As part of the cross‐national collaborative panic study, a double‐blind comparison of alprazolam, imipramine and placebo was performed in Scandinavian outpatients with panic disorder according to DSM‐III; 41 patients were randomly allocated to each drug. Doses were increased for 3 weeks to an average of about 6 mg alprazolam, 150 mg imipramine and a corresponding number of placebo capsules, which were then given for 5 weeks. No more than supportive psychotherapy was given. Key symptoms were rated weekly. The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months. Compliance at 3 weeks was 95% for alprazolam, 83% for imipramine and 88% for placebo; at 8 weeks 95% for alprazolam, 73% for imipramine and 46% for placebo. At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0% for alprazolam, 19% for imipramine and 31% for placebo; at 8 weeks the corresponding proportions were 3%, 11% and 16%. Intention‐to‐treat analysis showed that freedom from panic attacks was obtained for 68% with alprazolam, 61% with imipramine and 34% with placebo. Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms. Globally rated by physicians and patients, about 60% had complete remission with alprazolam and imipramine and 30% on placebo. At least partial remission was obtained in about 85% with alprazolam, 70% with imipramine and 40% with placebo. Alprazolam had a more rapid onset of action than imipramine on all symptoms. Side effects were generally mild, with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine. Tapering was uneventful without significant discontinuation phenomena. During taper and follow‐up, several patients in remission relapsed, leaving approximately 30% patients in complete remission in all groups. To obtain more stable improvement, either long‐term drug treatment or combinations of drug treatment and psychotherapy should be evaluated.

The pharmacokinetics of alprazolam was studied in 10 geriatric patients (5 males, 5 females) with neurotic depression during a 6-week period. After 0.5 mg of alprazolam on Day 1 the mean elimination half-life was 11.1 hr and Cmax 12.3 ng/ml. The pharmacokinetic evaluation on Day 1 (t 1/2, tmax) did not differ significantly from the evaluation on Day 42. The mean daily dosage on Day 42 was 1.6 mg alprazolam. The concentrations of the metabolites alpha-OH alprazolam and 4-OH alprazolam were less than 10% of that of alprazolam. All the patients improved clinically. The most common side effect was drowsiness, more often during the first week than the last week.

The short-acting hypnotic, triazolam 0.5 mg, was compared in a 7-day double-blind study with the longer acting drug, nitrazepam 5 mg. Of the 60 patients enrolled, 29 in each drug treatment group completed the study and were evaluated. All significant differences found favoured triazolam. On the first night, triazolam was found to be significantly more effective than nitrazepam in inducing and maintaining sleep and in increasing its overall duration. The patients' subjective preference, reflecting the depth of sleep experienced and the effect of the medication, reached highly significant levels in favour of triazolam. Later in the study the differences between the drugs disappeared although the depth of sleep as judged in the study was better with triazolam.