A network meta-analysis compared and ranked efficacy and acceptability of various pharmacological treatments used for panic disorder. Data from 70 randomized controlled trials (RCTs) of adults diagnosed with panic disorder with or without agoraphobia was analyzed. Evidence from 48 RCTs (n=10,118) indicate that most medications are more effective than placebo in terms of response to treatment; diazepam, alprazolam, and clonazepam ranked as most effective. Results from 64 RCTs (n=12,310) suggest most medications are associated with either a reduced or similar risk of study dropout (a proxy of acceptability) compared to placebo; alprazolam and diazepam had the lowest dropout rates. In terms of remission, data from 32 RCTs (n=8,569) indicate that most medications are more effective than placebo, with desipramine and alprazolam showing the most clinically meaningful improvement. According to data from 41 RCTs (n=7,853), only clonazepam and alprazolam show a strong reduction in the frequency of panic attacks compared to placebo. Data from 26 RCTs (n=7,044) indicate that symptoms of agoraphobia are most effectively reduced by citalopram, reboxetine, escitalopram, clomipramine, and diazepam, compared to placebo. When pooling medication classes, all classes of medication are more effective than placebo; response rate rank highest for tricyclic antidepressants, followed by benzodiazepines, and monoamine oxidase inhibitors. As a class, selective serotonin reuptake inhibitors (SSRIs) ranked fifth and serotonin-norepinephrine reuptake inhibitors (SNRs) ranked last in efficacy. However, when comparing classes directly, no differences emerged. Benzodiazepines are the only class associated with a lower dropout rate compared to placebo. Notably, the quality of studies comparing antidepressants with placebo is moderate, while the quality of studies comparing benzodiazepines with placebo and antidepressants is low. Overall, this network meta-analysis suggests that all classes of medications studied may be effective for treating panic disorder. Benzodiazepines appear to have a small but significant advantage in term of acceptability over other classes. Nearly all studies included in this analysis are of short duration, and longer-term RCTs (>8 weeks) are needed to better evaluate if and when benzodiazepines should be used given their propensity for abuse.
Guaiana G et al. Cochrane Database Syst Rev 2023;11(11):CD012729. Abstract