Risk of Hospitalization for Hypoglycemia in Older Patients with Diabetes Using Antipsychotic Drugs.

OBJECTIVE Antipsychotics may disrupt metabolic regulation in patients with diabetes mellitus. The risk of hypoglycemia in older users of antipsychotics with diabetes is largely unknown. Therefore, we investigated the association between the use of antipsychotic drugs and hypoglycemia requiring hospital admission in older patients with diabetes. METHODS In a nested case-control study using community pharmacy records linked to hospital admission data in the Netherlands (1998-2008), a cohort of 68,314 patients at least 65 years with diabetes was studied. Cases were patients from the study cohort with a first hospital admission for hypoglycemia; up to five comparison subjects were selected for each case. Exposure to antipsychotic drugs was the primary determinant of interest. Logistic regression analysis was performed to estimate the strength of the association between antipsychotic drug use and hypoglycemia, taking into account potential confounders. RESULTS Eight hundred fifteen patients were admitted to hospital for hypoglycemia. Current use of antipsychotic drugs was associated with an increased risk of hypoglycemia compared with non-use (adjusted OR: 2.26; 95% CI: 1.45-3.52; Wald χ(2) = 13.08, df = 1, p ≤0.001), especially in the first 30 days of treatment (adjusted OR: 7.65; 95% CI: 2.50-23.41; Wald χ(2) = 12.72, df = 1, p ≤0.001) and with higher doses (adjusted OR: 8.20; 95% CI: 3.09-21.75; Wald χ(2) = 17.90, df = 1, p ≤0.001). CONCLUSION Use of antipsychotic drugs by older patients with diabetes mellitus was associated with an increased risk of hospitalization for hypoglycemia. Our findings suggest that glucose levels should be monitored closely after initiation of antipsychotic drugs.

[1]  A. Hoofnagle,et al.  Acute, life-threatening hypoglycemia associated with haloperidol in a hematopoietic stem cell transplant recipient , 2006, Bone Marrow Transplantation.

[2]  A. Peiris,et al.  Drug-Induced Disorders of Glucose Tolerance , 1993, Annals of Internal Medicine.

[3]  B. Frier.  Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications , 2014, Nature Reviews Endocrinology.

[4]  D. Hutchins,et al.  A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United States. , 2003, Journal of clinical epidemiology.

[5]  D. Grobbee,et al.  Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus. , 2004, The Journal of clinical psychiatry.

[6]  M. Cesari,et al.  Olanzapine and hypoglycemic coma in a frail elderly woman. A case report. , 2003, Pharmacopsychiatry.

[7]  A. Hoes,et al.  Hospital discharge diagnoses of ventricular arrhythmias and cardiac arrest were useful for epidemiologic research. , 2005, Journal of clinical epidemiology.

[8]  J. Weng,et al.  Secondary diabetic ketoacidosis and severe hypoglycaemia in patients with established type 1 diabetes mellitus in China: a multicentre registration study , 2014, Diabetes/metabolism research and reviews.

[9]  B. Frier,et al.  Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. , 2005, Diabetes care.

[10]  P. Austin,et al.  Atypical antipsychotics and hyperglycemic emergencies: Multicentre, retrospective cohort study of administrative data , 2014, Schizophrenia Research.

[11]  H. S. Lau,et al.  Validation of pharmacy records in drug exposure assessment. , 1997, Journal of clinical epidemiology.

[12]  Willemijn M. Meijer,et al.  First year of life medication use and hospital admission rates: premature compared with term infants. , 2013, The Journal of pediatrics.

[13]  N. Fukui,et al.  Improvement in quetiapine‐induced hypoglycemia following a switch to blonanserin , 2012, Psychiatry and clinical neurosciences.

[14]  B. Furman.  THE HYPOGLYCAEMIC EFFECT OF 5‐HYDROXYTRYPTOPHAN , 1974, British journal of pharmacology.

[15]  U. Malabu,et al.  Disease burden evaluation of fall-related events in the elderly due to hypoglycemia and other diabetic complications: a clinical review , 2014, Clinical epidemiology.

[16]  Geoff M. Anderson,et al.  Antipsychotic drugs and the risk of hyperglycemia in older adults without diabetes: a population-based observational study. , 2011, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[17]  M. Rewers,et al.  Predictors of acute complications in children with type 1 diabetes. , 2002, JAMA.

[18]  A. Busti,et al.  Incidence of abnormal metabolic parameters and weight gain induced by atypical antipsychotics in elderly patients with dementia. , 2009, The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists.

[19]  K. Schulz,et al.  Compared to what? Finding controls for case-control studies , 2005, The Lancet.

[20]  F. Verhey,et al.  Prescribing pattern of psychotropic drugs in nursing home residents with dementia , 2011, International Psychogeriatrics.

[21]  M. Goldfracht,et al.  Antipsychotics and Diabetes: An Age-Related Association , 2008, The Annals of pharmacotherapy.

[22]  H. Lehnert,et al.  Insulin Secretion and Sensitivity after Single-Dose Amisulpride, Olanzapine or Placebo in Young Male Subjects: Double Blind, Cross-Over Glucose Clamp Study , 2012, Pharmacopsychiatry.

[23]  R. Herings,et al.  Dupuytren's contracture: a retrospective database analysis to determine hospitalizations in the Netherlands , 2011, BMC Research Notes.

[24]  P. Rochon,et al.  Exploring the Association Between Atypical Neuroleptic Agents and Diabetes Mellitus in Older Adults , 2003, Pharmacotherapy.

[25]  B. Stricker,et al.  Current use of thiazide diuretics and prevention of femur fractures. , 1996, Journal of clinical epidemiology.

[26]  E H Wagner,et al.  A chronic disease score from automated pharmacy data. , 1992, Journal of clinical epidemiology.

[27]  L. Radican,et al.  Association between hypoglycemia and inpatient mortality and length of hospital stay in hospitalized, insulin-treated patients , 2013, Current medical research and opinion.

[28]  S. Greenland,et al.  Simulation study of confounder-selection strategies. , 1993, American journal of epidemiology.

[29]  S. Schneeweiss,et al.  Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients , 2007, Canadian Medical Association Journal.

[30]  B. Lebowitz,et al.  Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: the CATIE-AD study. , 2009, The American journal of psychiatry.

[31]  Scott D Ramsey,et al.  New‐Onset Treatment‐Dependent Diabetes Mellitus and Hyperlipidemia Associated with Atypical Antipsychotic Use in Older Adults without Schizophrenia or Bipolar Disorder , 2012, Journal of the American Geriatrics Society.

[32]  L. de Jong-van den Berg,et al.  Prevalence, cumulative incidence, monotherapy and combination therapy, and treatment duration of frequently prescribed psychoactive medications in the Netherlands: retrospective database analysis for the years 2000 to 2005. , 2010, Clinical therapeutics.

[33]  R. Herings,et al.  Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme , 1995, The Lancet.

[34]  S. Benoit,et al.  Antipsychotic medications, glutamate, and cell death: a hidden, but common medication side effect? , 2013, Medical hypotheses.

[35]  D. Hutchins,et al.  Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States. , 2004, Journal of the American Medical Directors Association.

[36]  J. Guillebaud,et al.  Hypoglycaemic coma occurring during treatment with chlorpromazine and orphenadrine. , 1967, British medical journal.

[37]  Somnath Mondal,et al.  Oral aripiprazole-induced severe hypoglycemia. , 2012, Therapeutic drug monitoring.

[38]  M. Barry,et al.  Severe hypoglycemic reaction with haloperidol: report of a case. , 1969, The American journal of psychiatry.

[39]  N. Fukui,et al.  Hypoglycaemia induced by second generation antipsychotic agents in schizophrenic non-diabetic patients , 2009, BMJ : British Medical Journal.

[40]  T. Jones,et al.  The impact of a decade of changing treatment on rates of severe hypoglycemia in a population-based cohort of children with type 1 diabetes. , 2004, Diabetes care.

[41]  Lon S Schneider,et al.  Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. , 2005, JAMA.

[42]  Geoff M. Anderson,et al.  Antipsychotic drugs and hyperglycemia in older patients with diabetes. , 2009, Archives of internal medicine.

[43]  Y. Sugimoto,et al.  The involvement of the peripheral 5-HT2A receptor in peripherally administered serotonin-induced hyperglycemia in rats. , 1995, Life sciences.

[44]  Susan C. Miller,et al.  Antipsychotic use and the risk of diabetes in nursing home residents with dementia. , 2011, The American journal of geriatric pharmacotherapy.

[45]  J. Newcomer,et al.  Hyperglycemia and antipsychotic medications. , 2001, The Journal of clinical psychiatry.

[46]  Cory Siebe.  National Estimates of Insulin-related Hypoglycemia and Errors Leading to Emergency Department Visits and Hospitalizations , 2014 .

[47]  S. Govoni,et al.  No effect of atypical antipsychotic drugs on weight gain and risk of developing type II diabetes or lipid abnormalities among nursing home elderly patients with Alzheimer's disease. , 2006, Minerva medica.

[48]  A. Kablinger,et al.  Glucose Metabolism in Relation to Schizophrenia and Antipsychotic Drug Treatment , 2001, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[49]  D. Becu-Villalobos,et al.  New Insights into the Endocrine and Metabolic Roles of Dopamine D2 Receptors Gained from the Drd2–/– Mouse , 2010, Neuroendocrinology.

[50]  G. Grossberg,et al.  Atypical antipsychotics and the risk of diabetes in an elderly population in long-term care: a retrospective nursing home chart review study. , 2009, Journal of the American Medical Directors Association.

[51]  D. O’Reilly,et al.  Psychotropic Medications and the Transition Into Care: A National Data Linkage Study , 2013, Journal of the American Geriatrics Society.