A placebo‐controlled, double‐blind, clinical trial of paroxetine in depressed outpatients

Abstract

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.

Efficacy of Naltrexone and Acamprosate for Alcoholism Treatment: A Meta‐Analysis

“…To provide a comparator for the effects of the antidipsotropics, we examined 10 studies of SSRIs for treatment of major depression (Claghorn, 1992;Cohn and Wilcox, 1985;Dunbar et al, 1991;Fabre and Crimson, 1985;Feighner and Boyer, 1992;Mendels et al, 1999;Reimherr et al, 1988Reimherr et al, , 1990Rickels et al, 1989;Stahl, 2000). These studies were all double-blind, placebo-controlled trials, which were chosen primarily for their methodological comparability to the naltrexone and acamprosate studies.…”

Paroxetine combined with a 5-HT1A receptor antagonist reversed reward deficits observed during amphetamine withdrawal in rats

“…Advances in the treatment of depression indicate that the coadministration of pindolol accelerates the delayed onset of the antidepressant action of selective serotonin reuptake inhibitors (SSRIs) (Rickels et al 1989;Tome et al 1997a, b;Blier and de Montigny 1999;Bordet et al 1998;Zanardi et al 1998;McAskill et al 1998;Berman et al 1999;Martinez et al 2000). This acceleration of the SSRI antidepressant action may be through the 5-HT 1A receptor antagonist action of pindolol (Auerbach and Hjorth 1995;Romero et al 1996;Hjorth 1993;Kreiss and Lucki 1995;Artigas et al 1996;Blier and de Montigny 1994;Beyer et al 2002;Dawson and Nguyen 2000; however, see Cremers et al 2001), although this drug has widespread antagonist actions at 5-HT 1A , 5-HT 1B and β-adrenergic receptors (Assie and Koek 1996;Bourin et al 1998;Gobert and Millan 1999), and partial agonist actions at α-adrenergic receptors (Clifford et al 1998;Gobert and Millan 1999;Pauwels and Palmier 1994).…”

Effects of acute paroxetine administration on tryptophan metabolism and disposition in the rat

“…Paroxetine [(-)-trans-4-(4'-fluorophenyl)3-(3',4'-methylenedioxyphenoxymethyl)piperidine] is an antidepressant (Lund Laursen et al, 1985;Feighner & Boyer, 1989;Rickels et al, 1989) drug with a profile of a potent and selective 5-hydroxytryptamine (5-HT) uptake inhibitor (Thomas et al, 1987). Preliminary studies (A.M. Johnson, personal communication) indicate that paroxetine can, as other 5-HT uptake inhibitors (Fuller et al, 1974;Claassen et al, 1977;Ross et al, 1981), decrease 5-HT turnover in rat brain.…”