The introduction of new antipsychotics has resulted in the availability of drugs with
improved safety and tolerability as well as proven efficacy compared to the older
antipsychotics. New compounds might show new or different adverse effects that arise
in the post-marketing phase when a greater number of patients are treated. One goal
of the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) is the detection and description of severe, new, or rare adverse drug
reactions (ADRs). Between 1993 and 2000, 122,562 patients were monitored in 35 psychiatric
institutions, 86,349 patients of which received antipsychotics. Hyperglycemia related
to antipsychotics was observed in association with only two compounds so far: clozapine
and olanzapine (clozapine 2 cases, olanzapine 7 cases). In 6 of 9 patients, weight
gain preceded hyperglycemia. The relative frequency of these adverse drug related
events was 0.013 % for clozapine and 0.075 % for olanzapine. The symptomatology included
reversible hyperglycemia, worsening of existing diabetes, and new-onset diabetes.
Control for glycemic dysregulation should be maintained in clinical practice with
these drugs.
References
- 1 Arzneimittelkommission der Deutschen Ärzteschaft: Olanzapin: hyperosmolares Coma
diabeticum, Rhabdomyolyse, Nieren-insuffizienz. Deutsches Ärzteblatt 2002 11: A742-743
- 2
Baptista T, Lacruz A, de Mendoza S, Mendoza Guillen J M, Silvera R, Angeles F ,.
et al .
Body weight gain after administration of antipsychotic drugs: correlation with leptin,
insulin and reproductive hormones.
Pharmacopsychiatry.
2000;
33
81-88
- 3
Baptista T, Lacruz A, Angeles F, Silvera R, de Mendoza S, Mendoza M T,. et al .
Endocrine and metabolic abnormalities involved in obesity associated with typical
antipsychotic drug administration.
Pharmacopsychiatry.
2001;
34
223-231
- 4
Baptista T, Kin N M, Beaulieu S, De Baptista E A.
Obesity and related metabolic abnormalities during antipsychotic drug administration:
mechanisms, management and research perspectives.
Pharmacopsychiatry.
2002;
35
205-219
- 5
Baymiller S P, Ball P, McMahon R P, Buchanan R W.
Serum glucose and lipid changes during the course of clozapine treatment: the effect
of concurrent beta-adrenergic antagonist treatment.
Schizophr Res.
2003;
59
49-57
- 6
Bettinger T L, Mendelson S C, Dorson P G, Crismon M L.
Olanzapine-induced glucose dysregulation.
Ann Pharmacother.
2000;
34
865-867
- 7
Bonanno D G, Davydov L, Botts S R.
Olanzapine-induced diabetes mellitus.
Ann Pharmacother.
2001;
35
563-565
- 8
Fertig M K, Brooks V G, Shelton P S, English C W.
Hyperglycemia associated with olanzapine.
J Clin Psychiatry.
1998;
59
687-689
- 9
Fulton B, Goa K L.
Olanzapine: a review of its pharmacological properties and therapeutic efficacy in
the management of schizophrenia and related psychotic disorders.
Drugs.
1997;
53
281-298
- 10
Goldstein L E, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey G K,. et al .
New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment.
Psychosomatics.
1999;
40
438-443
- 11
Grohmann R, Rüther E, Engel R R, Hippius H.
assessment of adverse drug reactions in psychiatric inpatients with the AMSP drug
safety program: methods and first results for tricyclic antidepressants and SSRI.
Pharmacopsychiatry.
1999;
32
21-28
- 12
Grohmann R, Hippius H, Müller-Oerlinghausen B, Rüther E, Scherer J, Schmidt L G,.
et al .
Assesment of adverse drug reactions in psychiatric hospitals.
Eur J Clin Pharmacol.
1984;
26
727-734
- 13
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
- 14
Henderson D C, Cagliero E, Gray C, Nasrallah R A, Hayden D L, Schoenfeld D A,. et
al .
Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic
study.
Am J Psychiatry.
2000;
157
975-981
- 15
Kamran A, Doraiswamy P M, Jane J L, Hammett E B, Dunn L.
Severe hyperglycemia associated with high doses of clozapine.
Am J Psychiatry.
1994;
151
1395
- 16
Koller E, Schneider B, Bennett K, Dubitsky G.
Clozapine-associated diabetes.
Am J Med.
2001;
111
716-723
- 17
Koller E A, Doraiswamy P M.
Olanzapine-associated diabetes mellitus.
Pharmacotherapy.
2002;
22
841-852
- 18
Koro C E, Fedder D O, L’Italien G J, Weiss S S, Magder L S, Kreyenbuhl J.
Assessment of independent effect of olanzapine and risperidone on risk of diabetes
among patients with schizophrenia: population based nested case-control study.
Br Med J.
2002;
325
243-247
- 19
Liebzeit K A, Markowitz J S, Caley C F.
New onset diabetes and atypical antipsychotics.
Eur Neuropsychopharmacol.
2001;
11
25-32
- 20
Lindenmayer J P, Smith R C, Singh A, Parker B, Chou E, Kotsaftis A.
Hyperglycemia in patients with schizophrenia who are treated with olanzapine.
J Clin Psychopharmacol.
2001;
21
351-353
- 21
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
- 22
Mir S, Taylor D.
Atypical antipsychotics and hyperglycaemia.
Int Clin Psychopharmacol.
2001;
16
63-73
- 23
Mukherjee S, Decina P, Bocola V, Saraceni F, Scapicchio P L.
Diabetes mellitus in schizophrenic patients.
Compr Psychiatry.
1996;
37
68-73
- 24
Ober S K, Hudak R, Rusterholtz A.
Hyperglycemia and olanzapine.
Am J Psychiatry.
1999;
156
970
- 25
Popli A P, Konicki P E, Jurjus G J, Fuller M A, Jaskiw G E.
Clozapine and associated diabetes mellitus.
J Clin Psychiatry.
1997;
58
108-111
- 26
Ragucci K R, Wells B J.
Olanzapine-induced diabetic ketoacidosis.
Ann Pharmacother.
2001;
35
1556-1558
- 27
Roefaro J, Mukherjee S M.
Olanzapine-induced hyperglycemic nonketonic coma.
Ann Pharmacother.
2001;
35
300-302
- 28
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
- 29
Sowell M O, Mukhopadhyay N, Cavazzoni P, Shankar S, Steinberg H O, Breier A ,. et
al .
Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated
with olanzapine, risperidone, or placebo.
J Clin Endocrinol Metab.
2002;
87
2918-2923
- 30
Von Hayek D, Huttl V, Reiss J, Schweiger H D, Fuessl H S.
Hyperglykämie und Ketoacidose unter Olanzapin.
Nervenarzt.
1999;
70
836-837
- 31
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
Dr. med. PD Stefan Kropp
Abteilung Klinische Psychiatrie und Psychotherapie
Medizinische Hochschule Hannover, OE 7117
Carl-Neuberg-Str. 1
D-30625 Hannover
Germany
Phone: 0049-511-532-3167
Fax: 0049-511-532-3187
Email: kropp.stefan@mh-hannover.de