Frequency of Sexual Dysfunction in Patients Treated with Desvenlafaxine: A Prospective Naturalistic Study.

Despite being clinically underestimated, sexual dysfunction (SD) is one of the most frequent and lasting adverse effects associated with antidepressants. Desvenlafaxine is an antidepressant (AD) with noradrenergic and serotonergic action that can cause a lower SD than other serotonergic ADs although there are still few studies on this subject. OBJECTIVE: To check the frequency of SD in two groups of depressive patients: one group was desvenlafaxine-naïve; the other was made up of patients switched to desvenlafaxine from another AD due to iatrogenic sexual dysfunction. A naturalistic, multicenter, and prospective study of patients receiving desvenlafaxine (50-100 mg/day) was carried out on 72 patients who met the inclusion criteria (>18 years old and sexually active), who had received desvenlafaxine for the first time (n = 27) or had switched to desvenlafaxine due to SD with another AD (n = 45). Patients with previous SD, receiving either drugs or presenting a concomitant pathology that interfered with their sexual life and/or patients who abused alcohol and/or drugs were excluded. We used the validated Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) to measure AD-related sexual dysfunction and the Clinical Global Impression Scale for psychiatric disease (CGI-S) and for sexual dysfunction (CGI-SD) at two points in time: baseline and three months after the commencement of desvenlafaxine treatment. RESULTS: In desvenlafaxine-naïve patients, 59.2% of the sample showed moderate/severe sexual dysfunction at baseline, which was reduced to 44% at follow-up. The PSexDQ-SALSEX questionnaire total score showed a significant improvement in sexual desire and sexual arousal without changes in orgasmic function at follow-up (p < 0.01). In the group switched to desvenlafaxine, the frequency of moderate/severe SD at baseline (93.3%) was reduced to 75.6% at follow-up visit. Additionally, SD significantly improved in three out of four items of the SALSEX: low desire, delayed orgasm, and anorgasmia at follow-up (p < 0.01), but there was no significant improvement in arousal difficulties. The frequency of severe SD was reduced from 73% at baseline to 35% at follow-up. The CGI for psychiatric disease and for sexual dysfunction improved significantly in both groups (p < 0.01). There was a poor tolerability with risk of treatment noncompliance in 26.7% of patients with sexual dysfunction due to another AD, this significantly reduced to 11.1% in those who switched to desvenlafaxine (p = 0.004). CONCLUSION: Sexual dysfunction improved significantly in depressed patients who initiated treatment with desvenlafaxine and in those who switched from another AD to desvenlafaxine, despite this, desvenlafaxine treatment is not completely devoid of sexual adverse effects. This switching strategy could be highly relevant in clinical practice due to the significant improvement in moderate/severe and poorly tolerated SD, while maintaining the AD efficacy.

Contribution of baseline body mass index and leptin serum level to the prediction of early weight gain with atypical antipsychotics in schizophrenia.

AIM: This study investigated whether biochemical parameters add predictive information concerning risk for weight gain associated with treatment with atypical antipsychotics (AP) to that provided by baseline weight. METHODS: Weight changes were assessed in 25 patients with schizophrenia after 3-6 months of treatment. These patients were started on AP monotherapy owing to a first psychotic episode or resumed treatment after at least a 6-month period of abandonment. Anthropometric and biochemical data were collected and analyzed as predictors of early weight change. RESULTS: The baseline biochemical and anthropometric data were not significantly higher in the patients than in the healthy participants. During follow up, the patients had significant increases in body mass index and total cholesterol and apolipoprotein B level. The baseline weight and leptin level were predictive of weight gain during follow up, with an inverse association in both cases. CONCLUSION: Baseline weight and leptin level may help to assess the risk of early weight gain with AP.

Convergent evidence of the contribution of TP53 genetic variation (Pro72Arg) to metabolic activity and white matter volume in the frontal lobe in schizophrenia patients.

Abnormalities in white matter (WM) volumes and integrity in schizophrenia, together with post-mortem studies showing reduced expression of oligodendrocyte/myelination genes and apoptotic processes taking place in oligodendrocytes, suggest the interest of major regulators of apoptosis as candidate genes for some features related to myelin integrity in schizophrenia. Protein p53, encoded by TP53 gene, has a central role in the control of apoptosis and is involved in oligodendrocyte development. TP53 gene polymorphisms may account for variability in WM features, metabolic activity and biochemical markers of neuronal integrity and membrane turnover. Pro72Arg and Ins16bp polymorphisms at TP53 gene were analyzed in 20 DSM-IV schizophrenia patients. T1/T2-weighted sequences of these patients were acquired using a 1.5T Philips Gyroscan system. Scans were transformed into Talairach space and segmented into gray matter (GM), WM and cerebrospinal fluid (CSF) using Statistical Parametric Mapping under a ROI approach. Likewise dorsolateral prefrontal cortex (DLPFC) metabolic activity was measured using a procedure based on MRI/PET image fusion. In 13 of these patients proton magnetic resonance spectroscopy was used to examine N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) levels in dorsolateral-medial prefrontal cortex (DLMPFC). MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n=45). Patients Pro/Arg heterozygous (Pro72Arg polymorphism) showed a generalized deficit in whole-brain WM that was especially prominent in frontal lobe and a lower metabolic activity in the DLPFC as compared to Pro/Pro homozygous. Pro/Arg subjects also showed decreased NAA/Cho and increased Cho/Cr ratios in right DLMPFC. TP53 genetic variability influences WM volumes in frontal lobes and it seems to modulate the metabolic activity in this region. Our results suggest that TP53 might influence aspects of myelin and white matter integrity which may account for some of the frontal dysfunction features commonly described in these patients.