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					Original Research

Risk of Weight Gain Associated with Antipsychotic
Treatment: Results From the Canadian National
Outcomes Measurement Study in Schizophrenia
Roger S McIntyre, MD, FRCPC1, Kostas Trakas, MSc2, Daryl Lin, PhD3, Robert Balshaw, PhD4,
Pieway Hwang, PharmD2, Kimberly Robinson, BSc, MBA5, Andrew Eggleston, BPh, MMedSc6

            Background: Antipsychotic-induced weight gain occurs in a substantial percentage of treated persons. There re-
            mains a paucity of naturalistic data that describe relative weight-gain liability with the available novel atypical
            antipsychotics (NAPs). This investigation describes comparative NAP-induced weight gain in a prospective
            naturalistic cohort of persons with schizophrenia and related psychotic disorders.
            Methods: The Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS) is an ongoing
            prospective, longitudinal, naturalistic study involving 32 academic and community sites across Canada. Persons
            with DSM-IV–defined schizophrenia, schizophreniform or schizoaffective disorder, and psychosis not otherwise
            specified were consecutively enrolled. The overarching objectives of this initiative were to collect and compare
            global effectiveness, tolerability, safety, and humanistic outcomes in persons receiving commercially available
            NAPs in Canada. This analysis reports only weight change with the respective NAPs. Other outcomes were re-
            ported in separate companion papers.
            Results: A spectrum of weight-gain liability was noted with quetiapine (QUE) (mean 7.55 kg, SD 9.20; P =
            0.28), olanzapine (OLZ) (mean 3.72 kg, SD 0.56; P = 0.15), and risperidone (RIS) (mean 1.62 kg, SD 7.72; P =
            0.43). Categorically defined weight gain (that is, over 7% of baseline weight) was observed in 55.6% of QUE pa-
            tients, 24.1% of OLZ patients, and 23.7% of RIS patients. Adjusting for demographic and disease-specific con-
            founding factors, QUE patients had greater odds of gaining over 7% of their baseline weight, compared with RIS
            patients (odds ratio [OR] 3.62; 95%CI, 1.02 to 12.83; P = 0.05) . No statistical difference was detected between
            OLZ patients and RIS patients for over 7% of baseline weight (OR 1.54; 95%CI, 0.63 to 3.75; P = 0.12) or over
            10% weight gain (OR 1.44; 95%CI, 0.50 to 4.13; P = 0.58).
            Conclusion: Clinicians are reminded to monitor anthropometric and metabolic parameters in all NAP-treated
            persons. Clinically significant differences in weight gain liability exist among the available NAPs.
            (Can J Psychiatry 2003;48:689–694)
            Information on funding and support and author affiliations appears at the end of the article.

              Clinical Implications
              · Clinically significant weight gain is a significant adverse event in patients receiving novel antispsychotics (NAPs) in
                naturalistic settings.
              · Patients should be informed of the relative weight-gain potential of different NAPs, and primary preventive strategies
                should be initiated when prescribing these agents.
              · Physicians should monitor anthropometric indices (plasma glucose and lipid fractionation) and associated morbidity in
                NAP-treated patients.

              · The sample size was small and unevenly distributed; the study methodology was open and uncontrolled, introducing
                potential for bias.
              · Patients’ baseline weight prior to antipsychotic exposure and their weight-gain from previous antipsychotic agents
                were unknown, which may have confounded the results obtained in this study.
              · Activities and behaviours that are capable of modifying weight-gain accrual were not controlled (for example, exer -
                cise and smoking).

W Can J Psychiatry, Vol 48, No 10, November 2003                                                                                       689
The Canadian Journal of Psychiatry—Original Research

Key Words: schizophrenia, antipsychotics, risperidone,             available NAPs under conditions of routine practice.
olanzapine, quetiapine, weight gain                                CNOMSS included 32 university and community sites across
                                                                   Canada. A Scientific Advisory Committee (Appendix)
     he introduction of the novel atypical antipsychotics
T    (NAPs) has unequivocally advanced the pharmaco-
therapy of psychotic disorders. Compared with older agents,
                                                                   selected the sites. This selection was based on known infor-
                                                                   mation about the respective sites’ case mix and prior research
                                                                   participation. This study was approved by the Western Insti-
NAPs offer enhanced efficacy against positive and negative         tutional Review Board (WIRB) and, where applicable, by
symptoms, improve cognitive function and quality of life, and      local internal review boards.
demonstrate a diminished risk for acute extrapyramidal symp-
toms (EPS) and long-term tardive dyskinesia. NAPs are not,         Consecutive outpatients who were capable of providing
however, without adverse events. Sedation, sexual dysfunc-         consent were enrolled at each site if they had been diagnosed
tion, prolactin elevation, weight gain, and metabolic distur-      w ith s c h iz o p h r e n ia, s c h izo p h r e n if o r m d is o r d e r ,
bances have been variably observed with the available NAPs         schizoaffective disorder, or psychosis not otherwise specified
(1,2).                                                             (NOS) according to DSM-IV criteria (15). Patients over age
                                                                   16 years who manifested both single- and multiple-episode
Weight gain is a disquieting adverse event that significantly      chronic disorders were enrolled. All patients were capable
contributes to nonadherence, which portends relapse of ill-        and willing to provide informed consent or had a legal guard-
ness (3,4). Moreover, excess weight gain will presage obe-         ian or designate who could provide consent on their behalf.
sity- related morbidity, negatively affect self-esteem, and        All participants at the time of study entry were receiving an
increase risk for a myriad medical disorders (that is, hyperten-   antipsychotic agent. Use of any concomitant psychotropic
sion and diabetes mellitus) (5).                                   medications was permitted as clinically indicated. Patients
The body mass index (BMI; BMI = body weight in kilograms/          with a comorbid diagnosis were permitted to enter the study,
[height in metres]2) distribution in schizophrenia and bipolar     whereas patients with a primary diagnosis other than schizo-
disorder patients overlaps and exceeds estimates from the          phrenia and schizoaffective disorder or psychosis NOS were
general population (6). Further, persons with schizophrenia        excluded.
are at higher risk for various obesity-related disorders (7).      The primary efficacy parameters were the Brief Psychiatric
A large metaanalysis of 81 treatment trials (8) suggested that a   Rating Scale (BPRS) and the Clinical Global Impression
spectrum of weight-gain liability exists with NAP treatments,      (CGI) Improvement and Severity Scales (CGI-I and CGI-S)
with clozapine imparting the most weight gain and                  (9,16). Functional and humanistic outcomes were measured
ziprasidone the least. Although quetiapine (QUE) was not           with the Social and Occupational Functional Assessment
included in this analysis, other lines of data have suggested      Scale (SOFAS) and the Medical Outcomes Study Short-Form
that this agent also imparts significant weight gain in short-     36 (MOS–SF36) (10). All treatment-emergent adverse events
term trials (9–13). In aggregate, data from largely short-term     were identified and coded according to the Medical Dictio-
controlled studies with the commercially available NAPs            nary for Regulatory Activities (MedDRA). Patients were
have convincingly shown some weight gain with most agents.         weighed at baseline and every 3 months by their treating phy-
There remains, however, a paucity of comparative, prospec-         sician during regularly scheduled follow-up visits. (Fasting
tive, naturalistic data estimating and comparing weight-gain       blood glucose and lipid determination were obtained at the
accrual among these agents.                                        baseline visit and repeatedly throughout the study, with the
NAPs are recommended as first-line strategies in the contem-       results analyzed and reported in a companion paper.) Patient
porary treatment of schizophrenia (14). The objective of this      height was also assessed, permitting a BMI computation. To
investigation was to determine the relative risk of treatment-     be defined as overweight or obese, patients had a BMI of over
emergent weight gain among commercially available NAP              25 and 30, respectively (11). This report presents the
treatments in persons with schizophrenia and in those with         weight-change data with the NAP treatments. Other outcomes
related psychotic disorders, who were followed prospectively       harvested from this study will be reported in separate compan-
in a naturalistic setting.                                         ion papers.
                                                                   Medication assignment was determined clinically between
Methods                                                            the treatment provider and the patient. The study did not a pri-
The Canadian National Outcomes Measurement Study in                ori specify treatments with particular agents or emphasize a
Schizophrenia (CNOMSS) is an ongoing, prospective, natu-           requisite number of persons receiving any respective
ralistic study. The overarching objectives of the CNOMSS           treatment. Antipsychotic manipulation throughout patient
study were to estimate and compare the global effectiveness,       tenure in the study was determined as clinically indicated.
tolerability, and safety parameters of the commercially            Concomitant medications were permitted.

                                                                                     W Can J Psychiatry, Vol 48, No 10, November 2003
                                                                         Risk of Weight Gain Associated with Antipsychotic Treatment

               Table 1 Cohort demographics
                                                                            Patients in first analysis

                                                         Risperidone              Olanzapine             Quetiapine
                                                          (n = 111)                (n = 109)              (n = 23)
               Men, %                                       59.5                      78.0                  60.9
               Previously hospitalized, %                   44.1                      32.1                  47.8
               Mean (SD) age, years                       36.0 (11)                38.0 (11)              35.0 (13)
               Mean (SD) years with illness                9.0 (9)                 14.0 (11)               7.0 (9)
               Mean (SD) baseline BPRS                    –0.31 (24)               –0.38 (0.29)           –0.41 (0.32)
               Mean (SD) baseline weight, kilograms       84.2 (19.5)              86.8 (16.8)            84.8 (20.3)
               Mean (SD) last weight, kilograms           86.5 (22.0)              90.3 (19.3)            91.5 (21.4)
               Mean (SD) baseline dose, milligrams         3.6 (2.4)               14.5 (7.8)            253.9 (203.8)
               Mean (SD) last dose, milligrams             3.5 (2.4)               14.7 (8.0)            324.0 (250.7)
               Mean (SD) treatment duration, days        280.0 (312)              333.0 (255)            324.0 (226)
                                                                          Patients in second analysis

                                                         Risperidone              Olanzapine             Quetiapine
                                                           (n = 18)                (n = 32)               (n = 11)
               Men, %                                       50.0                      68.8                  27.3
               Previously hospitalized, %                   16.7                      37.5                  36.4
               Mean (SD) age, years                       42.6 (13.0)              37.0 (11.1)            47.5 (14.0)
               Mean (SD) years with illness               15.8 (13.2)              10.9 (9.4)             15.5 (14.7)
               Mean (SD) baseline BPRS                    –0.4 (0.28)              –0.4 (0.23)            –0.3 (0.22)
               Mean (SD) baseline weight, kilograms       88.7 (29.0)              84.4 (18.0)            89.1 (18.9)
               Mean (SD) last weight, kilograms           87.6 (30)                88.5 (22.7)            93.2 (24.3)
               Mean (SD) baseline dose, milligrams         3.6 (2.4)               11.2 (6.6)            341.0 (276)
               Mean (SD) last dose, milligrams             4.3 (2.6)               14.2 (9.1)            366.0 (266)
               Mean (SD) treatment duration, days        206.0 (155)              275.0 (150)            204.0 (228)

               BPRS = Brief Psychiatric Rating Scale

A total of 457 patients were consecutively enrolled between            model was used to derive ORs adjusted for drug, age, sex, diag-
June 1999 and November 2000. For the analysis, 2 groups of             nosis, disease characteristics (for example, positive or negative
patients were selected from the total CNOMSS cohort and                symptoms), baseline and endpoint total BPRS, hospitalizations
separately analyzed. The first group comprised patients who            in the past 2 years, and the estimated treatment duration with cur-
were treated with NAP (that is, no adjuvant antipsychotic              rent medication or current dosage of medication. Because RIS
agent) at enrollment into CNOMSS (n = 243). The second                 was the most frequently prescribed antipsychotic in Canada at
group included patients who initiated NAP after the baseline           the time of the analysis, all ORs were calculated relative to RIS.
visit (n = 38). Both continuous and categorical weight analy-
ses were conducted. Odds ratios (ORs) were calculated for the          Results
243 patients receiving risperidone (RIS), olanzapine (OLZ),            Table 1 presents the baseline demographics for each drug
or quetiapine (QUE) as their sole antipsychotic agent, adjust-         cohort. Men represented a higher proportion of the OLZ patients
ed for demographic and disease-specific factors using a logis-         (78%), compared with RIS (59.5%) (P = 0.003), and had lived
tic regression model (all tests used a = 0.05).                        with their illness longer than either RIS or QUE patients (P <
                                                                       0.001). Of patients, 76% and 77% (n = 142) were overweight
Patients were removed from the statistical analysis if a second        and obese, respectively, at both baseline and at the last follow-up
antipsychotic agent was added (conventional or atypical), if           visit. Likewise, 9.5% of patients gained enough body weight to
the medication was changed (conventional or atypical), or if           move from the overweight to obese classification by their last
the original agent was discontinued. Patients had an estimated         follow-up visit (OLZ 11%, QUE 8.7%, and RIS 8.1%).
mean treatment duration of 10 months. A logistic regression            Concomitant medication use was comparable among the drugs

W Can J Psychiatry, Vol 48, No 10, November 2003                                                                                   691
The Canadian Journal of Psychiatry—Original Research

 Table 2 Concomittant medications                                                                                       patients. No statistical differ-
                                                               Risperidone   Olanzapine     Quetiapine                  ence was detected between OLZ
                                                                (n = 111)     (n = 109)      (n = 23)           P       patients and RIS patients for 7%
 At baseline (%)                                                                                                        or more weight gain (OR 1.54;
          None                                                     68.5         65.1            60.9          0.57      95%CI, 0.63 to 3.75; P = 0.12)
          Antianxiety and (or) sedative hypnotics                  10.8         13.8            17.4          0.48      or 10% or more weight gain (OR
          Antidepressants                                          16.2         13.8            13.0          0.94      1.44; 95%CI, 0.50 to 4.13;
          Antiparkinsonians                                         9.9          6.4            —             0.64      P = 0.58).
          Mood stabilizers                                          3.6         12.8            13.0          0.08
 At last visit (%)                                                                                                       Weight gain was also assessed
          None                                                     44.1         46.8            47.8          0.09       in a second group of patients
          Antianxiety and (or) sedative hypnotics                  25.2         26.6            17.4          0.33       who were placed on atypical
          Antidepressants                                          29.7         26.6            26.1          0.68       monotherapy at a postbaseline
          Antiparkinsonians                                        18.0         12.8            —             0.29       visit (Table 1). Weight gain was
          Mood stabilizers                                          7.2         16.5               8.7        0.03       noted with OLZ (n = 32; mean
                                                                                                                         4.1 kg, SD 11.88; P = 0.05) and
Figure 1 Unadjusted percent weight gain from baseline                                                                    QUE (n = 11; mean 4.1 kg, SD
                                                                                                              12.77; P = 0.29), while RIS was weight
                                                                                                              neutral in this cohort (n = 18; mean –1.1
                                   60                                                                         kg, SD 3.87; P = 0.21). The duration of
                                        > 7% Weight Gain                                                      treatment did not differ significantly for
                                   50   > 10% Weight Gain                                                     the 3 treatment groups in this second anal-
      Proportion of Patients (%)

                                                                                                              ysis (mean duration of 8.1 months).
                                   40                                                                         Owing to sample size limitations, further
                                                            30.9                                              analyses , comparing patient clinical char-
                                   30                                                                         acteristics and outcome with weight gain
                                                                    18.5                                      liability were not conducted.
                                                                                                           Results from this analysis suggest that
                                    0                                                                      NAPs are associated with clinically sig-
                                        Risperidone          Olanzapine            Quetiapine              nificant and differential weight gain in
                                                                                                           naturalistic settings. The weight gain that
                                                                                                           we described with QUE was significantly
at baseline, although mood stabilizers were used significantly                       greater than the weight gain observed in RIS- and
more often by OLZ patients at their last visit (P = 0.03)                            OLZ-treated patients. Although weight gain with RIS and
(Table 2).                                                                           OLZ has been well described, there are fewer studies with
                                                                                     QUE. Borison and colleagues reported that 25% of patients
Analysis of the first cohort (that is, persons who received and                      who take QUE gained 7% or more of their baseline weight
[or] initiated NAP at baseline) indicated disparity in the abso-                     (placebo 4%) (12), whereas in a study comparing QUE with
lute weight gain among the 3 treatments. The spectrum of                             chlorpromazine, 27% of QUE patients gained 7% or more of
weight gain was as follows: QUE (n = 23, mean 7.55 kg, SD                            their baseline weight (13). Further, a review by Gunasekara
9.20), OLZ (n = 109, mean 3.72 kg, SD 8.56), and RIS (n =                            and Spencer reported that average weight gain at 6 weeks was
111, mean 1.62 kg, SD 7.72). Categorically defined signifi-                          2.1 kg, rising to 5.6 kg at 1 year in QUE-treated patients (17).
cant weight gain (7% or more of baseline) was observed in                            Contrary to these observations, data from Brecher and col-
55.6% of QUE patients, 24.1% of OLZ patients, and 23.7% of                           leagues suggested that QUE had only a minimal effect on
RIS patients (Figure 1). The percentage of patients who                              weight gain after 1 year of treatment (18).
gained 10% or more of their baseline weight was 38.9% in
QUE patients, 18.5% in OLZ patients, and 13.2% in RIS                                  A secondary finding in this analysis was that a spectrum of
patients. Adjusted for confounding factors, QUE patients had                           weight -gain liability exists with the available NAPs.
greater odds of gaining 7% or more (OR 3.62; 95%CI, 1.02 to                            Although the relative liability between RIS and QUE was
12.83; P = 0.05) and 10% or more (OR 3.91; 95%CI, 1.02 to                              convergent with the existing literature, the observation that
15.08; P = 0.05) of their baseline weight, compared with RIS                           RIS and OLZ had imparted similar weight gain was

                                                                                                         W Can J Psychiatry, Vol 48, No 10, November 2003
                                                                                     Risk of Weight Gain Associated with Antipsychotic Treatment

incompatible with most available data. This disagreement                             Appendix Investigators and locations for the study
with other studies may be due, in part, to the limitations inher-                    Investigator                   Location
ent in an observational study. Most important, CNOMSS                                Satish Shrikhande              Saskatoon
could not control for the duration or type of antipsychotic                          Jeff Reiss                     Winnipeg
treatment that was received prior to prospective data collec-                        K Zimmer                       Winnipeg
tion, because precise estimates of the treatment duration could                      J Polimeni                     Winnipeg
not be obtained at baseline for most patients in our study. This                     Ivan Kowalchuk                 Winnipeg
may b e cr itic a l: av a ilab le d a ta s u g g e s t th a t                        Charles Messeer                Regina, Regina General Hospital
antipsychotic-associated weight gain may be dura-                                    KV Ramachandran                North Battleford, Sakatchewan
tion-dependent (19). For example, for most individuals with                          John Dougan                    Acton, Ontario
schizophrenia, the rate of OLZ-induced weight gain has                               Alain Labelle                  Ottawa, Royal Ottawa Hospital
plateaued after about 30 to 52 weeks of treatment (1).                               Brian Hoffman                  Toronto, North York General Hospital
                                                                                     Ashok Malla                    London, London Health Sciences
Other limitations included a diagnostically heterogeneous                                                           Centre
sample (that is, many possible diagnoses and disease histo-                          Henry Leung                    Sault Ste Marie, Ontario, Sault Area
ries) reflective of routine clinical practice, the inclusion of
                                                                                     Wilson Lit                     Guelph, Homewood Health Centre
patients receiving concomitant medications, no control of
                                                                                     Sunny Johnson                  Mississauga
attempts to manage weight gain, and no reliable collection of
                                                                                     Linda Beauclair                Montreal, Allan Memorial Institute
smoking status for each patient in the study. Finally, this com-                     Pierre Landry                  Quebec City, Hôpital Louis-H
parative analysis had a significantly smaller sample of QUE                                                         LaFontaine
patients, making it difficult to model more complex relations                        Angelo Fallu                   Sherbrooke, Centre universitaire de
between weight gain and the NAPs. It is possible that a larger                                                      santé de l’Estrie
                                                                                     Java Moamal                    Hull, Quebec, Hôpital Pierre-Janet
sample size may realize a different outcome.
                                                                                     Jean Michel Beau               Malartic, Centre hospitalier Malartic
Introducing NAPs has permitted physicians to employ an                               Pierre Leouffre                Malartic, Centre hospitalier Malartic
alternative in managing schizophrenia. Compared with con-                            Richard Williams               Victoria, Jubilee Hospital
ventional antipsychotics, the NAPs offer an improved neuro-                          Geoff Smith                    Vancouver, St Vincent’s Hospital
logical profile but appear to impart a greater weight-gain                           Norman White                   Powell River, Community Site
liability. Weight gain in the range of 5% to 10% of the baseline                     Fiona McGregor                 Vernon, British Columbia, Vernon
                                                                                                                    Mental Health Centre
weight significantly increases the risk for a myriad medical
                                                                                     Paul Latimer                   Kelowna, Kelowna General Hospital
disorders already occuring at an increased prevalence in some
                                                                                     Pierre Chue                    Edmonton, Community Living Program
psychiatric populations (20). In this investigation, over 75%
                                                                                     Ruth Dickson                   Calgary, Peter Lougheed Hospital
of NAP-treated patients were statistically overweight or                             Stephen Boucher                Calgary, Peter Lougheed Hospital
obese, and all NAPs imparted weight gain.                                            David Dawson                   Calgary, Peter Lougheed Hospital
Research that attempts to identify biological mechanisms and                         Norman Costigan                Red Deer, Red Deer Regional Hospital
clinical variables associated with NAP-induced weight gain,                          Saibal Nandy                   Medicine Hat, Community Site
                                                                                     Hubert Colohan                 Claresholm, Claresholm Community
as well as appropriate management strategies, is underway.                                                          Centre
Clinicians are reminded to inform all patients of the capacity                       Herbert Cohan                  Claresholm, Claresholm Community
for weight gain with each agent. Moreover, anthropometric                                                           Centre
indices (for example, weight and BMI) and metabolic param-                           Lili Kopala                    Halifax, QE II Hospital
eters (for example, fasting glucose and lipid fractionation)                         Heather Milliken               Halifax, QE II Hospital
should be routinely monitored in treated persons.                                    Lorraine Lazier                Kentville, Valley Regional Hospital
                                                                                     Pam Forsythe                   Charlottetown, Community Site
                                                                                     Jamie Karagianis               St John’s, Community Site
                     Funding and Support
This study was supported by Janssen-Ortho Canada.

                                                                                     4. Fleischhacker W, Meise U, Gunther V, Kurz M. Compliance with antipsychotic
                               References                                               drug treatment: influence of side effects. Acta Psychiatr Scand Suppl
 1. Blin O, Micallef J. Antipsychotic-associated weight gain and clinical outcome
    parameters. J Clin Psychiatry 2001;62(Suppl 7):11–21.                            5. Allison DB, Casey DE. Antipsychotic-induced weight gain: a review of the liter-
 2. Brown CS, Markowitz JS, Moore TR, Parker NG. Atypical antipsychotics: Part          ature. J Clin Psychiatry 2001;62(Suppl 7):22–31.
    II: adverse effects, drug interactions, and costs. Ann Pharmacother
    1999;33:210 –7.                                                                  6. Elmslie JL, Mann JI, Silverstone JT, Williams SM, Romans SE. Determinants of
 3. Buis W. Patients’ opinions concerning side effects of depot neuroleptics. Am J      overweight and obesity in patients with bipolar disorder. J Clin Psychiatry
    Psychiatry 1992;149:844 –5.                                                         2001;62:486 –93.

W Can J Psychiatry, Vol 48, No 10, November 2003                                                                                                                   693
The Canadian Journal of Psychiatry—Original Research

 7. Dixon L, Weiden P, Delahanty J, Goldberg R, Postrado L, Lucksted A, and oth-       18. Brecher M, Rak I, Melvin K, Jones A. The long-term effect of quetiapine
    ers. Prevalence and correlates of diabetes in national schizophrenia samples.          (SeroquelTM) monotherapy on weight in patients with schizophrenia. Int J Psy-
    Schizophr Bull 2000;26:903–12.                                                         chiatry Clin Pract 2000;4:287– 91.
 8. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, and
    others. Antipsychotic-induced weight gain: a comprehensive research synthesis.     19. Wirshing DA, Spellberg BJ, Erhart SM, Marder SR, Wirshing WC. Novel
    Am J Psychiatry 1999;156:1686 –96.                                                     antipsychotics and new onset diabetes. Biol Psychiatry 1998;44:778–83.
 9. Overall JE, Beller SA. The Brief Psychiatric Rating Scale (BPRS) in
    geropsychiatric research: I. Factor structure on an inpatient unit. J Gerontol     20. Pi-Sunyer FX. Comorbidities of overweight and obesity: current evidence and
    1984;39:187–93.                                                                        research issues. Med Sci Sports Exerc 1999;31(Suppl 11):S602–S6008.
10. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey
    (SF-36). I. Conceptual framework and item selection. Med Care
11. WHO. Physical status: the use and interpretation of anthropometry. Report of a     Manuscript received September 2002, revised, and accepted May 2003.
    WHO Expert Committee. Technical Report Series 854. Geneva: WHO; 1995.              1
                                                                                         Head, Mood Disorders Psychopharmacology Clinic, University Health Net-
12. Borison RL, Arvanitis LA, Miller BG. ICI 204,636, an atypical antipsychotic: ef-
    ficacy and safety in a multicenter, placebo-controlled trial in patients with      work; Assistant Professor of Psychiatry, Department of Psychiatry, Univer-
    schizophrenia. US SEROQUEL Study Group. J Clin Psychopharmacol                     sity of Toronto, Toronto, Ontario.
    1996;16:158–69.                                                                      Manager, Health Economics and Outcomes Research, Janssen-Ortho Inc,
13. Peuskens J, Link CG. A comparison of quetiapine and chlorpromazine in the          Toronto, Ontario.
    treatment of schizophrenia. Acta Psychiatr Scand 1997;96:265–73.                     Biostatistician, Syreon Corporation, Vancouver, British Columbia.
14. Remington G, Chong SA. Conventional versus novel antipsychotics: changing          4
                                                                                         Senior Biostatistician, Syreon Corporation, Vancouver, British Columbia.
    concepts and clinical implications. J Psychiatry Neurosci 1999;24:431–41.          5
                                                                                         Associate Director of Health Economics and Outcomes Research,
15. American Psychiatric Association. Diagnostic and statistical manual of mental      Janssen-Ortho Inc, Toronto, Ontario.
    disorders, 4th ed. Text revision. Washington (DC): American Psychiatric Associ-    6
                                                                                         Director, Health Economics and Outcomes Research, Janssen-Ortho, Inc.,
    ation; 1994.
16. Beller SA, Overall JE. The Brief Psychiatric Rating Scale (BPRS) in gero-
                                                                                       Toronto, Ontario.
    psychiatric research: II. Representative profile patterns. J Gerontol              Address for correspondence: Dr RS McIntyre, Department of Psychiatry,
    1984;39:194–200.                                                                   University of Toronto, University Health Network, Toronto Western Hospi-
17. Gunasekara N, Spencer C. Quetiapine: a review of its use in schizophrenia. CNS     tal, 399 Bathurst Street, Toronto, ON M5T2S8
    Drugs 1998;9:325–40.                                                               e-mail:

              Résumé : Le risque de prise de poids associé au traitement antipsychotique :
              résultats de l’étude canadienne de mesure des résultats sur la schizophrénie
              Contexte : La prise de poids induite par les antipsychotiques se produit chez un pourcentage
              substantiel des personnes traitées. Il y a une rareté de données naturalistes qui décrivent la tendance
              relative à la prise de poids avec les nouveaux antipsychotiques atypiques (NAP) sur le marché. Cette
              étude décrit la prise de poids comparative induite par les NAP chez une cohorte naturaliste prospec-
              tive de personnes souffrant de schizophrénie et de troubles psychotiques reliés.
              Méthodes : L’étude canadienne de mesure des résultats sur la schizophrénie (ECMRS) est une étude
              prospective, longitudinale et naturaliste en cours dans 32 points universitaires et communautaires du
              Canada. Les personnes souffrant de schizophrénie, de trouble schizophréniforme ou schizo-affectif et
              de psychose non spécifiée, comme les définit le DSM-IV, ont été inscrites de façon consécutive. Les
              objectifs déterminants de cette initiative étaient de recueillir et de comparer les résultats de l’efficacité
              globale, de la tolérabilité, de l’innocuité et des répercussions humaines chez les personnes recevant
              des NAP offerts sur le marché au Canada. Cette analyse ne mentionne que les changements de poids
              selon les NAP respectifs. Les autres résultats apparaissent dans des articles complémentaires distincts.
              Résultats : Un spectre de la tendance à la prise de poids a été constaté : quétiapine (QUE) (ET moyen
              7,55 [9,20] kg, P = 0,28); olanzapine (OLZ) (ET moyen 3,72 [8,56] kg, P = 0,15); et rispéridone
              (RIS) (ET moyen 1,62 [7,72] kg, P = 0,43). La prise de poids définie catégoriquement (c’est-à-dire,
              plus de 7 % du poids de départ) a été observée chez 55,6 % des patients QUE, chez 24,1 % des pa-
              tients OLZ et chez 23,7 % des patients RIS. Après ajustement pour les facteurs confusionnels
              démographiques et propres à la maladie, les patients QUE avaient de plus fortes probabilités que les
              patients RIS de prendre plus de 7 % de leur poids de départ (OR 3,62; 95 % CI, 1,02 à 12,83; P =
              0,05). Aucune différence statistique n’a été détectée entre les patients OLZ et les patients RIS pour
              plus de 7 % du poids de départ (OR 1,54; 95 % CI, 0,63 à 3,75; P = 0,12) ou plus de 10 % de prise de
              poids (OR 1,44; 95 % CI, 0,50 à 4,13; P = 0,58).
              Conclusion : On rappelle aux cliniciens de surveiller les paramètres anthropométriques et
              métaboliques chez toutes les personnes traitées aux NAP. Des différences cliniquement significatives
              existent parmi les NAP sur le marché en ce qui concerne la tendance à la prise de poids.

                                                                                                         W Can J Psychiatry, Vol 48, No 10, November 2003

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