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Paroxetine/Clonazepam Combination May Offer No Overall Improvement Over Paroxetine Monotherapy in Panic Disorder Patients

Combined treatment with paroxetine and clonazepam results in more rapid response compared to paroxetine alone in treating patients with panic disorder, but there is no differential benefit beyond the initial weeks of therapy, say researchers.

Previous studies suggest that coadministration of benzodiazepine and antidepressant offers benefits early in therapy. However, combination regimens may also produce increased adverse effects, patient reluctance to discontinue benzodiazepine, and benzodiazepine withdrawal symptoms.

To determine whether the benefits of combined treatment continue, Mark H. Pollack of Massachusetts General Hospital, Boston, United States, and colleagues examined the efficacy and tolerability of 2 combination strategies for clonazepam and paroxetine compared to paroxetine alone in 60 outpatients with panic disorder.

Patients were randomised to receive paroxetine and placebo, paroxetine with clonazepam followed by tapered clonazepam discontinuation (PC-D), or paroxetine with clonazepam maintained throughout the study.

For all treatment regimens, the dose titration schedule goal was to receive 40 mg/day of paroxetine by week 4. For combination regimens, the goal was to receive 2 mg/day of clonazepam by week 4.

The primary outcome measures were the Panic Disorder Severity Scale scores and attainment of remission. Secondary outcome measures included the 14-item Hamilton Anxiety Rating Scale, 24-item Hamilton Depression Rating Scale, and Sheehan Disability Scale.

Results showed that all treatment groups achieved significant improvement. While a significant early advantage was observed for combination treatment groups, the outcome in all three groups was similar.

In the PC-D group, withdrawal symptoms were mild and no significant increase in dropout rates or panic symptoms during or after benzodiazepine discontinuation was observed. Additionally, the PC-D group showed a trend toward greater remission achievement.

The researchers note that the study results should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout.

This study was supported in part by a grant from Glaxo-SmithKline.



Journal of Psychopharmacology 2003;17:3:276-282. "Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder"

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