Full Article
Clinician Article
Drug treatment for panic disorder with or without agoraphobia: systematic review and network meta-analysis of randomised controlled trials.
PMID: 35045991
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FM/GP/Mental HealthRelevance - 7/7
Newsworthiness - 6/7 -
Family Medicine (FM)/General Practice (GP)Relevance - 6/7
Newsworthiness - 6/7 -
General Internal Medicine-Primary Care(US)Relevance - 6/7
Newsworthiness - 6/7 -
PsychiatryRelevance - 6/7
Newsworthiness - 5/7
Abstract
OBJECTIVE: To identify drug classes and individual selective serotonin reuptake inhibitors (SSRIs) with high rates of remission and low risk of adverse events in the treatment of panic disorder with or without agoraphobia.
DESIGN: Systematic review and network meta-analysis.
DATA SOURCES: Embase, Medline, and ClinicalTrials.gov from inception to 17 June 2021.
ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials that included adults aged =18 years with a diagnosis of panic disorder, compared drugs used to treat the panic disorder, and measured the outcomes of interest, including remissions, dropouts, and adverse events.
METHODS: Risk of bias in the included studies was assessed using the revised Cochrane risk of bias tool for randomised trials. Direct meta-analyses were performed using random effects models. A two stage network meta-analysis with surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of drug classes and individual SSRIs.
RESULTS: 87 studies including a total of 12 800 participants and 12 drug classes were eligible for inclusion. Almost all the studies (86/87) had some concern or were at high risk of bias. Network meta-analysis of remission with consistent results indicated that tricyclic antidepressants, benzodiazepines, monoamine oxidase inhibitors, SSRIs, and serotonin-noradrenaline reuptake inhibitors (SNRIs) were associated with significantly higher remission rates than placebo, with risk ratios of 1.39 (95% confidence interval 1.26 to 1.54), 1.47 (1.36 to 1.60), 1.30 (1.00 to 1.69), 1.38 (1.26 to 1.50), and 1.27 (1.12 to 1.45), respectively. SUCRAs identified benzodiazepines (84.5%, mean rank=2.4), tricyclic antidepressants (68.7%, 3.8), and SSRIs (66.4%, 4.0) as the top three best treatments for remission. However, tricyclic antidepressants, benzodiazepines, and SSRIs were also significantly associated with increased risk of adverse events compared with placebo, with risk ratios of 1.79 (1.47 to 2.19), 1.76 (1.50 to 2.06), and 1.19 (1.01 to 1.41), respectively. Consistency assumption of adverse events was upheld but could still be present on removal of studies with high percentages of women participants and those with agoraphobia. A SUCRA cluster ranking plot considering both remission and adverse events among all drug classes indicated that SSRIs were associated with high remission and low risk of adverse events. Among individual SSRIs, sertraline and escitalopram provided high remission with an acceptable risk of adverse events.
CONCLUSION: The findings suggest that SSRIs provide high rates of remission with low risk of adverse events for the treatment of panic disorder. Among SSRIs, sertraline and escitalopram were associated with high remission and low risk of adverse events. The findings were, however, based on studies of moderate to very low certainty levels of evidence, mostly as a result of within study bias, inconsistency, and imprecision of the findings reported.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020180638.
Clinical Comments
Family Medicine (FM)/General Practice (GP)
I rated this paper high especially because of the finding that all these studies have a high risk of bias.
FM/GP/Mental Health
The ongoing lack of certainty limits the value of this study. It makes sense, however, to prescribe sertraline and escitalopram first. We still need higher-certainty evidence to have any confidence; my clinical experience is less glowing than this work suggests.
Psychiatry
Excellent work that successfully addresses the lack of data regarding available pharmacologic treatments for panic disorder and suggests first-line pharmacologic agents for this disorder based on published and available data. All clinical psychiatrists are aware of and familiar with the challenges related to the treatment of panic disorder. Thus, this study adds highly to clinical practice, despite the exclusion of studies that compared concurrent psychotherapy with drug interventions and the overall high risk of bias of the included studies.
