Psychotherapy and a benzodiazepine combined for treating panic disorder

Panic disorder is characterised by the repeated occurrence of unexpected panic attacks, during which the individual experiences a strong fear with anticipation of death. These attacks are often accompanied by somatic symptoms such as palpitations, dyspnoea or faintness. Those suffering from panic disorder have persistent anticipatory fear of recurrent attacks and feel anxious even while they have no occurrence of panic attacks for a certain period. Panic disorder is strongly associated with an increased risk for agoraphobia and depression. The prevalence of panic disorder is reported to be around 2 to 3 percent in the general population. Two broad categories of treatment have been shown to be effective in treating panic disorder, one being pharmacotherapy with antidepressants or benzodiazepines, the other being psychotherapy. These treatments are often combined, yet the efficacy of combining psychotherapy and benzodiazepine for panic disorder is unclear, despite its widespread use. This review included randomised controlled trials comparing the combination of psychotherapy and a benzodiazepine with either the psychotherapy or the benzodiazapine alone for people with panic disorder. We were able to include only three trials in this review. Two could be used in the comparison of the combination of psychotherapy and benzodiazepine versus psychotherapy alone and one in the comparison of the combination with benzodiazepine. These comparisons involved just 166 patients and 77 patients, respectively. These small numbers make it difficult to detect any differences between combination treatments and either treatment alone. The trials which compared the combination of treatments with psychotherapy alone (both using behaviour therapy) indicated no differences in response between the two approaches, either during the intervention, at the end of the intervention, or at the last follow-up time point. The trial which compared the combination of treatments with a benzodiazepine alone demonstrated no differences in response during the intervention. Although the combination of treatments appeared to be more effective than the benzodiazepine alone at the end of treatment, no significant differences were observed at the 7-month follow-up. Before evidence-based treatment recommendations are possible, more randomised controlled trials are required, comparing the combination of psychotherapy and benzodiazepines with either treatment alone, and involving enough people to be able to detect a true difference between the treatments if one exists.

Authors' conclusions: 

The review established the paucity of high quality evidence investigating the efficacy of psychotherapy combined with benzodiazepines for panic disorder. Currently, there is inadequate evidence to assess the clinical effects of psychotherapy combined with benzodiazepines for patients who are diagnosed with panic disorder.

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Background: 

The efficacy of combining psychotherapy and benzodiazepines for panic disorder is unclear, despite widespread use.

Objectives: 

To examine the efficacy of the combination compared with either treatment alone.

Search strategy: 

Randomised trials comparing the combination of psychotherapy and benzodiazepine with either therapy alone for panic disorder were identified. The Cochrane Depression, Anxiety and Neurosis Group Studies and References Registers were searched. References of relevant trials and other reviews were checked. Experts in the field were contacted. Additional unpublished data were sought from authors of the original trials.

Selection criteria: 

Two authors independently checked the records retrieved by the searches to identify randomised trials comparing the combined therapy versus either of the monotherapies, among adults with panic disorder.

Data collection and analysis: 

Two authors independently checked eligibility, assessed quality and extracted data from the eligible trials using a standardised data extraction form. The primary outcome was "response" based on global judgement. Random-effects meta-analyses were conducted, combining data from included trials.

Main results: 

Three trials met eligibility criteria. A 16-week behaviour therapy intervention was used in two trials, and a 12-week cognitive-behaviour therapy intervention in the third. Duration of follow-up varied, ranging from 0 to 12 months.
Two trials (total 166 participants) provided data comparing combination with psychotherapy alone (both using behaviour therapy). No statistically significant differences were observed in response during the intervention (relative risk (RR) for combination 1.25, 95% CI 0.78 to 2.03, P = 0.35), at the end of the intervention (RR 0.78, 0.45 to 1.35, P = 0.37), or at the last follow-up time point, although the follow-up data suggested that the combination might be inferior to behaviour therapy alone (RR 0.62, 0.36 to 1.07, P = 0.08).
One trial (77 participants) compared combination with a benzodiazepine alone. No differences were found in response during the intervention (RR 1.57, 0.83 to 2.98, P = 0.17). Although the combination appeared to be superior to the benzodiazepine alone at the end of treatment (RR 3.39, 1.03 to 11.21, P = 0.05) the finding was only borderline statistically significant, and no significant differences were observed at the 7-month follow-up (RR 2.31, 0.79 to 6.74, P = 0.12).

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