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Objective: Youth diagnosed with ADHD are at heightened risk of depression. However, many do not develop depression. Individuals with specific cognitive biases are more likely to develop depression yet it remains untested whether these vulnerability-stress models apply to depression risk in youth with ADHD. Method: We examined whether interpretation and attention biases moderated the relation between stressful life events and depressive symptoms in a sample of adolescents (Mage = 14.42) with ADHD (n = 59) and without ADHD (n = 36). Results: Youth with ADHD experienced more stressful life events compared with those without ADHD. Interpretation biases moderated the association between stress and depressive symptoms in youth with and without ADHD. Attention biases moderated the association between stress and depressive symptoms in the non-ADHD youth only. Conclusion: These results enhance our understanding of vulnerability for depression in adolescence with ADHD and inform targeted prevention and treatment models during this critical developmental juncture. [ABSTRACT FROM AUTHOR]

Background: Stimulants remain the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) but are often associated with insufficient response or poor tolerability, leading to many patients not wishing to be treated with controlled substances.Aims: This randomized, placebo-controlled, proof-of-concept study (NCT02327013) evaluated the efficacy of a multimodal antidepressant, vortioxetine, in the treatment of ADHD, using a two-stage sequential parallel comparison design.Methods: Patients aged 18-55 years with a diagnosis of ADHD (DSM-5) and a total score ⩾24 on the Adult ADHD Investigator Symptom Rating Scale (AISRS) were randomized in study stage I with a 1:1:3 ratio to six weeks of treatment with vortioxetine 10 or 20 mg/day, or placebo ( n = 227). In study stage II, placebo non-responders (AISRS total score reduction <30% from stage I baseline) were re-randomized with a 1:1:1 ratio to six weeks of vortioxetine 10 or 20 mg/day, or placebo ( n = 59).Results: Across the two study stages combined, ADHD symptoms improved by approximately eight AISRS points in all treatment groups, showing no difference from placebo for either dose of vortioxetine, the study thus failing to meet its primary endpoint. However, both doses of vortioxetine separated from placebo in improving overall patient functioning, as measured by the Sheehan Disability Scale.Conclusion: Studies are warranted to further investigate this suggested benefit of a multimodal antidepressant for patient functioning in ADHD while addressing issues of non-adherence and placebo response. The study confirmed vortioxetine 10 mg and 20 mg as generally well-tolerated. [ABSTRACT FROM AUTHOR]

Introduction: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. Methods: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls (n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein- 1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). Results: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ≤ 0.05 and p ≤ 0.002, respectively). Conclusion: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature. [ABSTRACT FROM AUTHOR]

Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine's antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3 months after the final infusion. Methods: Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six openlabel intravenous ketamine infusions over 3 weeks. For the first three infusions, ketamine was administered at a dose of 0.5 mg/kg over 45 minutes; the dose was increased to 0.75 mg/kg over 45 minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale-28 items). Results: After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2 weeks after the final infusion. Conclusion: Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response. [ABSTRACT FROM AUTHOR]

Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD). Displacement of central [(11)C]GR205171 binding indicated that oral orvepitant doses of 30-60 mg/day provided >99% receptor occupancy for ≥24 h. Studies 733 and 833 randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM-D)≥22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day or placebo (1:1:1). Primary outcome measure was change from baseline in 17-item HAM-D total score at Week 6 analyzed using mixed models repeated measures. Study 733 (n=328) demonstrated efficacy on the primary endpoint (estimated drug-placebo differences of 30 mg: -2.41, 95% confidence interval (CI) (-4.50 to -0.31) p=0.0245; 60 mg: -2.86, 95% CI (-4.97 to -0.75) p=0.0082). Study 833 (n=345) did not show significance (estimated drug-placebo differences of 30 mg: -1.67, 95% CI (-3.73 to 0.39) p=0.1122; 60 mg: -0.76, 95% CI (-2.85 to 1.32) p=0.4713). The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD. [ABSTRACT FROM AUTHOR]

The article reflects on antidepressant and psychosocial treatments that are effective for major depressive disorder (MDD) and the absence of depressive symptoms which is not necessarily the presence of psychological well-being. It states that Well-Being Therapy (WBT) addresses the gap between positive and negative affect by inverting the usual focus of cognitive behavioral therapy (CBT) for depression. It conducts a study on investigating a suicide prevention screening program for college students at multiple Boston-area universities and mentions that despite the limitations of the study, the results provide preliminary support for the validity of the Clinical Positive Affect Scale (CPAS).

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Although the second-generation antipsychotic, aripiprazole (ARI), has been approved as an adjunct for treatment-resistant major depressive disorder (MDD), neither ARI nor any second-generation antipsychotic has been assessed in combination with an antidepressant at the initiation of a treatment trial for non-treatment-resistant MDD. The aim of the present study was therefore to assess the safety, tolerability, and remission rate in the treatment of MDD using the specific combination of venlafaxine-XR (VEN-XR) and ARI in a generalizable, difficult-to-treat group with chronic or recurrent MDD. Methods: Self-declared participants in primary care or psychiatric settings who had chronic or recurrent MDD and a minimum score of 14 on the 17-item Hamilton Rating Scale for Depression were included. Up to 12 weeks of open treatment with the combination of VEN-XR and ARI was provided. Participants began with VEN-XR, and ARI was added at week 2. Maximum allowable doses were 300 mg day-1 for venlafaxine-XR and 30 mg day-1 for ARI. Remission was defined as ≤ 5 on the 16-item Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR16). Results: Fifty outpatients with non-psychotic MDD were enrolled (mean age = 43±11 years; 38% male; QIDS-SR16=15±3). Mean exit dose of VEN-XR was 227±97 mg day-1, and the mean exit dose of ARI was 11±7 mg day-1. The combination was well tolerated; 16% of participants discontinued due to side-effects. Approximately 70% achieved remission at some point during the trial, and 66% achieved remission at study exit. Conclusions: To the best of the authors' knowledge this is the first study to combine an antidepressant and second-generation antipsychotic at the beginning of a treatment trial for chronic or recurrent non-treatment resistant MDD. VEN-XR and ARI combination appears to warrant further study in controlled trials. [ABSTRACT FROM AUTHOR]

Objective: We previously found that 46% of the first 1450 outpatients with depression participating in the multicentre Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project qualified for the designation of anxious depression. This study was designed to replicate and extend our initial findings in a subsequent, larger cohort of outpatient STAR*D participants with nonpsychotic major depressive disorder (MDD).Methods: Baseline clinical and sociodemographic data were collected on 2337 consecutive STAR*D participants. A baseline 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor score of 7 or higher was designated as anxious depression. We identified concurrent Axis I disorders with the Psychiatric Diagnostic Screening Questionnaire (PDSQ), using a 90% specificity threshold. Depressive symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30).Results: The prevalence of anxious depression in this population was 45.1%. Patients with anxious MDD were significantly more likely to be in primary care settings and to be women, nonsingle, unemployed, Hispanic, less educated, and suffering from severe depression, both before and after adjustment for overall depression severity. Patients with anxious depression were significantly more likely to meet PDSQ thresholds for generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, agoraphobia, hypochondriasis, and somatoform disorder, both before and after adjusting for baseline depression severity. Individuals with anxious depression were also significantly less likely to endorse IDS-C30 items concerning atypical features and were significantly more likely to endorse items concerning melancholic-endogenous depression features, both before and after adjusting for baseline depression severity.Conclusions: This study clearly replicates our previous STAR*D findings and supports the notion that anxious depression may be a valid diagnostic subtype of MDD, with distinct psychiatric comorbidities and clinical and sociodemographic features. [ABSTRACT FROM AUTHOR]

Objective: To compare response rates among patients with major depressive disorder (MDD) treated with either moclobemide, an antidepressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or selective serotonin reuptake inhibitors (SSRIs). Methods: Using a random-effects model, we combined 12 trials involving 1207 outpatients with MDD. Results: Patients treated with moclobemide were as likely to experience clinical response as those treated with SSRIs (risk ratio 1.08; 95% confidence interval, 0.92 to 1.26; P = 0.314). Simply pooling response rates for the 2 agents resulted in a 62.1% response rate for moclobemide and a 57.5% response rate for the SSRIs. A metaregression did not reveal a statistically significant relation between the mean moclobemide dosage for each study and the risk ratio for response rates. Further, we found no difference between the 2 treatments in overall discontinuation rates, discontinuation rates due to adverse events, or discontinuation rates due to lack of efficacy. Also, rates of fatigue or somnolence and of insomnia were similar between the 2 treatment groups. However, SSRI treatment was associated with higher rates of nausea, headaches, and treatment-emergent anxiety than was treatment with moclobemide. Conclusions: These results suggest that moclobemide and the SSRIs do differ with respect to their side effect profiles but not in their overall efficacy in the treatment of MDD. [ABSTRACT FROM AUTHOR]

Despite the efficacy of currently available antidepressant treatment, residual symptoms are common among individuals treated for major depressive disorder and are associated with an increased risk of relapse and poor psychosocial functioning. However, distinguishing treatment-emergent side effects from residual symptoms can be challenging for clinicians. Anxiety, sleep disturbance, somnolence/fatigue, apathy and cognitive dysfunction are among the more frequent residual symptoms. Approaches to the management of residual symptoms include addressing treatment-emergent side effects and co-morbid conditions, optimizing antidepressant dosing and using augmentation therapy. Clinicians are often guided in their decisions by anecdotal impressions. Studies assessing the evaluation and treatment of residual symptoms and side effects will contribute importantly to the optimal acute and long-term management of depression. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to examine the effect of identifying Chinese American patients as having major depressive disorder (MDD) to their primary care physicians (PCPs) on the latter's attention given to the treatment of depression. Methodology: Forty Chinese American patients from a primary care clinic were identified as having major depressive disorder (MDD), and their primary care physicians (PCPs) were notified of the diagnosis by letter. Three months later, medical records of subjects in the study were reviewed to see if their PCPs had intervened through referral and/or initiated treatment of depression. Results: PCPs documented intervention in 19 patients (47%) regarding their depression. Two of these patients (11%) were started on an antidepressant. Four (21%) accepted and 13 (68%) declined referral to mental health services. No intervention was recorded for 21 (53%) patients. Conclusion: We conclude that recognition alone of MDD among Chinese Americans in the community primary care setting does not lead to adequate initiation of treatment for depression by PCPs. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared to major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in severity of both depressive and anxiety symptoms in outpatients with major depression with comorbid anxiety disorder following fluoxetine treatment. We enrolled 123 outpatients (mean age 38.9 +/- 10.8 years; 49% women) with major depressive disorder accompanied by one or more current comorbid anxiety disorders in our study. Patients were treated openly with fluoxetine 20 mg/day for 8 weeks. Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D) and the patient-rated Symptom Questionnaire (SQ) Scales for Depression and Anxiety. The mood and anxiety disorder modules of the Structured Clinical Interview for DSM-III-R were administered at screen and endpoint. We used 'intent-to-treat' analysis in examining all patients assigned to treatment and completing the baseline visit. The mean number of comorbid anxiety disorders per patient was 1.5 +/- 0.68. The mean HAM-D-17 score and mean Clinical Global Impressions-Severity scores decreased significantly from baseline to endpoint (week 8) following fluoxetine treatment (p < 0.0001). There were significant decreases in all four SQ scale scores, from baseline to endpoint: depression, anxiety, somatic symptoms and anger-hostility (p < 0.0001). Fifty-three percent of patients (n = 65) were depression responders (i.e. > or = 50% decrease in HAM-D-17 score at endpoint) and 46% (n = 57) were remitters (HAM-D-17 < or = 7 at endpoint). Patients with panic disorder had significantly higher baseline HAM-D-17 scores compared to those without panic disorder (p < 0.01). Patients with comorbid obsessive-compulsive disorder (OCD) were significantly less likely to be responders to fluoxetine at endpoint (> or = 50% decrease in HAM-D-17) and to be remitters (HAM-D-17 score of s 7 at endpoint) compared to patients without comorbid OCD (p < 0.01). Of the 41 patients on whom endpoint Structured Clinical Interview for DSM-III-R modules for anxiety disorders were available, 49% (n = 20) no longer met criteria for one or more of their anxiety disorder diagnoses at endpoint. Our preliminary findings suggest that fluoxetine is effective in treating outpatients with major depression with comorbid anxiety disorders, with a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are required in larger samples to confirm our findings. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The authors report a case of treatment refractory bulimia nervosa successfully treated with dutoxetine, a combined serotonin and norepinephrine reuptake inhibitor, with complete remission of the patient's bingeing and purging behaviours. This case is discussed in the context of existing literature on the psychopharmacology of bulimia nervosa. [ABSTRACT FROM AUTHOR]