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Either a random-parameters logit (RPL) or latent class (LC) model can be used to model or explain preference heterogeneity in discrete-choice experiment (DCE) data. The former assumes continuous distribution of preferences across the sample, while the latter assumes a discrete distribution. This study compared RPL and LC models to explore preference heterogeneity when analyzing patient preferences for psoriasis treatments. Using DCE data collected from respondents with moderate-to-severe plaque psoriasis, we calculated and compared preference weights derived from RPL and LC models. We then compared how RPL and LC explain preference heterogeneity by exploring differences across subgroups defined by observed characteristics (i.e., country, age, gender, marital status, and psoriasis severity). While RPL and LC models resulted in the same mean preference weights, different preference-heterogeneity patterns emerged from the two approaches. In both models, country of residence and self-reported disease severity could be linked to systematic differences in preferences. The RPL also identified gender and marital status, but not age, as sources of heterogeneity; the LC membership probability model indicated that age was a significant factor, but not gender or marital status. Using data from a psoriasis patient survey to compare two widely used methods for exploring heterogeneity identified differences in results between stated-preferences: subgroup analysis in the RPL model and inclusion of subgroup characteristics in the class membership probability function of the LC model. Researchers should model data using the most adaptable approach to address the initial study question.

BACKGROUND: Head-to-head randomised studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available.OBJECTIVE: Assess efficacy and quality of life with ixekizumab vs. secukinumab treatment using matching-adjusted indirect comparisons.METHODS: Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved doses of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo-controlled studies. Comparisons were made using the Bucher (BU) and two modified versions of the Signorovitch method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse-variance meta-analysis.RESULTS: In meta-analysis of studies with active comparators, PASI 90 response rates were 12.7% (95% CI: 5.5%-19.8%; p=0.0005), 10.0% (2.1%-18.0%; p=0.01) and 11.2% (3.2%-19.1%; p=0.006) higher and PASI 100 response rates 11.7% (5.9%-17.5%; pCONCLUSION: Ixekizumab had higher PASI 90 and PASI 100 responses at Week 12 compared to secukinumab using adjusted indirect comparisons. This article is protected by copyright. All rights reserved.

Background Biologics are effective for the treatment of psoriasis. However, treatment outcomes may differ among biologic-naive patients and those switched from previous biological therapies. Objectives The study's objective was to investigate efficacy and safety of ixekizumab, a high-affinity anti-interleukin-17A antibody, in patients with psoriasis with and without previous exposure to biologics. Methods Data were integrated from the 12-week induction phase of two etanercept-controlled Phase III trials. Patients received 80 mg ixekizumab every 2 weeks (IXE Q2W; N = 736) or every 4 weeks (IXE Q4W; N = 733) following a 160-mg starting dose, or placebo (N = 361). Etanercept (50 mg twice weekly; N = 740) was administered as active control. Psoriasis Area and Severity Index (PASI) 75, PASI 90 and PASI 100 response rates at week 12 were evaluated in patients with or without previous exposure to biologics. Treatment effects were analysed with the Cochran–Mantel–Haenszel test stratified by study; missing values were imputed as non-response. Results Overall, 497 (19.3%) patients had prior exposure to biologics and 2073 (80.7%) were naive to biologic therapy. PASI 75 was achieved by 91.5% of biologic-experienced patients and 87.7% of biologic-naive patients for IXE Q2W, 76.2% and 82.2% for IXE Q4W, respectively, and 34.6% and 50.7%, respectively, for etanercept. Higher response rates favouring each ixekizumab dose over etanercept within subgroups were also seen regarding PASI 90 and PASI 100. Conclusions Contrary to etanercept, the efficacy of ixekizumab was similarly high in patients with and without previous exposure to biologics when administered 80 mg every 2 weeks.

Background The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. Method This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. Results TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. Discussion In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. Conclusions The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.

This study aimed to compare the effectiveness of duloxetine (DLX) and the anticonvulsants pregabalin (PGB) and gabapentin (GBP) for the treatment of diabetic peripheral neuropathic pain (DPNP) in routine clinical care.Data from a 6-month, noninterventional study involving 2575 patients in whom treatment of DPNP was initiated with or changed to DLX, PGB, or GBP (n=1523) were analyzed post hoc; patients treated with other medications or combinations were excluded from this analysis. Propensity scoring was used to compare patient groups, assessing Brief Pain Inventory (BPI), Clinical and Patient Global Impression (CGI/PGI), the Hospital Anxiety and Depression Scale (HADS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF 12).Mean median daily dosage over 6 months was 53.9 mg for DLX (N=931), 173.5 mg for PGB (N=248), and 727.8 mg for GBP (N=351). BPI average pain severity (last observation carried forward, mean [SD]) decreased by 2.3 [2.30] points for DLX patients, and by 1.9 [2.22] in PGB, and 1.1 [2.15] in GBP patients. This difference remained statistically significant (DLX vs. PGB: P=0.029; DLX vs. GBP: P0.001) after adjustment by propensity scores. Similar findings were also seen for the BPI interference score, CGI and PGI, the HADS anxiety score, the HADS depression score.When compared with DLX, the low doses of PGB and GBP used in this noninterventional study might have contributed to the lower effectiveness found for both anticonvulsants in the treatment of patients with DPNP.

The aim of this study was to explore the course of attention-deficit/hyperactivity disorder (ADHD) core symptoms, ADHD-related difficulties, and emotional expression during ADHD pharmacotherapy and associations between them. This prospective, observational study examines pediatric patients with ADHD who newly initiated stimulant, atomoxetine or a combination of both treatments. Data were collected at baseline; weeks 1, 2, and 4; and months 3, 6, 9, and 12. Physicians rated ADHD core symptoms using the ADHD Rating Scale (ADHD-RS); patients, parents, and physicians rated ADHD-related difficulties using the Global Impression of Perceived Difficulties (GIPD) Scale; and patients and parents rated emotional expression using the Expression of Emotion Scale for Children (EESC). Results were analyzed using mixed model repeated measures. Associations are presented by Spearman's correlations. Overall, 504 patients, mean age 9.6 years, 72.6% males, were analyzed. Fifty percent of patients started atomoxetine, 49.0% stimulant and 1% a combination of both. ADHD-RS, GIPD, and EESC scores decreased significantly in both monotherapy groups. Correlations between ADHD-RS and parent- or physician-rated GIPD scores were at-best moderate and increased over time but remained low to moderate for patient-rated GIPD [patient, r=0.43 (95% CI 0.34, 0.51); parent, r=0.58 (0.50, 0.64); physician, r=0.55 (0.48, 0.62)]. Correlations between ADHD-RS and patient- or parent-rated EESC scores were low at baseline (r

Objective Pain control is the main objective when treating patients with painful diabetic peripheral neuropathic pain (DPNP). However, DPNP is associated with further substantial patient burden that often is not appropriately addressed. Our study identified patients' needs and asked patients what they expected from DPNP treatment. Methods Baseline data were collected in a German prospective, non-interventional study in patients with DPNP starting or switching pain medication at the discretion of the investigator. DPNP severity was evaluated using Brief Pain Inventory (BPI) and Clinician/Patient Global Impression-Severity (CGI-S/PGI-S). Primary objective of this study was to evaluate for which interference item of the BPI DPNP patients expected most to improve due to DPNP therapy. Results We enrolled 2,576 patients with DPNP from 307 outpatient centers (mean [standard deviation {SD}] age: 65.8 years [11.5], 51.2% female). Mean (SD) CGI-S and PGI-S at baseline were 4.4 (0.91) and 4.5 (1.05), respectively. BPI average pain score was 5.1 (2.04). The BPI interference score was 4.8 (2.18); items most impaired at baseline were walking ability 5.5 (2.60) and general activity 5.4 (2.37). The most frequently chosen BPI interference items expected to improve as a result of the pain treatment were: General activity (29.3%; 95% confidence interval [CI] 27.5–31.0%) and walking ability (24.4%; 95% CI 22.8–26.1%), followed by sleep (14.7%), enjoyment of life (13.6%), mood (8.3%), normal work (7.7%), and relations with other people (1.9%). Conclusions The majority of patients identified “general activity” and “walking ability” as most relevant BPI interference items for which they expect improvement from DPNP treatment.

An increasing rate of antidepressant trials fail due to large placebo responses. This analysis aimed to identify variables influencing signal detection in clinical trials of major depressive disorder. Patient-level data of randomized patients with a duloxetine dose ≥60 mg/day were obtained from Lilly. Total scores of the Hamilton Depression Rating scale (HAM-D) were used as efficacy endpoints. In total, 4661 patients from 14 studies were included in the analysis. The overall effect size (ES), based on the HAM-D total score at endpoint, between duloxetine and placebo was −0.272. Although no statistically significant interactions were found, the following results for factors influencing ES were seen: a very low ES (−0.157) in patients in the lowest baseline HAM-D category and in patients recruited in the last category of the recruitment period (−0.122). A higher ES in patients recruited in centers with a site-size at but not more than 2.5 times the average site-size for the study (−0.345). Study characteristics that resulted in low signal detection in our database were: 5 points, a high variability of placebo response (SD > 7 points HAM-D), >6 post baseline visits per study, and use of an active control drug. Simpler trial designs, more homogeneous and mid-sized study sites, a primary analysis based on a higher cutoff blinded to investigators to avoid the influence of score inflation in mild patients and, if possible, studies without an active control group could lead to a better signal detection of antidepressive efficacy.

Concomitant painful physical symptoms in depressive patients frequently impair functioning and failure to treat these symptoms may adversely impact treatment outcomes of depression. Early vs. conventional switch of antidepressants were compared in patients with major depressive disorder (MDD) and moderate to severe pain.Pre-specified subgroup analysis of a 16-week, randomized, double-blind clinical study on MDD patients with30 mm overall pain visual analog scale (VAS). Patients not achieving 30% reduction Hamilton Depression Rating Scale (HAM-D) after 4 weeks escitalopram (10 mg/day) were randomized to duloxetine 60-120 mg/day (early switch) or continued on escitalopram (conventional switch) with non-responders at week 8 switching to duloxetine. Endpoints were time to confirmed response and remission, VAS pain severity, and Sheehan disability scale (SDS). Switch strategies were compared using Kaplan-Meier, logistic regression, and repeated measures analyses.No differences between early and conventional switching were found in time to confirmed response after randomization (3.9 vs. 4.1 weeks, p=0.511) or remission (6.0 vs. 8.0 weeks, p=0.238). Significantly lower VAS mean pain levels at for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time being awake in pain were found for patients in the early switching group. Time to achieving normal functioning (SDS total score6) was shorter in the early switching group (p=0.042). Safety results were comparable between switch strategies.In MDD patients with moderate to severe painful physical symptoms not improving after 4 weeks of treatment with escitalopram, an earlier switch to duloxetine may lead to better pain and functional outcomes.

The primary objective of this study was to evaluate the efficacy of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD)-related symptoms assessed as standard variables of a computer-based continuous performance test (cb-CPT) combined with a motion-tracking (MT) device. This was a 2-arm, 8-week, randomized, double-blind, placebo-controlled study in patients with ADHD (6-12 years). Therapy with ATX started with 0.5 mg/kg per day for 1 week, followed by 7 weeks on the target dosage of 1.2 mg/kg per day. Primary outcomes were cb-CPT/MT standard scores after 8 weeks using mixed models for repeated measurements. In addition, investigator-rated ADHD Rating Scale (ADHD-RS), Weekly Ratings of Evening and Morning Behavior (WREMB), and Clinical Global Impression - Severity-ADHD (CGI-S-ADHD) scores were assessed. Of 128 patients randomized, 125 were evaluated (ATX/placebo: 63/62). Baseline characteristics were comparable in both groups (overall, 80.2% boys; mean [SD] age, 9.0 [1.79] years; comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis, 40.0% oppositional defiant disorder/conduct disorder; prior stimulant treatment, 24.8%; ADHD-RS total score, 36.99 [11.56]). At week 8, all cb-CPT/MT q-scores were significantly reduced versus placebo (all P < 0.001) with effect sizes (ESs) of reaction time (RT) variation (ES = 0.71), mean RT (ES = 0.41), number of microevents (ES = 1.00), commission error rate (ES = 0.50), distance of movement (ES = 0.90), area of movement (ES = 1.08), omission error rate (ES = 0.70), time active (ES = 0.69), motion simplicity (ES = 0.38), and normalized variance of RT (ES = 0.50). Secondary end points also improved significantly in favor of ATX: ADHD-RS (total score ES = 1.30, P < 0.001; hyperactivity/impulsivity subscore ES = 1.37, P < 0.001; inattention subscore ES = 1.07, P < 0.001), WREMB (total score ES = 1.00, P < 0.001; morning subscore ES = 0.59, P = 0.002; evening subscore ES = 1.02, P < 0.001), CGI-S-ADHD (ES = 1.11, P < 0.001). The results of this study show that ATX for 8 weeks significantly reduced ADHD-related symptoms as measured by the cb-CPT/MT.

Objective: To compare the reduction of ADHD symptoms under atomoxetine in patients with and without comorbid oppositional defiant disorder (ODD) or conduct disorder (CD) using a computer-based continuous performance test (cb-CPT) combined with an infrared motion tracking (MT) device. Method: Secondary analysis of a placebo-controlled study in ADHD patients (6-12 years old) treated with atomoxetine (target dose: 1.2 mg/kg per day). Cb-CPT/MT scores were analyzed using ANCOVA (last observation carried forward [LOCF]). Results: The data ( N = 125) suggested a more pronounced atomoxetine effect in the group with comorbid ODD/CD as measured by all cb-CPT/MT parameters except for “normalized variation of reaction time” (nVRT). Conclusion: The results showed that atomoxetine reduced ADHD severity as measured by cb-CPT and MT parameters regardless of whether comorbid ODD/CD was present. The treatment effect of atomoxetine on hyperactivity appears to be more pronounced in the subgroup of patients with comorbid ODD/CD than in the subgroup without this comorbidity.

This study questions whether a lower starting dose of duloxetine (DLX) could be beneficial for patients with depression, in terms of tolerability and safety in routine clinical care.Post-hoc analyses of a multicenter, prospective, non-interventional, 6-month study in adult outpatients with a depressive episode was undertaken.Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), discontinuations due to TEAEs and hospitalizations due to depression, were all documented at 2 weeks, 4 weeks, 3 months and 6 months after treatment initiation/switch to DLX.Of 4517 patients enrolled, 4313 were included for TEAE evaluation. TEAEs occurred in 17.2% of patients, and SAEs occurred in 0.79% of patients, including one case of suicidal ideation. 1404 patients discontinued within 6 months (TEAEs: n = 119). Starting treatment with 30 mg/day DLX (72.7%) was favored in females, or after inadequate efficacy of previous antidepressant treatment; 60 mg/day DLX was favored in more severe depression and patients receiving concomitant pain medication.Initiating treatment with 60 mg/day DLX was not associated with poorer tolerability in this study. Physicians may be guided by their clinical experience to carefully consider the individual benefit/risk ratio and TEAE susceptibility when deciding to start treatment with a higher or a lower dose of DLX.

Objective: The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. Method: In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or placebo for 8 weeks. The primary endpoint was the ADHD Rating Scale (ADHD-RS) score; secondary endpoints were the Clinical Global Impression of ADHD-Improvement (CGI-I) and the Conners Teacher Rating Scale-Revised: Short Form (CTRS-R:S) score. Results: Baseline mean ADHD-RS scores for atomoxetine versus placebo were 40.7 and 38.6; after 8 weeks, mixed-effect model repeated-measure means were 31.6 (95% confidence interval 29.2-33.9) and 38.3 (36.0-40.6), respectively, with a difference in least square means of -6.7 (-10.0 to -3.4; p .1). There were no serious adverse events. Conclusions: A tomoxetine moderately improved ADHD symptoms in patients with ASD and was generally well tolerated. Adverse events in this study were similar to those in other studies with ADHD patients without ASD. J. Am. Acad. Child Adolesc. Psychiatry, 2012; 51(7):733-741. Clinical trial registration information A Randomized Double-Blind Study of A tomoxetine Versus Placebo for ADHD Symptoms in Children with ASD; www.clinicaltrials.gov; NCT00380692.

The effect of atomoxetine (ATX) on executive function has been assessed by means of questionnaires only. The aim of this study was therefore to evaluate the efficacy of ATX using standard variables of a computer-based continuous performance test (cb-CPT) combined with an infra-red motion-tracking device at different times of the day. One hundred twenty-eight girls and boys aged 6 to 12 years with a diagnosis of ADHD according to DSM-IV-TR criteria were randomized in the study. The primary efficacy measures were the q-scores of the cb-CPT combined with an infra-red motion-tracking device. The test comprises 13 neuropsychological variables that can be taken to reflect hyperactivity, inattention, or impulsivity. One hundred five patients completed the study (ATX group: n=54; placebo group: n=51). ATX (target dose 1.2 mg/kg/day) over 8 weeks was significantly superior to placebo in reducing hyperactivity, inattention, and impulsivity as measured by q-scores of 10 primary variables of the cb-CPT. Both groups of patients showed a circadian pattern of neuropsychological outcomes across the day as reflected by the cb-CPT combined with an infra-red motion-tracking device. In summary, this study demonstrated a positive effect of ATX on some aspects of executive function, inhibitory control, and hyperactivity compared with placebo.

The objective of this pooled analysis was to correlate parameters related to quality of life with attention-deficit/hyperactivity disorder (ADHD) core symptoms analyzing data of 5 atomoxetine clinical trials in children and adolescents with ADHD. Data from 5 clinical trials (4 from Europe and 1 from Canada) with similar inclusion/exclusion criteria and similar duration (8-12 weeks' follow-up) were included. All studies used the Child Health and Illness Profile, Child Edition (CHIP-CE), parent rating form at baseline and end point. Correlation coefficients and effect sizes to ADHD-Rating Scale (ADHD-RS) scores were calculated. A total of 794 patients aged 6 to 15 years (mean, 9.7 years), with mean (SD) baseline Clinical Global Impression of Severity of 4.8 (0.89) and ADHD-RS of 41.8 (8.04), were included. Baseline total CHIP-CE mean t score (standard, 50 [10]) was 28.9 (11.76), and the strongest impairments were seen in risk avoidance (30.2 [14.62]) and achievement (30.5 [10.4]) domains. At baseline, CHIP-CE versus ADHD-RS correlation was low (total, -0.345) except for the risk avoidance domain (total, -0.517). For changes from baseline to end point, a low correlation between the scales was found (total, -0.364; placebo-controlled studies only, n = 372). Quality of life impairment in ADHD was found in CHIP-CE total score and several domains. Correlations between CHIP-CE and ADHD-RS at baseline, end point, and for change from baseline to end point were low to moderate. These findings suggest that measuring quality of life adds clinically relevant insight beyond core symptom evaluation in children and adolescents with ADHD.

Atomoxetine may improve ADHD-related difficulties and hence the quality of life (QoL) in children and adolescents. Perception of these difficulties may differ with the rater perspective (patient, parent, physician) or patients’ sex. The objective of this study was to investigate QoL as reflected by perceived ADHD-related difficulties perceived from these three perspectives and compare boys and girls. Patients aged 6–17 with ADHD were treated with atomoxetine (target dose 0.5–1.2 mg/kg/day) in two studies. In both studies, ADHD-related difficulties were assessed after 8 and 24 weeks using the Global Impression of Perceived Difficulties (GIPD) instrument, which can be taken to reflect the patient’s QoL from the three perspectives. Data from the two studies were combined and analyzed together in order to compare boys and girls. Four hundred and twenty-one patients were treated with atomoxetine, 338 boys and 83 girls. Three hundred and fifty-five patients completed the 8-week study period. QoL, as reflected by perceived ADHD-related difficulties (measured with GIPD), improved over time. Mean GIPD total scores showed a similar course over time for all rater groups, although the patients rated the degree of difficulties significantly lower than parents and physicians. The sexes did not differ significantly in mean GIPD total scores. The GIPD scores over time suggest that patients’ QoL, as reflected by perceived ADHD-related difficulties, improved with time on atomoxetine. However, improvement did not differ significantly between boys and girls. Trial Registration: ClinicalTrials.gov Identifiers NCT00191516 and NCT00191737.

To report on (1) psychometric properties of the Rosenberg Self-Esteem Scale (SES) studied in adolescents with ADHD, (2) correlations of SES with ADHD scale scores, and (3) change in patient-reported self-esteem with atomoxetine treatment. ADHD patients (12-17 years), treated in an open-label study for 24 weeks. Secondary analyses on ADHD symptoms (assessed with ADHD-RS, CGI, GIPD scales) and self-esteem (SES) were performed. One hundred and fifty-nine patients were treated. A dichotomous structure of the SES could be confirmed. Reliability and internal consistency were moderate to excellent. Highest coefficients were found for the correlation between SES and GIPD scores. Self-esteem significantly increased over time, accompanied by an improvement of ADHD symptoms and related perceived difficulties. The Rosenberg SES was shown to be internally consistent, reliable, and sensitive to treatment-related changes of self-esteem. According to these findings, self-esteem may be an important individual patient outcome beyond the core symptoms of ADHD.

International audience; This 10-week study assessed the efficacy of atomoxetine in combination with psychoeducation compared to placebo and psychoeducation in the improvement of Quality of Life in Swedish stimulant-naive children and adolescents with attention deficit/hyperactivity disorder. A total of 99 patients were treated with atomoxetine (49 patients) or placebo (50 patients) for 10 weeks and assessed regarding broader areas of functioning using the Quality of Life measures Child Health and Illness Profile-Child Edition (CHIP-CE), Family Strain Index [FSI; equivalent to the Family Burden of Illness Module used in the study], Appraisal of Stress in Child-Rearing (ASCR), Five to fifteen (FTF), “I think I am” (“Jag tycker jag är”), and Children's Depression Rating Scale-Revised (CDRS-R) before and after the active treatment phase. Simultaneously, the patients' parents participated in a 4-session psychoeducation program. A statistically significant difference in favor of atomoxetine was seen in the improvement from baseline to study endpoint for the CHIP-CE domains “Achievement” and “Risk avoidance”, for the FSI total score, for the ASCR section (I) domain “Child as a burden”, for all FTF domains except for “Language and Speech”, and for the CDRS-R total score. No difference between treatment groups was observed in the patient-assessed evaluation of self-esteem using the “I think I am” scale. Atomoxetine combined with psychoeducation had a positive effect on various everyday coping abilities of the patients as well as their families during 10 weeks of treatment, whereas the patients' self-image and the parents' image of the climate in the family were not significantly improved.

Objective To study the longitudinal patterns of subjective wellbeing in schizophrenia using cluster analysis and their relation to recovery criteria, further to examine predictors for cluster affiliation, and to evaluate the sensitivity and specificity of baseline subjective wellbeing cut-offs for cluster affiliation. Methods Data was collected in an observational 36-month follow-up study of 2842 patients with schizophrenia in Germany. Subjective wellbeing was assessed using the SWN-K scale. Cluster analyses were applied based on Ward's procedure. Predictors were analyzed using logistic regression models. Optimal SWN-K total score cut-off points for cluster affiliation were analyzed using Cohen's kappa. Results 4 distinct clusters were identified: a stable low (33%), a stable moderate (31%), a stable high (16%), and a cluster with distinct initial improvement and then stable high subjective wellbeing (20%). Highly concordant patterns were also observed for symptoms, social functioning, and quality of life. Sensitivity and specificity of SWN-K total score cut-offs at baseline were 82.8% and 63.8% for ≤ 60 points for the stable low cluster and 84.7% and 95.4% for ≥ 80 points for the stable high cluster. Affiliation to the stable low cluster was related to a 0.6% chance of being in recovery at 3-year endpoint. Conclusions Long-term patterns of subjective wellbeing are stable and highly concordant with course of symptoms, functioning level, and quality of life. Baseline subjective wellbeing cut-off points were found to be sufficient predictors of outcome, which, particularly in case of impaired subjective wellbeing and low baseline functioning level, make early treatment adaptations mandatory.

The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever. Cytokines have been linked to the induction of both weight gain and drug-induced fever. We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion. Thirty patients suffering from schizophrenia, schizophreniform disorder or schizoaffective disorder were treated with either clozapine (mean modal dose: 266.7+/-77.9mg) or olanzapine (21.2+/-2.5mg) in a randomized, double-blind, 6-week study. Body mass index (BMI), tympanic temperature, and plasma levels of leptin and cytokines (tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 and 2 (sTNFR-1/2), soluble interleukin-2 receptors (sIL-2R), interleukin-6) were determined weekly. BMI, leptin and cytokines significantly increased over time, except interleukin-6 and sTNFR-1 in the olanzapine group. All cytokines numerically increased compared to baseline already during the first week of treatment in both groups. Leptin, TNF-alpha, sTNFR-1, sTNFR-2 and sIL-2R levels correlated with the BMI. Five patients who received clozapine (33%) developed drug-induced fever (>/=38 degrees C). In these, interleukin-6 peak levels were significantly (p

INTRODUCTION: Agitation is a common phenomenon in schizophrenia or acute mania. Because of the inability of patients to give informed consent in such situations, data from consenting studies are limited. METHODS: This observational prospective 5-day study evaluated the effectiveness of olanzapine in a sample of highly agitated patients with aggression. Primary endpoint was mean change of the PANSS-Excited Component (PANSS-EC) score. RESULTS: Mean PANSS-EC score at baseline was 25.5 points, 60.2% were severely agitated and 41.6% severely aggressive. A significant decrease in PANSS-EC total score (−13.3 points) was observed with rapid dose escalation and an average daily dose of 21.2 mg/day of olanzapine. 40 patients (24.1%) required treatment with another antipsychotic and 21 patients (12.7%) were not treated with olanzapine at day 5. At endpoint, 64.2% of patients were in remission of agitation. PANSS-EC reduction was not significantly different in patients with or without concurrent benzodiazepine use. DISCUSSION: Severe agitation with aggression may be well controlled with olanzapine in many cases, possibly by higher initial and overall doses of olanzapine. Controlled studies are needed to confirm these findings.

Objective Clinical management of aggression depends on the availability of easily administrable measurements allowing reliable evaluation. The present study's aim is to validate a Clinical Global Impression-Severity of Aggression scale (CGI-A). Method 558 inpatients with psychiatric disorders and an agitated–aggressive syndrome at baseline were continuously assessed over 5 days using CGI-A and the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC). Equipercentile linking, correlation analyses and linear regression were applied. Results Relationship between CGI-A and PANSS-EC total score was found to be linear. On a 5-level CGI-A scale, values of 1 to 5 points were found to correspond to PANSS-EC scores of 12.2, 16.7, 21.3, 25.8, and 30.4, respectively (average increase: 4.6). All findings remained stable when only data from patients with schizophrenia spectrum disorders were analyzed. Conclusions The CGI-A is proposed as a quickly administrable scale for the assessment of patients' aggressiveness.

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.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.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.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.

The second generation antipsychotics clozapine and olanzapine frequently induce weight gain. Randomized studies investigating abnormal eating behavior (food craving, binge eating) possibly associated with weight gain are lacking. Thirty patients with schizophrenia, schizophreniform, or schizoaffective disorder were included in this randomized, double-blind, parallel study comparing abnormal eating behavior using a standardized scale, clinical efficacy using the Brief Psychiatric Rating Scale 0-6 and Clinical Global Impression-Severity scale, and tolerability of clozapine and olanzapine. In both treatment groups, the number of patients reporting food craving, binge eating, or both increased over time. The likelihood to experience food craving at any time during drug treatment showed a trend (P = 0.068) to be higher in the olanzapine group (48.9%) compared with the clozapine group (23.3%). The likelihood to experience binge eating at any time during drug treatment was numerically but not statistically significantly higher in the olanzapine group (16.7%) than in the clozapine group (8.9%). In both groups, significant baseline-to-end point improvements of clinical symptoms (Brief Psychiatric Rating Scale 0-6: clozapine, 36.6 +/- 8.8 to 15.9 +/- 13.7; olanzapine, 36.7 +/- 9.9 to 19.1 +/- 13.8) and severity of illness (Clinical Global Impression-Severity scale: clozapine, 4.7 +/- 0.6 to 2.5 +/- 1.5; olanzapine, 4.5 +/- 0.6 to 2.3 +/- 1.2) were observed. These improvements did not differ significantly between groups. Olanzapine was more tolerable than clozapine; adverse events occurred significantly (P < 0.01) less frequently than in the clozapine group. These results suggest that both clozapine and olanzapine can induce food craving and binge eating, however, olanzapine possibly to a greater extent. Findings on clinical efficacy and safety are in accordance with previous reports.

Objective To assess the Quality of Life (QOL) in outpatients with schizophrenia under antipsychotics from two perspectives: a “subjective” perspective as rated by the patient and an “objective” perspective as rated by the physician. Method EASE (External Assessment of Quality of Life in Out-patients with Schizophrenia) is a 12-month, prospective, naturalistic study of the QOL in patients on antipsychotic treatment for schizophrenia in an out-patient setting in Germany. The study included 1462 patients who were initiated on a new antipsychotic or switched to another antipsychotic. The Subjective Well-being under Neuroleptics scale (SWN) and the Quality of Life Scale (QLS) were used to assess the QOL in these patients. The Clinical Global Impression (CGI) scale was used to assess overall symptom severity. Four cohorts were identified and evaluated: (a) patients treated with olanzapine monotherapy ( N = 1007), (b) another atypical antipsychotic as monotherapy ( N = 335), (c) a typical antipsychotic as monotherapy ( N = 32) and (d) combination therapy with more than one antipsychotic ( N = 88). Results QOL as assessed by both SWN and QLS improved in all treatment cohorts. SWN responses in the respective cohorts were (a) 52.3%, (b) 38.8%, (c) 31.3% and (d) 44.3%, whilst the QLS responses were (a) 58.2%, (b) 45.1%, (c) 59.4% and (c) 40.9%. Symptom severity as assessed by the CGI also improved over time regardless of the type of antipsychotic. An increase of one point on the CGI corresponded to a change in SWN total score of − 9.67 points and a change in QLS total score of − 13.36 points. Conclusions Both QOL and symptom severity improved over the 12-month study period, regardless of the type of antipsychotic taken. QOL improvement as perceived both from a “subjective” and an “objective” perspective was greatest in the cohort on olanzapine monotherapy.

Objective: Subjective well-being is considered important for compliance with antipsychotic treatment. The objective of this post hoc analysis of data from German patients in the Schizophrenia Outpatient Health Outcomes study was to investigate subjective well-being and compliance, with consideration of clinical symptoms and side effects, in outpatients diagnosed with schizophrenia. Method: In a multicenter observational study of 2960 patients with DSM-IV-defined schizophrenia recruited between January and December 2001, subjective well-being was measured during 12 months with the Subjective Well-Being Under Neuroleptic Treatment Scale, short version (SWN-K). Compliance was self- and physician-rated. The association of compliance with clinical parameters was assessed by logistic regression. Results: Factor analysis resulted in 3 factors: SWN-K (r 2 = 0.867), clinical symptoms (r 2 = 0.744), and side effects (r 2 = 0.420). The odds for being compliant were 1.363 times higher if the SWN-K score increased by 20 points. Changes in positive symptoms (OR = 0.773) and changes in extrapyramidal symptoms (OR = 0.830) were found to be associated with compliance. Conclusion: Compliance with antipsychotic medication was strongly associated with subjective well-being; further factors were clinical symptoms and side effects.

We evaluated individual patient data from phase II to IV clinical trials of duloxetine in major depressive disorder (MDD) (34 studies, 13,887 patients). Our goal was to identify clusters of patients with similar depressive symptom patterns at baseline, as measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), and to investigate their respective predictive value of outcomes as measured by the HAMD-17 total score. Five clusters were identified at baseline: 1) "Lack of insight"; 2) "Sleep/sexual/somatic"; 3) "Typical MDD"; 4) "Gastrointestinal/weight loss"; and 5) "Mild MDD". However, it should be noted that cluster descriptors are not mutually exclusive. Analyses of the HAMD-17 total score results over time were performed using the 18 randomized placebo and/or actively controlled studies representing 6723 patients. At the end of acute treatment (ranging from 4 to 36 weeks), different levels of effect sizes for active therapy (64.5% duloxetine) vs. placebo were detected by cluster. In 3 out of 5 clusters (representing about 80% of the patients), the effect size was significantly different from 0, in favor of active therapy. The effect size was largest in those clusters with severe somatic symptoms ("Sleep/sexual/somatic" cluster [-0.4170], and "Gastrointestinal/weight loss" cluster [-0.338]). In conclusion, our cluster analysis identified 5 clinically relevant MDD patient clusters with specific mean treatment outcomes. Identification of MDD clusters may help to improve outcomes by adapting MDD treatment to particular clinical profiles.

Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.

This multicentre, double-blind, parallel-group study in diabetic peripheral neuropathic pain addressed whether, in patients not responding to standard doses of duloxetine or pregabalin, combining both medications is superior to increasing each drug to its maximum recommended dose. For initial 8-week therapy, either 60 mg/day duloxetine (groups 1, 2) or 300 mg/day pregabalin (groups 3, 4) was given. Thereafter, in the 8-week combination/high-dose therapy period, only nonresponders received 120 mg/day duloxetine (group 1), a combination of 60 mg/day duloxetine and 300 mg/day pregabalin (groups 2, 3), or 600 mg/day pregabalin (group 4). Primary outcome (Brief Pain Inventory Modified Short Form [BPI-MSF] 24-hour average pain change after combination/high-dose therapy) was analyzed comparing combination (groups 2, 3 pooled) with high-dose monotherapy (groups 1, 4 pooled). Secondary end points included response rates, BPI-MSF severity items, and comparison of duloxetine and pregabalin in BPI-MSF average pain. Eight hundred four patients were evaluated for initial therapy and 339 for combination/high-dose therapy. There were no significant differences between combination and high-dose monotherapy regarding BPI-MSF average pain (mean change: combination: -2.35; high-dose monotherapy: -2.16; P = 0.370) and most secondary end points, which, however, consistently favoured combination therapy. Fifty-percent response rates were 52.1% for combination and 39.3% for high-dose monotherapy (P = 0.068). In exploratory analyses of the initial 8-week therapy uncorrected for multiple comparisons, 60 mg/day duloxetine was found superior to 300 mg/day pregabalin (P < 0.001). Both drugs and their combination were well tolerated. Although not significantly superior to high-dose monotherapy, combination therapy was considered to be effective, safe, and well tolerated.

Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness. Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled. There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.

Several post-hoc studies have shown that lack of early improvement reduces the chance of later response or remission. This post-hoc analysis evaluates different cut-off points of non-improvement at 4 weeks of escitalopram treatment to predict 8-week non-response and non-remission.This study consisted of MDD patients with an absence of improvement (30% reduction in baseline score of the HAMD-17) at Week 4 of escitalopram treatment (10mg/day) that continued escitalopram treatment (10-20mg/day) for a further 4-week period (n=251). Predictive, sensitivity and specificity values for the several definitions of non-improvement (≤ 25%, ≤ 20% and ≤ 15% reduction in the HAMD-17 baseline total score) at 4 weeks were calculated.Overall, 70.1% (176/251) of patients did not achieve response at Week 8 and 84.5% (212/251) did not achieve remission. The predictive value for non-response was high (71.4-74.3%) for all cut-off points of non-improvement tested. The respective values for non-remission were placed between 85.0% and 87.2%.This was a post-hoc subgroup analysis. The only drug assessed was escitalopram.Our data indicate that an absence of improvement,30% reduction in the HAMD-17, after 4 weeks of escitalopram treatment should prompt clinicians to consider a change in treatment strategy. Similar findings were previously reported for other antidepressants.

Objective: To compare the reduction of ADHD symptoms under atomoxetine (ATX) in patients with and without pretreatment with a stimulant medication using a computer-based Continuous Performance Test (cb-CPT) combined with an infrared motion tracking (MT) device. Method: Double-blind, placebo-controlled study in ADHD patients (6-12 years) treated with ATX (target dose = 1.2 mg/kg per day). The cb-CPT/MT scores were analyzed using ANCOVA (last observation carried forward). Results: Patient data ( n = 125) suggested a differential ATX treatment effect between pretreated and stimulant-naïve patients in terms of three cb-CPT/MT parameters. Conclusion: This secondary analysis provided evidence that ATX reduced ADHD symptom severity measured by cb-CPT/MT parameters regardless of stimulant pretreatment. A few differential effects were seen based on the cb-CPT/MT. However, no clear pattern could be identified and, overall, the observed differences have no larger clinical relevance. The ATX effect in this study seemed to be largely independent of any previous exposure to stimulants.

Objective: Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder. Methods: Patients with no or minimal improvement (= 50% reduction in HAMD(17)), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD(17)

Attention-deficit/hyperactivity disorder (ADHD) is associated with considerable impairment in health-related quality of life (HR-QoL). Atomoxetine has been found to improve HR-QoL in both children and adolescents. However, there is scarcity of data on gender differences in treatment responses to ADHD medications. This pooled analysis of five atomoxetine trials aimed to evaluate treatment differences with respect to HR-QoL and ADHD symptoms across genders. Data from 5 clinical atomoxetine trials (4 from Europe and 1 from Canada) with similar inclusion and exclusion criteria and similar durations (8- to 12-week follow-up) were included in the pooled analysis. All studies included the Child Health and Illness Profile—Child Edition (CHIP-CE) Parent Report Form. In addition, correlations between HR-QoL and ADHD core symptoms were compared between girls and boys. Data from 136 girls and 658 boys (mean age: 9.6 and 9.7 years, respectively) were pooled. Boys and girls were similarly impaired at baseline with minor differences in some of the subdomains. Treatment effect of atomoxetine was significant in both groups for the Risk Avoidance domain and its subdomains. No gender effect with both clinical and statistical significance was found for treatment outcome. Correlations between ADHD Rating Scale and CHIP-CE scores were similar in both genders and were generally low at baseline and moderate at endpoint and for the change from baseline to endpoint. Atomoxetine was effective in improving some aspects of HR-QoL in both genders without any significant differences across genders. Correlations between core symptoms of ADHD and HR-QoL were low to moderate in both boys and girls.

The primary objective of this study was to evaluate the efficacy of atomoxetine (ATX, target dose 1.2 mg/kg daily) on symptoms of oppositional defiant disorder (ODD) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). A secondary objective was to compare fast versus slow up-titration of ATX.This was a 3-arm, 9-week, randomized, placebo-controlled, double-blind study in ADHD patients (6-17 years) with comorbid ODD (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria A-C) or conduct disorder (CD). ATX-treatment arms were as follows-ATX-fast: 7 days 0.5 mg/kg, then 1.2 mg/kg; ATX-slow: 7 days each at 0.5 and 0.8 mg/kg, then 1.2 mg/kg. Primary outcome was the Swanson, Nolan, and Pelham Rating Scale-Revised (SNAP-IV) ODD-score after 9 weeks (Mixed Effects Model for Repeated Measures, ATX-up-titration groups pooled).In total, 181 patients were randomized, and 180 evaluated (ATX-fast/ATX-slow/placebo: 60/61/59). Baseline characteristics were comparable (84.4% boys; mean age 11.0 years; DSM-IV: 100% ADHD, 75.6% with combined type, 74.4% ODD, 24.4% CD; SNAP-IV ODD-scores, mean ± standard deviation 15.5 ± 4.35). At week 9, SNAP-IV ODD scores were significantly lower versus placebo in both ATX-groups (least square mean [95% confidence interval]: ATX-fast 8.6 [7.2;9.9]; ATX-slow 9.0 [7.7;10.3]; placebo 12.0 [10.6;13.5]; least square mean, ATX-pooled minus placebo: -3.2 [-5.0, -1.5], effect size: -0.69, p 0.001). SNAP-IV ADHD-scores, CD symptoms (investigator-rated Attention-Deficit and Disruptive Behavior Disorders Instrument, disruptive behavior), Clinical Global Impressions-Severity, and individual treatment behaviors showed corresponding results. Post-hoc analyses indicated interrelationships between the medication effects on ADHD, ODD, and CD symptom scores. For ATX-slow, time to early dropout was significantly longer versus placebo (Hazard Ratio [95% confidence interval]: 3.57 [1.42;8.94]; p = 0.007). Clinically relevant adverse effects (fatigue, sleep disorders, nausea, and gastrointestinal complaints; weeks 1-3) were reported in 60.0% of ATX-fast, 44.3% of ATX-slow, and 18.6% of placebo group patients.ATX for 9 weeks significantly reduced symptoms of ODD/CD and ADHD; slower ATX-up-titration may be better tolerated.

This study examined the differential effects of first- (FGAs) versus second-generation antipsychotics (SGAs) on subjective well-being in patients with schizophrenia.Data were collected in an observational 3-year follow-up study of 2224 patients with schizophrenia. Subjective well-being was assessed with the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K). Differential effects of FGAs versus SGAs were analyzed using marginal structural models in those patients taking antipsychotic monotherapy.The marginal structural model, which analyzed the differential effect on the SWN-K total score, revealed that patients on SGAs had significantly higher SWN-K total scores, starting at 6 months (3.02 points; P = 0.0061, d = 0.20) and remaining significant thereafter (end point: 5.35 points; P = 0.0074, d = 0.36).Results of this large observational study are consistent with a small but clinically relevant superiority of SGAs over FGAs in subjective well-being extending previous positive findings of differential effects on quality of life.

To evaluate the effect of atomoxetine on quality of life (QoL) and family burden in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant (ODD) or conduct disorder (CD).This secondary analysis was based on a randomized, double-blind, 9-week study of atomoxetine (target dose 1.2 mg/kg body weight) versus placebo. The study included 180 patients (atomoxetine 121, placebo 59), aged 6-17 years. QoL was measured using the KINDL-R questionnaire. The total score encompasses six dimensions (or subscales) measuring QoL in terms of "physical well-being", "emotional well-being", "self-esteem", "friends", "family", and "school". Family burden of illness was measured using the FaBel questionnaire.With atomoxetine, the KINDL-R total score improved significantly (P = 0.021) more than with placebo. This improvement also applied to the subscales except for "physical well-being" (opposite effect) and "school" (no effect). No significant treatment group differences were seen on the FaBel questionnaire. No differences were found between the fast and slow titration groups in terms of ADHD, ODD, and disruptive behavior severity. Furthermore, no such differences were observed for QoL and family burden.This study suggests positive effects of atomoxetine on quality of life, as measured by the KINDL-R scores on emotional well-being, self-esteem, friends and family, in children and adolescents with ADHD and comorbid ODD/CD. No significant treatment effects were seen on family burden, as measured by FaBel total score.

Background Conventional antipsychotics augmented with benzodiazepines have been the standard acute treatment for psychiatric emergencies for more than 50 years. The inability of patients to give informed consent limits randomised, controlled studies. This observational study on immediate therapy for aggression and impulse control in acutely agitated patients (IMPULSE) evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications (AP) in a non-interventional setting. Methods This was a comparative, non-randomised, prospective, open-label, observational study. Treatment over the first 5 days was classified according to whether any olanzapine, risperidone, or haloperidol was included or not. Documentations (PANSS-excited component, CGI-aggression, CGI-suicidality, tranquilisation score) were at baseline (day 1) and days 2–6 after start of AP. Results During the short treatment-period, PANSS-EC and CGI-aggression scores improved in all cohorts. 68.7% of patients treated with olanzapine, 72.2% of patients treated with risperidone, and 83.3% of patients treated with haloperidol received concomitant benzodiazepines (haloperidol vs. non-haloperidol: p < 0.001). More patients treated with olanzapine (73.8%) were fully alert according to a tranquilisation score and active at day 2 than patients treated with risperidone (57.1%) or haloperidol (58.0%). Conclusion Current medication practices for immediate aggression control are effective with positive results present within a few days. In this study, concomitant benzodiazepine use was significantly more frequent in patients receiving haloperidol.

Quality of life (QoL) in patients with schizophrenia has been assessed both from physician and patient perspectives, but little is known about agreement between these perspectives and predictors of agreement. The aim of this study was to analyze a large sample of patients with schizophrenia to discover patterns of physician and patient-rated QoL in patients with schizophrenia and identify predictors for these patterns. This study (EASE) was designed to investigate the QoL and subjective well-being in out-patients with schizophrenia during antipsychotic treatment in a naturalistic setting. Assessments were carried out at baseline and at 3, 6, 9 and 12 months, using the quality of life scale (QLS) and the subjective well-being on neuroleptics scale (SWN-K). A hierarchical cluster analysis was used to define groups of patients based on the SWN-K and QLS total scores at all visits. 1174 patients were included in the cluster analyses that were based on SWN-K and QLS total scores over time. Four distinct clusters were identified: patients with: (1) continuously high QoL (23.2%), (2) continuously moderate QoL (45.8%), (3) continuously low QoL (11.2%), and (4) improving QoL (19.9%). Clusters 1-3 were stable in terms of QoL, whilst cluster 4 changed towards improvement. Various predictors for the four clusters were identified. In the cluster with improving QoL, the absence of treatment with an oral conventional antipsychotic pre-study and no medication change due to lack of efficacy at baseline were predictors for improvement. In the cluster with continuously high QoL, no medication change due to lack of efficacy and lowest CGI-S scores at baseline were predictors. Oral conventional antipsychotic treatment pre-study was predictive for the cluster with continuously moderate QoL. In the cluster with continuously low QoL, medication change due to lack of efficacy and highest CGI-S scores were predictors. These findings suggest that various factors may predict whether a patient with schizophrenia experiences a continuously high QoL, a continuously moderate QoL, a continuously low QoL, or improving QoL whilst on antipsychotic treatment.

Objective: Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia. Method: 392 never-treated patients with schizophrenia were assessed over 3 years. Combined remission and recovery required concurrent achievement of symptomatic and functional remission as well as adequate quality of life for at least 6 and 24 months respectively. Predictors were analysed using stepwise logistic regression models. Results: At 3 years, remission rates for symptoms, functioning and subjective wellbeing were 60.3%, 45.4% and 57.0%; recovery rates were 51.7%, 35.0% and 44.3%. Of those, 28.1% were in combined remission and 17.1% in combined recovery. Predictors mainly included the baseline functional status and early remission within the first 3 months. Conclusion: The proportion of patients who met combined remission or recovery criteria is low. Early treatment adaptations in case of early non-remission are mandatory.

Objective Recently, the Remission in Schizophrenia Working Group proposed symptomatic remission criteria and pointed to the lack of data regarding functional remission and quality of life in schizophrenia. This post hoc analysis of data from German patients in the Schizophrenia Outpatient Health Outcomes study assessed rates and predictors of symptomatic and functional remission as well as adequate subjective well-being/quality of life in a large cohort of patients with schizophrenia. Method Data were collected in an observational 24-month follow-up study of 2960 patients with DSM-IV-defined schizophrenia recruited between January and December 2001. Complete remission required that patients achieved symptomatic remission mirroring the Remission in Schizophrenia Working Group criteria, functional remission, and a level of adequate subjective well-being over at least 6 months. Results At endpoint, 47.2% of the patients achieved symptomatic remission, 26.6% achieved functional remission, and 42.2% achieved adequate subjective well-being. At endpoint, 12.8% were in complete remission. In 35.1% of patients, none of the 3 remission criteria were achieved. Only 8.7% of early nonremitted cases achieved remission at endpoint. Each single remission component as well as complete remission was mainly predicted by early remission within the first 3 months. First-line treatment with atypical antipsychotics increased the likelihood of complete remission compared to conventional antipsychotics. Conclusions Despite advances in pharmacologic and psychosocial treatments in schizophrenia, close to 90% of the patients in this study did not fulfill the combined remission criteria. This was in part attributable to the low functional remission rate, particularly the low employment rate. The finding that the course of the disorder depends on early outcome not only in previously untreated but also in more chronically ill patients points toward a critical "window of opportunity" in the course of treatment.

Perception of quality of life (QOL) may differ depending on the perspective. This 12-month, prospective, naturalistic study compared QOL ratings in outpatients on antipsychotic treatment for schizophrenia both from a “subjective” patient rated and an “objective” physician rated perspective. Included were 1462 patients. Two scales were used to assess patient and physician perspectives: the Subjective Well-being on Neuroleptics (SWN) scale and the Quality of Life Scale (QLS). Linear correlation was found between both ratings: 10 points on the SWN corresponded to 9.35 points on the QLS. Spearman's correlation coefficients increased over time up to r = 0.71 at Month 12. Patients were grouped into four cohorts depending on the degree of concordance between SWN and QLS ratings. Several factors affecting the concordance of both ratings were identified. Compared to the cohort with QLS = SWN, higher QOL ratings by the physician (QLS ≫ SWN) were more likely in females than in males (OR = 1.36; 95% CI 1.00 – 1.85) and in older than in younger patients (≤ 30 years vs. > 50 years: OR = 0.58, 95% CI 0.34 – 0.998), but less likely in patients with high baseline CGI-severity (CGI > 4; OR = 0.63; 95% CI 0.47 – 0.86) or treatment with oral typicals before baseline (OR = 0.53; 95% CI 0.31 – 0.91). Higher QOL ratings by the patient (SWN ≫ QLS) were less likely in patients with psychotherapy before baseline (OR = 0.54; 95% CI 0.36 – 0.81), medication intolerability before baseline (OR = 0.53; 95% CI 0.36 – 0.78) or patient request of treatment change at baseline (OR = 0.64; 95% CI 0.42 – 0.96). The combination of several factors predicted concordant ratings, including male sex, young age, high CGI at baseline, and psychotherapy prior to the study.

Sensory profiles are heterogeneous in neuropathic pain disorders, and subgroups of patients respond differently to treatment. To further explore this, patients in the COMBO-DN study were prospectively assessed by the Neuropathic Pain Symptom Inventory (NPSI) at baseline, after initial 8-week therapy with either duloxetine or pregabalin, and after subsequent 8-week combination/high-dose therapy. Exploratory post hoc cluster analyses were performed to identify and characterize potential subgroups through their scores in the NPSI items. In patients not responding to initial 60mg/d duloxetine, adding 300mg/d pregabalin for combination treatment was particularly effective regarding the dimensions pressing pain and evoked pain, whereas maximizing the duloxetine dose to 120mg/d appeared more beneficial regarding paresthesia/dysesthesia. In contrast, adding 60mg/d duloxetine to 300mg/d pregabalin in case of nonresponse to initial pregabalin led to numerically higher decreases in all NPSI dimensions/items compared to maximizing the pregabalin dose to 600mg/d. Cluster analysis revealed 3 patient clusters (defined by baseline scores for the 10 NPSI sensory items) with different pain profiles, not only in terms of overall pain severity, but also across NPSI items. Mean Brief Pain Inventory average pain improved in all clusters during combination/high-dose therapy. However, in patients with severe pain, the treatment effect showed a trend in favor of high-dose monotherapy, whereas combination therapy appeared to be more beneficial in patients with moderate and mild pain (not significant). These complementary exploratory analyses further endorse the idea that sensory phenotyping might lead to a more stratified treatment and potentially to personalized pain therapy.