REVIEW OF: Chawla N et al, BMJ 2022;376:e066084

STUDY TYPE: Systematic review and network meta-analysis

Many medications are effective for panic disorder (PD), including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs). Guidelines recommend SSRIs first line, but it’s not clear how these options compare in efficacy and tolerability. This network meta-analysis aimed to address that.

The investigators searched three databases to identify randomized controlled trials that evaluated medications to treat PD (with or without agoraphobia). A total of 87 studies involving 12,800 participants and 12 drug classes met the inclusion criteria. The mean age was 35 years, the majority were women (64%), and the average duration of PD was 6.9 years. The authors used a two-stage network meta-analysis to estimate the relative efficacy of drug classes and individual SSRIs. The probability that each individual agent had the best balance of efficacy and tolerability was measured using the surface under the cumulative ranking (SUCRA). SUCRA values are presented in parentheses below, where higher values indicate a higher rank. 

The two main outcomes were remission (defined as no panic attacks for at least one week at the end of study) and dropout rates. The secondary outcomes were adverse effects and symptom scores for depression and anxiety as measured by the HAM-D, MADRS, and HAM-A rating scales. 

For remission, the most effective treatments were benzodiazepines (84.5%), TCAs (68.7%), and SSRIs (66.4%). The least effective were beta blockers (9%) and buspirone (33.2%). Dropout rates were the lowest for benzodiazepines and benzodiazepines plus TCAs, and highest for buspirone and MAOIs. However, adverse effects were lowest for buspirone and SNRIs, and highest with TCAs and benzodiazepines.

In terms of secondary outcomes, overall anxiety was most effectively decreased by SSRIs plus beta blockers (97.5%), TCAs plus benzodiazepines (70.9%), and SSRIs alone (62.9%). SNRIs and buspirone were the least effective (31.6% and 33%, respectively). For comorbid depressive symptoms, the top ranked treatments were SSRIs plus beta blockers (99.7%), benzodiazepines (69.9%), and TCAs (66.4%).

When considering the balance of efficacy and tolerability, SSRIs rose to the top, and sertraline and escitalopram ranked at the top within that class. Although fluvoxamine, paroxetine, and fluoxetine had favorable efficacy profiles, they were also associated with a higher risk of adverse effects. Citalopram had minimal efficacy and a high risk of adverse effects.

Network meta-analyses are limited by an underlying assumption that studies of varied design are comparable. In particular, this analysis was further limited by a high risk of within-study bias, inconsistency and imprecision of reported findings, and short trial durations.

CARLAT TAKE

Among pharmacotherapy options, this study supports sertraline and escitalopram as the first choice for panic disorder. Interpret with caution, as the limitations are many.