Background: Panic disorder (PD) is a devastating illness, with numerous patients experiencing significant functional disability and many not achieving full remission with first-line pharmacologic and psychotherapeutic treatments.

Methods: A search of PubMed, Cochrane Library, and PsychINFO databases was used to identify publications focused on evidence-based treatment of PD.

Results: Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are standard first-line pharmacologic treatments for PD. Many other antidepressants can be considered as alternatives to SSRIs, including serotonin-norepinephrine reuptake inhibitors, serotonin multimodal agents, tricyclic antidepressants, monoamine oxidase inhibitors, and mirtazapine. Certain anticonvulsants and antipsychotics may be helpful; however, the evidence base is limited. Buspirone, beta blockers, and hydroxyzine can be considered third-line agents. Currently, there is minimal data supporting the use of electroconvulsive therapy or repetitive transcranial magnetic stimulation (rTMS). There is very little evidence justifying the use of medical cannabis or over-the-counter supplements for PD, and these treatments have risk for adverse effects. Research strongly supports the use of cognitive-behavioral therapy (CBT) for PD.

Conclusions: Many options exist for the management of PD. Treatments with the strongest evidence include SSRIs, other antidepressants, and CBT. Newer interventions approved for the treatment of depression, such as serotonin multimodal agents, esketamine, and rTMS, merit further investigation for use in PD.