AAGP 2009: Benzodiazepine Prescriptions Increase After FDA Atypical-Antipsychotic Warning

Trend May Be a Cause for Concern, Investigators Say

Caroline Cassels

March 09, 2009

March 9, 2009 (Honolulu, Hawaii) — In the wake of a 2005 Food and Drug Administration (FDA) black-box warning related to off-label prescribing of atypical antipsychotics in elderly patients with dementia, physicians appear to be turning to benzodiazepines to control dementia-related psychosis — a practice that may be less than optimal.

New research presented here at the American Association for Geriatric Psychiatry 2009 Annual Meeting showed a statistically significant increase in prescriptions of benzodiazepines to older patients with dementia following the warning, which was prompted by evidence showing a link between atypical antipsychotics and an increased risk of cerebrovascular events and sudden death.

Dr. Shilpa Srinivasan

"We believe this increase [in benzodiazepine use] may be an unintended consequence of the FDA advisory," lead investigator Shilpa Srinivasan, MD, from the University of South Carolina, in Columbia, told Medscape Psychiatry.

Behavioral disturbances are common in dementia, affecting more than 50% of patients, and represent a major challenge for clinicians as well as patients' families who are faced with managing agitated and sometimes aggressive behavior.

In the absence of approved agents, many physicians have turned to off-label use of both conventional antipsychotics (CAs) as well as atypical agents, also known as second-generation antipsychotics (SGAs).

Benzodiazepines Exception to the Rule

The purpose of the study, said Dr. Srinivasan, was to examine the effect of the 2005 FDA mortality advisory on prescribing trends. It included 8171 patients over the age of 50 years with dementia. Of these individuals, 3932 (48%) had dementia and a comorbid psychiatric diagnosis. The mean age of the participants was 76 years, and 77% were female.

Investigators analyzed prescription data for a variety of psychotropic medications 2 years before and 2 years after the April 2005 warning in the same cohort of individuals. (A similar black-box warning was issued against conventional antipsychotics in June 2008.)

Medications included SGAs, CAs, antidepressants, benzodiazepines, mood stabilizers, and nonbenzodiazepine anxiolytics.

With the exception of benzodiazepines, the investigators found the use of psychotropic agents in all classes of medications decreased after the advisory in the overall study population — from 78% to 74% pre- and postadvisory, respectively.

SGA prescriptions declined from 42% preadvisory to 31% postadvisory and CA prescriptions dropped from 7% to 4%. In addition, nonbenzodiazepine anxiolytics and mood stabilizers decreased in the overall sample.

However, benzodiazepines increased in the overall sample, from 41% in the preadvisory period vs 47% after the warning. In patients with dementia plus a comorbid psychiatric condition, they increased from 45% to 53%. In patients with dementia only they increased from 37% to 41%.

Unexpected Finding

The fact that prescriptions of benzodiazepines increased was unexpected, said Dr. Srinivasan.

"This was a very interesting finding and one we did not expect to see. There are data showing there are negative effects associated with benzodiazepines in elderly people, including falls and cognitive decline.

"There are other data that have come out subsequent to the advisory about the potential role of other agents such as [selective serotonin-reuptake inhibitors] SSRIs and other antidepressants in ameliorating some of the behavioral and psychological symptoms, and yet we did not see a raised signal for the use of these agents," she said.

Dr. Srinivasan added that she believes there is a role for antipsychotics in managing dementia-related psychosis. However, she said, physicians must consider the risks and benefits of these medications as well as appropriate monitoring in this vulnerable population.

"The [FDA] advisories are important and remind us that we are dealing with a frail older adult population and that it behooves us to use even more care in our prescribing practices and patterns," she said.

American Association for Geriatric Psychiatry 2009 Annual Meeting: Abstract NR 86. Presented March 6, 2009.


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