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
