No abstract

Nefazodone is a phenylpiperazine antidepressant with 5-HT2 antagonism and 5-HT reuptake inhibition. Two hundred and eighty-three out-patients with a diagnosis of DSM-III-R major depression of at least one-month duration (65% ill for over 6 months), and a mean score of 24 on the 17-item Hamilton Rating Scale for Depression (HRSD), were randomised to treatment with nefazodone, imipramine, or placebo. The double-blind treatment period was 8 weeks in duration. Nefazodone's antidepressant efficacy was comparable with imipramine's, with both drug treatments significantly better than placebo in a variety of outcome measures. For example, after 8 weeks of therapy, 78% of nefazodone and 83% of imipramine but only 55% of placebo patients (P < 0.01) were globally much or very much improved. Nefazodone was better tolerated than imipramine, with fewer drop-outs and a lower incidence of side-effects during treatment.

Sixty-seven patients with panic disorder were treated with single-blind placebo for one week before being randomized to 6 weeks of double-blind treatment with either lorazepam or alprazolam. Both drugs showed significant and comparable antipanic efficacy throughout the course of the study. With the exception of sedative effects, both drugs were well-tolerated at a mean daily dose of 7 mg for lorazepam and 3 mg for alprazolam. Lorazepam appeared to be as effective as alprazolam in the acute treatment of panic disorder.

A placebo‐controlled, randomized, double‐blind study was carried out in outpatients suffering from major unipolar depressive disorder to assess the efficacy and tolerability of paroxetine in the treatment of depression. The study lasted for six weeks. After a placebo washout period of 4 to 14 days patients took 20mg of paroxetine or matched placebo as a morning dose for one week; thereafter the dose of paroxetine could be titrated between 10 and SOmg/day. Patients were evaluated at baseline, weekly during the first four weeks of the study, and at the end of sixweeks; patients who entered a six‐week extensionphasewere evaluated at 9 and 12 weeks. Evaluations were carried out using HAMD (including ECDEU factors), MADRS, HSCL, Covi anxiety and Raskin depression scales, CGI, and a seven‐point rating of global improvement. Adverse events and laboratory values were also recorded at each assessment. One hundred and eleven patients entered the study, and efficacy data were available for 102 of these (49 on paroxetine and 53 on placebo). Efficacy measurements demonstrated significantly greater clinical improvement with paroxetine than placebo after two weeks of treatment, and this became even more marked after six weeks. Patients who continued treatment for a further six weeks maintained their clinical improvement. When adverse events were examined, statistically significant differences between paroxetine and placebo were seen only for sweating, diarrhoea, nausea, and somnolence. No significant changes were seen in any of the laboratory parameters measured. If these results are confirmed in future studies, paroxetine will represent an important addition to the treatments available for depression.

In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS)