Rejean Fontaine

An open clinical trial of fluoxetine in the treatment of obsessive-compulsive disorder.

In a 9-week open label study, seven outpatients with obsessive-compulsive disorder were treated with fluoxetine, a selective inhibitor of neuronal reuptake of serotonin. After a 7-day placebo washout period, patients were given a dose of 40 mg/day, which was gradually increased to a maximum of 80 mg/day. A significant improvement was found in the symptomatology of patients as measured on the obsessive-compulsive subscale of the Comprehensive Psychopathological Rating Scale (p less than 0.001) and the Clinical Global Impression of severity of illness (p less than 0.01). These findings support the hypothesis that serotonergic antidepressants may be useful in the treatment of obsessive-compulsive disorder and underline the need to carry out double-blind clinical trials to confirm these results.

Clonazepam in the treatment of panic disorder: a double-blind, placebo-controlled trial investigating the correlation between clonazepam concentrations in plasma and clinical response.

Thirty-two outpatients with a DSM-III diagnosis of panic disorder or agoraphobia with panic attacks were randomly assigned to 4 weeks of treatment with clonazepam or placebo, after a 1-week placebo washout period. Twenty-nine patients entered the double-blind phase of the study and were eligible for intent-to-treat analysis. Clonazepam-treated patients experienced significantly fewer panic attacks, and these were of lesser intensity and short duration than those in placebo-treated patients (p < 0.001). Clonazepam was also superior to placebo with respect to symptoms of anxiety and depression (p < 0.001). The mean dose of clonazepam at week 4 was 2.2 mg (standard deviation, 0.7 mg). There was significant (p < 0.05) correlation between drug concentration in plasma and decrease in the global measure of the severity of panic disorder (r = 0.68); similar trends were seen for the decreases in frequency (r = 0.60) and severity (r = 0.55) of panic attacks, but not between concentration in plasma and decline in generalized anxiety. The most common adverse event was drowsiness, which occurred in 9 of 13 clonazepam-treated patients.

Fluoxetine in the treatment of obsessive compulsive disorder

In a 9-week open-label study, 7 outpatients with obsessive compulsive disorder were treated with fluoxetine, a selective inhibitor of neuronal reuptake of serotonin. A significant improvement was found in the symptomatology of patients as measured on the obsessive compulsive subscale of the Comprehensive Psychopathological Rating Scale (p less than 0.001) and the Clinical Global Impression of severity of illness (p less than 0.01). These findings support the hypothesis that serotoninergic antidepressants may be useful in the treatment of obsessive compulsive disorder.

Bromazepam and diazepam in generalized anxiety: a placebo-controlled study with measurement of drug plasma concentrations.

In a double-blind, placebo-controlled study, 48 anxious outpatients with a primary diagnosis of generalized anxiety disorder were randomly assigned to 4 weeks of treatment with bromazepam (18 mg/day), diazepam (15 mg/day), or placebo, after a 1-week washout period. From week 1 onward both active drugs were superior to placebo in relieving anxiety symptoms. Bromazepam was found to be significantly more effective than diazepam with respect to the somatic anxiety factor and the total score for the Hamilton Anxiety Rating Scale and the fear/anxiety factor of the Patients Self-Rating Symptom Scale. Plasma concentrations of diazepam plus active metabolites were correlated significantly (r = 0.60, p < 0.05) with the percentage reduction in self-rating anxiety scores. Bromazepam plasma concentration measurements showed greater variability than those of diazepam and were not found to be correlated significantly with clinical response. It is suggested that the use of strict diagnostic criteria (1978 draft of the third edition of Diagnostic and Statistical Manual of Mental Disorders), adequate sample sizes, and a 4-week study period gave increased sensitivity for the detection of significant differences between the two benzodiazepines.

Obsessive disorder with self-mutilation: a subgroup responsive to pharmacotherapy.

Obsessive-compulsive disorder (OCD) can be considered a complex entity with possibly different subgroups responsive to specific treatment. This article presents two cases of OCD with self-mutilation, successfully treated with serotonergic antidepressants. The authors discuss a sub-group of OCD patients whose rituals present as self-destructive behavior and are responsive to pharmacotherapy.

New concepts in benzodiazepine therapy: Rebound anxiety and new indications for the more potent benzodiazepines

Abrupt withdrawal of benzodiazepine treatment in generalized anxiety patients was found to induce a rebound anxiety state in addition to minor physical symptoms. Controlled clinical trials suggest that the newer high potency benzodiazepines (alprazolam, clonazepam and bromazepam) have novel psychiatric indications and greater anxiolytic effect than the classical benzodiazepines. Alprazolam, a triazolobenzodiazepine, was superior to placebo in the treatment of panic disorder, for which medium or low potency benzodiazepines are generally inefficacious. Clonazepam, an anticonvulsant which increases 5HT synthesis, was more efficacious than lithium in reducing manic symptoms. Bromazepam, a new potent benzodiazepine, was superior to diazepam in the treatment of generalized anxiety disorder.

Zopiclone and Triazolam in Insomnia Associated with Generalized Anxiety Disorder: a Placebo-controlled Evaluation of Efficacy and Daytime Anxiety

In a double-blind placebo-controlled study, following a 1 week washout, 75 outpatients suffering from generalized anxiety disorder with severe insomnia as the target symptom were randomly assigned to 4 weeks of treatment with zopiclone 7.5 mg, triazolam 0.5 mg or placebo at bedtime. Zopiclone was significantly better than placebo on most sleep parameters. Triazolam tended to be superior to placebo, but its superiority was significant only on the sleep induction factor. Triazolam-treated patients presented significantly more day-time-interdose anxiety than zopiclone as assessed by the weekly HARS and Clinical Global Assessment of Anxiety. Although daytime-interdose anxiety was observed with both drugs, this treatment emergent symptom was more frequent and severe with triazolam. Side-effects were of a mild to moderate intensity for both zopiclone and triazolam; however, taste perversion frequently appeared with zopiclone. Although both drugs share similar pharmacological properties and bind to benzodiazepine receptors, they differ significantly with respect to side-effects and daytime anxiety.

Bromazepam and lorazepam in generalized anxiety: a placebo‐controlled study with measurement of drug plasma concentrations

Sixty outpatients with a diagnosis of generalized anxiety were randomly assigned to 4 weeks of treatment with bromazepam, lorazepam or placebo, following a 1‐week placebo washout period. There was no significant difference in the anxiolytic effects of bromazepam and lorazepam, both of which were superior to placebo. However, lorazepam‐treated patients tended to have a more depressed mood than those treated with bromazepam. Drug‐treated patients had consistently less cognitive impairment than those treated with placebo, the difference being statistically significant (P .05) in the case of bromazepam. The most frequent side‐effects reported with each drug were drowsiness, which tended to subside with time, and depression, which tended to emerge toward the end of the 4‐week period. There was a positive correlation (r = 0.64) between age and bromazepam plasma concentration per unit dose, adjusted for weight, and a negative correlation (r =−0.50) between weight and lorazepam plasma concentration per unit dose, adjusted for age.

Comparison of withdrawal of buspirone and diazepam: A placebo controlled study

In a 8-week double-blind placebo controlled study, 48 outpatients with generalized anxiety disorder were randomized to diazepam, buspirone, a non-benzodiazepine anxiolytic, or placebo. During the treatment phase of 4 weeks duration diazepam was found to be significantly better than placebo and buspirone. Following abrupt withdrawal by placebo substitution the diazepam group showed a gradual relapse maximal after two weeks while the buspirone and the placebo groups did not differ. There were more cases of rebound anxiety with diazepam as compared to buspirone or placebo. In addition, there were three early terminations related to rebound anxiety in the diazepam group while there were none in the placebo and buspirone groups. There were significantly more new symptoms in the diazepam group than in the placebo or buspirone group.

An open clinical trial of clonazepam in the treatment of patients with recurrent panic attacks.

Imipramine, phenelzine and alprazolam have each been shown to be efficacious in the treatment of panic disorder and in agoraphobia with panic attacks. Clonazepam, a 1,4 benzodiazepine derivative used mainly in neurology as an anti-epileptic, has specific pharmacodynamic and pharmacokinetic properties which would make it an advantageous antipanic agent. We report 8 cases of recurrent panic attacks which were successfully treated with clonazepam.