Prescribing Benzodiazepine with Antidepressants Can Cause Patient Dependence

Combining benzodiazepine with an antidepressant treatment regimen can create an addictive habit, according to a recent study from the Northeastern University Bouvé College of Health Sciences.

In a clinical trial, researchers paired a benzodiazepine anxiolytic with an antidepressant for approximately 10% of patients starting medication treatment for major depression in a large US population study. 12.3% of those patients continued the benzodiazepine for longer than 6 months and 2.4% continued it after stopping the antidepressant.

"Because benzodiazepine dependency may develop quickly, practice guidelines recommend only short-term benzodiazepine use," said Matthew Miller, MD, MPH, ScD, Northeastern University Bouvé College of Health Sciences, Boston MA, and colleagues in the study.

Little is currently known about the degree to which benzodiazepine usage continues after the drugs are initiated concurrently, even while an estimated 10-57% of patients treated with antidepressants also receive a benzodiazepine during their course of treatment. The largest study to examine that drug usage was conducted by the Veterans Health Administration, which found that 14.1% of patients initiating the combination in 2007 remained on the benzodiazepine for at least 1 year.

Researchers sought to characterize the use of benzodiazepines in combined prescription with antidepressants in the proportion of US adults who had commercial insurance. They also sought to identify factors associated with subsequent long-term use of the benzodiazepine.

Miller and colleagues identified 765,130 adults with a diagnosis of major depression who were started on an antidepressant between 2001 and 2014, finding 10.6% started on the combination. The frequency of initiating treatment with both agents increased over the study period, from 6.1% of those starting an antidepressant in 2001, to a peak of 12.5% in 2012.

That prescribing pattern was consistent across physician type and age. Factors associated with likelihood of the prescribed combination included a separate diagnosis of anxiety, or complaints of insomnia. Additional factors, with less statistically significant association, included having recent psychotherapy, or a history of self-harm.

A short-term quantity of benzodiazepine for 1-7 days was prescribed in 13.5%, with that limited initial quantity more likely prescribed by family practitioners (15.1%) than psychiatrists (6.7%). More than 50 benzodiazepine pills were initially prescribed in 26.1% of patients receiving the drug combination. 12.3% of patients starting treatment with the combination continued taking the benzodiazepine for at least 6 months and 5.7% for at least 1 year.

Miller and colleagues speculate that the increasing prevalence of combined prescribing may have been influenced by a 2001 Cochrane publication and 2009 update, which described evidence for the combination increasing adherence to antidepressant treatment by reducing adverse reactions. In addition, they indicate, there was increasing recognition of anxiety co-occurring with depression. They also suggest that more psychiatrists than family practitioners may have prescribed the combination because of their familiarity with benzodiazepines and treating patients with more severe depression or comorbid anxiety.

"When prescribed carefully in appropriate patients, benzodiazepines are considered to be useful medications," Miller and colleagues acknowledge. "Still, the decision to simultaneously initiate benzodiazepine therapy at antidepressant initiation and the preference for short-term treatment are influenced by concerns about benzodiazepines, including dependency, emergency department visits, and increased risk of fractures, motor vehicle crashes, and overdose."

The evaluation of long-term benzodiazepine use following initial treatment of major depression with a benzodiazepine and antidepressant combination was published on-line June 7 in JAMA Psychiatry.

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