fluvoxamine and femoxetine

Narcolepsy is a disorder of the central nervous system, the main symptoms of which are excessive daytime sleepiness (EDS) and cataplexy (an abrupt and reversible decrease in or loss of muscle tone, affecting the limbs and/or trunk, elicited by emotional stimuli). Narcolepsy has an adverse impact on people's quality of life. Together with stimulant drugs (used to control EDS), antidepressants are usually recommended to counteract cataplexy. In addition, some antidepressants are also reported to improve EDS.. To evaluate the effects of antidepressant drugs on EDS, cataplexy, quality of life, and their side effects in people with narcolepsy.. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), PsycINFO (1872 to 2003), and CINAHL (1981 to 2003). Bibliographies of identified articles were reviewed to find additional references. Unpublished randomised trials were searched for by consulting governmental and non-governmental clinical trial registers, disease-specific websites, investigators and experts in the field, pharmaceutical companies/manufacturers.. Parallel or cross-over randomised or quasi-randomised controlled trials testing the treatment of narcolepsy with any type of antidepressant drug versus no treatment, placebo, or another antidepressant drug.. Two reviewers independently selected trials for inclusion and extracted data. Outcomes were: (a) elimination of EDS; (b) mean reduction of EDS; (c) elimination of cataplexy; (d) 50% or greater reduction in cataplexy frequency; (e) mean reduction of cataplexy; (f) mean improvement in quality of life; (g) adverse events; (h) withdrawal from treatment.. Two cross-over trials were included. The methodological quality of both studies was unclear and so the influence of common biases was impossible to define. As the trials tested two different comparisons (one femoxetine versus placebo, the other fluvoxamine versus clomipramine) meta-analysis was not performed. In the first trial (10 participants) femoxetine had no significant effect in eliminating or reducing EDS; a significant reduction of cataplexy was in favour of femoxetine. Mild and transient side effects were reported in the femoxetine treatment period by two participants. In the second trial the authors inappropriately treated the trial design as a parallel study and no conclusions can be reached in favour of either drug.. There was no good quality evidence that antidepressants are effective for narcolepsy or improve quality of life. Despite the clinical consensus recommending antidepressants for cataplexy there is scarce evidence that antidepressants have a positive effect on this symptom. There is a clear need for well-designed randomised controlled trials to assess the effect of antidepressants on narcolepsy.

Topics: Antidepressive Agents; Cataplexy; Clomipramine; Fluvoxamine; Humans; Narcolepsy; Piperidines; Randomized Controlled Trials as Topic

The inhibitory potencies of selective serotonin (5-hydroxytryptamine, 5-HT) uptake inhibitors on isolation-induced aggressive behaviour in male mice were studied. Furthermore, the role of postsynaptic 5-HT1A receptors in the mediation of aggressive behaviour was studied. The selective 5-HT uptake inhibitors, sertraline, floxetine, femoxetine and fluvoxamine, showed weak antiaggressive effects, and citalopram and paroxetine were ineffective. This rank of potencies corresponded with neither uptake inhibitory potencies in vitro nor potentiation of 1-5-hydroxytryptophan (1,5-HTP)-induced motor effects in vivo, as citalopram and paroxetine were among the most potent compounds in these tests. A subeffective dose of 1,5-HTP (110 mumol/kg = 25 mg/kg, s.c.) potentiated the antiaggressive effect of citalopram and paroxetine more than 110 and 1600 times, respectively. The effects of sertraline, fluvoxamine, fluoxetine and femoxetine were only potentiated 3, 36, 4 and 16 times, respectively. The 5-HT releasing compound fenfluramine inhibited the aggressive behaviour dose dependently, and depletion of 5-HT by treatment with p-chloro-phenylalanine methyl ester attenuated this effect significantly. p-Chloro-phenylalanine methyl ester was ineffective itself, but potentiated the antiaggressive effect of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamin)tetralin (8-OH-DPAT). The beta-adrenoceptor/5-HT1A receptor antagonist, (-)-penbutolol, reversed the antiaggressive effects of 8-OHDPAT. In conclusion, selective 5-HT uptake inhibitors act in different ways on isolation-induced aggressive behaviour, and postsynaptic 5-HT1A receptors are involved in mediating the aggressive behaviour.

Topics: 1-Naphthylamine; 5-Hydroxytryptophan; 8-Hydroxy-2-(di-n-propylamino)tetralin; Aggression; Analysis of Variance; Animals; Behavior, Animal; Brain; Citalopram; Dose-Response Relationship, Drug; Fenclonine; Fluoxetine; Fluvoxamine; Male; Mice; Paroxetine; Penbutolol; Piperidines; Rats; Rats, Wistar; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Selective Serotonin Reuptake Inhibitors; Sertraline; Synaptosomes