| Drug Name: | Klonopin / Clonazepam |
| Dosage: | 2 – 4 mg |
| Packages: | 30 – 360 pills |
| Payment Method: | VISA, MASTERCARD, Paypal |
| Shipment: | US-US EU-EU int. |
| Buy Now: | Visit DrugStore |
Why was clonazepam chosen for this study instead of other benzodiazepines?
Background
The role of combining benzodiazepines with selective serotonin reuptake inhibitors (SSRIs) in the initial management of panic disorder remains under discussion. Although this therapeutic approach is frequently applied in clinical practice, clear evidence on the most effective strategy for coadministration is lacking. This study aimed to evaluate the efficacy of early coadministration of clonazepam with sertraline in patients with panic disorder.
Methods
Fifty individuals diagnosed with panic disorder were enrolled in a randomized, double-blind trial. All participants received open-label sertraline for 12 weeks (target dose: 100 mg/day). In addition, patients were randomized to receive either clonazepam (0.5 mg three times daily) or placebo during the first 4 weeks. Clonazepam was tapered over the following 3 weeks and then discontinued.
Results
Thirty-four patients (68%) completed the study. Discontinuation rates were comparable between the sertraline/placebo and sertraline/clonazepam groups (38% vs 25%, P = .5). Intent-to-treat analysis showed a significantly higher proportion of responders in the sertraline/clonazepam group compared with sertraline/placebo at week 1 (41% vs 4%, P = .003). A difference was also observed at week 3 (63% vs 32%, P = .05), but not at later time points.
Conclusion
The findings suggest that early symptom stabilization in panic disorder can be achieved more effectively with a sertraline/clonazepam regimen compared with sertraline alone. This supports the clinical relevance of combined therapy as a safe and practical option for rapid improvement of panic symptoms.
Study Purpose
The aim of this study was to assess, under controlled conditions, whether the early coadministration of clonazepam, a benzodiazepine, with the SSRI sertraline would promote faster clinical stabilization of panic disorder symptoms compared with sertraline alone. We hypothesized that this combined approach would provide more rapid improvement in key symptoms—including panic attacks, anticipatory anxiety, distress linked to attacks, and agoraphobic avoidance—without producing excessive short- or long-term adverse effects or compromising early treatment benefits.
Context
Although combining benzodiazepines with SSRIs is common in routine care, evidence from controlled studies is still limited. Previous work has shown the short-term efficacy of imipramine/alprazolam regimens, though tapering difficulties hindered long-term outcomes. Other reports, including paroxetine/clonazepam trials, suggest early benefit with fewer problems during discontinuation. Ongoing studies continue to evaluate the role of combined therapy, but available data point to this approach as a promising, safe, and clinically relevant option for achieving rapid stabilization in patients with acute panic disorder.
Klonopin (Clonazepam) 2mg (US) 90 pills
373.54 $
Klonopin (Clonazepam) 2mg (US) 120 pills
452.00 $
Klonopin (Clonazepam) 2mg (US) 180 pills
610.08 $
Klonopin (Clonazepam) 2mg (US) 240 pills
766.99 $
Medication Doses
Adherence to the planned dosing protocol was generally high. By the end of week 3, patients were titrated to a sertraline dose of 100 mg/day, which was maintained through study completion (sertraline/clonazepam group [n = 20]: mean ± SD = 100 ± 0 mg; sertraline/placebo group [n = 24]: 98 ± 10 mg; P = .37). Most participants tolerated the fixed clonazepam regimen of 0.5 mg three times daily (1.5 mg/day) until tapering began at the end of week 4. At that time, mean ± SD doses were 1.45 ± 0.17 mg for the sertraline/clonazepam group (n = 20) and 1.45 ± 0.14 mg for the sertraline/placebo group (n = 24; P = .93). Tapering was completed by the end of week 7, with the exception of one patient in each group whose taper extended to week 8.
During the trial, two patients required additional benzodiazepine therapy on an as-needed basis for severe panic symptoms. In the clonazepam group, one patient began PRN use of lorazepam at week 8, taking 2–3 doses of 0.5 mg per week until study completion. In the placebo group, one patient initiated PRN alprazolam at week 5, taking one 0.25-mg tablet approximately every other week through the end of the study.
Study Treatments
At the randomization visit, all patients began open-label sertraline therapy, starting with 25 mg daily. The dosage was increased to 50 mg/day at the end of week 1 and then to 100 mg/day by the end of week 2. A daily dose of 100 mg was established as the target, based on prior evidence indicating that most patients with panic disorder respond within the 50–100 mg/day range. The sertraline dose was maintained from week 3 onward, with patients required to take at least 50 mg daily to remain in the study.
At the first visit, participants were additionally randomized, using a computer-generated schedule, to receive either active clonazepam (0.5 mg orally, three times daily; 1.5 mg/day) or a visually identical placebo. In cases of excessive sedation, the dose was reduced to two capsules per day. After 4 weeks of treatment, klonopin or placebo was gradually tapered over 3 weeks: reduced to 0.5 mg twice daily during week 5, then to 0.5 mg once daily during week 6, and finally to 0.25 mg daily in week 7 before discontinuation. Sertraline treatment was continued throughout, including an additional 5 weeks following clonazepam taper.
Comment
Controlled data from this trial support the efficacy and safety of early coadministration of clonazepam with sertraline as a rapid stabilization strategy for patients with moderate to severe panic disorder. Intent-to-treat analyses of three out of four primary outcome measures demonstrated superior early improvement in the combination group compared with sertraline alone. Although secondary measures did not show statistically significant differences—likely due to the limited sample size—the omnibus MANOVA including all continuous measures revealed highly significant effects (P < .005).
Importantly, prior exposure to psychotropic medication did not explain the enhanced early response in the sertraline/clonazepam group. Furthermore, clonazepam use did not impair long-term treatment outcomes: both groups achieved comparable clinical improvement during taper and at study completion. In contrast to earlier findings with alprazolam combinations, these results suggest not only rapid stabilization but also sustained treatment benefits through and after benzodiazepine discontinuation. Possible contributing factors include the use of clonazepam, with its longer half-life, the more gradual taper schedule (3 weeks vs 2 weeks in previous work), and the greater capacity of SSRIs compared to tricyclic antidepressants to maintain clinical efficacy during benzodiazepine withdrawal.