Combination Treatment With Benzodiazepines and SSRIs for Comorbid Anxiety and Depression: A Review

Objective: To review the literature on the co-occurrence of anxiety with depressive disorders and the rationale for and use of combination treatment with benzodiazepines and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs) for treating comorbid anxiety and depression.

Data Sources: PubMed and PsycINFO were searched using terms identified as relevant based on existing practice guidelines. The primary search terms were anxiety, anxiety disorders, depression, depressive disorders, comorbidity, epidemiology, benzodiazepines, antidepressants, pharmacology, clinical trials, and pharmacotherapy. Reference lists of identified articles were also reviewed to ensure capture of relevant literature.

Study Selection: Publications were selected for inclusion in the review if they applied to adult populations and specifically addressed the comorbidity of anxiety and depression, their epidemiology, or their management. Case reports and case series were not considered for inclusion.

Data Extraction: Each author assessed the publications independently for content related to the review topics. Findings considered relevant to the clinical understanding and management of comorbid anxiety and depression were incorporated into the review.

Data Synthesis: Comorbidity is very common among patients with anxiety and depressive disorders, and, even when full criteria for 2 separate disorders are not met, subsyndromal symptoms are often present. Little controlled research has explored how benzodiazepines and SSRIs/SNRIs may be usefully combined, yet their combination is frequently employed in clinical practice. Patients with comorbidities are likely to have poorer treatment outcomes and have greater utilization of health care resources. Currently SSRIs/SNRIs are considered first-line therapy and are effective in both anxiety and depressive states. Nevertheless, many patients have only a partial response or have difficulty tolerating efficacious doses of antidepressant monotherapy. Benzodiazepines appear to improve treatment outcomes when an anxiety disorder co-occurs with depression or for depression characterized by anxious features. Specifically, they may provide benefits both in terms of speed of response and overall response.

Conclusions: Long-term management plans for anxiety disorder with or without comorbid depression should include strategies for acute or short-term care, long-term maintenance, and episodic or breakthrough symptoms. Combination therapy with benzodiazepines and antidepressants in appropriate clinical settings may improve outcomes over monotherapy in some patients.