No Long-term Antidepressant Adherence Benefit Seen With Simultaneous Benzodiazepine Use

Benzodiazepines and related drugs frequently used before and after diagnosis of Alzheimer's disease
Benzodiazepines and related drugs frequently used before and after diagnosis of Alzheimer’s disease
Starting benzodiazepines simultaneously with antidepressants does not seem to influence antidepressant adherence.

The practice of prescribing a combination of both benzodiazepines and antidepressants in adults recently diagnosed with depression has increased over the past decade, found a new study. Yet starting benzodiazepines simultaneously does not appear to influence whether patients are still taking antidepressants 6 months later.

“We observed no clinically meaningful difference in antidepressant treatment length between simultaneous new users and non-simultaneous new users,” wrote Greta A. Bushnell, MSPH, of the University of North Carolina at Chapel Hill Gillings School of Global Public Health, and her colleagues.

“Because of the risks associated with benzodiazepines and the potentially modifiable factors associated with long-term use among simultaneous new users, the decision to simultaneously initiate benzodiazepine therapy at antidepressant therapy initiation and the benzodiazepine regimen require careful consideration of potential benefits and harms,” the investigators wrote in JAMA Psychiatry.

Potential harms can include dependency, overdose, emergency department visits, and increased risk of fractures and car accidents.

The researchers analyzed data on 765,130 adults, age 18 to 64, from an insurance claims database spanning January 2001 through December 2014. The majority of the subjects (66%) were women, and median age was 39. The subjects had all recently been diagnosed with depression but had not taken either antidepressants or benzodiazepines within the previous year.

The percentage of subjects who began taking benzodiazepines and antidepressants at the same time increased from 6.1% in 2001 to 11.3% in 2014. Antidepressants included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, tricyclic antidepressants, and others.

Overall, 10.6% of the sample initiated simultaneous treatment with antidepressants and benzodiazepines. A simultaneous prescription was more likely in patients receiving treatment from a psychiatrist rather than another type of doctor.

“The difference between physician type might be related to psychiatrists’ increased familiarity with benzodiazepines, treatment preferences and training,” the researchers noted. Other possible factors they listed included “the severity of their patient’s depression or comorbid anxiety, or the possibility that patients diagnosed by psychologists are more likely to receive prescriptions from another physician because of prescribing restrictions.”

Use of benzodiazepines dropped off fairly quickly after initiation: 64% of patients who filled the first prescription did not fill any subsequent prescriptions, and only 12.3% continued benzodiazepines for at least 6 months. However, the percentage of patients still taking antidepressants 6 months after they started taking them was similar whether they had been prescribed benzodiazepines or not.

Patients were more likely to continue taking benzodiazepines long-term if their first prescription included a long-acting benzodiazepine or was valid for a longer period of time, or if they had recently filled a prescription for opioids.

“Although we did not look at whether opioid use was continued after simultaneous antidepressant and benzodiazepine new use, the association between a recent baseline opioid prescription and long-term benzodiazepine use is particularly concerning because of the known risks of concurrent use of these substances and their pharmacologic interactions,” the investigators wrote. 

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Bushnell G, Stürmer T, Gaynes B, Pate V, Miller M. Simultaneous antidepressant and benzodiazepine new use and subsequent long-term benzodiazepine use in adults with depression, United States, 2001-2014 [published online June 7, 2017]. JAMA Psychiatry.