The effects of antipsychotic-related weight gain have both medical and psychiatric components. In particular, medication compliance is adversely affected by excessive weight gain, with weight gain being a wellknown cause of treatment nonadherence (Bernstein 1988; Silverstone et al. 1988) and subsequent psychotic relapse (Rockwell et al. 1983).

During the 2000 American Psychiatric Association meeting, investigators at the Columbia­St. Luke’s Obesity Research Center released survey data examining this link between obesity and antipsychotic medication compliance. They found that obese patients were 13 times as likely to request discontinuation of their current antipsychotic agent because of concerns about weight gain and 3 times as likely to be noncompliant with treatment compared with nonobese individuals (Weiden et al. 2000). Patients who gain weight on antipsychotics also utilize health care resources more than patients who do not experience weight gain (Allison and Mackell 2000).

The first step in the battle against obesity and novel antipsychotic medication­associated weight gain is to appreciate the severity of this ubiquitous problem. Much as clinicians became aware of tardive dyskinesia as a long-term extrapyramidal side effect related to conventional antipsychotic therapy, there is increasing concern among mental health professionals about the long-term impact of weight gain. The initial choice of antipsychotic agent appears to play a significant role in the development of weight gain.

Moreover, the concomitant use of other agents associated with weight gain, such as lithium or valproate, has been demonstrated to increase weight gain at 1 year to 16 pounds in risperidone-treated inpatients and over 27 pounds in olanzapine-treated inpatients (Meyer 2002). A new antipsychotic that came to the United States market in the last quarter of 2002, aripiprazole, looks promising in terms of its weight gain profile (Petrie et al. 1997), adding another medication to the armamentarium of novel antipsychotic agents with low propensity for weight gain. In this age of second-generation antipsychotic medications, we need to routinely ask patients if they notice a change in their waist size or increased appetite, and intervene early, when weight gain is modest (i.e., 5 pounds).

Prevention in this case may be the greatest cure. Physicians should routinely measure weight at each visit, and BMI should be recorded. The National Heart, Lung and Blood Institute (NHLBI) has posted a useful, free BMI calculator for Palm operating system­based PDAs on its Web site (hin.nhlbi.nih.gov/bmi_palm.htm). An even more important predictor of diabetes and the dysmetabolic syndrome (also known as syndrome X, a quartet of symptoms including hypertriglyceridemia, diabetes, hypertension, and abdominal obesity) (Groop and Orho-Melander 2001) is waist circumference, a reflection of visceral adiposity (Park et al. 2001).

Central adiposity is more highly associated with diabetes, the dysmetabolic syndrome, and subsequent increased risk of coronary artery disease. A waist circumference of 40 inches in males and 35 inches in females should prompt referral for more thorough health screening of lipids, glucose, and blood pressure. These combined medical consequences of obesity may thus offset to some extent the benefit gained from the antipsychotic agent’s life-saving potential (Fontaine et al. 2001). Patients with schizophrenia should be given nutritional counseling and recommendations for an exercise regimen, given their propensity for poor dietary habits and sedentary lifestyle. Primary care practitioners, family members, and other caregivers should be alerted to the risk of obesity during treatment with certain novel antipsychotics, as the potential complications of weight gain in patients with schizophrenia can be serious.

It is also essential that patients be educated regarding the weight gain liability of their antipsychotic medication to minimize the risks of obesity and its related health consequences. Multiple cases of new-onset diabetes (Wirshing et al. 2001a), hyperlipidemia (Meyer 2001; Wirshing et al. 2001b), and sleep apnea have been reported as potentially associated with antipsychotic-related weight gain (Furst et al. 2002), although there may also be effects of certain novel antipsychotics on glucose tolerance and lipids independent of their effects on weight. (Monitoring recommendations for serum lipids and blood glucose are discussed in Chapter 4 and Chapter 6, respectively, in this volume.)

Donna A. Wirshing, M.D.
Jonathan M. Meyer, M.D.

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