Clonazepam Augmentation Of Paroxetine In The Treatment Of Panic Disorder: A One Year Naturalistic Follow-Up Study

Background: Recent studies have examined the proper role of benzodiazepine pharmacotherapy in the treatment of Panic Disorder (PD). The purpose of this naturalistic outcome study is to evaluate the possible clinical benefits and safety of paroxetine/ clonazepam combination therapy in the acute treatment phase (weeks 1-16) of PD. We also compare the treatment outcome of paroxetine plus short-term clonazepam versus paroxetine monotherapy at one year follow-up. Method: Seventy-seven patients with PD with or without agoraphobia participated in our study. All 77 patients received paroxetine (up to 40 mg per day) and 30/77 patients received paroxetine plus clonazepam (up to 1.5 mg/day) for the first 12 weeks of treatment. Patients were assigned to receive clonazepam in a non-randomized fashion. A gradual clonazepam taper was started after week 8, and the clonazepam was discontinued at week 12. The patients in both groups were then continued on paroxetine monotherapy for a total of 12 months. The Panic Self-Questionnaire" (PSQ) was administered to all patients on a monthly basis for one year. Results: The majority of the patients responded well to the pharmacological treatment. Patients showed a statistically significant improvement at four weeks, eight weeks, sixteen weeks and twelve months follow-up. At four weeks and eight weeks follow-up, the paroxetine-clonazepam group reported lower levels of panic symptoms compared to the paroxetine monotherapy group (df:1, p<0.01). At the sixteen week, and twelve month follow-up visits, there were no statistically significant differences between the two groups (p=NS) in terms of treatment response. Also, there was no significant difference between the PD and the PD with Agoraphobia (PDA) groups at baseline and at all follow-up points. Age, sex and, duration of illness had no significant effect on treatment outcome. Conclusion: The combination of paroxetine and clonazepam was more beneficial than paroxetine alone during the acute phase of treatment. During the subsequent maintenance phase, however, there was no significant difference between the two groups. We suggest that clonazepam may be useful as an anti-panic agent during the acute treatment phase of PD, but long-term use is not recommended.