Behavioral interventions such as calorie restriction, exercise, and behavioral modification are key elements to successful, sustained weight loss (NHLBI 2000; NHLBI also has posted on its Web site a practical guide for obesity evaluation and management: http://www.nhlbi.nih.gov/guidelines/ obesity/practgd_c.pdf). There is little in the way of published data on behavioral interventions for weight loss in psychotic patients, and the few studies tend to be methodologically weak. In one small (n = 14) 14-week study, patients in a residential setting achieved, on average, 10 pounds more weight loss when given behavioral interventions compared with a control group (Rotatori 1980).

Work by Wirshing and colleagues demonstrated that simple stepwise behavioral interventions were modestly successful in risperidone- and olanzapine-treated subjects, but had little effect in clozapine-treated subjects (Wirshing et al. 1999). The interventions are listed below.

1. Patients were instructed to weigh themselves and report their weight to the clinic nurse at each visit (every 1­4 weeks).

2. If this simple behavioral intervention failed (a gain of 10 pounds was generally considered sufficient to warrant further intervention), patients were instructed to keep a detailed diary of all food intake over a several-week period; the diary was reviewed and recommendations made for changes in diet. If the food diary failed to maintain or decrease weight, patients were referred to a clinical nutritionist.

3. If the previous measures failed, individuals were sent to the Wellness Clinic at the medical center, which involved a more rigorous evaluation of both dietary and exercise habits and added education, exercise classes, and group support.

Although it is true that not all subjects availed themselves of these services, there is no reason to think that any one drug group would have more or fewer “noncooperative” patients. Final weight gains reported by Wirshing and colleagues for olanzapine and risperidone were 2.4 ± 1.3 kg and 2.3 ± 0.8 kg, respectively, compared with maximum weight gains achieved on these medications of 6.8 ± 1.0 kg (olanzapine) and 5.0 ± 0.6 kg (risperidone). In addition to this work, there have been reports suggesting that there may be some benefit to programs such as Weight Watchers in addressing novel antipsychotic­associated weight gain, although the dropout rate was quite high (10 of 21) in one recent study, and only the men experienced significant weight loss (Ball et al. 2001).

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

References

1. Allison DB, Mentore JL, Heo M, et al: Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 156:1686-1696, 1999a
2. Allison D, Fontaine K, Moonseong H, et al: The distribution of body mass index among individuals with and without schizophrenia. J Clin Psychiatry 60:215- 220, 1999b
3. Allison D, Mackell J: Healthcare resource use and body mass index among individuals with schizophrenia. Poster presented at the annual meeting of the New Clinical Drug Evaluation Unit, Boca Raton, FL, May 2000
4. Aronne LJ: Epidemiology, morbidity, and treatment of overweight and obesity. J Clin Psychiatry 62 (suppl 23):13-22, 2001
5. Aulakh CS, Hill JL, Yoney HT, et al: Evidence for involvement of 5-HT1C and 5-HT2 receptors in the food intake suppressant effects of 1-(2,5-dimethoxy- 4-iodophenyl)-2-aminopropane (DOI). Psychopharmacologia 109:444-448, 1992
6. Ball MP, Coons VB, Buchanan RW: A program for treating olanzapine-related weight gain. Psychiatr Serv 52:967-969, 2001
7. Baptista T, Hernandez L, Prieto LA, et al: Metformin in obesity associated with antipsychotic drug administration: a pilot study. J Clin Psychiatry 62:653-655, 2001
8. Basson BR, Kinon BJ, Taylor CC, et al: Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol or risperidone. J Clin Psychiatry 62:231-238, 2001
9. Bernstein JG: Psychotropic drug induced weight gain: mechanisms and management. Clin Neuropharmacol 11 (suppl 1):S194-S206, 1988
10. Berry SA, Mahmoud RA: Normalization of olanzapine associated abnormalities of insulin resistance and insulin release after switch to risperidone: the risperidone rescue study. Poster presented at the 40th annual meeting of the American College of Neuropsychopharmacology, Kona, HI, December 2001
11. Brecher M, Melvin K: Effect of long term quetiapine monotherapy on weight in schizophrenia. Poster presented at the annual meeting of the American Psychiatric Association, New Orleans, Louisiana, May 2001
12. Bromel T, Blum W, Ziegler A, et al: Serum leptin levels increase rapidly after initiation of clozapine treatment. Mol Psychiatry 3:76-80, 1998
13. Bustillo JR, Buchanan RW, Irish D, et al: Differential effect of clozapine on weight: a controlled study. Am J Psychiatry 153:817-819, 1996
14. Cerulli J, Lomaestro B, Malone M: Update on the pharmacotherapy of obesity.Ann Pharmacother 32:88-102, 1998
15. Colditz GA: Economic costs of obesity and inactivity. Med Sci Sports Exerc 31 (suppl 11):S663-S667, 1999
16. Correa N, Opler LA, Kay SR, et al: Amantadine in the treatment of neuroendocrine side effects of neuroleptics. J Clin Psychopharmacol 7:91-95, 1987
17. Davidson S, Judd F, Jolley D, et al: Cardiovascular risk factors for people with mental illness. Aust N Z J Psychiatry 35:196-202, 2001
18. DeFronzo RA, Goodman AM: Multicenter Metformin Study Group: efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 333:541-549, 1995
19. Eder U, Mangweth B, Ebenbichler C, et al: Association of olanzapine-induced weight gain with an increase in body fat. Am J Psychiatry 158:1719-1722, 2001
20. Flegal KM, Troiano RP: Changes in the distribution of body mass index of adults and children in the US population. Int J Obes Relat Metab Disord 24:807-818, 2000
21. Fontaine KR, Heo M, Harrigan EP, et al: Estimating the consequences of antipsychotic induced weight gain on health and mortality rate. Psychiatry Res 101(3):277-288, 2001
22. Fontbonne A, Charles MA, Juhan-Vague I, et al: The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. Diabetes Care 19:920-926, 1996
23. Furst BA, Champion KM, Pierre JM, et al: Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin. Biol Psychiatry 51:264-265, 2002
24. Garattini S, Mennini T, Samain R: Reduction of food intake by manipulation of central serotonin: current experimental results. Br J Psychiatry 155 (suppl 8):41-51, 1989
25. Geodon. New York, Pfizer, 2001 [package insert]
26. Goodall E, Oxtoby C, Richards R, et al: A clinical trial of the efficacy and acceptability of D-fenfluramine in the treatment of neuroleptic-induced obesity. Br J Psychiatry 153:208-213, 1988
27. Green AI, Patel JK, Goisman RM, et al: Weight gain from novel antipsychotic drugs: need for action. Gen Hosp Psychiatry 22:224-235, 2000
28. Groop L, Orho-Melander M: The dysmetabolic syndrome. J Intern Med 250:105- 120, 2001
29. Gupta S, Droney T, Al-Samarrai S, et al: Olanzapine: weight gain and therapeutic efficacy. J Clin Psychopharmacol 19:273-275, 1999
30. Henderson DC, Cagliero E, Gray C, et al: Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study. Am J Psychiatry 157:975-981, 2000
31. Hilgar E, Quiner S, Ginzel I, et al: The effect of orlistat on plasma levels of psychotropic drugs in patients with long-term psychopharmacotherapy. J Clin Psychopharmacol 22:68-70, 2002
32. Jones AM, Rak IW, Raniwalla J, et al: Weight changes in patients treated with quetiapine. Poster presented at the annual meeting of the American Psychiatric Association, Chicago, IL, May 2000
33. Kingsbury SJ, Fayek M, Trufasiu D, et al: The apparent effects of ziprasidone on plasma lipids and glucose. J Clin Psychiatry 62:347-349, 2001
34. Kinon BJ, Basson BR, Gilmore JA, et al: Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia. J Clin Psychiatry 62:92-100, 2001
35. Knapp M: Schizophrenia costs and treatment cost-effectiveness. Acta Psychiatrica Scand Suppl 102:15-18, 2000
36. Knight A: Astemizole: a new, non-sedating antihistamine for hay fever. J Otolaryngol 14:85-88, 1985
37. Kolokowska T, Gadhvi H, Molyneux S: An open clinical trial of fenfluramine in chronic schizophrenia: a pilot study. Int Clin Psychopharmacol 2:83-88, 1987
38. Kraepelin E: Dementia Praecox and Paraphrenia. Edinburgh, E & S Livingstone, 1919
39. Kraus T, Haack M, Schuld A, et al: Body weight and leptin plasma levels during treatment with antipsychotic drugs. Am J Psychiatry 156:312-314, 1999
40. Leadbetter R, Shutty M, Pavalonis D, et al: Clozapine-induced weight gain: prevalence and clinical relevance. Am J Psychiatry 149:68-72, 1992
41. Luque C, Rey J: Sibutramine: a serotonin-norepinephrine reuptake-inhibitor for the treatment of obesity. Ann Pharmacother 33:968-978, 1999
42. Marder S, Davis JM, Chouinard G, et al: The effects of risperidone on the five dimensions of schizophrenia. J Clin Psychiatry 58:538-546, 1997
43. McElroy S, Suppes T, Keck P, et al: Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry 47:1025-1033, 2000
44. McIntyre RS, Trakas K, Lin D, et al: Risk of adverse events associated with antipsychotic treatment: results from the Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS). Abstract presented at the 40th annual meeting of the American College of Neuropsychopharmacology, Kona, HI, December 2001
45. Meyer JM: Novel antipsychotics and severe hyperlipidemia. J Clin Psychopharmacol 21:369-374, 2001
46. Meyer JM: A retrospective comparison of lipid, glucose and weight changes at one year between olanzapine and risperidone treated inpatients. J Clin Psychiatry 63: 425-433, 2002
47. Mokdad AH, Ford ES, Bowman BA, et al: Diabetes trends in the U.S.: 1990-1998. Diabetes Care 23:1278-1283, 2000a
48. Mokdad AH, Serdula MK, Dietz WH, et al: The continuing epidemic of obesity in the United States. JAMA 284:1650-1651, 2000b
49. Morrison JA, Cottingham EM, Barton BA: Metformin for weight loss in pediatric patients taking psychotropic drugs. Am J Psychiatry 159:655-657, 2002
50. Must A, Spadano J, Coakley EH, et al: The disease burden associated with overweight and obesity. JAMA 282:1523-1529, 1999
51. Myers A, Rosen JC: Obesity stigmatizationa and coping: relation to mental health symptoms, body image, and self-esteem. Int J Obes Relat Metab Disord 23:221-230, 1999
52. National Heart, Lung and Blood Institute (NHLBI): Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Available at: http://www.nhlbi.nih.gov/guidelines/obesity/practgd_c.pdf. November 2000
53. Nemeroff CB: Dosing the antipsychotic medication olanzapine. J Clin Psychiatry 58 (suppl 10):45-49, 1997
54. Norton J, Potter D, Edward K: Sustained weight loss associated with topiramate. Epilepsia 38 (suppl 3):S60, 1997
55. Park YW, Allison DB, Heymsfield SB, et al: Larger amounts of visceral adipose tissue in Asian Americans. Obes Res 9:381-387, 2001
56. Pelleymounter M, Cullen M, Baker M, et al: Effects of the obese gene production body weight regulation in ob/ob mice. Science 269:240-243, 1995
57. Petrie J, Saha A, McEvoy J: Aripiprazole, a new atypical antipsychotic: phase II clinical trial result. Eur Neuropsychopharmacol 7 (suppl 2):S227, 1997
58. Pfizer: Briefing document for ziprasidone HCl presented at the FDA Psychopharmacological Drugs Advisory Committee, July 19, 2000
59. Reinstein M, Sirotovskaya L, Jonas L, et al: Effect of clozapine-quetiapine combination therapy on weight and glycaemic control. Clin Drug Invest 18:99-104, 1999
60. Risperdal. Titusville, NJ, Janssen Pharmaceutica, 1999 [package insert]
61. Rockwell WJ, Ellinwood EH, Trader DW: Psychotropic drugs promoting weight gain: health risks and treatment implications. South Med J 76:1407-1412, 1983
62. Rosenfeld W, Schaefer P, Pace K: Weight loss patterns with topiramate therapy. Epilepsia 38 (suppl 3):S58, 1997
63. Rotatori AF, Fox R, Wicks A: Weight loss with psychiatric residents in a behavioral self-control program. Psychol Rep 46:483-486, 1980
64. Samanin R, Garattini S: The pharmacology of serotonergic drugs affecting appetite, in Nutrition and the Brain, Vol 8. Edited by Wurtman RJ, Wurtman JJ. New York, Raven, 1990, pp 163-192
65. Sacchetti E, Guarner L, Bravi D: H2 antagonist nizatidine may control olanzapine-associated weight gain in schizophrenic patients. Biol Psychiatry 48:167-168, 2000
66. Schlosser E: Fast Food Nation: The Dark Side of the All-American Meal. Boston, Houghton Mifflin, 2001
67. Schotte A, Janssen PF, Megens AA, et al: Occupancy of central neurotransmitter receptors by risperidone, clozapine, and haloperidol measured ex vivo by quantitative autoradiography. Brain Res 631:191-202, 1993
68. Seroquel. Wilmington, DE, AstraZeneca, 2000 [package insert]
69. Silverstone T, Smith G, Goodall E: Prevalence of obesity in patients receiving depot antipsychotics. Br J Psychiatry 153:214-217, 1988
70. Taylor DM, McAskill R: Atypical antipsychotics and weight gain: a systematic review. Acta Psychiatr Scand 101:416-432, 2000
71. Tecott L, Sun L, Arkana S: Eating disorder and epilepsy in mice lacking 5-HT_2C serotonin receptors. Nature 374:542-546, 1995
72. Theisen FM, Linden A, Geller F, et al: Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication. J Psychiatr Res 35:339-345, 2001
73. Umbricht DS, Pollack S, Kane JM: Clozapine and weight gain. J Clin Psychiatry 55 (suppl B):157-160, 1994
74. Weiden PJ, Allison DB, Mackell JA, et al: Obesity as a risk factor for antipsychotic noncompliance. Poster presented at the annual meeting of the American Psychiatric Association, Chicago, IL, May 2000
75. Werneke U, Taylor D, Sanders TA: Options for pharmacological treatment of obesity in patients treated with atypical antipsychotics. Int Clin Psychopharmacol 17:145-160, 2002
76. Wirshing D, Wirshing W, Kysar L, et al: Novel antipsychotics:comparison of weight gain liabilities. J Clin Psychiatry 60:358-363, 1999
77. Wirshing DA, Pierre JM, Eyeler J, et al: Risperidone associated new-onset diabetes. Biol Psychiatry 50:1489-1489, 2001a
78. Wirshing D, Boyd J, Meng L, et al: Antipsychotic medication: impact on coronary artery disease risk factors. Biol Psychiatry 49:175S, 2001b
79. Wolf A, Colditz G: Current estimates of the economic cost of obesity in the United States. Obes Res 6:97-106, 1998
80. Yanovski J, Yanovski S: Recent advances in basic obesity research. JAMA 282:1504-1506, 1999
81. Yanovski S, Yanovski J: Obesity. N Engl J Med 346:591-602, 2002
82. Zyprexa. Indianapolis, IN, Eli Lilly, 2000 [package insert]