Effect of regulatory warnings on antipsychotic prescription rates among elderly patients with dementia: a population-based time-series analysis

Background: Three warnings of serious adverse events associated with the use of atypical antipsychotic drugs among elderly patients with dementia were sent to health care professionals in Canada. We assessed the impact of these warnings on prescription rates of antipsychotic drugs in this patient population. Methods: We used prescription drug claims data from Ontario to calculate prescription rates of atypical and conventional antipsychotic drugs among elderly patients with dementia from May 1, 2000, to Feb. 28, 2007. We performed a time-series analysis to estimate the effect of each warning on rates of antipsychotic drug use. Results: Before the first warning, growth in the use of atypical antipsychotics was responsible for an increasing rate of overall antipsychotic use. Each warning was associated with a small relative decrease in the predicted growth in the use of atypical antipsychotic drugs: a 5.0% decrease after the first warning, 4.9% after the second and 3.2% after the third (each p < 0.05). The overall prescription rate of antipsychotic drugs among patients with dementia increased by 20%, from 1512 per 100 000 elderly patients in September 2002, the month before the first warning, to 1813 per 100 000 in February 2007, 20 months after the last warning. Interpretation: Although the warnings slowed the growth in the use of atypical antipsychotic drugs among patients with dementia, they did not reduce the overall prescription rate of these potentially dangerous drugs. More effective interventions are necessary to improve postmarket drug safety in vulnerable populations.

[1]  J. Sareen,et al.  Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults , 2008, Canadian Medical Association Journal.

[2]  E. Rahme,et al.  The effects of coxib formulary restrictions on analgesic use and cost: regional evidence from Canada. , 2007, Health policy.

[3]  Nathan Herrmann,et al.  Clinical practice guidelines for severe Alzheimer’s disease , 2007, Alzheimer's & Dementia.

[4]  Kelvin Lam,et al.  Antipsychotic Drug Use and Mortality in Older Adults with Dementia , 2007, Annals of Internal Medicine.

[5]  Philip S. Wang,et al.  Medicaid's prior authorization program and access to atypical antipsychotic medications. , 2007, Health affairs.

[6]  M. Schnitzler,et al.  Use of nesiritide before and after publications suggesting drug-related risks in patients with acute decompensated heart failure. , 2006, JAMA.

[7]  A. Kesselheim,et al.  The rise and fall of Natrecor for congestive heart failure: implications for drug policy. , 2006, Health affairs.

[8]  J. Avorn,et al.  Risk of death in elderly users of conventional vs. atypical antipsychotic medications. , 2005, The New England journal of medicine.

[9]  C. Lyketsos,et al.  Antipsychotic drugs in dementia: what should be made of the risks? , 2005, JAMA.

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

[11]  B. Kuehn FDA warns antipsychotic drugs may be risky for elderly. , 2005, JAMA.

[12]  A. Stergachis,et al.  Impact of mailed warning to prescribers on the co‐prescription of tramadol and antidepressants , 2005, Pharmacoepidemiology and drug safety.

[13]  S. Normand,et al.  Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study , 2005, BMJ : British Medical Journal.

[14]  E. Wooltorton Olanzapine (Zyprexa): increased incidence of cerebrovascular events in dementia trials , 2004, Canadian Medical Association Journal.

[15]  Craig R Ramsay,et al.  INTERRUPTED TIME SERIES DESIGNS IN HEALTH TECHNOLOGY ASSESSMENT: LESSONS FROM TWO SYSTEMATIC REVIEWS OF BEHAVIOR CHANGE STRATEGIES , 2003, International Journal of Technology Assessment in Health Care.

[16]  E. Wooltorton Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[17]  A K Wagner,et al.  Segmented regression analysis of interrupted time series studies in medication use research , 2002, Journal of clinical pharmacy and therapeutics.

[18]  G. Elwyn,et al.  Understanding risk and lessons for clinical risk communication about treatment preferences , 2001, Quality in health care : QHC.

[19]  Michael J. Goodman,et al.  Contraindicated use of cisapride: impact of food and drug administration regulatory action. , 2000, JAMA.

[20]  J. Stoker,et al.  The Department of Health and Human Services. , 1999, Home healthcare nurse.

[21]  Paul Grootendorst,et al.  Coding accuracy of administrative drug claims in the Ontario Drug Benefit database. , 2003, The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique.