Determinants of Pharmacologic Treatment Failure in Panic Disorder

Background: We systematically assessed reasons for failure of pharmacologic treatment for panic disorder in patients referred to a specialty anxiety and mood disorders clinic and examined possible determinants of treatment-resistant panic disorder.

Method: Interview data were obtained from 106 patients with DSM-III-R panic disorder seen in consultation. Data for each of 252 past medication trials included dose, duration of treatment, side effects, outcome, and reason for discontinuation. T tests and chi-square analyses were used to compare demographic and clinical characteristics of patients failing versus responding to adequate trials and those with and without intolerable medication side effects.

Results: Of 252 medication trials, 190 used effective antipanic medications, and only 59 (23%) were adequate in dose and duration. The most common reason for treatment failure was intolerable side effects, occurring in 51 (27%) of 190 trials using effective antipanic medications. Patients discontinuing treatment due to adverse effects had higher Hamilton Rating Scale for Anxiety scores and were less likely to have a history of substance abuse. Discontinuation due to side effects was significantly more common with tricyclic antidepressants than with benzodiazepines. True treatment resistance was reported in 14 (24%) of 59 adequate medication trials. Treatment-resistant patients were younger and had a higher lifetime rate of major depression.

Conclusion: Although use of ineffective medications or inadequate trials were important factors, the most common reason for treatment failure was side effects, especially with tricyclic antidepressants. True treatment resistance was less common, since few medication trials were adequate in dose and duration, and may be associated with comorbidity.