Sexual dysfunction (SD) is a common and underestimated effect of antidepressants. Healthy volunteers are the most adequate group to study this adverse event avoiding influence of depression itself. Sexual acceptability of agomelatine (a melatonergic agonist and 5HT(2C) antagonist) paroxetine and placebo by using the Psychotropic-Related Sexual Dysfunction Salamanca Sex Questionnaire (PRSEXDQ-SALSEX) was explored. A total of 92 healthy male volunteers were randomised to agomelatine (25 or 50 mg), paroxetine 20 mg or placebo for 8 weeks. SD, defined as at least one sexual impairment in one of the following PRSEXDQ-SALSEX items (decreased libido, delayed orgasm/ejaculation, anorgasmia/no ejaculation and erectile dysfunction), was evaluated at baseline and after 2, 4 and 8 weeks. At the last post-baseline assessment, SD was significantly lower in each agomelatine group (22.7% on 25 mg and 4.8% on 50 mg) than in the paroxetine group (85.7%; p < 0.0001). In the placebo group, 8.7% of volunteers reported a SD. The percentages of volunteers with moderate or severe SD were 4.5% for agomelatine 25 mg, 4.8% for agomelatine 50 mg, 61.9% for paroxetine 20 mg and 0% in the placebo group (p < or = 0.0001 agomelatine versus paroxetine). There is a much lower risk of having SD with agomelatine than paroxetine in healthy male volunteers, which confirms the better sexual acceptability profile of agomelatine compared with the SSRIs.

Carisoprodol was authorised in 1959 without a full pharmacokinetic–pharmacodynamic (PK–PD) characterisation. We designed a crossover, double-blind, placebo-controlled, randomized clinical trial to characterize the PKs of carisoprodol and its main active metabolite, meprobamate, after single (350 mg), multiple (350 mg/8 h, 14 days), and double (700 mg) doses of carisoprodol. Thirteen healthy volunteers were enrolled. After a single (350 mg) dose, the main carisoprodol parameters were (mean ± SD) Cmax: 2580 ± 1214 ng/mL, AUC0-∞: 8072 ± 6303 h x ng/mL, and half-life (T1/2): 2 ± 0.8 h. For meprobamate, the parameters were Cmax: 2181 ± 605 ng/mL and 34529 ± 7747 h x ng/mL y 9 ± 1.9 h. Different profiles were found for extensive and poor 2C19 metabolizers. After 14 days of treatment (350 mg/8 h) the results for carisoprodol were (mean ± SD) Cmax: 2504 ± 730 ng/mL, AUC0-∞: 7451 ± 3615 h x ng/mL, and T1/2: 2 ± 0.7 h. For meprobamate (a steady state was reached), the parameters were Cmax: 5758 ± 1255 ng/mL and 79699 ± 17978 h x ng/mL y 8.7 ± 1.4 h. The study allowed for the full characterization of the pharmacokinetic profile of carisoprodol and meprobamate. Accumulation of meprobamate but not of carisoprodol was evident after 14 days of treatment.

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