A new study, published in the Journal of Psychiatric Research, investigates the predictors of long-term benzodiazepine (BZD) use. Hata and colleagues identify high-risk factors linked to the continuation of BZDs as well as factors that influence discontinuation.
The researchers write:
“This study revealed the factors associated with the long-term use of BZDs, including elderly patients, psychiatrist prescribers, high dosage of BZD, and concurrent use of BZD. In contrast, factors associated with the discontinuation of BZDs included using hypnotic types of BZDs and concurrent use of psychotropic drugs such as antipsychotics or alternative drugs to BZDs.”
Benzodiazepines have been prescribed across the globe over the past four decades for various conditions such as insomnia, anxiety, panic disorder, and muscle spasticity. This new research out of Japan seeks to identify the antecedents to the pervasive trend of long-term benzodiazepine use, despite a parallel body of research proposing its harmful effects. Long-term benzodiazepine use is associated with severe adverse effects including daytime drowsiness, lightheadedness, ataxia (loss of control of bodily movements), psychomotor disturbance, and anterograde amnesia (loss of ability to form new memories).
Though short-term use is said to be safe, Hata et al. acknowledge, “Long-term use carries the risk of dependence, withdrawal syndrome, cognitive impairment, diminishing effect, tolerance, and difficulty in discontinuing treatment.” They add that some patients experience symptoms of withdrawal after just 2-4 weeks of undergoing treatment, including rebound insomnia and anxiety.
“In response to these risks, although several international clinical guidelines and expert consensus statements have been published that recommend limiting the long-term use of BZDs, especially in older patients, the prevalence of long-term use remains widespread. Thus reducing the long-term use of BZD is an important worldwide issue,” Hata and colleagues write.
Utilizing information from the electronic health-record database within a university hospital in Osaka Japan, the authors “aimed to describe the tendency to prescribe BZDs in the last 12 years and to elucidate the predictors of BZD discontinuation in an extended age group of patients, who were prescribed BZDs.” Criteria set to define predictors of BZD continuation included: age older than 18 years, outpatients of all clinical departments, oral administration, and the absence of a BZD prescription in the last year in order to strictly use the new user design. BZD continuation, similar to other studies, is defined as the receipt of at least one BZD prescription within three months, as BZD prescriptions in Japan are limited to one time per 30 or 90 days. The authors utilized the Kaplan-Meier event-free curve to calculate the event-free probability, the event being the discontinuation of BZD prescription, and the Multivariate Cox regression analysis to assess associated predictors.
Compared with other studies observing the long-term use of BZDs, these numbers are strikingly high. Of the 92,005 outpatients within all clinical departments of the hospital, 8,006 were prescribed BZDs. Of the 3,470 patients who met the more specific criteria of the study, 57.8% used BZDs for more than 36 months. Hata et al. surmise the discrepancy could be attributed to their sample, which included a high proportion of elderly patients. The mean age was 60 years old, and 50.5% of the total cohort was 65 years or older.
While other studies have identified substantial racial and sex biases when prescribing benzodiazepines, Hata and colleagues add several other predictive factors to the list, finding that age, dosage, and prescriber type were all associated with extended benzodiazepine use.
The authors conclude, “Continuation of BZDs was significantly associated with age 65 years or greater, psychiatrist-prescribers, dosage of 5 mg or more of a DZP-equivalent daily dose, and concurrent use of BZDs.”
Among the potential predictors, Hata et al. found that concurrent use of alternative drugs as well as the use of hypnotic BZDs predicted eventual discontinuation. Though, prior research indicates hypnotic BZDs are associated with higher risk of chronic use, warranting more studies evaluating the type of BZD in its relation to long-term use. This study’s small sample size and international location limits the ability to generalize the results. The authors declare the need for more clinical trials in order to assess the efficacy and safety of other drugs and to promote complementary therapies that may be more helpful long-term without the use of BZDs.
This study supports the efforts of nations across the globe aimed at limiting the use of benzodiazepines and provides research that illustrates how to predict and prevent such use. Though the long-term use of BZD is widely known to have harmful effects, the trend is nevertheless persisting. By augmenting a list of predictors for long-term BZD use and highlighting nuances that lead to discontinuation, studies like this serve to influence prescription practices to be better informed, designed, and executed.
Hata, T., Kanazawa, T., Hamada, T., Nishihara, M., Bush, A. I., Yoneda, H.,…Katsumata, T. (2017). What can predict and prevent the long-term use of benzodiazepines? Journal of Psychiatric Research, 97, 94-100. http://dx.doi.org/10.1016/j.jpsychires.2017.11.012 (Link)