Duloxetina: efficacia clinica, sicurezza e tollerabilità nel trattamento del disturbo depressivo maggiore
Year: 2007
Type: article
Abstract: Summary Objective Existing therapies for depressive disorder (MDD) often fail to provide full remis- sion. Scientific data suggest that drugs which combine both serotonin and norepine- phrine reuptake blockade may be more effective in providing better remission rates. Du- loxetine, recently approved for the treatment of MDD, is an inhibitor of serotonin and norepinephrine reuptake, with weak effects on dopamine reuptake. This article reviews the literature on with regard to its pharmacodynamics, pharmacokinetics and clinical efficacy both at short- (8 to 9 weeks) and long-term (up to 52 weeks) in adults and elderly, as well as safety and tolerability, with particular regard to incidence of adverse effects, gastrointestinal, cardiovascular and sexual tolerability. Methods A search of Medline was performed using the terms duloxetine and major depres- sive disorder, with no restriction on year. Results In vitro and in vivo studies show high affinity of to human serotonin and norepinephrine transporters, with a weak affinity to dopamine transporter or serot- oninergic, adrenergic, muscarinic, histaminergic receptors. Duloxetine is extensively metabolized by CYP450 2D6 and 1A2. The drug exhibits linear, dose-dependent phar- macokinetics. No dose adjustment appears to be needed, based on age. Duloxetine has shown efficacy in acute treatment (8 to 9 weeks) in reducing depressive symptoms compared with placebo, and recipients have shown significant improvements in global functioning compared with placebo. An adequate response was found even regarding somatic symptoms of depression, especially pain. Response and remission rates have been shown to be comparable to, or greater than, those seen with fluoxetine or paroxetine. Data following long-term treatment (ranging up to 52 weeks), although based primarily on open arm or placebo-controlled studies, suggest that ef- ficacy and tolerability of are maintained in chronic treatment. Duloxetine is generally safe and well tolerated, with nausea, dry mouth, and fatigue being the most common treatment-related adverse effects. Nausea occurred early in treatment, with mild to moderate severity, and tended to resolve without discontinuation of duloxetine. Adverse cardiovascular effects do not appear to result in sustained elevations in blood pressure, QTc-interval prolongation, or other electrocardiographic changes. The incidence of acute-phase treatment-related sexual dysfunction in patients receiving du- loxetine, in one study, was significantly higher than that observed in patients receiving placebo. However, during long-term treatment, the incidence of dysfunction in patients receiving did not differ significantly from that in placebo-treated patients. Table I shows inhibition of norepinephrine transporter (NAT) and serotonin transporter (SERT) binding in vitro by and venlafaxine. Table II shows affinity of duloxe- tine and venlafaxine for human serotonin receptor subtypes, other neuronal receptors and blockade of monoamine oxidase activity. Table III shows selected pharmacokinetic parameters of duloxetine. Table IV shows selected studies on the efficacy of in the treatment of depressive disorder. Table V shows treatment-related adverse events with duloxetine.
Authors: Emanuele Tarolla, R. Brugnoli, P. Pancheri
Language: Italian
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2242054914