Abstract
BackgroundWith antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety. However, with mortality risks associated with this concomitant use yet to be examined, it remains unclear as to whether this concomitant therapy offers any benefits in treating depression.MethodsWe conducted a population-based cohort study using South Korea’s nationwide healthcare database from 2002 to 2017. Of 2.6 million patients with depression, we identified 612,729 patients with incident depression and newly prescribed ADs or BZDs, by excluding those with a record of diagnosis or prescription within the 2 years prior to their incident diagnosis. We classified our study cohort into two discrete groups depending on the type of AD treatment received within 6 months of incident diagnosis—AD monotherapy and AD plus BZD (AD+BZD) therapy. We matched our study cohort in a 1:1 ratio using propensity scores to balance baseline characteristics and obtain comparability among groups. The primary outcome was all-cause mortality, and patients were followed until the earliest of outcome occurrence or end of the study period. We conducted multivariable Cox proportional hazards regression analysis to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) for the risk of mortality associated with AD+BZD therapy versus AD monotherapy.ResultsThe propensity score-matched cohort had 519,780 patients with 259,890 patients in each group, where all baseline characteristics were well-balanced between the two groups. Compared to AD monotherapy, AD+BZD therapy was associated with an increased risk of all-cause mortality (adjusted HR, 1.04; 95% CI, 1.02 to 1.06).ConclusionsConcomitantly initiating BZDs with ADs was associated with a moderately increased risk of mortality. Clinicians should therefore exercise caution when deciding to co-prescribe BZDs with ADs in treating depression, as associated risks were observed.
Highlights
With antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety
The following patients were excluded from our study: (1) those diagnosed with depression (ICD-10: F32, F33), bipolar disorders (F31), manic episodes (F30), or persistent mood disorders (F34) within 2 years prior to cohort entry, to restrict the analysis to incident patients with depression; (2) those prescribed any ADs or BZDs within 2 years prior to cohort entry to restrict to new users of ADs or BZDs; (3) those aged < 18 years at cohort entry as depression is unlikely to be prevalent and because AD or BZD use is not advised in this age group; and (4) missing demographic information
AD plus BZD (AD+BZD) therapy was associated with a moderately increased risk of all-cause mortality and all-cause hospitalization when compared to AD monotherapy; the top 20 frequent causes of hospitalization are shown in Additional file 6: Table S3
Summary
With antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety. BZDs are sometimes continued for longer periods than intended in real-world clinical practice, possibly owing to their dependency—one study found that approximately 12% of patients who received concomitant BZD and AD therapy (AD+BZD) continued long-term BZD use [9]. Despite such prevalence, uncertainties remain regarding the safety of AD+BZD therapy for the treatment of patients with depression. No previous study, observational or randomized controlled trial, has assessed the risk of mortality associated with AD+BZD therapy, as compared with AD therapy alone, among depressed patients. The benefit or harm associated with AD+BZD therapy remains uncertain with limited real-world evidence available on its use
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
