Combination of psychotherapy and benzodiazepines versus either therapy alone for panic disorder: a systematic review

Abstract

Background: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone.

Methods: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials.

Results: Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6-12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment. One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials.

Conclusion: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects.

Figure 1

Psychotherapy plus benzodiazepine vs. psychotherapy alone: response at 2–4 months during acute phase treatment. Relative risk of response was calculated using both CGI [20] and Mobility Alone [41].

Figure 2

Psychotherapy plus benzodiazepine vs. psychotherapy alone: global severity at 2–4 months during acute phase treatment. Standardised mean difference was calculated using both CGI [20] and Mobility Alone [41].

Figure 3

Psychotherapy plus benzodiazepine vs. psychotherapy alone: response after the end of acute treatment. Relative risk of response was calculated using both CGI [20] and Mobility Alone [41].

Figure 4

Psychotherapy plus benzodiazepine vs. psychotherapy alone: global severity after the end of acute treatment. Standardised mean difference was calculated using both CGI [20] and Mobility Alone [41].

Figure 5

Psychotherapy plus benzodiazepine vs. psychotherapy alone: response at 6–12 months after treatment termination. Relative risk of response was calculated using both CGI [20] and Mobility Alone [41].

Figure 6

Psychotherapy plus benzodiazepine vs. psychotherapy alone: global severity at 6–12 months after treatment termination. Standardised mean difference was calculated using both CGI [20] and Mobility Alone [41].