Background: The Veterans Health Administration has established a National Center for Medication Safety to help manage the risks of medications prescribed in VA healthcare systems (medical centers and associated community-based outpatient clinics). One of the Center's primary methods for managing risks is by distributing educational bulletins. Sometimes these bulletins recommend specific actions to mitigate newly recognized risks of medications. Follow-up studies are needed to examine changes in recommended safety practices and to provide crucial information about the effects of following a specific safety recommendation on patient outcomes. In August 2011 a national safety bulletin based on case reports and studies of cardiac conduction was issued for a very commonly prescribed antidepressant, citalopram. The bulletin specifically recommended that doses should no longer exceed 40 milligrams (mg) per day to reduce an unquantified risk of a life threatening cardiac arrhythmia. Immediately prior to distribution of the safety bulletin, more than 265,000 Veterans were being treated with citalopram, and approximately twenty percent had prescriptions for doses that exceeded the new safety recommendation;presumably because the higher doses were needed to obtain an adequate clinical response.
Specific Aim :
The specific aim of this research is to compare the risk of hospital admissions, cardiac ventricular arrhythmias, worsening depression or death when prescribed doses of citalopram within VA healthcare systems that were over 40 mg per day just prior to the safety bulletin were reduced to 40 mg per day or less as recommended or continued to be prescribed. Methods: Databases available in secure VA Informatics and Computing Infrastructure (VINCI) will be utilized. All of the more than 46,000 at-risk Veterans who had a citalopram prescription for a dose exceeding 40 milligrams per day within 3 months prior to the safety bulletin will be followed for approximately one year as long as they continued to fill citalopram prescriptions to determine whether and when their dose was reduced as recommended. The propensity for each citalopram prescription to be for 40 mg per day or less during follow- up will be estimated by logistic regression including a number of demographic, comorbidity, medication and other healthcare variables that may be directly or indirectly related to the study outcomes as well as the dose that was prescribed. Cox regression analysis with a time-varying citalopram dose indicator and propensity scores will be used to estimate adjusted hazard ratios to compare the study outcomes when patients received a citalopram prescription for a reduced dose of 40 mg per day or less compared to patients who continued to get citalopram prescriptions for more than 40 mg per day. Impact: This follow-up study of an exemplary safety communication will fill an important gap in information about patient outcomes and help VA policymakers and providers determine whether further actions are warranted to address this particular risk associated with a very commonly prescribed antidepressant. In addition, this research will be a prototype for future follow-up studies of safety bulletins that are intended to mitigate medication risks within VA healthcare systems.

Public Health Relevance

Retrospective data compiled by the Veteran's Health Administration will be utilized to help the VA Center for Medication Safety, Pharmacy Benefits Management Services and National Center for Patient Safety examine changes in prescribing and patient outcomes after a medication safety bulletin was distributed to VA healthcare systems nationwide. The bulletin reiterated a U.S. Food and Drug Administration recommendation to limit daily doses of citalopram, a commonly prescribed antidepressant, to mitigate a newly recognized risk of a potentially lethal cardiac arrhythmia. However, higher than recommended doses that were being prescribed for more than 50,000 Veterans when the safety bulletin was issued, were presumably clinically necessary to ameliorate depression. The proposed study will compare patient outcomes when the recommendation to limit the prescribed dose was or was not followed. The study results will help healthcare providers and policymakers decide whether further actions to improve the safety of citalopram within VA healthcare systems are warranted.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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HSR-1 Medical Care and Clinical Management (HSR1)
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Minneapolis VA Medical Center
United States
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