Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice.

AIMS: To evaluate the safety and tolerability of duloxetine during routine clinical care in women with stress urinary incontinence (SUI) in Germany, and in particular, to identify previously unrecognized safety issues as uncommon adverse reactions, and the influence of confounding factors present in clinical practice on the safety profile of duloxetine. METHODS: Office-based urologists, gynaecologists and primary care physicians were asked to document women newly started on treatment for moderate to severe symptoms of SUI. Six thousand eight hundred and fifty-four patients from urologist/gynaecologist practices and 5879 primary care patients were assessed. In a two-armed, observational study with parallel 12 week (urologists and gynaecologists) or 24 week (primary care physicians) design, patients were treated with duloxetine or other conservative treatment. The main outcome measure was the occurrence of adverse events (AEs). RESULTS: Baseline characteristics differed slightly between patient groups and studies. Duloxetine doses in most patients were lower than recommended. Overall, AE frequency with duloxetine was lower than in controlled studies (15.9% (95% CI 14.9, 16.9) and 9.1% (95% CI 8.2, 10.0) in the 12 and 24 week treatment groups, respectively), but exhibited a similar qualitative spectrum. In the logistic regression models, the following factors were associated with greater AE risk: investigator specialization (gynaecologist vs. urologist and primary care physician), initial duloxetine dose (80 vs. 20 mg day(-1) ) and use of any concomitant medication. Within the 24 week study, a positive screen for depressive disorder was surprisingly common, but no case of attempted suicide was reported in either study. CONCLUSIONS: Our results from German clinical practice show that women with SUI were often treated with duloxetine doses lower than recommended. This was associated with a low incidence of AEs. Suicide attempts were not reported.

Comparably high retention and low relapse rates in different subpopulations of bipolar patients in a German non-interventional study.

BACKGROUND: Although a range of pharmacotherapeutical options are available for the treatment of bipolar disorder, patient non-adherence to prescribed treatment regimens and early treatment discontinuation remain among the primary obstacles to effective treatment. Therefore, this observational study assessed time on mood stabilizing medication and retention rates in patients with bipolar disorder (BD). METHODS: In an 18-month, prospective, multicenter, non-interventional study conducted in Germany 761 outpatients (≥18 years) with BD and on maintenance therapy were documented. For analysis, patients were stratified by baseline medication: monotherapy olanzapine (OM, N = 186), lithium (LM, N = 152), anticonvulsants (N = 216), other mood stabilizing medication (OMS, N = 44); combination therapy olanzapine/lithium (N = 47), olanzapine/anticonvulsant (N = 68), other combinations (OC, N = 48). Continuation on medication was assessed as retention rates with 95% confidence intervals. Time to discontinuation and relapse-free time were calculated by Kaplan-Meier analysis. A relapse was defined as increase to CGI-BP >3, worsening of CGI-BP by ≥2 points, hospitalization or death related to BD. A Cox regression was calculated for the discontinuation of mood stabilizing therapy (reference: OM). Logistic regression models with stepwise forward selection were used to explore possible predictors of maintenance of treatment and relapse. RESULTS: After 540 days (18 months), the overall retention rate of baseline medication was 87.7%, without notable differences between the cohorts. The overall mean time on mood stabilizing treatment was 444.7 days, with a range of 377.5 (OMS) to 481 (LM) by cohort. 74.0% of all patients were without relapse, with rates between the cohorts ranging from 58.4% (OC) to 80.2% (LM). CONCLUSIONS: Retention rates exceeded controlled trial results in all treatment cohorts, in addition to other explanations possibly reflecting that the physicians were expertly adapting treatment regimens to the individual patient's disease characteristics and special needs.

Prevalence of metabolic syndrome in patients with schizophrenia, and metabolic changes after 3 months of treatment with antipsychotics--results from a German observational study.

BACKGROUND: This observational study explored the prevalence of metabolic syndrome (MetS) in adult in- and outpatients with untreated or treated schizophrenia at baseline, and month-3 after initiation or switch of antipsychotic treatment. METHODS: MetS-prevalence (AHA/NHLB-definition) was assessed and Clopper-Pearson 95% confidence intervals (CIs) were calculated. Factors associated with MetS were explored through univariate and multivariate logistic regressions (both visits). RESULTS: MetS-prevalence was 44.3% (CI 39.8;48.9) at baseline and 49.6% (CI 45.0;54.2) at month-3. Previously unmedicated patients showed the lowest baseline MetS-prevalence (24.7%, CI 18.3;32.1). MetS-prevalence was not significantly different, regardless if patients previously received typical or atypical antipsychotics. Increased MetS-risk was associated with somatic comorbidity and non-smoking at both visits, and with non-psychiatric co-medication, male sex, and increased C-reactive protein at month-3. CONCLUSIONS: At baseline, MetS was most prevalent in patients with previous antipsychotic medication. Limited metabolic changes were observed 3 months after switch/initiation of antipsychotic therapy. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: n.a.

Effectiveness of atomoxetine and quality of life in children with attention-deficit/hyperactivity disorder as perceived by patients, parents, and physicians in an open-label study.

OBJECTIVES: Health-related quality of life in children with attention-deficit/hyperactivity disorder (ADHD) may improve with atomoxetine treatment. However, the degree of improvement may be perceived differently by patients, parents, and physicians. The primary aim of this study was to investigate ADHD-related difficulties as perceived from these three perspectives and to compare the perspectives. The degree of perceived difficulties was taken to reflect the health-related quality of life of patients in the study. A second objective was to assess the effectiveness of atomoxetine in children with ADHD in an open-label setting. METHODS: Children aged 6-11 years with ADHD were treated for 24 weeks with atomoxetine at a target dose of 0.5-1.2 mg/kg per day. ADHD-related difficulties were assessed after 8 and 24 weeks of treatment using the newly devised Global Impression of Perceived Difficulties (GIPD) scale. This instrument, that has not yet been psychometrically validated, reflects patient quality of life from the three perspectives. Agreement among the perspectives was determined using Cohen's kappa. RESULTS: A total of 262 patients was treated with atomoxetine. The mean dose for the respective visit intervals ranged between 1.15 and 1.17 mg/kg per day. Quality of life as reflected by the degree of perceived difficulties improved over time. Change in GIPD scores was greatest within the first 2 weeks. The course of the mean GIPD total scores over time showed a similar pattern among the three different rater perspectives. However, patients perceived the degree of difficulties as significantly less compared to parents and physicians. Agreement of ratings was highest between physicians and parents. CONCLUSIONS: Results from the GIPD suggest that patient quality of life improves with time on atomoxetine. The effectiveness of atomoxetine in an open-label study was very similar to the effectiveness shown in placebo-controlled trials.

Atomoxetine treatment and ADHD-related difficulties as assessed by adolescent patients, their parents and physicians.

BACKGROUND: The degree of ADHD-related difficulties - reflecting overall impairment, social functioning, and quality of life - may be perceived differently by adolescent patients, parents and physicians. The primary aim of this study was to investigate ADHD-related difficulties during atomoxetine treatment, as perceived by the three different raters. Secondary objectives focused on effectiveness and tolerability of atomoxetine treatment in a population of adolescent patients with ADHD. METHODS: Adolescents with ADHD, aged 12-17 years, received open-label atomoxetine (0.5-1.2 mg/kg/day) up to 24 weeks. ADHD-related difficulties at various times of the day were rated using the Global Impression of Perceived Difficulties (GIPD) instrument. Inter-rater agreement was analyzed using Cohen's Kappa with 95% confidence intervals (95% CI). ADHD-Rating Scale (ADHD-RS) and Clinical Global Impression Severity (GGI-S) scores were assessed by the investigator; and spontaneous adverse events, vital signs and laboratory parameters were collected for tolerability assessments. RESULTS: 159 patients received atomoxetine. Patients' baseline mean GIPD total ratings were significantly lower than parents' and physicians' scores (12.5 [95%CI 11.6;13.5] vs. 17.2 [16.2;18.2] and 18.8 [17.8;19.8]). For all raters, GIPD scores significantly improved over time. Changes were greatest within the first two weeks. Kappa coefficients varied between 0.186 [0.112;0.259] and 0.662 [0.529;0.795], with strongest agreements between parent and physician assessments, and significant improvements of patient/physician agreements over time (based on 95% CIs). ADHD-RS and CGI-S scores significantly improved over the course of the study (based on 95% CIs). Tolerability results were consistent with earlier reports. CONCLUSION: ADHD-related difficulties were perceived differently by the raters in this open-label trial, but consistently improved during atomoxetine treatment. The GIPD instrument appeared sensitive to treatment-related change. These primarily quantitative findings may guide future studies to more systematically investigate the clinical and practical relevance of the differences observed. Additionally, in order to further validate these results, placebo- and comparator-controlled trials are recommended as well as inclusion of healthy controls and other patient populations. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov: NCT00191737.