Clonazepam May Reduce Risk of Relapse in Patients With Panic Disorder

While most patients with panic disorder respond to selective serotonin reuptake inhibitors, benzodiazepines, and/or a combination of the two, the risk of relapse after drug discontinuation is known to be high. A study in the Journal of Clinical Psychopharmacology now suggests that patients who take clonazepam may be at a lower risk of relapse than those treated with paroxetine.

The findings were based on an observational, prospective, six-year follow-up study of patients with panic disorder who participated in an open, randomized trial in which they were assigned to take either clonazepam (0.5 mg/d to 2 mg/d) or paroxetine (10 mg/d to 40 mg/d) for eight weeks. Patients who responded to the assigned monotherapy after eight weeks continued this treatment for 34 months; partial or nonresponders were offered a combined treatment with clonazepam and paroxetine. After 34 months in the long-term study, clonazepam and paroxetine were tapered (four months for clonazepam taper, and six weeks for paroxetine taper).

Of the 95 patients who completed the three-year study, 10 failed to achieve remission. The researchers conducted follow-up assessments with the 85 patients who achieved remission at years 1, 2, 3, 5, and 6 following the discontinuation of clonazepam, paroxetine, or a combination of the two. These assessments evaluated the number of panic attacks the patients experienced per month, Clinical Global Impression-Severity (CGI-S) scores, and the 14-item Hamilton Anxiety Rating Scale (HAM-A) scores. (Patients were considered to have relapsed if they were receiving psychotherapy or medication for panic disorder symptoms, had CGI-S scores greater than 1, or had panic attacks in the month preceding the assessment.)

Over the course of the follow-up period, cumulative relapse rates increased from 50% (n=33) at 1 year to 89.4% (n=76) at 6 years. However, one-year relapse rates were lower in patients previously treated with clonazepam (p=0.001) compared with those treated with paroxetine. Similarly, patients treated with clonazepam showed consistently lower relapse rates at 6 years compared with patients who had not taken clonazepam.

According to lead author Rafael C. Freire, M.D., Ph.D., of the Federal University of Rio de Janeiro and colleagues, the study suggests that despite long-term treatment, patients with panic disorder remain at high risk of recurrence when treatment is discontinued. “Treatment with clonazepam appears to protect these patients against relapse, but further studies are needed to support this affirmation,” the authors concluded.

For related information, see the Psychiatric News article “Benzodiazepines: Experts Urge Balance.”

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