Azapirones versus placebo for panic disorder in adults

Why is this review important?

Panic disorder is common in the general population and is often associated with various psychiatric disorders. Azapirones are a class of drugs occasionally used in the treatment of panic disorder, although none has been approved by a regulatory agency for this purpose. They are associated with less drowsiness, psychomotor impairment, alcohol potentiation and potential for addiction or abuse. However, azapirones are not widely used for panic disorder. Evidence for their efficacy in treating panic disorder is unclear. It is important to find out if azapirones are effective and acceptable in the treatment of panic disorder.

Who will be interested in this review?

Patients and general practitioners.

What questions does this review aim to answer?

This review aims to answer the following questions for panic disorder in adults:

1. Are azapirones more effective than placebo?
2. Are azapirones more acceptable than placebo?
3. What kind of adverse effects do azapirones have compared with placebo?

Which studies were included in the review?

We searched electronic database to find all relevant studies published between 1950 and January 2014. To be included in the review, studies had to be randomised controlled trials that compared azapirone with placebo for panic disorder in adults. We include three studies involving a total of 170 people in the review. All three looked at the same type of azapirone, a drug called buspirone. The review authors rated the quality of the evidence as 'low' to moderate'.

What does the evidence from the review tell us?

There was not enough information to work out whether azapirones are any more or less effective than placebo in causing substantial improvements in panic disorder overall.

A small amount of moderate-quality evidence suggests that the acceptability of azapirones for panic disorder is lower than for placebo.

There was not enough information to compare any differences in adverse effects caused by azapirones and placebo.

What should happen next?

Studies with larger sample sizes and fewer risks of bias should be carried out. Studies should report how participants were allocated to each treatment, and whether the trials were financially sponsored by the manufacturer of the drug. Study protocols should be registered to avoid selective reporting of outcomes by authors.

Trials need to test azapirones other than buspirone to determine their effectiveness.

Remission or response should be reported as the efficacy outcome and longer-term outcomes need to be addressed to establish whether the effect is transient or durable.

Trials should better report any harms experienced by participants during the trial.

Authors' conclusions: 

The efficacy of azapirones is uncertain due to the lack of meta-analysable data for the primary outcome and low-quality evidence for secondary efficacy outcomes. A small amount of moderate-quality evidence suggested that the acceptability of azapirones for panic disorder was lower than for placebo. However, only trials of one azapirone (namely buspirone) were included in this review; this, combined with the small sample size, limits our conclusions. If further research is to be conducted, studies with larger sample sizes, with different azapirones and with less risk of bias are necessary to draw firm conclusions regarding azapirones for panic disorder.

Read the full abstract...
Background: 

Panic disorder is common in the general population. It is often associated with other psychiatric disorders, such as drug dependence, major depression, bipolar disorder, social phobia, specific phobia and generalised anxiety disorder. Azapirones are a class of drugs used as anxiolytics. They are associated with less drowsiness, psychomotor impairment, alcohol potentiation and potential for addiction or abuse than benzodiazepines. However, azapirones are not widely used in the treatment of panic disorder and evidence for their efficacy is unclear. It is important to find out if azapirones are effective and acceptable in the treatment of panic disorder.

Objectives: 

To assess the effects of azapirones on panic disorder in adults, specifically:

1. to determine the efficacy of azapirones in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison with placebo;
2. to review the acceptability of azapirones in panic disorder, with or without agoraphobia, in comparison with placebo; and
3. to investigate adverse effects of azapirones in panic disorder with or without agoraphobia, including general prevalence of adverse effects, compared with placebo.

Search strategy: 

We searched the Cochrane Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR, search date: 10th January 2014), which includes relevant randomised controlled trials from The Cochrane Library (all years), MEDLINE (1950-), EMBASE (1974-), and PsycINFO (1967-).

Selection criteria: 

Randomised controlled trials that compared azapirones with placebo for panic disorder in adults.

Data collection and analysis: 

Three review authors independently identified studies, assessed trial quality and extracted data. We contacted study authors for additional information.

Main results: 

Three studies involving 170 participants compared the azapirone buspirone with placebo. No study provided enough usable information on our primary efficacy outcome (response). For our primary acceptability outcome, moderate-quality evidence indicated that azapirones had lower acceptability than placebo: risk ratio (RR) for dropouts for any reason 2.13 (95% confidence interval (CI) 1.11 to 4.07; 3 studies, 170 participants. Evidence for secondary efficacy outcomes were of low quality. Results on efficacy between azapirone and placebo in terms of agoraphobia (standardised mean difference (SMD) -0.01, 95% CI -0.56 to 0.53; 1 study, 52 participants), general anxiety (mean difference (MD) -2.20, 95% CI -5.45 to 1.06; 2 studies, 115 participants) and depression (MD -1.80, 95% CI -5.60 to 2.00; 1 study, 52 participants) were uncertain. None of the studies provided information for the assessment of allocation concealment or sequence generation. Conflicts of interest were not explicitly expressed. The risk of attrition bias was rated high for all three studies. Information on adverse effects other than dropouts for any reason was insufficient to include in the analyses.

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