Fortschr Neurol Psychiatr 2003; 71(6): 312-322
DOI: 10.1055/s-2003-39593
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Diabetes mellitus Typ II - induziert durch „atypische” Neuroleptika?

Diabetes Mellitus Type II - Induced by “Atypical” Neuroleptics?T.  Wetterling1
  • 1Klinik für Psychiatrie und Psychotherapie I, J.-W.-Goethe-Universität, Frankfurt/M. (Direktor: Prof. Dr. K. Maurer)
Further Information

Publication History

Publication Date:
10 June 2003 (online)

Zusammenfassung

Nach der Markteinführung der so genannten „atypischen” Neuroleptika ist mehrfach über erhöhte Blutzuckerwerte und auch über einen Diabetes mellitus Typ II bei Patienten, die mit diesen Medikamenten behandelt wurden, berichtet worden. In dieser Übersicht sollen die bisher in der Literatur beschriebenen Berichte und Studien referiert werden. Einige epidemiologische Studien zeigen, dass ein Diabetes mellitus im Vergleich zu klassischen Neuroleptika gehäuft bei „atypischen” auftritt. Nach den bisher vorliegenden Daten ist eine Hyperglykämie und ein Diabetes mellitus Typ II besonders bei Patienten, die mit Clozapin und Olanzapin behandelt wurden, beobachtet worden. Auch eine diabetische Ketoazidose wurde vor allem bei der Behandlung mit diesen Medikamenten berichtet. Die zugrunde liegenden Pathomechanismen sind noch nicht hinreichend geklärt. Einige Befunde deuten darauf hin, dass wahrscheinlich einer durch „atypische” Neuroleptika gesteigerten Sekretion von Insulin und möglicherweise auch Leptin eine wichtige Rolle zukommt. Da Übergewicht ein wichtiger Risikofaktor für einen Diabetes mellitus Typ II ist, kommt möglicherweise auch der gewichtsinduzierenden Wirkung von atypischen Neuroleptika eine wichtige Rolle zu. Da ein Diabetes mellitus Typ II häufig zu schwerwiegenden Folgeerkrankungen führt, sollte den Blutzuckerwerten in der Behandlung mit „atypischen” Neuroleptika mehr Aufmerksamkeit gewidmet werden.

Abstract

After the introduction of the so-called „atypical antipsychotics” in the clinical practice hyperglycemia as well as increased triglyceride and cholesterol serum levels were reported in patients treated with some of these agents. The studies and case reports available up to now were reviewed. Some epidemiologic studies show that diabetes mellitus occurs more often in patients treated with atypical antipsychotics if compared to conventional antipsychotics. The available data show that hyperglycemia and diabetes mellitus type II were particularly observed in patients receiving clozapine and olanzapine. Also diabetic ketoacidosis was most frequently reported in patients treated with these drugs. The underlying pathomechanism still remains widely unclear. There is some evidence for an important role of insulin and also leptin. Their secrection seems to be influenced by some atypical antipsychotics. Since overweight is a known risk-factor for diabetes mellitus type II, the weight inducing effect of atypical antipsychotics may also play an important role. Since diabetes mellitus type II often lead to severe diseases, the serum glucose levels should be paid more attention in the treatment with atypical neuroleptics.

Literatur

  • 1 Naber D, Lambert M, Krausz M. Atypische Neuroleptika in der Behandlung schizophrener Patienten. 2. Aufl. Bremen: Uni-Med 2000
  • 2 Kane J M. What makes an antipsychotic “atypical”?.  CNS Drugs. 1997;  7 947-948
  • 3 Gründer G, Vernaleken I, Benkert O. Welche Eigenschaften machen ein Neuroleptikum „atypisch”?.  Nervenarzt. 2001;  72 833-843
  • 4 Henderson D C. Clozapine: Diabetes mellitus, weight gain, and lipid abnormalities.  J Clin Psychiatry. 2001;  62 Suppl 23 39-44
  • 5 Kato M M, Goodnick P J. Antipsychotic medication: Effects on regulation of glucose and lipids.  Expert Opin Pharmacother. 2001;  2 1571-1582
  • 6 Liebzeit K A, Markowitz J S, Caley C F. New onset diabetes and atypical antipsychotics.  Eur Neuropsychopharmacol. 2001;  11 25-32
  • 7 Lindenmayer J-P, Nathan A-M, Smith R C. Hyperglycemia associated with the use of atypical antipsychotics.  J Clin Psychiatry. 2001;  62 Suppl 23 30-38
  • 8 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
  • 9 Mir S, Taylor D. Atypical antipsychotics and hyperglycaemia.  Int Clin Psychopharmacol. 2001;  16 63-74
  • 10 Wirshing D A. Adverse effects of atypical antipsychotics.  J Clin Psychiatry. 2001;  62 Suppl 21 7-10
  • 11 Taylor D M, McAskill R. Atypical antipsychotics and weight gain - a systemic review.  Acta Psychiatr Scand. 2000;  101 416-432
  • 12 Wetterling T. Gewichtszunahme - eine unterschätzte Nebenwirkung atypischer Neuroleptika?.  Fortschr Neurol Psychiat. 2000;  68 546-556
  • 13 Aronne L J. Epidemiology, morbidity, and treatment of overweight and obesity.  J Clin Psychiatry. 2001;  62 Suppl 23 13-22
  • 14 Chan J M, Rimm E B, Colditz G A, Stampfer M J, Willett W C. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men.  Diabetes Care. 1994;  17 961-969
  • 15 Colditz G A, Willett W C, Rotnitzky A, Manson J E. Weight gain as a risk factor for clinical diabetes mellitus in women.  Ann Intern Med. 1995;  122 481-486
  • 16 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997 20: 1183-1197
  • 17 American Diabetes Association . National standards for diabetes self-management and American Diabetes Association review criteria.  Diabetes Care. 1999;  22 Suppl 2 S111-S114
  • 18 Scherbaum W A, Lauterbach K W, Joost H G. Hrsg .Evidenz-basierte Diabetes-Leitlinien DDG: Definition, Klassifikation und Diagnostik des Diabetes mellitus. 1. Aufl. 2001
  • 19 Hauner H. Verbreitung des Diabetes mellitus in Deutschland.  DMW. 1998;  123 777-782
  • 20 Wetterling T. Hyperlipidämie - Nebenwirkung bei Behandlung mit einem atypischen Neuroleptikum (Zotepin)?.  Psychiat Prax. 2002;  29 438-440
  • 21 Liebl A, Neiss A, Spannheimer A, Reitberger U, Wagner T, Gortz A. Kosten des Typ-2-Diabetes in Deutschland. Ergebnisse der CODE-2 Studie.  DMW. 2001;  126 585-589
  • 22 Ashton W D, Nanchahal K, Wood D A. Body mass index and metabolic risk factors for coronary heart disease in women.  Eur Heart J. 2001;  22 46-55
  • 23 Beckman J A, Creager M A, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management.  JAMA. 2002;  287 2570-2581
  • 24 Kasani J. The blood sugar curve in mental disease. The schizophrenic (dementia praecox) groups.  Arch Neurol Psychiatry. 1926;  16 414-419
  • 25 Lorenz W F. Sugar intolerance in dementia praecox and other mental disorders.  Arch Neurol Psychiatry. 1922;  8 184-196
  • 26 Meduna L J, Vaichulis J A. A hyperglycemia factor in the urine of so-called schizophrenics.  Dis Nerv Syst. 1948;  9 248-250
  • 27 Simon W, Garvey J T. Glucose tolerance in chronic schizophrenia and senile state.  Arch Neurol Psychiatry. 1951;  65 717-723
  • 28 Aldrich C K. Glucose tolerance in disturbed schizophrenic patients.  Arch Neurol Psychiatry. 1948;  60 498-503
  • 29 Braceland F J, Meduna L V, Vaichulis J A. Delayed action of insulin in schizophrenia.  Am J Psychiatry. 1945;  102 108-110
  • 30 Dixon L, Weiden P, Delahanty J, Goldberg R, Postrado L, Lucksted A, Lehman A. Prevalence and correlates of diabetes in national schizophrenia samples.  Schizophr Bull. 2000;  26 93-102
  • 31 Mukherjee S, Decina P, Bocola V, Saraceni F, Scapicchio P L. Diabetes mellitus in schizophrenic patients.  Compr Psychiatry. 1996;  37 68-73
  • 32 Dynes J B. Diabetes in schizophrenia and diabetes in nonpsychotic medical patients.  Dis Nerv Sys. 1969;  30 341-344
  • 33 Thonnard-Neumann E. Phenothiazines and diabetes in hospitalized women.  Am J Psychiatry. 1956;  113 827-828
  • 34 Thonnard-Neumann E. Phenothiazines and diabetes in hospitalized women.  Am J Psychiatry. 1968;  124 978-982
  • 35 Allison D B, Fontaine K R, Heo M, Mentore J L, Cappeleri 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;  60 215-220
  • 36 Delay J, Deniker P, Harl J M. Utilisation en therapeutique psychiatrique d'une phenothiazine d'action centrale elective (4560 R.P.).  Ann med-psychol. 1952;  110 112-131
  • 37 Courvoisier S, Fournel J, Ducrot R, Kolsky M, Koetschet P. Proprietes pharmacodynamiques du chlorhydrate de chloro-3 (dimethylamino-3′propyl) 10 phenothiazine.  Arch Int Pharmacodyn. 1953;  92 305-361
  • 38 Hiles B W. Hyperglycemia and glycosuria following chlorpromazine therapy.  JAMA. 1956;  162 1651
  • 39 Goncalves N, Grueneberg F. Einzeitige orale Glukosebelastung bei langfristig neuroleptisch behandelten Schizophrenen.  Pharmakopsychiatrie. 1975;  8 289-295
  • 40 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
  • 41 Newcomer J W, Haupt D W, Fucetola R, Melson A K, Schweiger J A, Cooper B P, Selke G. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia.  Arch Gen Psychiatry. 2002;  59 337-345
  • 42 Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlqvist 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
  • 43 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: a claims-based approach.  Arch Gen Psychiatry. 2001;  58 1172-1177
  • 44 Koller E, Schneider B, Bennett K, Dubitsky G. Clozapine-associated diabetes.  Am J Med. 2001;  111 716-723
  • 45 Koller E A, Doraiswamy P M. Olanzapine-associated diabetes mellitus.  Pharmacotherapy. 2002;  22 841-852
  • 46 Koro C E, Fedder D O, L'Italien G J, Weiss S S, Magder L S, Kreyenbuhl J, Revicki D A, Buchanan R W. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study.  BMJ. 2002;  325 243-245
  • 47 Sernyak M J, Leslie D L, Alarcon R D, Losonczy M F, Rosenheck R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia.  Am J Psychiatry. 2002;  159 561-566
  • 48 Wang P S, Glynn R J, Ganz D A, Schneeweiss S, Levin R, Avorn J. Clozapine use and risk of diabetes mellitus.  J Clin Psychopharmacol. 2002;  22 236-243
  • 49 Cavazzoni P, Baber R W, Kwong K. et al . A pharmacological study of diabetes mellitus and antipsychotic treatment in the United States. 41th meeting of the New Clinical Drug Evaluation Unit, Phoenix, Arizona, 28. - 31. 5. 2001 (zitiert in Kretschmar A. Internistische Fragestellungen in der Neuroleptika-Therapie.  Nervenheilkunde. 2001;  Suppl 7 9-11)
  • 50 Cavazzoni P, Hornbuckle K, Carlson C, Wu J, Breier A, Kotsanos J, Holman R. Diabetes mellitus and antipsychotic treatment in the United Kingdom. (E. Lilly-gesponsortes) Poster, 23th CINP-Congress, Montreal, 23. - 27. 6. 2002
  • 51 L'Italien G J, Stump T E, Farewell W R, Wang J, Tafessee E, Tierney W M. The effects of olanzapine and risperidone use on new-onset diabetes and weight gain among schizophrenic patients. (Bristol-Myers Squibb-gesponsortes) Poster, 23th CINP-Congress, Montreal, 23. - 27. 6. 2002
  • 52 Farwell W R, Stump T E, Wang J, Tafesse E, L'Italien G J, Iwamoto T, Tierney W M. Do olanzapine and risperidone cause weight gain and diabetes?.  Int J Neuropsychopharmacol. 2002;  5 Suppl S170
  • 53 Shermock K M, Fuller M A, Secic M, Grogg A. Relationship between antipsychotics and the development of diabetes in a VA population. (Janssen-gesponsortes) Poster, 23th CINP-Congress, Montreal, 23. - 27. 6. 2002
  • 54 Sowell M O, Cavazzoni P, Roychowdhury S M, Breier A. Antipsychotics and diabetes: Lack of evidence for a causal relationship?. (E. Lilly-gesponsortes) Poster, 23th CINP-Congress, Montreal, 23. - 27. 6. 2002
  • 55 Buchanan R W, Koro C E, L'Italien G J, Weiss S, Magder L S, Fedder D O. An assessment of the independent effect of olanzapine and risperidone on the relative risk of diabetes in schizophrenia patients. (Bristol-Myers Squibb-gesponsortes) Poster, 23th CINP-Congress, Montreal, 23. - 27. 6. 2002
  • 56 Gianfranco F, Grogg A, Mahmoud R, Mackowitz J, Nasrallah H A. Association of new-onset diabetes and antipsychotics: Findings from a large health plan database. (Janssen-gesponsortes) Poster, 39th Annual meeting of the American College of Neuropharmacology, San Juan, Puerto Rico, 10. - 14. 12. 2000
  • 57 Chue P, Welch R. Investigation of the metabolic effects of antipsychotics in patients with schizophrenia. (Janssen-gesponsortes) Poster, 23th CINP-Congress, Montreal, 23. - 27. 6. 2002
  • 58 Meyer J M. A rectrospective comparison of weight, lipid, and glucose changes between olanzapine- and risperidone-treated inpatients: metabolic outcomes after 1 year.  J Clin Psychiatry. 2002;  63 425-433
  • 59 Glick I D, Romano S J, Simpson G, Horne R L, Weiden P, Pigott T, Bari M. Insulin resistance in olanzapine- and ziprasidone-treated patients: Results of a double-blind, controlled 6 week trial. (Pfizer gesponsortes) Poster, 154th APA Annual meeting, New Orleans, 5. - 10. 5. 2001
  • 60 Henderson D C, Cagliero E, Gray C, Nasrallah R A, Hayden D L, Schoenfeld D A, Goff D C. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study.  Am J Psychiatry. 2000;  157 975-981
  • 61 Melkersson 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
  • 62 Lindenmayer J P, Patel R. Olanzapine-induced ketoacidosis with diabetes mellitus.  Am J Psychiatry. 1999;  156 1471
  • 63 Meyer J M. Novel antipsychotics and severe hyperlipidemia.  J Clin Psychopharmacol. 2001;  21 369-374
  • 64 Procyshyn R M, Pande S, Tse G. New-onset diabetes mellitus associated with quetiapine.  Can J Psychiatry. 2000;  45 668-669
  • 65 Domon S E, Cargile C S. Quetiapine-associated hyperglycemia and hypertriglyceridemia.  J Am Acad Child Adolesc Psychiatry. 2002;  41 495-496
  • 66 Sobel M, Jaggers E D, Franz M A. New-onset diabetes mellitus associated with the initiation of quetiapine treatment.  J Clin Psychiatry. 1999;  60 556-557
  • 67 Wirshing D A, Pierre J M, Eyeler J, Weinbach J, Wirshing W C. Risperidone-associated new-onset diabetes.  Biol Psychiatry. 2001;  50 148-149
  • 68 Croarkin P E, Jacobs K M, Bain B K. Diabetic ketoacidosis associated with risperidone treatment?.  Psychosomatics. 2000;  41 369-370
  • 69 Haupt D W, Newcomer J W. Risperidone-associated diabetic ketoacidosis.  Psychosomatics. 2001;  42 279-280
  • 70 Daniel D G, Zimbroff D L, Potkin S G, Reeves K R, Harrigan E P, Lakshminarayanan M I. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group.  Neuropsychopharmacology. 1999;  20 491-505
  • 71 Keck Jr P, Buffenstein A, Ferguson J, Feighner J, Jaffe W, Harrigan E P, Morrissey M R. Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial.  Psychopharmacology. 1998;  140 173-184
  • 72 Kingsbury S J, Fayek M, Trufasiu D, Zada J, Simpson G M. The effects of ziprasidone on cholesterol, triglycerides and glucose.  J Clin Psychiatry. 2001;  62 347-349
  • 73 Bapista T, Lacruz A, de Mendoza S, Mendoza Guilleri J M, Silvera A, Angeles F, Mendoza M T, Hernandez L. Body weight gain after administration of antipsychotic drugs: correlation with leptin, insulin and reproductive hormones.  Pharmacopsychiatry. 2000;  33 81-88
  • 74 Allison D B, Mentore J L, Heo M, Chandler L P, Cappeleri J C, Infante M C, Weiden P J. Antipsychotic-induced weight gain: a comprehensive research synthesis.  Am J Psychiatry. 1999;  156 1686-1696
  • 75 Regenold W T, Thapar R K, Marano C, Gavirneni S, Kondapavuluru P V. Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use.  J Affect Disord. 2002;  70 19-26
  • 76 Melkersson 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
  • 77 Melkersson K I, Hulting A L. Insulin and leptin levels in patients with schizophrenia or related psychoses - a comparison between different antipsychotic agents.  Psychopharmacology (Berl). 2001;  154 205-212
  • 78 Sowell M O, Mukhopadhyay N, Cavazzoni P, Shankar S, Steinberg H O, Breier A, Beasley Jr C M, Dananberg J. Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone, or placebo.  J Clin Endocrinol Metab. 2002;  87 2918-2923
  • 79 Ardizzone T D, Bradley R J, Freeman 3rd  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
  • 80 Wozniak K M, Linnoila M. Hyperglycemic properties of serotonin receptor antagonists.  Life Sci. 1991;  49 101-109
  • 81 Brömel T, Blum W F, Ziegler A, Schulz E, Bender M, Fleischhaker C, Remschmidt H, Krieg J-C, Hebebrand J. Serum leptin levels increase rapidly after initiation of clozapine therapy.  Mol Psychiatry. 1998;  3 76-80
  • 82 Kraus T, Haack M, Schuld A, Hinze-Selch D, Kuhn M, Uhr M, Pollmächer T. Body weight and leptin plasma levels during treatment with antipsychotic drugs.  Am J Psychiatry. 1999;  156 312-314
  • 83 Litman R E, Peterson S W, Singh I, Robbins D C, Berry S A. 2-hr postprandial glucose, lipid, and body mass indices in olanzapine-treated schizophrenia patients before and after switching to risperidone: A prospective trial. (Janssen-gesponsortes) Poster, 23th CINP-Congress, Montreal, 23. - 27. 6. 2002
  • 84 Schultz S K, Arndt S, Ho B C, Oliver S E, Andreasen N C. Impaired glucose tolerance and abnormal movements in patients with schizophrenia.  Am J Psychiatry. 1999;  156 640-642
  • 85 Beasley Jr C M, Tollefson G D, Tran P V. Safety of olanzapine.  J Clin Psychiatry. 1997;  58 Suppl 10 3-17

Prof. Dr. T. Wetterling

Klinik für Psychiatrie und Psychotherapie · Gerontopsychiatrie · Vivantes Klinikum Hellersdorf

Myslowitzer Str. 45

12621 Berlin ·

Email: t.wetterling@klinikhellersdorf.de