A Randomized, Naturalistic, Parallel-Group Study for the Long-Term Treatment of Panic Disorder With Clonazepam or Paroxetine

Abstract

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

Pharmacological treatment for generalized anxiety disorder in adults: an update

“…The third study, although evaluating patients with panic disorder, compared clonazepam and paroxetine and found that in addition to improved efficacy in the clonazepam group, there were also significantly fewer adverse effects. This was demonstrated in the short term (8 weeks) and the long term (3 years) [66,67]. Clonazepam, however, elicited a therapeutic response sooner and was better tolerated in the long-term.…”

Efficacy and Tolerability of Benzodiazepines versus Antidepressants in Anxiety Disorders: A Systematic Review and Meta-Analysis

“…Also, participants treated with clonazepam reported fewer AE than those taking paroxetine (73 vs. 95%; p = 0.001). Furthermore, responders (n = 105) entered a 3-year continued monotherapy with either clonazepam or paroxetine, and clonazepam led to a significantly greater clinical improvements and fewer side effects than paroxetine [39]. …”

“…This was also confirmed to occur in panic disorder by the results of our meta-analysis. As to long-term effects, Nardi et al [39], at a 3-year follow-up of continued monotherapy with either clonazepam or paroxetine in panic disorder, showed that not only was long-term treatment with clonazepam still better in terms of clinical improvement than paroxetine, but it also led to significantly fewer AE. More specifically, during long-term treatment, participants taking paroxetine experienced sexual dysfunctions, drowsiness/fatigue, memory/concentration problems and insomnia more frequently than those treated with clonazepam.…”

Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology

“…Double-blind studies indicate that continuing SSRI or clomipramine treatment from 12-52 weeks is associated with an increase in overall treatment response rates [I (PCT)] (Ballenger, 1998;Lecrubier and Judge, 1997;Lepola et al, 1998). The relative effectiveness and acceptability of differing medications over long-term treatment is uncertain, but a 12-month comparison of the efficacy and tolerability of differing SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine) suggests that fluvoxamine is less likely to be associated with weight gain or sexual adverse effects [III] (Dannon et al, 2007); and the findings of a randomised naturalistic parallel-group study of 34 months of continuation treatment with clonazepam or paroxetine suggest that clonazepam is marginally more effective and better tolerated [II] (Nardi et al, 2012).…”