Clonazepam placebo-controlled studies

The prior study by Davidson et al. was followed by a placebo-controlled study of clonazepam in 75 patients [Davidson et al. 1993]. Prior studies had been strongly supportive of the efficacy of the agent in social phobia but had... 

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

Kutcher S, Williamson P, MacKenzie S, et al. Successful clonazepam treatment of neuroleptic-induced akathisia in older adolescents and young adults a double-blind, placebo-controlled study. J Clin Psychopharmacol 1989 9 403-406. 

Several open trials have reported significant improvement or remission of panic attacks in patients given clonazepam ( 60, 61, 62, 63, 64, 65 and 66). One double-blind, placebo-controlled study comparing the efficacy of alprazolam, clonazepam, and placebo found both drugs superior to placebo and comparable with each other (67). Because favorable response to clonazepam usually occurs early in treatment, lack of initial improvement may predict treatment failure ( 42, 61, 68). Interdose and morning rebound anxiety have not been reported. Clonazepam is not approved by the FDA for panic attacks, and because there are only a few controlled studies, there is only limited knowledge about its efficacy for this indication. 

There is only one small (n = 12) double-blind, placebo-controlled study showing clonazepam to be effective in pediatric panic disorder and none in posttraumatic stress disorder (156). 

Barnett SD, Kramer ML, Casat CD, Connor KM, Davidson JR (2002) Efficacy of olanzapine in social anxiety disorder a pilot study. J Psychopharmacol 16 365-368 Beauclair L, Fontaine R, Annable L, Holobow N, Chouinard G (1994) Clonazepam in the treatment of panic disorder a double-blind, placebo-controlled trial investigating the correlation between clonazepam concentrations in plasma and clinical response. J Clin Psychopharmacol 14 111-118... 

Moroz G, Rosenbaum JF. Efficacy, safety, and gradual discontinuation of clonazepam in panic disorder a placebo-controlled, multicenter study using optimized doses. J Clin Psychiatry 1999 60 604-612. 

In a randomized, double-blind, placebo-controlled, crossover study in 15 men (mean age 22 years), diazepam 10 mg and clonazepam 1 mg infused over 30 minutes both reduced insulin sensitivity and increased plasma glucose, but the effect of clonazepam was significantly greater (53). 

Clonazepam is widely used for the treatment of sleep disturbances related to post-traumatic stress disorder, despite very limited published data supporting its use for this indication. In a randomized, single-blind, placebo-controlled, crossover trial of clonazepam 1 mg at bedtime for 1 week followed by 2 mg at bedtime for 1 week in six patients with combat-related post-traumatic stress disorder there were no statistically significant differences between clonazepam and placebo (4). Adverse effects of clonazepam were generally mild and essentially indiscernible from those attributed to placebo. Only one patient elected to continue taking clonazepam at the end of the trial. The small sample size was a significant limitation of the study. 

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