant depression. These patients appear to have a higher propensity for poor health outcomes, and the severity of their conditions may make weight management difficult. Yet the weight gain associated with the atypicals tends to be greater than for other psychiatric drugs.
Weight gain associated with antipsychotics varies substantially, depending on the study and the particular medication. In a commonly cited meta-analysis of 81 studies examining weight gain after ten weeks of antipsychotic treatment, the greatest weight gain was observed with olanzapine and clozapine (greater than 3 kg) and the least with ziprasidone, fluphenazine, and haloperidol (0 to 1 kg).4 In general, there appears to be an initial surge in weight gain with a plateau later.
Medication Noncompliance Issues
Research on schizophrenia demonstrates the importance of medication and treatment compliance for preventing unnecessary hospitalizations and relapses. There is good evidence that medication nonadherence clearly is associated with higher service use and costs.5 Because older antipsychotics are more likely to cause movement disorders, often leading patients to discontinue the medications, many prescribers have turned to using the atypicals. Thus, there is an incentive to mitigate the weight gain associated with the atypicals, as increasing weight also might lead some patients to discontinue the medications. A similar argument can be made for other psychotropics with significant benefits but associated with weight gain.
Mortality and Weight Gain
In addition, poor health is common among psychiatric patients.6 People with schizophrenia have a dramatically shorter lifespan than the general population,7,8 and rates of a number of chronic physical illnesses are higher in people with schizophrenia than in the general population.3 This population's higher-than-average suicide rates and poor lifestyle choices may contribute to this disparity.
This increased mortality rate likely also can be attributed to medically induced cardiovascular disease. In other words, the very medications highly effective in addressing schizophrenia's psychotic symptoms are strongly tied to weight gain and increased glucose intolerance, possibly leading to increased rates of cardiovascular disease and premature death. Some evidence even suggests that patients with schizophrenia might have a higher baseline risk of obesity and some of its concomitant effects,3 playing strong roles in cardiovascular disease and diabetes.
Therefore, the weight gain sometimes observed among individuals being treated for schizophrenia and other psychiatric conditions likely reflects a combination of medication effects, genetic predisposition, and lifestyle factors.
Promoting Weight Loss
Atypicals hold substantial promise for improving the lives of people with schizophrenia, but the association with weight gain is a reason for concern.
Little evidence exists on the role of behavioral interventions to improve health outcomes and increase treatment adherence in mentally ill patients with medically associated weight gain. Symptoms of psychiatric conditions may decrease motivation and the ability to independently pursue and adhere to exercise and diet regimens that may be effective in countering weight gain associated with medical treatment.9 Nonetheless, clinicians are recommended to advise behavioral interventions related to nutrition, diet, and exercise, as well as carefully monitor weight changes, especially in the period immediately following medication treatment initiation.3
National Institute of Health guidelines for weight management and reduction in the general population include modifications in diet, behavior, and physical activity.10 Yet motivating individuals to begin and maintain a lifestyle change is difficult, even in the absence of concomitant psychiatric and medical conditions.
In one of the few studies on behavioral weight management in the mentally ill population, Menza et al studied the potential for a multimodal weight control program to be effective in a small population undergoing treatment for schizophrenia or schizoaffective disorder.11 Participants achieved significant benefits in outcomes, including weight, body mass index (BMI), hemoglobin A1c levels, and blood pressure.