SSRIs Associate With Most Favorable Treatment Profile for Panic Disorders

Mature woman taking medication.
Researchers from Mahidol University in Thailand searched publication databases through June 2021 for studies of interventions for the treatment of panic disorders.

A systematic review and meta-analysis found that panic disorder may safely and effectively be treated with selective serotonin reuptake inhibitors (SSRIs). These findings were published in BMJ.

Researchers from Mahidol University in Thailand searched publication databases through June 2021 for studies of interventions for the treatment of panic disorders. The primary outcome was remission, as defined by no panic attacks for ≥1 week. Additional outcomes were symptom scores for depression and anxiety and safety outcomes.

A total of 87 studies comprising 12,800 participants met the inclusion criteria. Patients were aged mean 35.0 years, 63.7% were women, and the duration of panic disorder was 6.9 years.

For studies which assessed remission (n=50; n=9481 participants), patients who received benzodiazepines (risk ratio [RR], 1.49; 95% CI, 1.36-1.63; I2, 13.18%), paroxetine (RR, 1.42; 95% CI, 1.12-1.79; I2, 55.77%), tricyclic antidepressants (RR, 1.37; 95% CI, 1.27 to 1.47; I2, 0%), sertraline (RR, 1.30; 95% CI, 1.10-1.54; I2, 0%), and venlafaxine (RR, 1.26; 95% CI, 1.08-1.48; I2, 52.02%) were more likely to achieve remission than placebo.

In a network meta-analysis, benzodiazepines (RR, 1.47; 95% CI, 1.36-1.60), tricyclic antidepressants (RR, 1.39; 95% CI, 1.26-1.54), SSRIs (RR, 1.38; 95% CI, 1.26-1.50), monoamine oxidase inhibitors (RR, 1.30; 95% CI, 1.00-1.69), and serotonin-noradrenaline reuptake inhibitors (SNRIs; RR, 1.27; 95% CI, 1.12-1.45) monotherapy outperformed placebo. Benzodiazepines were superior to beta blockers (RR, 1.98; 95% CI, 1.03-3.79) and SNRIs (RR, 1.16; 95% CI, 1.00-1.34).

Overall, the most effective treatments to achieve remission were benzodiazepines (84.5%), tricyclic antidepressants (68.7%), and SSRIs (66.4%) and the least effective were β blockers (9%) and buspirone (33.2%).

Regarding dropout rate, the treatments associated with the lowest rates were benzodiazepines (87.5%), benzodiazepines plus tricyclic antidepressants (74.1%), and noradrenergic plus specific serotonergic antidepressant (63.3%), and the highest dropout rates were observed for buspirone (4.4%) and monoamine oxidase inhibitors (34.3%).

The studies found that anxiety scores were most effectively reduced by SSRIs plus β blockers (97.5%), tricyclic antidepressants plus benzodiazepines (70.9%), and SSRIs alone (62.9%). The most effective treatments at lowering depression scores were SSRIs plus β blockers (99.7%), benzodiazepines (69.9%), and tricyclic antidepressants (66.4%).

Risk for adverse effects were associated with use of benzodiazepines (RR, 1.92; 95% CI, 1.69-2.18; I2, 32.7%), tricyclic antidepressants (RR, 1.51; 1.19-1.92; I2, 82.5%), and venlafaxine (RR, 1.10; 1.02-1.18; I2, 0%) compared with placebo.

This analysis was limited by the fact that most studies were published >20 years ago and had poor study methodology and/or reporting.

The study authors concluded, “Our findings suggest that SSRIs offer important benefit with low risk for drug treatment of panic disorder. […] The findings should be interpreted with caution, however, as the results were based on evidence with moderate to very low levels of certainty.”


Chawla N, Anothaisintawee T, Charoenrungrueangchai K, et al. Drug treatment for panic disorder with or without agoraphobia: systematic review and network meta-analysis of randomized controlled trials.Int Clin Psychopharmacol. 2015;30(4):183-92. doi:10.1097/YIC.0000000000000078