Review Paper

Atypical Antipsychotics in Psychiatric Practice: Practical Implications for Clinical Monitoring

Marie-Josée Poulin, MD, FRCPC¹, Leonardo Cortese, MD, FRCPC², Richard Williams, MB, BS, MPhil, FRCPsych, FRCPC³, Nina Wine, MD, FRCPC⁴, Roger S McIntyre, MD, FRCPC⁵

Objective: To provide practical recommendations for monitoring patients both before and during treatment with atypical antipsychotics, to assist clinicians in implementing preventative measures against diabetes, and to establish baselines according to which clinicians should initiate diabetes treatment. Method: A working group of Canadian specialists in psychiatry and endocrinology reviewed peer-reviewed clinical studies published in this area and other relevant papers and abstracts. Results: The reviewed studies further confirm that atypical antipsychotic medications are the most effective components in the medical management of many psychotic conditions; they also further emphasize the need to more stringently monitor and recognize diabetes risk factors inherent in these patients. Recommendations are based on a review of the available data, on expert opinion and consensus, and on current Canadian guidelines for the treatment of schizophrenia and management of diabetes. Conclusion: Patients with psychiatric disorders, most particularly schizophrenia and mood disorders, have an increased risk for type 2 diabetes and should be screened frequently, especially when other risk factors are present. The resulting recommendations offer practical steps for effectively screening patients prior to and during treatment with atypical antipsychotics. They include 1) how to conduct an initial baseline assessment, 2) when and how to monitor blood glucose and lipid levels, and 3) how to educate patients regarding such lifestyle issues as nutrition, exercise, and diet. (Can J Psychiatry 2005;50:555–562) Click here for author affiliations.  Click here for information on funding and support Clinical Implications Atypical antipsychotic medications are the most effective components in the medical management of many psychotic conditions. There is more frequent reporting of diabetes associated with olanzapine and clozapine; however, it remains unclear whether this reflects intrinsic liability differences with these agents. Patients with psychiatric disorders, in particular schizophrenia and mood disorder (major depression and bipolar disorder) patients, have an increased risk for type 2 diabetes and should be screened frequently. It is necessary to more stringently monitor and recognize the diabetes risk factors inherent in these patients. Limitations Research is lacking on the relation between mood or psychotic disorders, antipsychotic drugs, and diabetes. Research is also lacking on which risk factors are involved in the few patients who experience diabetes when taking atypical antipsychotics. Research is limited on the mechanisms that contribute to the elevated risk of diabetes in patients with psychotic and mood disorders. Key Words: depression, diabetes, schizophrenia, bipolar disorder, atypical antipsychotics, monitoring, screening, endocrine, baseline assessment, blood glucose, blood lipids Résumé : Les antipsychotiques atypiques dans la pratique psychiatrique les implications pratiques de la surveillance clinique

There has been a resurgence of interest in the relation between psychotropic medications, mental illnesses, and the endocrine system. The Canadian Diabetes Association’s most recent guidelines, which list schizophrenia as a risk factor for diabetes (1); recent Health Canada and FDA labelling changes to atypical antipsychotics; the Canadian Diabetes Association Physician Statement; and the American Diabetes Association–American Psychiatric Association’s recent consensus statement (2), which suggests a link between atypical antipsychotics and diabetes, have stimulated increased interest in this topic.

This paper describes a brief review of the peer-reviewed literature published in this area, as well as other relevant papers and abstracts. The review was undertaken by a working group of Canadian specialists in psychiatry and endocrinology. The primary aim of this paper is to provide practical recommendations for monitoring patients prior to and during treatment with atypical antipsychotics. Further aims are to assist clinicians by offering effective preventive measures against diabetes and to generate clinical recommendations for glucose monitoring and management. The recommendations are based on expert opinion and consensus (3), on current Canadian guidelines for the treatment of schizophrenia and the management of diabetes, and on a review of the available data. This paper is not intended by be a review of extant data describing associations between atypical antipsychotics and glucose homeostatic disturbances.

Diabetes and Psychiatric Illness: Overview

Increased Risk of Mortality

People with schizophrenia and mood disorders have significantly higher mortality rates than the general population (4,5). They also manifest an increased prevalence and severity of several medical conditions, including diabetes; nevertheless, they are more likely to be underdiagnosed and undertreated (4–8). Schizophrenia and mood disorders are risk factors for diabetes for several reasons, which include, but are not limited to, poor overall health, lifestyle and level of access to health care, as well as treatment with antipsychotic agents (1,4,8–13).

New guidelines and reviews from the Canadian Diabetes Association identify schizophrenia as a major risk factor for diabetes (1). Additionally, recent class labelling changes for atypical antipsychotic agents indicate that glucose homeostatic disturbances are associated with some atypical antipsychotics. However, the relation between mood or psychotic disorders, antipsychotic drugs, and diabetes is not well understood (14–26).

There have been several comprehensive reviews of the extant literature describing associations between the use of atypical antipsychotics and metabolic disruption (27–31). Almost all reviews agree that in predisposed persons, several of the atypical antipsychotics impart signficant weight gain and increase the risk for glucose homeostatic disturbances and dyslipidemia. There are numerically more reports of metabolic disruption and decompensation with clozapine and olanzapine than with risperidone or quetiapine. The association between the use of ziprasidone and aripiprazole and metabolic disruption is not at this time established (32–37).

Clinical guidelines for the treatment of schizophrenia recommend treatment with an antipsychotic agent (4). Of the available antipsychotics, atypical antipsychotics offer an improved efficacy, tolerability, and safety profile, compared with first-generation antipsychotics (4,38). Notwithstanding, atypical antipsychotics have adverse events (for example, weight gain and sedation), which reduce patient acceptance. The choice of an antipsychotic should be individualized to each patient, with consideration of the risks and benefits of treatment (39,40).

Screening and monitoring of weight, diet, and exercise in patients with mood and psychotic disorders will help limit or eliminate weight gain and obesity as added risk factors (41–50). Patients with schizophrenia and mood disorders should be screened frequently, especially in the presence of other risk factors for type 2 diabetes (see Table 1) (51).

Baseline Assessment

Patients with psychotic and mood disorders are at increased risk for obesity and diabetes (52–55). Weight gain during treatment with psychotropic agents may further increase these risks; however, the relation between the use of psychotropic agents, obesity, and diabetes is complex and, while correlative, is not necessarily causative. Baseline assessment of morbidities and risk factors may guide and further inform clinical issues (51).

An initial comprehensive baseline assessment of patients with mood and psychotic disorders should include a thorough medical and family history; an assessment of diabetes risk factors (1); recording of weight, BMI, and vital signs; a metabolic laboratory analysis including fasting glucose; and a fasting cholesterol profile including triglycerides, total cholesterol, and high-density lipoprotein cholesterol levels (51) (Table 2).

Patient Education, Monitoring, and BMI

That the patient understands the role of nutrition and exercise is a vital therapeutic goal in preventing diabetes (56,57). Strategies for weight control include focusing on total caloric consumption; encouraging variety in food, including 5 to 10 servings of fruit and vegetables daily; reducing intake of saturated fats and keeping total dietary fat below 30% of total caloric intake; avoiding high-calorie snacks and sugary drinks; ensuring adequate water consumption; and encouraging physical activity, including a minimum of 30 minutes of exercise 3 to 4 times weekly. Canada’s Food Guide to Healthy Eating is a useful tool for nutrition education (58). Pharmacologic agents may compliment dietary approaches in overweight or obese patients (14–24,54,55).

Obesity, and abdominal obesity in particular, are risk factors for type 2 diabetes. While diabetes, schizophrenia, mood disorders, and atypical antipsychotics are all associated with weight gain, the rapid onset of diabetes in some patients suggests that weight gain does not always play a primary role (9,56). Some evidence exists to show that careful monitoring of weight and diet can prevent significant weight gain during treatment with antipsychotic agents (59–81). A clinical focus on body weight (Table 3) is important in treating patients with psychotic and mood disorders, since they are at risk for obesity. Monitoring body weight in psychiatric patients should include obtaining baseline weight, abdominal circumference, and BMI; closely monitoring weight during antipsychotic treatment; educating patients about the health concerns associated with weight gain (51); and encouraging physical activity and a healthy diet.

BMI is determined by measuring a patient’s weight (in kilograms) and dividing by his or her height (in metres squared) (82). A calculation of the patient’s BMI at baseline and again at 2, 4, 6, and 8 weeks provides a useful monitor in the prevention of treatment-associated weight gain and obesity. A BMI over 25 is considered overweight and a BMI over 30 is considered obese (Table 4).

Screening for Type 2 Diabetes: Blood Glucose and Lipid Levels

Measures of blood glucose and lipid levels provide key indicators of diabetes, IFG, and metabolic syndrome (51). The Canadian Diabetes Association recommends screening individuals with no risk factors every 3 years beginning at age 40 years. In light of the risk for diabetes in patients with psychiatric illness, testing for hyperglycemia becomes an important tool for clinical monitoring of these patients (51). The preferred screening method for hyperglycemia is the FPG test. An FPG level of 7 mmol/L or a random glucose level of 11.1 mmol/L suggests a diagnosis of diabetes (Figure 1). A fasting plasma glucose level between 5.7 mmol/L and 6.9 mmol/L warrants further testing of IGT with a 2-hour plasma glucose in a 75-g oral glucose test (Figure 1). A fasting glucose level below 5.7 mmol/L clinically indicates rescreening. In light of the preexisting risk for type 2 diabetes with psychotic and mood disorders, screening for type 2 diabetes in patients with these illnesses should be considered at diagnosis and there-after, regardless of age and other risk factors (Figure 1). In patients with multiple risk factors who are treated with antipsychotic therapy, fasting or random plasma glucose should be checked at regular intervals of 1, 3, and 6 months after initiation of medication. If weight gain is rapid, more frequent monitoring may be warranted (Figure 2).

Figure 1 Canadian Diabetes Association flow chart for screening for type 2 diabetes, IFG and IGT (1)

^aSee Table 1
^bIn the absence of other risk factors, an FPG of 5.7 to 6.0 mmol/L does not require further investigation, except routine screening at appropriate intervals.
^cA confirmatory laboratory glucose test (either an FPG, casual PG, or a 2hPG in a 75-g OGTT) must be done on another day in all cases in the absence of unequivocal hyperglycemia accompanied by acute metabolic decompensation.
Reproduced with permission from the Canadian Diabetes Association

Figure 2 Proposed screening and monitoring of patients taking antipsychotic medications

Canadian recommendations include routine screening of blood lipids in men over age 40 years and in postmenopausal women over age 50 years (59). Routine screening is also recommended for patients with schizophrenia and mood disorders or other risk factors for diabetes (59). In addition to monitoring glucose levels in these patients, clinicians should obtain total cholesterol, LDL-C, and HDL-C levels, given the links between type 2 diabetes and lipid disorders in the metabolic syndrome (45,53). Screening for lipid disorders may include (fasting or nonfasting) measurement of total cholesterol and HDL-C. The target lipid level for high-risk diabetes patients is < 2.5 mmol/L LDL-C and a total ratio of cholesterol to HDL-C of < 4.0 (53). Hyperglycemia or elevated lipids may require treatment with hypoglycemic and lipid-lowering agents (Figure 1).

Funding and Support

Research conducted by the Working Group was sponsored by an unrestricted educational granted from Eli Lilly Canada, Inc.

References

1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2003 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2003;27 (Suppl 2).

2. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596–601.

3. McIntyre RS, Konarski JZ, Leiter L, Yale J-F, Lau D, Stip E, and others. Schizophrenia, glycemia and antipsychotic medications: an expert consensus review. Can J Diabetes 2005;29:113–21.

4. Canadian Psychiatric Association. Canadian clinical practice guidelines for the treatment of schizophrenia. Can J Psychiatry 1998;43(Suppl 2):25S–40S.

5. Barraclough B, Brown S, Inskip H. Causes of the excess mortality of schizophrenia. Br J Psychiatry 2000;177:212–7.

6. Hoyer EH, Mortensen PB, Olesen AV. Mortality and causes of death in a total national sample of patients with affective disorders admitted for the first time between 1973 and 1993. Br J Psychiatry 2000;176:76–82.

7. Fratti C, Klersy C, Madini S, Piccinelli M, Politi P, Segagni LG, and others. Mortality in psychiatric patients 5 to 21 years after hospital admission in Italy. Psychol Med 2002;32:227–37.

8. Cradock-O’Leary J, Lee ML, Wang M, Yano EM, Young AS. Use of general medical services by VA patients with psychiatric disorders. Psychiatr Serv 2002;53:874–8.

9. Bennett K, Dubitsky G, Koller E, Schneider B. Clozapine-associated diabetes. Am J Med 2001;111:716–23.

10. Miller AL, Weiden PJ. Which side effects really matter? Screening for common and distressing side effects of antipsychotic medications. J Psychiatr Pract 2001;7:41–68.

11. McIntyre RS. Psychotropic drugs and adverse events in the treatment of bipolar disorders revisited. J Clin Psychiatry 2002;63(Suppl 3):15–20.

12. Kennedy SH, McCann SM, McIntyre RS. Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities. Can J Psychiatry 2001;46:273–81.

13. Collins P, Ryan MC, Thakore JH. Impaired fasting glucose tolerance in first episode, drug-naive patients with schizophrenia. Am J Psychiatry 2003;160:284–9.

14. Bogardus C, Hanson K, Pratley RE, Weyer C. Long-term changes in insulin action and insulin secretion associated with gain, loss, regain and maintenance of body weight. Diabetologia 2000;43;36–46.

15. Cooper PB, Fucetola R, Haupt DW, Melson AK, Newcomer JW, Schweiger JA, and others. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry 2002;59:337–45.

16. Mukherjee S. High prevalence of type II diabetes in schizophrenic patients. Schizophr Res 1995;15:195.

17. Bocola V, Decina P, Mukherjee S, Saraceni F, Scapicchio P. Diabetes mellitus in schizophrenic patients. Compr Psychiatry 1996;37:68–73.

18. Barker A, Gordon H, Hindley N, Mohan D. Scizophrenia and diabetes mellitus. Br J Psychiatry 1999;174:180–1.

19. Delahanty J, Dixon L, Goldberg R, Lucksted A, Postrado L, Weiden P, and others. Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull 2000;26:903–12.

20. Lilliker S. Prevalence of diabetes in a manic-depressive population. Compr Psychiatry 1980;21:270–5.

21. Ahearn E, Carroll B, Cassidy F. Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients. Am J Psychiatry 1999;156:1417–20.

22. Luna B, Feinglos MN. Drug-induced hyperglycemia. JAMA 2001;286:1945–8.

23. Raskin J. Nouveaux antipsychotiques atypiques et anomalies du métabolisme du glucose: risque réel ou exagéré. Perspective Professionnelle 2001.

24. Alarcon RD, Leslie DL, Losonczy MF, Rosenheck R, Sernyak MJ. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry 2002;159:561–6.

25. Allison DB, Beasely CM, Berg PH, Cavazonni P, Malinckrodt C, Mukhopadhyay N, and others. Random blood glucose levels in patients with schizophrenia treated with typical and atypical antipsychotic agents: an analysis of data from double-blind randomized controlled clinical trials. Paper presented at the International Congress on Schizophrenia Research; 2001 April 28–May 2; Whistler (BC).

26. Gianfrancesco F, Grogs A, Mahmoud R, Nasrallah HA. Differential effects of antipsychotics on type II diabetes: findings from a large health plan database. Paper presented at the 39th Annual Meeting of the American College of Neuropsychopharmacology; 2000 December; San Juan (PR).

27. McIntyre RS, Konarski JZ. Tolerability profiles of atypical antipsychotics in the treatment of bipolar disorder. J Clin Psychiatry 2005;66 (Suppl 3):28–36.

28. McIntyre RS, Konarski JZ. Bipolar disorder, overweight/obesity, and disorders of glucose metabolism. Current Psychiatry 2005;Suppl:11–20.

29. Woo V, Harris SB, Houlden RL, for the Clinical and Scientific Section, Canadian Diabetes Association. Canadian Diabetes Association position paper: antipsychotic medications and associated risks of weight gain and diabetes. Can J Diabetes 2005;29:111–2.

30. McIntyre RS, Mancini DA, Pearce MM, Silverstone P, Chue P, Misener VL, and others. Mood and psychotic disorders and type 2 diabetes: a metabolic triad. Can J Diabetes 2005;29:122–32.

31. McIntyre RS, Konarski JZ, Misener VL, Kennedy SH. Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications. Ann Clin Psychiatry 2005;17(2):82–93.

32. Lage MJ, Kemner JE, Loosbrock D, Hill AL. Use of atypical antipsychotics and the incidence of diabetes: evidence from a claims database. Paper presented at the American Psychiatric Association 53rd Institute on Psychiatric Services Convention;2001; Orlando (FL).

33. Gupta S, Steinmeyer C, Frank B, Madhusoodanan S, Lockwood K, Lentz B, and others. Hyperglycemia and hypertriglyceridemia in real world patients on antipsychotics therapy. Am J Therapeutics 2003;10:348–55.

34. Bellnier TJ, Decatur A, Ginsberg G, Ortega T, Patil K. The prevalence of metabolic disturbances in state hospital patients prior to use of antipsychotics and after the widespread use of atypical antipsychotics. Paper presented at the CPNP Annual Meeting; 2003 May; Charleston (SC).

35. Bellnier TJ, Decatur A, Ginsberg G, Ortega T, Patil K. The prevalence of metabolic disturbances in schizophrenic and bipolar 1 patients prior to antipsychotic use. Paper presented at the American Psychiatric Association Annual Meeting; 2003 May; San Francisco (CA).

36. Sowell MO, Mukhopadhyay N, Cavazzoni P, Carlson C, Mudaliar S, Chinnapongse S, and others. Evaluation of insulin sensitivity in healthy volunteers treated with olanzapine, riperidone, or placebo: a prospective, randomized study using the two-step hyperinsulinemic, euglycemic clamp. J Clin Endocrinol Metab 2003;88:5875–80.

37. Sernyak MJ, Leslie DL, Alarcon RD, Losonczy MF, Rosenheck R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry 2002;159:561–6.

38. Bradford D, Chakos M, Hoffman E, Lieberman J, Sheitman B. Effectiveness of second generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry 2001;158:518–26.

39. Meltzer HY. Putting metabolic side effects into perspective: risk versus benefits of atypical antipsychotics. J Clin Psychiatry 2001;62(Suppl 27):35–9.

40. Mauskopf J, Muroff M, Gibson PJ, Grainger D. Estimating the costs and benefits of new drug therapies: atypical antipsychotic drugs for schizophrenia. Schizophr Bull 2002;28:619–35.

41. Jackson ML, Labouvie E, Latner JD, Stunkard AJ, Wilson GT, Zelitch DS. Effective long-term treatment of obesity: a continuing care model. Int J Obes Relat Metab Disord 2000;24:893–8.

42. Blackburn GL, Chan S, Greenberg I. Nonpharmacologic and pharmacologic management of weight gain. J Clin Psychiatry 1999;60(Suppl 21):31–6.

43. Clinical guidelines on the identification, evaluation and treatment of overweight and obesity in adults [on-line]. National Heart, Lung and Blood Institute (NHLBI); 1998. Available: www.nhlbi.nih.gov/guidelines/obesity/ ob_home.htm. Accessed 2005 June 2.

44. Fox R, Rotatori AF, Wicks A. Weight loss with psychiatric residents in a behavioral self-control program. Psychol Rep 1980:46:483–6.

45. Knox JM. A study of weight reducing diets in psychiatric in-patients. Br J Psychiatry 1980;136:287–9.

46. Klein B, Primavera LH, Simon WE, Steel RI. Reinforcement and weight loss in schizophrenics. Psychol Rep 1972;30:581–2.

47. Ball MP, Coons VB, Buchanan RW. A weight management program for treatment of olanzapine related weight gain. Schizophr Res 2001;49:256.

48. Cazenave M, Gershon S, Sletten IW. Effects of caloric restriction on behavior and body weight during chlorpromazine therapy. Dis Nerv Syst 1967;28:519–22.

49. Fox R, Rotatori AF. Behavioral weight reduction program for mentally handicapped persons: a self-control approach. Baltimore (MD): University Park Press; 1981.

50. Citrome L, Czobor P, Lyndenmayer JP, McEvoy JP, Sheitman B, Volavka J, and others. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry 2003;160:290–6.

51. Keck PE, Buse J, Dagogo JS, D’Alessio D, Daniels S, McElroy S, and others. Managing metabolic concerns in patients with severe mental illness. Edina (MN): McGraw Hill Healthcare Information Group; 2003.

52. Allison DB, Fontaine KR, Heo M, Mentore JL, Cappelleri JC, Chandler LP, and others. The distribution of body mass index among individuals with and without schizophrenia. J Clin Psych 1999;60:215–20.

53. Stanton JM. Weight gain associated with neuroleptic medication: a review. Schizophr Bull 1995;21:463–72.

54. Delahanty J, Dixon L, Goldberg R, Lucksted A, Postrado L, Weiden P, and others. Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull 2000;26:903–12.

55. Cavazzoni P. A pharmacoepidemiological study of diabetes mellitus and antipsychotic treatment in the United States. Presented at the National Institute of Mental Health, New Clinical Drug Evaluation Unit (NCDEU) 39th Annual Meeting; 2001 May; Phoenix (AZ).

56. Eriksson JG, Hamalainen H, Ilanne-Parikka P, Lindstrom J, Tuomilehto J, Valle TT, and others. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–50.

57. Barrett-Connor E, Fowler SE, Hamman RF, Knowler WC, Lachin JM, Walker EA, and others. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.

58. Canada’s Food Guide to Healthy Eating [on-line]. Health Canada. Available: http://www.hc-sc.gc.ca/hpfb-dgpsa/onpp-bppn/food_guide_rainbow_e.html. Accessed 2005 June 2.

59. Fodor G, Frohlich J, Genest J, McPherson R. Recommendations for the management of dysipidemia and the prevention of cardiovascular disease: summary of the 2003 update. CMAJ 2003;169:921–4.

60. Shaper A, Wannamethee S. Weight change and duration of overweight and obesity in the incidence of type 2 diabetes. Diabetes Care 1999;22:1266–72.

61. Doraiswamy PM, Koller EA. Olanzapine-associated diabetes mellitus. Pharmacotherapy 2002;22:841–52.

62. Antochi R, Emery PC, Stavrakaki C. Olanzapine in the treatment of pervasive developmental disorders: a case series analysis. J Psychiatry Neurosci 2004;29:57–60.

63. King DJ, Wager E. Haematologic safety of antipsychotic drugs. J Psychopharmacol 1998;12:283–8.

64. Kennedy SH, McCann SM, McIntyre RS. Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities. Can J Psychiatry 2001;46:273–81.

65. Devlin MJ, Wilson GT, Yanovski SZ. Obesity: what mental health professionals need to know. Am J Psychiatry 2000;157:854–66.

66. Bleau PJ, Katzman MA, Sehon AA: Maladie psychiatrique et changements de la masse corporelle. Santé Mentale 1999;2:1–4.

67. Meyer JM. Awareness of obesity and weight issues among chronically ill inpatients: a pilot study. Ann Clin Psychiatry 2002;14:39–45.

68. Lippman S, Munski F, Podolskaya A, Sedky K, Shahab H, Vanina Y, and others. Body weight changes associated with psychopharmacology. Psychiatr Serv 2002;53:842–7.

69. Coodin S. Body mass index in persons with schizophrenia. Can J Psychiatry 2001;46:549–55.

70. Meltzer HY, Fleischhaker WW, Casey DE, Zorn SH, Blin O, Micallef J, and others. Weight gain: a growing problem in schizophrenia management. J Clin Psychiatry 2001;62(Suppl 7):3–37.

71. Almeras N, Demers MF, Villeneuve J. Les Nouveaux antipsychotiques et le gain de poids. Quebec Pharmacie 2001;48:571–4.

72. Ganguli R. Weight gain associated with antipsychotic drugs. J Clin Psychiatry 1999;60(Suppl 21):20–4.

73. Berisford MA, Goldstein D, Kysar L, Marder SR, Mintz J, Wirshing DA, and others. Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry 1999;60:358–63.

74. Citrome L, Czobor P, Lindenmayer JP, McEvoy J, Sheitman B, Volavka J, and others. Antipsychotic-induced weight gain and therapeutic response: a differential association. J Clin Psychopharmacol 2002;22:244–51.

75. Allison DB, Cappelleri JC, Chandler LP, Infante MC, Heo M, Mentore JL, and others. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999;156:1686–96.

76. Baptista T, Contreras Q, Delgado C, Lacruz A, Mejias MA, Meza T, and others. Antipsychotic drugs and obesity: is prolactin involved? Can J Psychiatry 2001;46:829–34.

77. Dhavale D, Frye MA, Keck PE, Leverich GS, McElroy SL, Suppes T, and others. Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry 2002;63:207–13.

78. Buysse DJ, Fagiolini A, Frank E, Houk PR, Mallinger AG, Swartz HA, and others. Prevalence of obesity and weight change during treatment in patients with bipolar disorder. J Clin Psychiatry 2002;63:528–33

79. Elmslie JL, Mann JI, Romans SE, Silverstone JT, Williams SM. Determinants of overweight and obesity in patients with bipolar disorder. J Clin Psychiatry 2001;62:486–92.

80. Malhorta S, McElroy SL. Medical management of obesity associated with mental disorders. J Clin Psychiatry 2002;63(Suppl 4):24–32.

81. Aquila R. Management of weight gain in patients with schizophrenia. J Clin Psychiatry 2002;63(Suppl 4):33–6.

82. Calculate your body mass index [on-line]. National Heart, Lung, and Blood Institute, National Institutes of Health. Available: http://nhlbisupport.com/bmi/bmi-m.htm. Accessed 2005 June 2.

Author(s)

Manuscript received June 2004, revised, and accepted March 2005.

1. Active Staff, Centre Hospitalier Affilié Universitaire de Québec, Hôpital de l’Enfant-Jésus, Quebec, Quebec; Clinical Professor of Psychiatry, Université Laval, Laval, Quebec; Clinical Director, Psychosis and the Perinatal Psychiatry Programs at Robert-Giffard Hospital, Quebec, Quebec.

2. Clinical Director, Windsor Regional Hospital, University of Western Ontario, Windsor, Ontario.

3. Director, Royal Jubilee Hospital, Victoria, British Columbia; Clinical Professor, University of British Columbia, Victoria, British Columbia.

4. Endocrinologist, Lifestyle Metabolism Centres, Thornhill, Ontario.

5. Head, Mood Disorders Psychopharmacology Unit, University Health Network–Toronto Western Hospital, Toronto, Ontario; Assistant Professor of Psychiatry, University of Toronto, Toronto, Ontario.

Address for correspondence: Dr M-J Poulin, Centre hospitalier affilié universitaire de Québec, 1401, 18e rue, Quebec, QC G1J 1Z4

e-mail: louise.croteau@cha.quebec.qc.ca

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