Weight Gain Associated with Antipsychotic Drugs

Rohan Ganguli Weight Gain Associated With Antipsychotic Drugs Rohan Ganguli, M.D. © CopyrightWeight gain has been 2000 reported Physicians with nearly every antipsychotic Postgraduate drug on the market Press, (molindone Inc.is an exception). Weight gain occurs no matter what the patient’s age, sex, or race and is seen with both oral and depot drug formulations. Numerous studies have found that patients gain weight when treated with a conventional antipsychotic, such as chlorpromazine, fluphenazine, and haloperidol. The newer, novel antipsychotics offer advantages over conventional antipsychotics, especially a relative lack of extrapyramidal symptoms, but some still have the disadvantage of causing weight gain. Clozapine and olanzapine in particular appear to cause substantial weight gain, much more so than do most conventional neuroleptics and novel agents such as risperidone. Given the risks to health and treatment com- pliance associated with weight gain and obesity, clinicians should monitor weight during the course of antipsychotic therapy and consider switching agents if excessive weight gain occurs. (J Clin Psychiatry 1999;60[suppl 21]:20–24) One personal copy may be printed e have known for some time that treatment with CONVENTIONAL NEUROLEPTICS Wantipsychotic drugs is associated with weight gain. A few years after the first neuroleptic medications One of the earliest studies to examine weight gain asso- were introduced, researchers were reporting clinically sig- ciated with antipsychotic drugs in a large number of pa- nificant gains in weight among patients treated with these tients was conducted by Klett and Caffey.1 This study drugs.1 Today, we have available several newer anti- evaluated changes in weight in 396 men with chronic psychotic medications, which offer advantages over con- schizophrenia who were treated with chlorpromazine, ventional neuroleptics in that they are less likely to cause promazine, phenobarbital, or placebo for 12 weeks, fol- extrapyramidal symptoms, tardive dyskinesia, and certain lowed by a 12-week crossover between some patients in other adverse effects. Yet weight gain remains a problem the antipsychotic and placebo groups. Although by week 6 with many of these newer agents. slight differences in weight gain were apparent between Clinicians treating patients with schizophrenia and the patients treated with the phenothiazines chlorproma- other psychotic disorders now have many psychotropic zine and promazine and those receiving a control medica- drugs from which to choose. Since the efficacy of each of tion (phenobarbital or placebo), clear evidence of consid- these agents has been demonstrated (although individual erable weight gain in the phenothiazine groups compared patients may have varying responses to the same drug), with the control groups was seen at week 12. The patients drug selection becomes a matter of comparing adverse ef- who gained the most weight were those who were treated fect profiles. In this brief literature review, the goal is to with a phenothiazine throughout the 24-week study pe- examine weight gain reported with conventional neurolep- riod. Among patients whose medication was switched tics and with newer antipsychotics and to determine which from a phenothiazine to phenobarbital or placebo for the drugs might be the best choice for preventing or minimiz- last 12 weeks of the study, weight tended to return to pre- ing antipsychotic-associated weight gain. treatment levels. In a study conducted 10 years later, Holden and Holden2 used a somewhat complicated study design to evaluate the effects of chlordiazepoxide, thioridazine, and From the Department of Psychiatry, University of a combination of these drugs on weight and clinical Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pa. changes in 22 men with chronic schizophrenia. Each pa- Presented, in part, at the symposium “Weight Gain tient was randomly assigned to 1 of 3 medication se- Associated With the Use of Psychotropic Medications,” which quences. The first group received in order placebo, chlor- was held August 26, 1998, Boston, Mass., and supported by an unrestricted educational grant from Janssen Pharmaceutica, diazepoxide, placebo, chlordiazepoxide plus thioridazine, L.P. placebo, and thioridazine, each for a consecutive 8-week Reprint requests to: Rohan Ganguli, M.D., Western Psychiatric Institute and Clinic, 3811 O’Hara St., Pittsburgh, period. The other two groups received the same medica- PA 15213-2593. tions but in a different order. This study design allowed 20 J Clin Psychiatry 1999;60 (suppl 21) Weight Gain and Antipsychotics Figure 1. Baseline Weight and Change in Weight at 12 and 36 treated with loxapine lost weight progressively over the Weeks in Patients Treated With Selected Antipsychotic 36-week treatment period. Agentsa Weight gain with conventional neuroleptics is just as 14 * likely with depot formulations as with oral tablets, as Johnson and Breen reported in 1979.5 In this prospective 12 Week 12 10 Week 36 study of 132 outpatients with schizophrenia attending a 8 ** depot clinic, 55% of patients treated with depot flupen- ** 6 thixol or fluphenazine gained a significant amount of 4 weight, with 28% gaining more than 6.6 lb and 7% gaining 2 more than 15.4 lb within 6 months. Expressed as a per- © Copyright 2000 Physicianscentage Postgraduate of body weight, 11% Press,of patients gainedInc. more than Weight (lb) Weight 0 –2 10% of their initial body weight, 26% gained more than * 5% of initial body weight, and 46% gained more than 2% –4 * –6 of initial body weight. There was no significant difference –8 in weight change between the flupenthixol and fluphena- –10 ** zine groups. There was a trend toward less weight gain Haloperidol Thiothixene Fluphenazine Thioridazine Loxapine with lower doses of each drug, but overall the correlation (mean = (mean = (mean = (mean = (mean = 152.3 lb, 161.7 lb, 167.6 lb, 165.7 lb, 166.1 lb, between weight and dose was not statistically significant. N = 15) N = 15) N= 14) N = 15) N = 18) My colleagues and I have also examined the relation- aData from reference 4. All N = week 36. ship between weight and use of depot neuroleptics (M.B. *p < .05 vs. baseline. **p < .01 vs. baseline. Lake, M.D., R. Ganguli, M.D., unpublished data, 1996). One personal copy mayThe be study printed included 125 patients with schizophrenia whose psychotic symptoms were being well controlled with de- investigators to evaluate changes in weight during 66 epi- pot injections of haloperidol or fluphenazine. Data on sodes of treatment with active drug and 66 episodes of height, weight, and dose of medication were obtained as treatment with placebo. During the periods when patients part of the patients’ routine care, and body mass index were treated with chlordiazepoxide, thioridazine, or both, (BMI) was calculated for each patient. Seventy-six of the weight gain averaged between 5 and 11 lb. There were no 125 patients were asked to complete a questionnaire, statistically significant differences in weight gain between which asked whether the patients believed they were over- chlordiazepoxide and thioridazine given alone. During the weight and to what they attributed their weight gain. We placebo periods, patients lost an average of 5 lb, with found that 42% of male patients and 49% of female pa- the greatest average weight loss (7.5 lb) occurring during tients were classified as obese (defined as a BMI > 28 the first placebo period. kg/m2 for men and > 27 kg/m2 for women). Of the 76 pa- Dufresne et al.3 conducted a 6-week study in which tients surveyed, 54 (71%) believed they were overweight, patients with schizophrenia were randomly assigned to with more women than men considering themselves over- receive haloperidol (N = 12), molindone (N = 10), or thio- weight. Of those who thought of themselves as over- ridazine (N = 13). At the end of the study period, patients weight, 34 (63%) attributed their obesity to the anti- receiving molindone lost a mean of 5 lb, those in the thio- psychotic medication. There was no overall correlation ridazine group gained a mean of 6 lb, and those in the between the weekly dose of medication and BMI or be- haloperidol group had no change in weight. Doss,4 how- tween duration of treatment and BMI, although we did ever, reported significant weight loss in patients treated note a trend toward an inverse correlation between dose of with thioridazine. In this retrospective chart review, the haloperidol and BMI (i.e., patients taking higher doses of author reviewed data on body weight for 78 randomly se- haloperidol were less likely to have an unhealthy BMI). lected patients with schizophrenia who had been treated Thus, our recent findings support Johnson and Breen’s5 with haloperidol, thiothixene, fluphenazine, thioridazine, earlier conclusion that, in general, weight change and dose or loxapine. Weights were recorded at baseline and after of depot medication are not significantly related. As a re- 12 and 36 weeks of treatment. As shown in Figure 1, pa- sult, administering lower doses of depot haloperidol, flu- tients treated with haloperidol, thiothixene, and fluphena- phenazine, or flupenthixol would not necessarily be an ef- zine all gained weight, while those receiving thioridazine fective means of preventing or minimizing weight gain. and loxapine lost weight. Weight gain with haloperidol ap- Early studies of conventional neuroleptics gave the im- peared to plateau by week 36, which was not the case for pression that weight gain was tied to symptom improve- thiothixene and fluphenazine; patients taking these drugs ment.6 Holden and Holden,2 for example, noted that continued to gain weight throughout the study period. Pa- greater clinical improvement was significantly associated tients taking thioridazine had little change in weight at with greater weight gain (p < .01) and that greater clinical week 12 but lost a significant amount by week 36. Patients deterioration was associated with greater weight loss J Clin Psychiatry 1999;60 (suppl 21) 21 Rohan Ganguli (p < .01).

Load more