Apathy in the context of treated major depressive disorder (MDD) is a common but understudied symptom. This multicenter, double-blind, randomized study investigated whether switching from a selective serotonin reuptake inhibitor (SSRI) to a serotonin-norepinephrine reuptake inhibitor (SNRI), compared with switching to another SSRI, improved apathy symptoms in patients who had been treated with a SSRI for MDD for ≥ 3 months, were no longer depressed (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤ 15), and continued to have apathy (Apathy Evaluation Scale--Clinician rated version [AES-C] total score >30). Following 8 weeks of treatment, both the duloxetine (SNRI, 244 patients) and escitalopram (SSRI, 239 patients) groups significantly improved from baseline on the AES-C total score (least squares mean change [standard error]: duloxetine -13.9 [0.54]; escitalopram -13.5 [0.54], both P < 0.001), and on the secondary apathy, depression, and functional outcomes. There were no significant differences between the two groups on any measure, including AES-C total score (least squares mean difference [95% confidence interval]: -0.4 [-1.87 to 1.10], P = 0.612; primary objective). There was a significant within-group improvement in apathy in the subgroup who received escitalopram before and during the study. There were few differences in safety between the two groups. This study did not support the hypothesis that switching from a SSRI to a SNRI has a beneficial effect on apathy symptoms. However, given the study limitations, it is possible that more specific targeting of the noradrenergic pathway would be of benefit.

Objective: To assess how threshold oppositional defiant disorder (ODD), inattention, and hyperactivity-impulsivity affect the response to atomoxetine versus methylphenidate. Method: Systematic review of randomized controlled trials (RCTs; ≥6 weeks follow-up). The primary measure was core symptom response—≥40% reduction in ADHD Rating Scale-IV–Parent Version: investigator administered and scored total or domain subscores, as appropriate. Results: Data from 1,391 children and adolescents (823 atomoxetine, 568 methylphenidate; 7 RCTs) were meta-analyzed. The mean difference in response rates for patients with ODD was 0.6% (95% confidence interval [CI] = −11.9%-13.1%). The “without ODD” patient group showed significant between-trial heterogeneity ( p < .001). Response rate differences for patients meeting the threshold for inattention or hyperactivity-impulsivity were −3.1% (95% CI = −11.5%-5.3%) and −4.9% (95% CI = −14.3%-4.4%), respectively. Conclusions: Meeting the threshold criteria for oppositionality, inattention, or hyperactivity-impulsivity did not alter core ADHD symptom response to atomoxetine versus methylphenidate, which was equivalent.

Objective: Previous studies comparing atomoxetine and methylphenidate to treat ADHD symptoms have been equivocal. This noninferiority meta-analysis compared core ADHD symptom response between atomoxetine and methylphenidate in children and adolescents. Method: Selection criteria included randomized, controlled design; duration 6 weeks; and assessment of ADHD Rating Scale–IV–Parent Version: Investigator Administered and Scored (ADHDRS) scores. Six-week response rates, defined as ≥40% reduction in ADHDRS total score, were compared using a noninferiority margin of −15%. Results: Seven studies met inclusion criteria ( N = 1,368). After 6 weeks, 53.6% (95% confidence interval [CI] 48.6%-58.4%) of atomoxetine-treated patients ( n = 811) had responded compared with 54.4% (47.6%-61.1%) for methylphenidate ( n = 557), with atomoxetine demonstrating noninferiority to methylphenidate (absolute difference −0.9%, 95% CI −9.2%-7.5%). Conclusion: After 6 weeks of treatment atomoxetine and methylphenidate had comparable efficacy in reducing core ADHD symptoms in children and adolescents.

ObjectiveThis post hoc analysis of a multicenter, single‐arm, open‐label trial (the Attributes of Response in Depressed Patients Switched to Treatment with Duloxetine [ARDENT] study) assessed the relationship between functional improvement in the Sheehan Disability Scale (SDS) and clinical outcomes of mood, pain, and anxiety over 8 weeks after switching treatment to duloxetine in patients with major depressive disorder.MethodsAnalyses included all 195 patients who completed the study. Pearson's correlation and multivariate regression analyses were used to evaluate the relationship between change from baseline in SDS total score and 17‐item Hamilton Rating Scale for Depression (HAMD17) Maier score (mood), Brief Pain Inventory‐Short Form average pain score (pain), and Hamilton Anxiety Rating Scale total score (anxiety) at week 8.ResultsAt week 8, change in SDS total score was positively correlated with change in mood (r = 0.49), anxiety (r = 0.44), and pain (r = 0.40). Multivariate linear regression coefficients for mood and pain were estimated at 1.21 (standard error [SE] = 0.184) and 1.16 (SE = 0.180), respectively (both p < 0.0001) compared with 0.02 (SE = 0.097; p = 0.82) for anxiety. Overall, 43% of patients achieved both HAMD17 and SDS total remission.ConclusionsFunctional improvement at 8 weeks was positively correlated with mood, pain, and anxiety in patients with major depressive disorder switched to duloxetine. Change in mood and pain exerted a relatively stronger joint effect on functioning than did anxiety in this patient population. Copyright © 2011 John Wiley & Sons, Ltd.

Objective. To assess the reliability and validity of the Integral Inventory for Depression (IID) scale using post hoc analyses of data from a multi-country study (ClinicalTrials.gov:NCT00561509) of patients with major depressive disorder (MDD). Methods. Patients (N = 1629) completed the IID (comprising two separate dimensions for emotional and physically painful symptoms; maximum score of 65) and a reference scale (16-item Quick Inventory of Depressive Symptomatology Self-Report) at baseline and at follow-up (8 and 24 weeks). Physicians rated MDD symptoms using the Clinical Global Impressions of Severity scale at each visit. Inter-item correlation, internal consistency, external validity, factor structure, and exploratory analysis of an optimal severity cut-off point were assessed. Results. The IID displayed two distinct dimensions (i.e. painful and emotional) with little item redundancy and good internal consistency (Cronbach's alpha > 0.83 at each visit). The IID displayed good external validity (Pearson's correlations coefficients >0.60 at each visit) and statistically significant agreement (McNemar's test; P < 0.001 at follow-up) with the reference scale. Results suggest that a cut-off score of <= 24 had adequate precision (>80%) to identify patients with and without moderate MDD. Conclusions. Results suggest that the IID may be a reliable and valid tool for assessing emotional and painful symptoms of MDD.

Objective: To assess how threshold oppositional defiant disorder (ODD), inattention, and hyperactivity-impulsivity affect the response to atomoxetine versus methylphenidate. Method: Systematic review of randomized controlled trials (RCTs; ≥6 weeks follow-up). The primary measure was core symptom response—≥40% reduction in ADHD Rating Scale-IV–Parent Version: investigator administered and scored total or domain subscores, as appropriate. Results: Data from 1,391 children and adolescents (823 atomoxetine, 568 methylphenidate; 7 RCTs) were meta-analyzed. The mean difference in response rates for patients with ODD was 0.6% (95% confidence interval [CI] = −11.9%-13.1%). The “without ODD” patient group showed significant between-trial heterogeneity ( p < .001). Response rate differences for patients meeting the threshold for inattention or hyperactivity-impulsivity were −3.1% (95% CI = −11.5%-5.3%) and −4.9% (95% CI = −14.3%-4.4%), respectively. Conclusions: Meeting the threshold criteria for oppositionality, inattention, or hyperactivity-impulsivity did not alter core ADHD symptom response to atomoxetine versus methylphenidate, which was equivalent.

Introduction: Reports from non-Asian populations indicate that painful physical symptoms are associated with poorer clinical and functional outcomes in patients with Major Depressive Disorder (MDD). This paper shows the changes in disease characteristics and quality of life in Taiwanese MDD patients, with or without painful physical symptoms, over 3 months' observation.Methods: Taiwanese patients from an observational study of six East Asian countries/regions were classified as painful physical symptom positive (PPS+) or negative (PPS-) based on a mean score of >= 2 or <2, respectively, on the modified Somatic Symptom Inventory. Changes from baseline in outcomes were compared between the groups.Results: Of 194 patients with MDD, 69% were PPS+ at baseline. These PPS+ patients were more depressed (17-item Hamilton Depression Rating Scale total; mean [SD] 27.1 [6.26] versus 21.8 [5.94] PPS-, P<0.001), in more pain (Visual Analog Scale overall; median [range] 73.5 [9-100] versus 40 [0 to 80] PPS-, P<0.001) and had poorer quality of life at baseline (EuroQoL; mean [SD] 42.9 [18.26] versus 59.8 [18.21] PPS-, P<0.001). At endpoint (n = 118), PPS- patients showed greater improvement on depression outcomes (Clinical Global Impression of Severity; P = 0.011) and had a higher remission rate (52.8 % versus 14.6% PPS+, P = 0.007).Discussion: Painful physical symptoms were frequently observed in Taiwanese patients with MDD. As PPS are associated with more severe depression, poorer quality of life, and poorer remission outcomes, clinical management should address both the mental and physical symptoms associated with this disorder.

Objective: this study assessed treatment outcomes of Latin American patients with bipolar I disorder (manic or mixed episodes) who included olanzapine in their treatment regimen compared with patients who did not. Materials and methods: patients from seven Latin American countries participated in this prospective, observational, noninterventional, open-label study