Although treatment guidelines recommend limited benzodiazepine use in the treatment of major depressive disorder (MDD), benzodiazepines continue to be prescribed for long-term use in up to 40% of patients. In an effort to discover the reason for this, Rizvi and colleagues1 found that benzodiazepine use in MDD is not necessarily linked to illness severity or complexity but is associated with specific diagnostic and symptom characteristics, with anhedonia being a stand-out.
The specific aims of this naturalistic cross-sectional study were to determine whether benzodiazepine use in MDD is related to illness severity or complexity and identify clinical predictors of use. The study included 326 outpatients (age range, 18 to 60 years) at a tertiary care psychiatric facility. The authors collected detailed information on current medication regimens and administered a structured diagnostic interview. They also measured symptom severity, quality of life, and personality characteristics. Scales and other tools used included the MINI-Plus; Hamilton Rating Scale for Depression (17-item; HRSD-17); Montgomery-Asberg Depression Rating Scale; Trimodal Anxiety Questionnaire (TAQ); Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ); Sheehan Disability Scale; Endicott Work Productivity Scale; NEO-Five Factor Inventory; and Klein Trauma and Abuse-Neglect scale. Comparisons were then made between patients who were and were not taking benzodiazepines on a daily basis (based on documented medication history).
The prevalence rate of regular benzodiazepine use in the study cohort was 25%, and the majority of users (80%) were taking benzodiazepines as adjunctive therapy. Clonazepam and lorazepam were the most frequently taken medications (by 51% and 46% of users, respectively).
Depression and anxiety scores were not significantly different between groups, although anhedonia scores (extracted from the HRSD-17) were higher in the benzodiazepine group (P < .001). Also, none of the patients met criteria for benzodiazepine abuse or dependence.
Beyond these factors, characteristics emerged that differentiated regular benzodiazepine users from nonusers.
Users tended (P < .05) to be female (72% vs 60%); unemployed (44% vs 24%); and have a history of child abuse (40% vs 27%). They also were more likely to have history of hospitalization for MDD (32% vs 16%; P < .01), and have comorbid panic disorder (24% vs 7%, P < .001) or OCD (17% vs 7%, P < .05). However, logistic regression on sex, employment status, hospitalization, comorbidity, NEO-openness (ie, willingness to engage in a variety of experiences), and TAQ total score revealed that anhedonia was the strongest predictor of regular benzodiazepine use.
Primarily used as sedative hypnotics for alleviation of MDD-associated anxiety and insomnia, benzodiazepines are not recommended for more than 4 weeks of use. This is due to the little known impact of long-term use, as well as to avoid potential abuse and adverse effects, such as memory, attention, and psychomotor deficits. .
The bottom line
These study results suggest a distinction between functioning and depression severity in benzodiazepine users, say the authors of the study. Although users did not demonstrate greater MDD severity, they nevertheless seem to represent a more impaired population based on quality-of-life and functioning scales. Given the cross-sectional design of the study, whether patients who receive benzodiazepines represent a more chronically ill and psychiatrically complex group from the outset or whether long-term benzodiazepine use contributes to worse outcomes is unclear. Animal studies have shown that chronic use may decrease gamma-aminobutryic acid (GABA) release. Future studies should evaluate whether chronic benzodiazepine use in MDD reduces GABA concentrations and, if so, what impact this has on anhedonia and anxiety in MDD, which have both been linked to alterations in GABA function.
1. Rizvi SJ, Sproule BA, Gallaugher L, et al. Correlates of benzodiazepine use in major depressive disorder: The effect of anhedonia. J Affect Disord. 2015;187:101-105.