Sexual dysfunction during treatment with serotonergic and noradrenergic antidepressants: Clinical description and the role of the 5-HTTLPR

Objectives. Sexual dysfunction (SD) is a frequently reported side-effect of antidepressant treatment, particularly of selective serotonin reuptake inhibitors (SSRIs). In the multicentre clinical and pharmacogenetic GENDEP study (Genome-based Therapeutic Drugs for Depression), the effect of the serotonin transporter gene promoter polymorphism 5-HTTLPR on sexual function was investigated during treatment with escitalopram (SSRI) and nortriptyline (tricyclic antidepressant). Methods. A total of 494 subjects with an episode of DSM-IV major depression were randomly assigned to treatment with escitalopram or nortriptyline. Over 12 weeks, depressive symptoms and SD were measured weekly with the Montgomery-Asberg Depression Rating Scale, the Antidepressant Side-Effect Checklist, the UKU Side Effect Rating Scale, and the Sexual Functioning Questionnaire. Results. The incidence of reported SD after 12 weeks of treatment was relatively low, and did not differ significantly between antidepressants (14.9% escitalopram, 19.7% nortriptyline). There was no significant interaction between the 5-HTTLPR and antidepressant on SD. Improvement in depressive symptoms and younger age were both associated with lower SD. The effect of age on SD may have been moderated by the 5-HTTLPR. Conclusions. In GENDEP, rates of reported SD during treatment were lower than those described in previous reports. There was no apparent effect of the 5-HTTLPR on the observed decline in SD. © 2011 Informa Healthcare.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Thioridazine for schizophrenia.

Background Thioridazine is an antipsychotic that can still be used for schizophrenia although it is associated with the cardiac arrhythmia, torsades de pointe. Objectives To review the effects of thioridazine for people with schizophrenia. Search strategy For this 2006 update, we searched the Cochrane Schizophrenia Group's Register (June 2006). Selection criteria We included all randomised clinical trials comparing thioridazine with other treatments for people with schizophrenia or other psychoses. Data collection and analysis We reliably selected, quality rated and extracted data from relevant studies. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) on an intention-to-treat basis. Main results This review currently includes 42 RCTs with 3498 participants. When thioridazine was compared with placebo (total n=668, 14 RCTs) we found global state outcomes favoured thioridazine (n=105, 3 RCTs, RR 'no change or worse' by 6 months 0.33 CI 0.2 to 0.5, NNT of 2 CI 2 to 3). Thioridazine is sedating (n=324, 3 RCTs, RR 5.37 CI 3.2 to 9.1, NNH 4 CI 2 to 74). Generally, thioridazine did not cause more movement disorders than placebo. Twenty-seven studies (total n=2598) compared thioridazine with typical antipsychotics. We found no significant difference in global state (n=743, 11 RCTs, RR no short-term change or worse 0.98 CI 0.8 to 1.2) and medium-term assessments (n=142, 3 RCTs, RR 0.99, CI 0.6 to 1.6). We found no significant differences in the number of people leaving the study early 'for any reason' (short-term, n=1587, 19 RCTs, RR 1.07 CI 0.9 to 1.3). Extrapyramidal adverse events lower for those allocated to thioridazine (n=1082, 7 RCTs, RR use of antiparkinsonian drugs 0.45 CI 0.4 to 0.6). Thioridazine did seem associated with cardiac adverse effects (n=74, 1 RCT, RR 'any cardiovascular adverse event' 3.17 CI 1.4 to 7.0, NNH 3 CI 2 to 5). Electrocardiogram changes were significantly more frequent in the thioridazine group (n=254, 2 RCTs, RR 2.38, CI 1.6 to 3.6, NNH 4 CI 3 to 10). Six RCTs (total n=344) randomised thioridazine against atypical antipsychotics. Global state rating did not reveal any short-term difference between thioridazine and remoxipride and sulpiride (n=203, RR not improved or worse 1.00 CI 0.8 to 1.3). Limited data did not highlight differences in adverse event profiles. Authors' conclusions Although there are shortcomings, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used antipsychotics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems and higher level of ECG changes. We would advocate the use of alternative drugs, but if its use in unavoidable, cardiac monitoring is justified