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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., (© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.)

The purpose of this work is to describe the effect of duloxetine on functioning as measured by the Sheehan disability scale (SDS) compared with placebo in patients with major depressive disorder (MDD). Pooled data from six randomized, parallel, double-blind, placebo-controlled duloxetine studies in adult MDD patients were analyzed at the short-term (7-13 weeks) and the long-term (>24 weeks) endpoint. The primary variable was the SDS total score. Secondary variables included functional remission (SDS total ≤ 6) rates, Hamilton rating scale for depression total score, and pain visual analog scale. Analysis of covariance and logistic regression methods were used to assess differences in treatment and identify prognostic baseline factors. In total, 2496 patients (1424 duloxetine; 1072 placebo) were included. The between-treatment difference of -2.52 between duloxetine and placebo in the SDS total score at the short-term endpoint was statistically significant in favor of duloxetine vs. placebo (95% confidence interval: -3.17, -1.87; P < 0.001). The endpoint functional remission rates were 39.5% with duloxetine and 28.7% with placebo. Time since first depression episode, antidepressant pretreatment (yes/no), baseline visual analog scale pain (≤30 / >30 mm), and sex were significant prognostic factors. The effect of duloxetine was maintained at the long-term endpoint. Duloxetine is effective in improving MDD patients' functioning. Further antidepressant studies focusing on functioning would be helpful.

Introduction: In depressed patients tricyclic antidepressants and selective serotonin and noradrenaline reuptake inhibitors can reduce not only depressive, but also painful physical symptoms. We investigated whether under treatment with duloxetine pain improves earlier than mood., Methods: Data were obtained within a prospective 6-month multi-centre naturalistic study in adult out-patients with depressive episodes treated with duloxetine (fl exible doses: 30-120 mg/day). Pain and mood were assessed daily by visual analogue scales. For responders (n = 622) "time to 50 % pain response" and "time to 50 % mood response" were determined by counting the earliest day between day 0 and 27, at which the patient achieved 50 % improvement., Results: Mean time to 50 % pain response (mean 6.3 days, SD 5.3) was significantly shorter than time to 50 % mood response (mean 7.6 days, SD 6.0, mean difference 1.3 days, SD 6.4; p < 0.0001)., Discussion: In duloxetine-responders to both pain and mood, self-rated pain improved slightly earlier than self-rated mood. The short temporal dissociation between pain and mood improvement might be explained by an earlier conscious perception of pain than mood changes., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: To investigate the association of the change of painful physical symptoms (PPS) after 4 weeks, with the 6-month treatment outcomes of depressive symptoms in patients treated with duloxetine in clinical practice., Methods: Multicenter, prospective, 6-month, non-interventional study in adult outpatients with a depressive episode and starting treatment with duloxetine. Depression severity was assessed by the clinician (Inventory for Depressive Symptomatology [IDS-C]) and patient (Kurz-Skala Stimmung/Aktivierung [KUSTA]). Somatic symptoms and PPS were assessed using the patient-rated Somatic Symptom Inventory (SSI) and visual analog scales (VAS) for pain items. Association of change in PPS with outcomes of depressive symptoms was analyzed based on mean KUSTA scores (mean of items mood, activity, tension/relaxation, sleep) and achievement of a 50% reduction in the total IDS-C score after 6 months using linear and logistic regression models, respectively., Results: Of the 4,517 patients enrolled (mean age: 52.2 years, 71.8% female), 3,320 patients (73.5%) completed the study. 80% of the patients had moderate to severe overall pain (VAS > 30 mm) at baseline. A 50% VAS overall pain reduction after 4 weeks was associated with a 13.32 points higher mean KUSTA score after 6 months, and a 50% pain reduction after 2 weeks with a 6.33 points improvement. No unexpected safety signals were detected in this naturalistic study., Conclusion: Pain reduction after 2 and 4 weeks can be used to estimate outcomes of long-term treatment with duloxetine. PPS associated with depression have a potential role in predicting remission of depressive symptoms in clinical practice.

Objective: To assess the cost-effectiveness of duloxetine compared with conservative therapy in women with stress urinary incontinence (SUI)., Methods: Cost and outcome data were taken from the Stress Urinary Incontinence Treatment (SUIT) study, a 12-month, prospective, observational, naturalistic, multicenter, multicountry study. Costs were assessed in UK pound and outcomes in quality adjusted life years using responses to the EuroQol (EQ-5D); numbers of urine leaks were also estimated. Potential selection bias was countered using multivariate regression and propensity score analysis., Results: Duloxetine alone, duloxetine in combination with conservative treatment, and conservative treatment alone were associated with roughly two fewer leaks per week compared with no treatment. Duloxetine alone and with conservative treatment for SUI were associated with incremental quality-adjusted life-years (QALYs) of about 0.03 over a year compared with no treatment or with conservative treatment alone. Conservative treatment alone did not show an effect on QALYs. None of the interventions appeared to have marked impacts on costs over a year. Depending on the form of matching, duloxetine either dominated or had an incremental cost-effectiveness ratio (ICER) below pound900 per QALY gained compared with no treatment and with conservative treatment alone. Duloxetine plus conservative therapy had an ICER below pound5500 compared with no treatment or conservative treatment alone. Duloxetine compared with duloxetine plus conservative therapy showed similar outcomes but an additional cost for the combined intervention., Conclusions: Although the limitations of the use of SUIT's observational data for this purpose need to be acknowledged, the study suggests that initiating duloxetine therapy in SUI is a cost-effective treatment alternative.

Background: Duloxetine was found safe and effective in the treatment of moderate to severe female stress urinary incontinence (SUI) in controlled clinical trials; complementary data from routine clinical practice are still wanted., Objectives: To explore the use of various initial duloxetine doses by physicians in the treatment of female SUI in routine clinical practice and its implications on drug safety and patients' subjective impression of effectiveness., Methods: Adult women treated with duloxetine for SUI symptoms were documented as part of an ongoing large-scale observational study in Germany. Data collected at baseline, after 4 and 12 weeks, were evaluated by initial doses. Statistics were descriptive, 95% confidence intervals were calculated for adverse event (AE) rates., Results: A total of 7888 adult women were treated with duloxetine; their mean age was 61.4 years, body mass index 27 kg/m(2), incontinence episode frequency (IEF) 14.0 per week. Previous SUI treatments were observed in 52.2%, comorbidities in 60.4% of the patients. A total of 90.7% reported reduced frequency of SUI-episodes, 12.1% any AE; nausea (5.7%) and vertigo (1.6%) were reported most frequently. In all, 52.2% of patients were initiated on a duloxetine dose of 40 mg/day. Only minor differences in patient characteristics, effectiveness and tolerability were associated with varying initial duloxetine doses., Conclusions: Many women received lower duloxetine doses than expected based on evidence-based dosing recommendations. Although SUI patients in this study had a higher health risk because of old age and multiple comorbidities than in previous controlled clinical trials, AE rates were lower, possibly because of the observational character of the study and/or the use of rather low doses. Similar AE rates for varying initial doses possibly reflect sensible dose-adjustment to individual needs.

Painful physical symptoms (PPS) are common in patients with depression. Our objective was to evaluate the presence of PPS in a sample of SSRI non- or partial-responders with MDD and examine the effect of a switch to duloxetine on those PPS. Outpatients who met criteria for MDD despite having taken an SSRI antidepressant for at least 6 weeks, and who had a Hamilton depression rating scale total score of at least 15 and a clinical global impression of severity score of at least 3, were randomized to switch to duloxetine by either a direct switch or a start-taper switch method. PPS were assessed at baseline and at the study endpoint using various measures including six visual analog scales (VAS) for pain (overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake), the pain subscale of the symptom questionnaire-somatic subscale, and the bodily pain subscale of the short form-36 item health survey. Clinically significant levels of pain (mean baseline VAS scores >30 mm) were seen across all VAS pain measures prior to switching. Switch to duloxetine was associated with significant improvements on all pain measures regardless of switch method, and there was evidence for an earlier reduction in pain in the start-taper switch group. In summary, MDD patients who were non- or partial-responders to SSRI treatment were found to have clinically significant pain which improved significantly following switch to duloxetine regardless of the switch method utilized.

Objective: We hypothesized that combining antidepressant medication with a standardized telephone adherence support intervention would lead to superior outcomes in the treatment of depression compared with antidepressant medication alone., Method: Patients with depression were randomized to receive the antidepressant duloxetine alone (DLX), or duloxetine plus a standardized telephone intervention (DLX+TI), for 12 weeks of open-label treatment. The primary outcome measure was remission (HAMD 17 total score 90% at every visit) in both groups., Conclusions: A telephone intervention in combination with antidepressant medication (duloxetine) did not improve depression outcomes compared with antidepressant alone in this clinical trial, perhaps due to high drug adherence in both treatment groups. Addition of a telephone intervention was, however, associated with increased reporting of AEs.

Objective: To compare 2 methods of switching selective serotonin reuptake inhibitor (SSRI) non-responders or partial responders to duloxetine., Method: Adult outpatients with DSM-IV major depressive disorder, a Hamilton Rating Scale for Depression (HAM-D(17)) total score of >or= 15, and a Clinical Global Impressions-Severity of Illness score of >or= 3 despite at least 6 weeks of SSRI treatment were randomly assigned to either abrupt discontinuation of SSRI immediately followed by initiation of duloxetine (direct switch [DS]; N = 183) or tapered discontinuation of SSRI over 2 weeks and simultaneous administration of duloxetine (start-taper switch [STS]; N = 185). Efficacy, safety, and tolerability outcomes associated with these 2 switch methods were compared following switch and after 10 weeks of duloxetine treatment. The study was conducted from August 2004 to March 2006., Results: There was a significant improvement in depressive symptom severity in both switch groups as measured by mean change in HAM-D(17) total score (p