Excessive body weight gain (BWG) is a common side effect of some typical and atypical antipsychotic drugs (APs). Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. BWG may be related to increased appetite that is due to drug interaction with the brain monoaminergic and cholinergic systems and to the metabolic/endocrine effects of hyperprolactinemia. Subjects with schizophrenia and bipolar disorders manifested a significantly high prevalence of diabetes, even before the introduction of atypical APs. However, clozapine and olanzapine appear to display a high propensity to induce glucose dysregulation and dyslipidemia. Sudden BWG, insulin resistance, increased appetite, and related endocrine changes also may be involved in the development of glucose intolerance and dyslipidemia in predisposed individuals. Patients should be informed of these side effects in order to prevent excessive BWG, and their blood glucose and lipids should be monitored before treatment and then at regular intervals. Nutritional advice must be given and regular physical exercise recommended. An appropriate selection of APs ought to be based on drug efficacy for specific patients and assessment of relevant risk factors such as propensity to gain weight; family or personal history of diabetes or hyperlipidemia; and elevated fasting serum glucose, lipid, or insulin levels. At present, there is no standardized pharmacological treatment for AP-induced BWG. Some studies have assessed the effects of agents such as amantadine, orlistat, metformin, nizatidine, and topiramate on AP-induced BWG. Further studies will provide tools to identify patients at high risk for obesity and metabolic abnormalities during AP administration.
Excessive body weight gain (BWG), glucose intolerance, and dyslipidemia during treatment with antipsychotic drugs (APs) were reported in the late 1950s [14]
[101]. However, after 1990, interest in these problems increased noticeably, mainly because of the high propensity of some new atypical APs to induce these side effects (Fig. [1]). The APs are currently used in diverse mental disorders. Hence, excessive BWG and metabolic dysfunction are not exclusive of subjects with schizophrenia. In the case of bipolar disorders, AP-induced BWG may be additive to that induced by mood stabilizers [14]
[48]
[101].
The clinical features [2]
[14]
[24]
[133]
[139]
[140] and mechanisms [14]
[34]
[68]
[87]
[93]
[101]
[130] of BWG and metabolic dysfunction have been previously reviewed. In this article, we focus on a unified theory to explain these side effects, based on the interaction of APs with brain neurotransmitters involved in appetite regulation.
This review comprises the following sections: 1) the clinical features of AP-induced BWG; 2) the effects of APs on carbohydrate and lipid metabolism in humans and experimental animals; 3) mechanisms involved in BWG, glucose, and lipid dysregulation; 4) strategies for prevention and treatment of these side effects; and 5) research perspectives in the field.
The following sources were consulted: MEDLINE, Cochrane database system, and PsychINFO. Numerous articles referred to in leading articles also were consulted. The literature on this subject has increased so rapidly that it was impossible to include all the data recently published. For the first two sections, references that illustrate current controversies in the field were selected.
Abbreviations
APs:antipsychotic drugs
BMI:body mass index
BW:body weight
BWG:body weight gain
DM:diabetes mellitus
Type 2 DM:non-insulin dependent diabetes mellitus
Key words
Antipsychotic drugs - diabetes - dyslipidemia - gonadal steroids - insulin resistance - leptin - obesity - prolactin
References
-
1
Allison D B, Fontaine K R, Heo M, Mentore J L, Cappelleri J C, Chandler L P, Weiden P J, Cheskin L J.
The distribution of body mass index among individuals with and without schizophrenia.
J Clin Psychiatry.
1999;
60
215-20
-
2
Allison D B, Mentore J L, Heo M, Chandler L P, Cappelleri J C, Infante M C, Weiden P J.
Antipsychotic-induced weight gain: a comprehensive research synthesis.
Am J Psychiatry.
1999;
156
1686-1696
-
3 Allison D B, Cavazzoni P, Beasley C M, Berge P H, Mukhopadhyay N, Mallinckrodt C, Holcombe J, Taylor C C, Breier A, Buse J B. 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. International Congress on Schizophrenia Research. Whistler British Columbia; February 2001
-
4
Allison B D, Casey D E.
Antipsychotic-induced weight gain: a review of the literature.
J Clin Psychiatry..
2001;
62 suppl 7
22-31
-
5
Ammon H PT, Orci L, Steinker J.
Effect of chlorpromazine on insulin release in vivo and in vitro in the rat.
J Pharmacol Exp Ther..
1973;
187
423-429
-
6
Anghelescu I, Klawe C, Benkert O.
Orlistat in the treatment of psychopharmacologically induced weight gain.
J Clin Psychopharmacol.
2000;
20
716-717
-
7
Ardizzone T D, Bradley R J, Freeman A M, Dwyer D S.
Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine.
Brain Res.
2001;
923
82-90
-
8
Baptista T, Parada M A, Murzi E.
Puberty modifies sulpiride effects on body weight in rats. Neurosci.
Lett.
1988;
92
161-164
-
9
Baptista T, Hernández L, Hoebel B G.
Systemic sulpiride increases dopamine metabolites in the lateral hypothalamus.
Pharmacol Biochem Behav.
1990;
37
227-229
-
10
Baptista T, Molina M G, de Quijada M, Calanche I, Acosta A, Pàez X, Hernàndez L.
Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy women: relationship with body weight regulation.
Pharmacopsychiatry.
1997;
30
256-262
-
11
Baptista T, López M E, Teneud L, Contreras Q, Araujo de Baptista E, Weiss S RB, Musseo E, Hernàndez L.
Amantadine in the treatment of neuroleptic-induced obesity in rats: behavioral, endocrine and neurochemical correlates.
Pharmacopsychiatry.
1997;
30
43-54
-
12
Baptista T, Alvarez L, LaCruz A, de Mendoza S, Hernández L.
Glucose tolerance and serum insulin levels in an animal model of obesity induced by subacute or chronic administration of antipsychotic drugs.
Prog Neuro-Psychopharmacol & Biol Psychiat.
1999;
23
277-287
-
13
Baptista T, Reyes D, Hernández L.
Antipsychotic drugs and reproductive hormones: relationship to body weight regulation.
Pharmacol Biochem Behav.
1999;
62
409-417
-
14
Baptista T.
Body weight gain induced by antipsychotic drugs: mechanisms and management.
Acta Psychiatr Scand.
1999;
100
3-16
-
15
Baptista T, Lacruz A, Acosta A, Colasante C, de Quijada M, Mendoza S, Hernàndez L.
Naltrexone does not prevent the weight gain and hyperphagia induced by the antipsychotic drug sulpiride in rats.
Appetite.
2000;
34
77-86
-
16 Baptista T, Lacruz A, Paez X, Hernandez L. Why male rats do not gain weight during administration of antipsychotic drugs?. Society for Neuroscience Annual Meeting San Diego, CA; 2001 session 648.8
-
17
Baptista T, Lacruz A, Angeles F, Silvera R, Mendoza M T, Mendoza S, Hernàndez L.
Endocrine and metabolic profile in the obesity associated to typical antipsychotic drug-administration.
Pharmacopsychiatry.
2001;
34
223-231
-
18
Baptista T, Alvarez L, Cubillan-Bollero E, de Mendoza S, Hernàndez L.
Metformin in the obesity associated to antipsychotic dug administration: a pilot study.
J Clin Psychiat.
2001;
62
653-655
-
19
Baptista T, Lacruz A, Meza T, Contreras Q, Delgado C, Hernandez L.
Antipsychotic drugs and obesity: Is prolactin involved.
Can J Psychiatry.
2001;
46
829-834
-
20 Baptista T. Atypical Antipsychotic drugs and glucose dysregulation. Can J Psychiatry 2002 47: (in press)
-
21
Baruch R, Poluin M, Thakar A, Karagianis J.
Amantadine induces weight loss in patients treated with olanzapine.
Schiz Res.
2002;
S3
1-269
-
22
Basson B R, Kinon B J, Taylor C C, Szymanski K A, Glimore J A, Tollfeson G D.
Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol or risperidone.
J Clin Psychiatry.
2001;
62
231-238
-
23 Beasley C M, Sowell M O, Mukhopadhyay N, Cavazzoni P, Shankar S, Steinberg H O, Breier A, Danahberg J. Assessment of insulin secretory responses using the hyperglycemic clamp in normal subjects treated with olanzapine, risperidone or placebo. 40th Annual Meeting of the American College of Neuropsychopharmacology December 21, 2001
-
24
Blin O, Micallef J.
Antipsychotic-associated weight gain and clinical outcome parameters.
J Clin Psychiatry.
2001;
62 suppl 7
11-21
-
25
Bonaccorsi A, Garattini S, Jori A.
Studies on the hyperglycemia-induced by chlorpromazine in rats.
Brit J Pharmacol.
1964;
23
93
-
26
Bouchard R H, Demers M F, Simoneau I, Almeras N, Villenueve J, Mottard J P, Cadrin C, Lemieux I, Després J P.
Atypical antipsychotics and cardiovascular risk in schizophrenic patients.
J Clin Psychiatry.
2001;
21
110-111
-
27
Brambrilla F, Guerrini A, Guastalla A, Rovere C, Riggi F.
Neuroendocrine effects of haloperidol therapy in chronic schizophrenia.
Psychopharmacologia (Berl).
1975;
44
17-22
-
28
Brambilla F, Guastalla A, Guerrini A, Riggi F, Rovere C, Zanoboni A, Zanoboni-Muciaccia W.
Glucose-insulin metabolism in chronic schizophrenia.
Dis Nerv Sys.
1976;
37
8-103
-
29
Bray G A, Greenway F L.
Current and potential drugs for treatment of obesity.
Endocr Rev.
1999;
20
805-875
-
30 Breier A, Tanaka Y, Roychudry S, Clarke W S. Nizatidine for the prevention of olanzapine-associated weight gain in schizophrenia and related disorders-randomized controlled and double-blind studies. 4th International Meeting of the College of Psychiatric and Neurologic Pharmacists (CPNP) March 25-28, 2001 San Antonio, Texas;
-
31
Brochu M, Tchernof A, Dionne I J, Cites C K, Eltabbkh G H, Sims E A, Poehlman E T.
What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?.
J Clin Endocrinol Metab.
2001;
86
1020-1025
-
32
Bryden K, Kopala L C.
Body mass index increase of 58 % associated with olanzapine.
Am J Psychiatry.
1999;
156
1835-1836
-
33
Budman C L, Gayer B A.
Low blood glucose and olanzapine.
Am J Psychiatry.
2001;
158
500-510
-
34
Casey D E, Zorn S H.
The pharmacology of weight gain with antipsychotics.
J Clin Psychiatry.
2001;
62 suppl 7
4-10
-
35
Cassidy F, Ahearn E, Carroll B J.
Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients.
Am J Psychiatry.
1999;
156
1417-1420
-
36 Cavazzoni P, Baker R W, Kwong K, Hombuckle K, Hutchins D, Jovanovic L, Kotsanos J, Breier A, Buse J. A pharmacoepidemiological study of diabetes mellitus and antipsychotic treatment in the US. Presented at the 41th annual meeting of the New Clinical Drug Evaluation Unit May 28-31, 2001 Phoenix, Ariz
-
37
Centorrino F, Baldessarini R J, Kando J C, Frankenburg F R, Vopicelli S A, Flood J G.
Clozapine and metabolites: concentrations in serum and clinical findings suring treatment of chronically psychotic patients.
J Clin Psychopharmacol.
1994;
14
119-125
-
38
Cohen S, Glazewski R, Khan S, Khan A.
Weight gain with risperidone among patients with mental retardation: effect of calorie restriction.
J Clin Psychiatry.
2001;
62
114-116
-
39
Correa N, Opler L A, Kay S R, Birmaher B.
Amantadine in the treatment of neuroendocrine side effects of neuroleptics.
J Clin Psychopharmacol.
1987;
7
91-95
-
40 Cottingham E M. Metformin leads to weight loss in adolescents who gained weight on psychotropic drugs. Am Psychiat Assoc 2000 Chicago, IL;
-
41 Daniel D G, Weiden P, O’Sullivan R L. Improvements in indices of health status in outpatients with schizophrenia following a switch to ziprasidone from conventional antipsychotics, olanzapine or risperidone. New Research Abstracts, 153rd Annual Meeting of the American Psychiatric Association May 16, 2000 Chicago, IL; Abstract NR359 : 154
-
42
Dixon L, Weiden P, Delahanty J, Goldberg R, Postgrado L, Lucksted A, Lehman A.
Prevalence and correlates of diabetes in national schizophrenia samples.
Schizophr Bull.
2000;
26
903-912
-
43
Dursun S M, Devarajan S.
Clozapine weight gain, plus topiramate weight loss.
Can J Psychiat.
2000;
45
198
-
44
Dynes J B.
Diabetes in schizophrenia and diabetes in nonpsychotic medical patients.
Dis Nerv Sys.
1969;
30
341-344
-
45
Ebenezer I S.
Effects of the 5-HT1A agonist 8 - 0H-DPTA on food intake in food-deprived rats.
Neuroreport.
1992;
3
1019-1022
-
46
Eckel R H.
Insulin resistance: an adaptation for weight maintenance.
The Lancet.
1992;
340
1452-1453
-
47
Eder U, Mangweth B, Ebenbichler C, Weiss E, Hofer A, Hummer M, Kemmler G, Lechleitner M, Fleischhacer W W.
Association of olanzapine-induced weight gain with an increase in body fat.
Am J Psychiatry.
2001;
158
1719-1722
-
48
Elsmlie J L, Silverstone J T, Mann J I, Williams S M, Romans S E.
Prevalence of overweight and obesity in bipolar patients.
J Clin Psychiat.
2000;
61
179-184
-
49
Erfurth A, Kuhn G.
Topiramate monotherapy in the maintenance treatment of bipolar I disorder: effect on mood, weight and serum lipids.
Neuropsychobiology.
2000;
42 (suppl 11)
50-61
-
50
Erle G, Basso M, Federspil G, Sicolo N, Scandellari C.
Effect of chlorpromazine on blood glucose and plasma insulin in man.
Eur J Clin Pharmacol.
1977;
11
15-18
-
51
Figlewicz D P, Schwartz M W, Seeley R J, Chavez M, Baskin D G, Woods S C, Porte D.
Endocrine regulation of food intake and body weight.
J Lab Clin Med.
1996;
127
328-332
-
52
Floris M, Lejeune J, Debert W.
Effect of amantadine on weight gain during olanzapine treatment.
Eur Neuropsychopharmacol.
2001;
11
181-182
-
53
Fox I, Auberger H.
Effect of neuroleptoanalgesia on blood sugar tolerance in humans.
Acta Anaesthesiol Scand (Suppl).
1966;
23
3-11
-
54
Ghaeli P, Dufresne R L.
Serum triglyceride levels in patients treated with clozapine.
Am J Health Syst Pharm.
1996;
53
2079-2081
-
55 Glick I D, Fryburg D, O’Sullivan R I. Ziprasidone’s benefits versus olanzapine in weight gain and insulin resistance. In: New Research Abstracts of the 154th Annual Meeting of the American Psychiatric association 2001 New Orleans, LA; Abstract NR261 : 71
-
56
Gopalaswamy A K, Morgan R.
Too many chronic mentally disabled patients are too fat.
Acta Psychiat Scand.
1985;
72
254-258
-
57
Gordon A, Proce L H.
Mood stabilization and weight loss with topiramate.
Am J Psychiatry.
1999;
156
968-969
-
58
Grimm J J.
Interaction of physical activity and diet: implications for insulin-glucose dynamics.
Public Health Nutr.
1999;
2 (3A)
363-368
-
59 Guyton A C. Textbook of Medical Physiology. 1991 Philadelphia; W.B. Saunders pp. 855-867
-
60
Hagen C, Pederson P B, Jensen S B, Faber O K, Jensen T.
The effects of sulpiride-induced hyperprolactinemia on glucose tolerance and insulin secretion in normal subjects.
Clin Endocrinol (Oxf).
1979;
10
55-60
-
61
Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlquvist R.
Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications.
J Clin Psychiatry.
1998;
59
294-299
-
62
Hagg S, Soderberg S, Ahren B, Olsson T, Mjorndal T.
Leptin concentrations are increased in subjects treated with clozapine or conventional antipsychotics.
J Clin Psychiatry.
2001;
62
843-848
-
63
Harris R BS.
Leptin-much more than a satiety signal.
Ann Rev Nutr.
2000;
20
45-75
-
64
Haupt D W, Newcomer J W.
Hyperglycemia and antipsychotic medication.
J Clin Psychiatry.
2001;
suppl 27
15-26
-
65
Heikkinen H, Outakoski J, Merilaeinen V, Tuomi A, Huttunen M O.
Molindone and weight loss.
J Clin Psychiat.
1993;
54
160-161
-
66
Henderson D C, Cagliero E, Gray C, Narallah R A, Hayden D L, Schoenfeldt D A, Goff D C.
Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study.
Am J Psychiat.
2000;
157
975-981
-
67 Henderson D C, Cagliero E, Borbs C P. Atypical antipsychotic agents and glucose metabolism. Bergman’s MINMOD Analysis. Presented at the 40th annual meeting of the New Clinical Drug Evaluation Unit 2000 Boca Raton, Fla, US;
-
68
Henderson D C.
Clinical experience with insulin resistance, diabetic ketoacidosis, and type 2 diabetes mellitus in patients treated with atypical antipsychotics.
J Clin Psychiatry.
2001;
suppl 27
10-14
-
69
Henry R R, Wallace P, Olefsky J M.
Effects of weight loss on mechanisms of hyperglycemia in obese noninsulin dependent diabetes mellitus.
Diabetes.
1998;
35
990-998
-
70
Herrán A, García-Unzueta M T, Amado J A, de la Maza M T, Alvarez C, Vasquez-Barquero L.
Effects of long-term treatment with antipsychotics on serum leptin levels.
Brit J Psychiatry.
2001;
179
59-62
-
71
Hutton J.
The economics of treating obesity.
Pharmacoeconomics.
1994;
5
66-72
-
72
Jalenques Y, Tauveron Y, Albuisson E, Audy V, Fleury-Duhamel N, Coudert A J.
Weight gain as a predictor of long-term clozapine efficacy.
CNS Drugs.
1996;
12
16-25
-
73
Jones B, Rasson B E, Walker D J, Crawford A MK, Kinon B J.
Weight change and atypical antipsychotic treatment in patients with schizophrenia.
J Clin Psychiatry.
2001;
62 (suppl 2)
41-44
-
74
Kahn B B, Lier J S.
Obesity and insulin resistance.
J Clin Invest.
2000;
106
473-481
-
75
Kasper S, Müller-Spanh F.
Review of quetiapine and its clinical applications in schizophrenia. Exp.
Opin Pharmacother.
2000;
1
783-801
-
76
Kendrick T.
Cardiovascular and respiratory risk factors and symptoms among general practice patients with long-term mental illness.
Brit J Psychiatry.
1996;
169
733-739
-
77
Kinon B J, Basson B R, Gilmore J A, Tollefson G D.
Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia.
J Clin Psychiatry.
2001;
62
92-100
-
78
Kinsbury S J, Fayek M, Trufasiu D, Zada J, Simpson G M.
The apparent effects of ziprasidone on plasma lipids and glucose.
J Clin Psychiatry.
2001;
62
347-349
-
79
Kissebah A H, Krakower G R.
Regional adiposity and morbidity.
Physiol Rev.
1994;
74
761-811
-
80
Korenyi C, Lowestein B.
Chlorpromazine induced diabetes.
Dis Nerv Sys.
1968;
29
827-828
-
81
Kraus Y, Eylon L, Cerasi E.
Calcium-binding proteins and insulin release. Differential effects of phenothiazines on first- and second-phase secretion and on islet cAMP response to glucose.
Acta Endocrinol (Copenh).
1987;
116
241-246
-
82
Lamberti J S, Bellnier T, Schwarkopz S B.
Weight gain among schizophrenic patients treated with clozapine.
Am J Psychiatry.
1992;
149
689-690
-
83
Leadbetter R, Shutty M, Pavalonis D, Vieweg V, Higgins P, Downs M.
Clozapine-induced weight gain: prevalence and clinical relevance.
Am J Psychiatry.
1992;
149
68-72
-
84
Lechin F, Coll-Garcìa E, van der Dijs B, Bentolila A, Peña F, Rivas C.
The effects of dopaminergic blocking agents on the glucose tolerance test in 6 humans and 6 dogs.
Experientia.
1979;
35
886-887
-
85
Lebovitz H E.
Diagnosis, classification and pathogenesis of diabetes mellitus.
J Clin Psychiatry.
2001;
62 (suppl 27)
5-9
-
86
Liebzeit K A, Markowitz J S, Caley C F.
New onset diabetes and atypical antipsychotics.
Eur Neuropsychopharmacol.
2001;
11
25-32
-
87
Lindenmayer J P, Nathan A N, Smith R C.
Hyperglycemia associated with the use of atypical antipsychotics.
J Clin Psychiatry.
2001;
suppl 23
30-38
-
88
Lorenz W F.
Sugar tolerance in dementia praecox and other mental disorders.
Arch Neurol Psychiatry.
1922;
8
184-196
-
89
Lund B C, Perry P J, Brooks J M, Arndt S.
Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia and hypertension.
Arch Gen Psychiatry.
2001;
58
1172-1176
-
90 Mahmoud R, Gianfrancesco F, Grogg A M, Nasrallah A H. Differential effects of antipsychotics on type II diabetes: findings from a large health plan database. Presented at the 39th annual meeting of the American College mof Neuropsychopharmacology Dec 10-14, 2000 San Juan Puerto Rico;
-
91
Marmomier C, Chapelot D, Louis-Sylvestre J.
Metabolic and behavioral consequences of a snack consumed in a satiety state.
Am J Clin Nutr.
1999;
70
854-866
-
92
Martin A, Landau J, Leebens P, Ulizio K, Cicchetti D, Scahill L, Leckman J F.
Risperidone-associated weight gain in children and adolescentes: a retrospective chart review.
J Child Adoles Psychopharmacol.
2000;
10
259-268
-
93
McIntyre R S, McCann S M, Kennedy S H.
Antipsychotic metabolic effects: weight gain, diabetes mellitus and lipid abnormalities.
Can J Psychiatry.
2001;
46
273-281
-
94 McIntyre R S, Trakas K, Robinson K, Eggleston A. Weight gain associated with antipsychotic treatment: result from the Canadian National outcomes measurement study in schizophrenia. 40th Annual Meeting of the American College of Neuropsychopharmacology December 21, 2001
-
95
Meguid M M, Fetissiv S O, Varma M, Sato T, Zhang L, Laviano A, Rossi-Fanelli F.
Hypothalamic dopamine and serotonin in the regulation of food intake.
Nutrition.
2000;
16
843-857
-
96
Melkerson K I, Hulting A L, Brismar K E.
Different influences of classical antipsychotics and clozapine on glucose-insulin homeostasis in patients with schizophrenia or related psychoses.
J Clin Psychiatry.
1999;
60
783-791
-
97
Melkerson K I, Hulting A L, Brismar K E.
Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses.
J Clin Psychiatry.
2000;
61
742-749
-
98
Melkerson K I, Hulting A L.
Insulin and leptin levels in patients with schizophrenia or related psychoses-a comparison between different antipsychotic agents.
Psychopharmacol.
2001;
154
205-212
-
99
Melkerson K I, Khan A, Hilding A, Hulting A L.
Different effects of antipsychotics drugs on insulin release in vitro.
Eur Neuropsychopharmacol.
2001;
11
327-332
-
100
Meltzer H Y.
The role of serotonin in antipsychotic drug action.
Neuropsychopharmacol.
1999;
21
106S-115S
-
101
Meyer J M.
Effects of atypical antipsychotics on weight and serum lipid levels.
J Clin Psychiatry.
2001;
62 (suppl 27)
27-34
-
102
Mir S, Taylor D.
Atypical antipsychotics and hyperglycemia.
Int Clin Psychopharmacol.
2001;
16
63-73
-
103
Mukherjee S, Schnur D B, Reddy R.
Family history of type 2 diabetes in schizophrenic patients.
Lancet.
1989;
1
495
-
104
Mukherjee S, Decina P, Bocola V, Saraceni F, Scapicchio P L.
Diabetes mellitus in schizophrenic patients.
Compr Psychiatry.
1996;
37
68-73
-
105
Must A, Spadano J, Coakley E H, Field A E, Colditz G, Dietz W H.
The disease burden associated with overweight and obesity.
JAMA.
1999;
282
1523-1529
-
106
Mystokowski P, Schwartz M W.
Gonadal steroids and energy homeostasis in the leptin era.
Nutrition.
2000;
16
937-946
-
107
Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verriele L, Audinot V, Millan M J.
Agonist and antagonist actions of antipsychotic agents as 5-HT1A receptors: a [35S]GTPgammaS binding study.
Eur J Pharmacol.
1998;
355
245-256
-
108 Nguyen C T, Ortiz T, Franklin D, Maguire G. Nutritional education in minimizing weight gain associated with antipsychotic therapy. Am Psychiat Assoc (APA) May 5-10, 2001 New Orleans;
-
109
Osser D N, Najarian D M, Dufresne R L.
Olanzapine increase weight and serum triglycerides.
J Clin Psychiatry.
1999;
60
767-770
-
110
Penn J V, Martini J, Radka D.
Weight gain associated with risperidone.
J Clin Psychopharmacol.
1996;
16
259-260
-
111
Pollmächer T, Haack M, Schuld A, Kraus T, Hinze-Selch D.
Effects of antipsychotic drugs on cytokine networks.
J Psychiat Res.
2000;
34
369-382
-
112 Pouzet B, Sonne Hansen R. Preclinical investigation for antipsychotics induced weight gain. Schiz Res 2002 S3: pp.158
-
113
Ravusin E, Bouchard C.
Human genomics and obesity: finding appropriate drug targets.
Eur J Pharmacol.
2000;
410
131-145
-
114
Reinstein M F, Sirotovskaya L A, Jones L E.
Effect of clozapine-quetiapine combination therapy on weight and glycaemic control.
Clin Drug Invest.
1999;
18
99-104
-
115
Reynolds G P, Zhang Z J, Zhang X B.
Association of antipsychotic drug-induced weight gain with a polymorphism of the promotor region of the 5HT2C receptor gene.
Schiz Res.
2002;
S3
1-269
-
116
Richelson E.
Receptor pharmacology of neuroleptics: relation to clinical effects.
J Clin Psychiatry.
1999;
60 (suppl 10)
5-14
-
117
Richelson E, Souder T.
Binding of antipsychotic drugs to human brain receptors: focus on newer generation compounds.
Life Sci.
2000;
68
29-39
-
118
Rietschel M, Naber D, Oberländer H, Holzbach R, Fimmers R, Eggermann K, Möller H J, Propping P, Nöthen M M.
Efficacy and side-effects of clozapine: testing for association with allelic variation in the dopamine D4 receptor gene.
Neuropsychopharmacol.
1996;
15
491-496
-
119
Rietschel M, Naber D, Fimmers R, Möller H, Propping P, Nöthem M M.
Efficacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor.
Neuroreport.
1997;
8
1999-2003
-
120
Sacchetti E, Guarneri L, Bravi D.
H2 antagonist nizatidine may control olanzapine-associated weight gain in schizophrenic patients.
Biol Psychiat.
2000;
48
167-168
-
121
Seeger T F, Seymour P A, Schmidt A W, Zorn S H, Schulz D W, Lebel L A, McLean S, Guanovsky V, Howard H R, Lowe J A.
Ziprasidone (CP88.059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity.
J Pharmacol Exp Ther.
1995;
275
101-113
-
122
Shapira N A, Goldsmith T D, McElroy S L.
Treatment of binge-eating disorder with topiramate: a clinical case series.
J Clin Psychiat.
2000;
61
368-372
-
123
Sheitman B B, Bird P M, Binz W, Akinly L, Sanchez C.
Olanzapine-induced elevation of plasma trygliceride levels.
Am J Psychiatry.
1999;
156
1471-1472
-
124
Silverstone T, Smith G, Goodall E.
Prevalence of obesity in patients receiving depot antipsychotics.
Br J Psychiatry.
1988;
153
214-217
-
125
Simpson G M, Varga E.
Clozapine: a new and unusual antipsychotic agent.
Psychopharmacol Bull.
1975;
11
14-15
-
126
Simpson M M, Goetz R R, Devlin M J, Goetz S A, Walsh B T.
Weight gain and antipsychotic medication: differences between antipsychotic-free and treatment periods.
J Clin Psychiatry.
2001;
62
694-700
-
127
Spivak B, Roittman S, Vered Y, Mester R, Graff E, Talmon Y, Guy N, Gonen N, Weizman A.
Diminished suicidal and aggressive behavior, high plasma norepinephrine levels, and serum triglyceride levels in chronic neuroleptic-resistant schizophrenic patients maintained on clozapine.
Clin Neuropharmacol.
1998;
21
245-250
-
128
Stedman T, Welhan J.
The distribution of adipose tissue in female in-patients receiving psychotropic drugs.
Br J Psychiatry.
1993;
162
249-250
-
129
Steppan C M, Bailey S T, Bhat S, Brown E J, Banerjee R R, Wright C M, Patel H R, Ahima R S, Lazar M A.
The hormone resistin links obesity to diabetes.
Nature.
2001;
409
292-293
-
130
Sussman N.
Review of atypical antipsychotics and weight gain.
J Clin Psychiatry.
2001;
suppl 23
5-12
-
131
Swinburn B A, Nyomba B I, Saad M F, Zurlo F, Raz I, Knowler W C, Patel H R, Ahima R S, Lazar M A.
Insulin resistance associated with lower rates of weight gain in Pima Indians.
J Clin Invest.
1991;
88
168-173
-
132
Tatsumi M, Jansen K, Blakely R D, Richelson E.
Pharmacological profile of neuroleptics at human monoamine transporters.
Eur J Pharmacol.
1999;
368
277-283
-
133
Taylor D M, McAskill R.
Atypical antipsychotics and weight gain-a systematic review.
Acta Psychiat Scand.
2000;
101
416-432
-
134
Teter C J, Early J J, Gibbs C M.
Treatment of affective disorder and obesity with topiramate.
Ann Pharmacother.
2001;
34
1262-1265
-
135
Theisen F M, Cichon S, Linden A, Martin M, Remschmidt H, Hebebrand J.
Clozapine and weight gain.
Am J Psychiatry..
2001;
158
5
-
136
Theisen F M, Geller F, Schafer H, Martin M, Remschmidt H, Hebebrand J.
Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication.
J Psychiat Res.
2001;
35
339-345
-
137
Thonnard-Neumann E.
Phenothiazines and diabetes in hospitalized women.
Am J Psychiatry.
1968;
124
978-982
-
138
Tuomilehto J, Lindstrom J, Eriksson J G, Valle T T, Hamalainen H, Llanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M.
Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with Impaired Glucose Tolerance.
N Engl J Med.
2001;
344
1343-1350
-
139
Wetterling T, Müßigbrodt H E.
Weight gain: side effects of atypical neuroleptics?.
J Clin Psychopharmacol.
1999;
19
316-321
-
140
Wetterling T.
Bodyweight gain with atypical antipsychotics: A comparative review.
Drug Safety.
2001;
24
59-73
-
141
Wirshing D A, Spellberg B J, Erhart S M, Marder S R, Wirshing W C.
Novel antipsychotics and new onset diabetes.
Biol Psychiatry.
1998;
44
778.783
-
142
Wirshing D A, Wirshing W C, Kysar L, Berisford M A, Goldstein D, Pashdag J, Mintz J, Marder S R.
Novel antipsychotics : comparison of weight gain liabilities.
J Clin Psychiatry.
1999;
60
358-363
-
143
Wiznieski K, Buczko W.
The central pharmacological effect of chlorpromazine in rats with alloxan-diabetes.
Biochem Pharmacol.
1967;
16
2227-2230
-
144 World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO consultation on obesity Geneva; June 3-5, 1997
-
145
Yazici K M, Erbas T, Yazici A H.
The effect of clozapine on glucose metabolism.
Exp Clin Endocrinol Diabetes.
1998;
106
475-477
-
146
Zimmermann U, Rechlin T H, Plaskacewicz G J, Barocka A, Wildt L, Kaschka P.
Effect of Naltrexone on weight gain and food craving induced by tricyclic antidepressants and lithium: an open study.
Biol Psychiat.
1997;
41
747-749
-
147
Zofkova I, Stolba P.
Effect of calcitriol and trifluoperazine on glucose stimulated ß cell function in healthy humans.
Exp Clin Endocrinol.
1990;
96
185-191
-
148
Zoler M L.
Antipsychotics linked to weight gain, diabetes.
Clin Psychiatr News.
1999;
27
20
Trino Baptista
Douglas Hospital Research Center (F1116)
6875 LaSalle Blvd
Verdun, Québec
H4H1R3
Canada
Fax: +(514) 888-4064
eMail: baptri@douglas.mcgill.ca
