Estimating the prevalence and impact of antidepressant-induced sexual dysfunction in 2 European countries: a cross-sectional patient survey

OBJECTIVE: Sexual dysfunction is a common side effect of antidepressant treatment, but recognition of the problem is variable. The aim of this study was to estimate the prevalence and impact of sexual dysfunction during antidepressant treatment in 2 European countries. METHOD: A cross-sectional survey of 502 adults in France and the United Kingdom. All participants were diagnosed with depression and taking a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI), starting within the previous 3 months. Information was gathered about other medications and conditions known to impair sexual functioning, recent changes in sexual functioning, and the impact of any changes. The Medical Outcomes Study 12-Item Short-Form Health Survey and the Arizona Sexual Experience Scale were administered to measure health status and sexual functioning. Data were collected from June to July of 2002. RESULTS: Applying a prevalence estimate algorithm, 26.6% of the French sample and 39.2% of the U.K. sample were classified as having antidepressant-induced sexual dysfunction; 34.2% of men and 32.5% of women were classified with antidepressant-induced sexual dysfunction. There was no clear pattern of antidepressant-induced sexual dysfunction related to specific antidepressants. Patients with antidepressant-induced sexual dysfunction reported that changes in sexual functioning negatively affected their self-esteem, mood, and relationships with sexual partners. 23.8% of the French sample and 25.2% of the U.K. sample reported that they perceived that their partner was dissatisfied with their sex life. CONCLUSION: The prevalence of antidepressant-induced sexual dysfunction in this study is similar to previous estimates reported in the literature. The impact of antidepressant-induced sexual dysfunction is substantial and negatively affects quality of life, self-esteem, mood, and relationships with sexual partners

Prevalence and impact of antidepressant-associated sexual dysfunction in three European countries: replication in a cross-sectional patient survey

Sexual dysfunction is a common but often unrecognized side effect of many antidepressants. Building upon the results of a previous investigation, this study aimed to assess the prevalence and impact of antidepressant-associated sexual dysfunction (AASD) in three European countries. A cross-sectional survey of 704 adults in Germany, Spain, and The Netherlands was used in the study. All participants had recently started taking a selective serotonin reuptake inhibitor or serotonin— noradrenaline reuptake inhibitor. Information about other medications and conditions known to impair sexual functioning was gathered, and changes in sexual functioning and the impact of such changes were assessed. The SF-12 and Arizona Sexual Experience Scale (ASEX) were administered to measure health status and sexual functioning. AASD was defined using ASEX scores and information regarding changes in sexual functioning. ASEX scores generally exceeded the threshold defining sexual dysfunction: 67.2% in the German, 79.4% in the Spanish, and 73.3% in the Dutch samples. The prevalence of AASD was conservatively estimated to be between 37.1% (German sample) and 61.5% (Spanish sample). Overall, 46.4% of male and 52.1% of female participants were classified with AASD. Patients classified with AASD reported significantly worse quality of life (QoL), self-esteem, mood, and relationships with partners, compared with non-AASD patients. There were significant differences between patients with and without AASD in SF-12 Mental Component scores, with AASD patients displaying poorer mental well-being. Sexual dysfunction is a frequent occurrence during antidepressant treatment, and is associated with reduced QoL and self-esteem, and negative effects on mood and relationships

Efficacy and safety of Bimagrumab in sporadic inclusion body myositis

Objective To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM). Methods Participants (aged 36–85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co–primary outcome measures were 6-minute walk distance (6MWD) and safety. Results Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24–104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively). Conclusion Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint

Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial

Background Inclusion body myositis is an idiopathic inflammatory myopathy and the most common myopathy affecting people older than 50 years. To date, there are no effective drug treatments. We aimed to assess the safety, efficacy, and tolerability of bimagrumab-a fully human monoclonal antibody-in individuals with inclusion body myositis. Methods We did a multicentre, double-blind, placebo-controlled study (RESILIENT) at 38 academic clinical sites in Australia, Europe, Japan, and the USA. Individuals (aged 3685 years) were eligible for the study if they met modified 2010 Medical Research Council criteria for inclusion body myositis. We randomly assigned participants (1:1:1:1) using a blocked randomisation schedule (block size of four) to either bimagrumab (10 mg/kg, 3 mg/kg, or 1 mg/kg) or placebo matched in appearance to bimagrumab, administered as intravenous infusions every 4 weeks for at least 48 weeks. All study participants, the funder, investigators, site personnel, and people doing assessments were masked to treatment assignment. The primary outcome measure was 6-min walking distance (6MWD), which was assessed at week 52 in the primary analysis population and analysed by intention-to-treat principles. We used a multivariate normal repeated measures model to analyse data for 6MWD. Safety was assessed by recording adverse events and by electrocardiography, echocardiography, haematological testing, urinalysis, and blood chemistry. This trial is registered with ClinicalTrials.gov, number NCT01925209; this report represents the final analysis. Findings Between Sept 26, 2013, and Jan 6, 2016, 251 participants were enrolled to the study, of whom 63 were assigned to each bimagrumab group and 62 were allocated to the placebo group. At week 52, 6MWD change from baseline did not differ between any bimagrumab dose and placebo (least squares mean treatment difference for bimagrumab 10 mg/kg group, 17.6 m, SE 14.3, 99% CI -19.6 to 54.8; p=0.22; for 3 mg/kg group, 18.6 m, 14.2, -18.2 to 55.4; p=0.19; and for 1 mg/kg group, 1.3 m, 14.1, -38.0 to 35.4; p=0.93). 63 (100%) participants in each bimagrumab group and 61 (98%) of 62 in the placebo group had at least one adverse event. Falls were the most frequent adverse event (48 [76%] in the bimagrumab 10 mg/kg group, 55 [87%] in the 3 mg/kg group, 54 [86%] in the 1 mg/kg group, and 52 [84%] in the placebo group). The most frequently reported adverse events with bimagrumab were muscle spasms (32 [51%] in the bimagrumab 10 mg/kg group, 43 [68%] in the 3 mg/kg group, 25 [40%] in the 1 mg/kg group, and 13 [21%] in the placebo group) and diarrhoea (33 [52%], 28 [44%], 20 [32%], and 11 [18%], respectively). Adverse events leading to discontinuation were reported in four (6%) participants in each bimagrumab group compared with one (2%) participant in the placebo group. At least one serious adverse event was reported by 21 (33%) participants in the 10 mg/kg group, 11 (17%) in the 3 mg/kg group, 20 (32%) in the 1 mg/kg group, and 20 (32%) in the placebo group. No significant adverse cardiac effects were recorded on electrocardiography or echocardiography. Two deaths were reported during the study, one attributable to subendocardial myocardial infarction (secondary to gastrointestinal bleeding after an intentional overdose of concomitant sedatives and antidepressants) and one attributable to lung adenocarcinoma. Neither death was considered by the investigator to be related to bimagrumab. Interpretation Bimagrumab showed a good safety profile, relative to placebo, in individuals with inclusion body myositis but did not improve 6MWD. The strengths of our study are that, to the best of our knowledge, it is the largest randomised controlled trial done in people with inclusion body myositis, and it provides important natural history data over 12 months

Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial

Neurological Motor Disorder

Testing for local dependency in dichotomous and polytomous item response models

item response theory, item cluster, Mantel-Haenzsel test, multiple inference, NAEP, DIMTEST, Yen'sQ 3 ,