Efficacy and safety of pharmacological interventions for panic disorder with or without agoraphobia: A systematic review and network meta-analysis, accounting for dose
In brief
Several panic drugs reduced symptoms, but strongest estimate came from weaker studies
Across 92 trials involving 14,510 people, several medicines, including fluvoxamine, fluoxetine and alprazolam, reduced anxiety symptoms versus placebo; fluvoxamine and sustained-release alprazolam also reduced weekly panic attacks. The largest estimated benefit was for brofaromine, but it came from lower-quality evidence, so the comparisons do not establish a clear best treatment.
- Journal
- Journal of affective disorders (Q1)
- Published
- 2 November 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Michele Fornaro, Chiara Di Lorenzo, Daniela Caldirola, Giampaolo Robert Perna
- PMID
- 42971365
- DOI
- 10.1016/j.jad.2026.122668
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (paper of the day, 4 November 2026): Network meta-analysis compares panic disorder pharmacotherapies and harms
Abstract
BACKGROUND: Panic disorder (PD) features recurrent and unpredictable panic episodes accompanied by a variety of somatic symptoms. This is the first network meta-analysis (NMA) accounting for dose that explores direct and indirect comparisons focusing on pharmacotherapy for PD, with and without agoraphobia. METHODS: We conducted a NMA searching for RCTs comparing pharmacological interventions against each other/or placebo in patients with PD, indexed in PubMed/MEDLINE,Embase,Web-of-Science/Scopus(from inception up to 2026, April 3). Co-primary outcomes were the change in anxiety symptoms/response and the change in weekly frequency of panic attacks. Tolerability/remission/acceptability, as well as the risk of specific adverse events, were secondary outcomes. Confidence-In-Network-Meta-Analysis was appraised. RESULTS: Overall, 92 RCTs, encompassing 36 different treatment combinations, involved 14,510 participants. Sensitivity analysis, including non-sponsored studies only and excluding outliers for major effect modifiers, indicated that brofaromine (SMD = -2.47; 95%CI = -3.57;-1.47), alprazolam (SMD = -0.66; 95%C.I. = -1.11;-0.22), alprazolam sublingual (SMD = -0.61; 95%C.I. = -1.14;-0.06); fluvoxamine (SMD = -0.53; 95%C.I. = -0.79;-0.26), fluoxetine (SMD = -0.52; 95%C.I. = -0.81;-0.22), alprazolam substained-release (SMD = -0.41; 95%C.I. = -0.70;-0.13) outperformed placebo for anxious symptoms reduction. Imipramine, alprazolam, and brofaromine outperformed placebo for response. Fluvoxamine (SMD = -0.33; 95%C.I. = -0.61;-0.04) and alprazolam sustained-release (SMD = -0.30; 95%C.I = -0.58;-0.01) outperformed placebo in the change in weekly frequency of panic attacks. However, a meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus score showed that larger SMDs (i.e., brofaromine) were associated with lower AMSTAR scores, reflecting lower study quality. CONCLUSIONS: Our findings align with previous NMAs and current guidelines, updating and expanding knowledge by concurrently appraising different drugs/doses through refined transitivity/sensitivity analyses.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.