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. 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 NVP-TAE 226 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 < 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 LGR4 antibody after the last warning. Interpretation Even though 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. Concern is growing over the effectiveness of actions taken by drug regulatory companies on safety information that becomes available to them after a drug has been licensed and marketed.1C3 Drug regulators such as Health Canada hope that disseminating information on new safety issues through Dear Healthcare Professional letters will shift how the stakeholders involved in drug utilization manufacturers, public and private insurers, pharmacists, physicians and the public think about the trade-off between risks and benefits. Ultimately, this should lead to safer prescribing decisions. The introduction of newer, atypical antipsychotic drugs risperidone, olanzapine and quetiapine in the 1990s was heralded as a breakthrough in the treatment NVP-TAE 226 of schizophrenia and other psychiatric conditions. All 3 of these drugs were approved by Health Canada for the treatment of schizophrenia, but only risperidone was approved for short-term symptomatic management of inappropriate behaviour due to aggression or psychosis in patients with severe dementia. On Oct. 11, 2002, Janssen-Ortho, the drug company that markets risperidone in Canada, after conversation with Health Canada, sent a letter to health professionals warning of safety issues with the use of risperidone in elderly patients with dementia. On Mar. 10, 2004, Eli Lilly, the manufacturer of olanzapine, after conversation with Health Canada, sent a letter to health professionals warning of safety issues with the use of olanzapine in elderly patients with dementia. On June 22, 2005, Health Canada circulated a letter warning health professionals of safety issues with the use of risperidone, olanzapine or quetiapine in elderly patients with dementia. The content of the 3 warnings is usually summarized in Table 1; the full text of the letters is usually available online from Health Canada.4C6 Table 1 We sought to examine the effects of these warnings on the use of the atypical antipsychotic agents pointed out in the warnings as well as the use of conventional antipsychotic drugs. Methods Study cohort We obtained data from your Ontario Drug Benefit database on all prescription drug claims submitted from May 1, 2000, to Feb. 28, NVP-TAE 226 2007, for the 3 newer, atypical antipsychotic drugs (risperidone, olanzapine and quetiapine) and a list of older standard antipsychotic drugs (a complete list of these drugs is available in Appendix 1, at www.cmaj.ca/cgi/content/full/179/5/438/DC2). The Ontario Drug Benefit program covered without restriction the use of the 3 atypical antipsychotic drugs and all of these standard brokers for patients 65 years of age and older for the entire study period. We included standard antipsychotic brokers in light of the results of observational studies suggesting that the risk of death associated with these drugs is usually greater than the risk associated with atypical antipsychotic brokers.7,8 In this context, examination of the overall use of antipsychotic drugs, conventional and atypical, should provide a comprehensive measure of the impact of the warnings on patient safety. The Ontario Drug Benefit database contains claims for prescription drugs submitted by pharmacists for reimbursement. Each claim contains information around the drug, the date on which the drug was dispensed, whether the patient was in a nursing home and a unique claimant identifier. The claims have very low error rates for data around the drugs and dates dispensed. 9 We sorted the claims by date and by unique claimant identifier. To identify patients with a history of dementia, we linked the unique identifier from your drug claim to hospital discharge abstracts from your Canadian Institute for Health Information and physician claims data from your Ontario Health Insurance Plan in the 5 years before the date of the drug claim to NVP-TAE 226 look for a dementia-related diagnosis. We also looked for claims for cholinesterase inhibitors (a class of drugs used only in patients with dementia to treat cognitive decline) submitted to the Ontario Drug Benefit program in the year before the antipsychotic drug claim. We have used this technique to identify patients with.