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Background. Exposure to acute stress is associated with reduced reward processing in laboratory studies in animals and humans. However, less clear is the association between reward processing and exposure to naturalistic stressful life events. The goal of the current study was to provide a novel investigation of the relation between past 6-month stressful life events and reward processing, and the extent to which this relation was moderated by depression diagnostic status and state symptoms of anhedonia. Methods. The current study included a secondary analysis of data from 107 adults (37 current-depressed, 25 past-depressed, 45 never-depressed; 75% women) drawn from two previous community studies. Past 6-month stressful life events were assessed with a rigorous contextual interview with independent ratings. Response to monetary reward was assessed with a probabilistic reward task. Results. Among current-depressed participants, and among both current- and past-depressed participants with high levels of anhedonia, greater exposure to independent life events outside of individuals' control was significantly associated with poorer reward learning. In direct contrast, among those with low levels of anhedonia, greater exposure to independent life events was significantly associated with a greater overall bias toward the more frequently rewarded stimulus. Conclusions. Results suggest that depression and anhedonia are uniquely associated with vulnerability to blunted reward learning in the face of uncontrollable stressors. In contrast, in the absence of anhedonia symptoms, heightened reward processing during or following independent stressful life event exposure may represent an adaptive response. [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.)

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.)

Introduction Many individuals with major depressive disorder (MDD) do not respond to initial antidepressant monotherapy. Adjunctive aripiprazole is recommended for treatment non-response; however, the impacts on quality of life (QoL) for individuals who receive this second-line treatment strategy have not been described. Methods We evaluated secondary QoL outcomes in patients with MDD (n=179). After 8 weeks of escitalopram, non-responders (<50% decrease in clinician-rated depression) were treated with adjunctive aripiprazole for 8 weeks (n=97); responders continued escitalopram (n=82). A repeated-measures ANOVA evaluated change in Quality of Life Enjoyment and Satisfaction Short Form scores. QoL was described relative to normative benchmarks. Results Escitalopram responders experienced the most QoL improvements in the first treatment phase. For non-responders, QoL improved with a large effect during adjunctive aripiprazole treatment. At the endpoint, 47% of patients achieving symptomatic remission still had impaired QoL. Discussion Individuals who were treated with adjunctive aripiprazole after non-response to escitalopram experienced improved QoL, but a substantial degree of QoL impairment persisted. Since QoL deficits may predict MDD recurrence, attention to ways to support this outcome is required. [ABSTRACT FROM AUTHOR]

One of the biggest challenges in treating depression is the heterogeneous and qualitative nature of its clinical presentations. This highlights the need to find quantitative molecular markers to tailor existing treatment strategies to the individual's biological system. In this study, high-resolution metabolic phenotyping of urine and plasma samples from the CAN-BIND study collected before treatment with two common pharmacological strategies, escitalopram and aripiprazole, was performed. Here we show that a panel of LDL and HDL subfractions were negatively correlated with depression in males. For treatment response, lower baseline concentrations of apolipoprotein A1 and HDL were predictive of escitalopram response in males, while higher baseline concentrations of apolipoprotein A2, HDL and VLDL subfractions were predictive of aripiprazole response in females. These findings support the potential of metabolomics in precision medicine and the possibility of identifying personalized interventions for depression. Caspani et al. report on sex-specific plasma lipoproteins predictive of response to two commonly used antidepressants. The authors show that lipoproteins belonging to the same main class but differing in size and density exhibit distinct associations with depression and with response to pharmacotherapy, highlighting the importance of evaluating lipoprotein subclass in depression research. [ABSTRACT FROM AUTHOR]

Background: Non-response to first-line treatment for major depressive disorder (MDD) is common; for such individuals, quality of life (QoL) impairments can be severe. Identifying predictors of QoL changes may support the management of cases with persistent depressive symptoms despite adequate initial pharmacological/psychological treatment.Objective: The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy.Methods: We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement.Results: Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain.Conclusion: The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms.Clinical Trials Registry: ClinicalTrials.gov identifier: NCT016557. [ABSTRACT FROM AUTHOR]

Background: Cognitive deficits are detectable in major depressive disorder (MDD). The cognitive impact of antidepressants remains unclear, as does the cognitive effects of aripiprazole in MDD, a commonly used adjunct with putative pro-cognitive properties.Objectives: In this multi-centre, open-label study, cognitive changes associated with escitalopram monotherapy and adjunctive aripiprazole were examined.Methods: Acutely depressed participants with MDD (n = 209) received 8 weeks of escitalopram. Non-responders received an additional 8 weeks of adjunctive aripiprazole (ESC-ARI, n = 88), while responders (ESC-CONT, n = 82) continued escitalopram monotherapy (n = 39 lost to attrition). ESC-ARI, ESC-CONT and matched healthy participants (n = 112) completed the Central Nervous System Vital Signs cognitive battery at baseline, 8 and 16 weeks. Linear mixed models compared participants with MDD cognitive trajectories with healthy participants.Results: Participants with MDD displayed poorer baseline global cognition (assessed via the Neurocognitive Index), composite memory and psychomotor speed vs healthy participants. There were no statistically significant changes in participants with MDD receiving escitalopram monotherapy from baseline to week 8 in the neurocognitive index, reaction time, complex attention, cognitive flexibility, memory or psychomotor speed. Overall symptom severity changes were not associated with cognitive changes. The ESC-CONT group displayed no significant cognitive changes from weeks 8 to 16; reaction time worsened in the ESC-ARI group (p = 0.008) from weeks 8 to 16, independent of symptom change.Conclusions: Escitalopram monotherapy in acute MDD did not result in significant cognitive improvements. We provide novel evidence that escitalopram continuation in responders does not adversely affect cognition, but adjunctive aripiprazole in escitalopram non-responders worsens reaction time. Treatments targeting cognitive dysfunction are needed in MDD. CLINICALTRIALS.Gov Identifier: NCT01655706; 2 August, 2012. [ABSTRACT FROM AUTHOR]

Background: A growing body of research has shown that consumption of probiotics can improve symptoms associated with mood and anxiety disorders through activity of the gut-brain axis. However, the effects of probiotics have yet to be tested in a clinical sample of treatment-naïve patients diagnosed with Major Depressive Disorder (MDD). The aim of this 8-week, open-label pilot study is to examine changes in depressive symptoms before and after the introduction of a probiotic supplement in 10 treatment-naïve MDD patients and to provide data on the feasibility of conducting a larger double-blind, randomized, placebo-controlled trial in the same patient population. Here we report on the clinical outcome measures of the study. Methods: Participants recruited from the community in Kingston, Ontario, Canada consumed a probiotic supplement containing Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (CEREBIOME®) at a dose of 3 × 109 CFU once per day for 8 weeks. Clinical symptoms of depression were measured using a validated battery of clinical scales and self-report questionnaires (CAN-BIND protocol). Data was collected at baseline, week 4, and week 8. Results: Significant improvements in affective clinical symptoms were observed at week 4 and were sustained at week 8. Significant improvements in subjective sleep quality were observed by week 8. No side effects or adverse effects associated with the probiotic supplement were observed. Conclusions: The findings from this study support the existing evidence in this emerging field for probiotics having a role in alleviating symptoms of depression in treatment-naïve, moderately depressed patients and indicate that the probiotic supplement is safe and well-tolerated in this population. However, further comprehensive studies are required to draw conclusions. [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 Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe. [ABSTRACT FROM AUTHOR]

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Neurostimulation Treatments" is the fourth of six sections of the 2016 guidelines.Results: Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance.Conclusions: There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments. [ABSTRACT FROM AUTHOR]

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Complementary and Alternative Medicine Treatments" is the fifth of six sections of the 2016 guidelines.Results: Evidence-informed responses were developed for 12 questions for 2 broad categories of complementary and alternative medicine (CAM) interventions: 1) physical and meditative treatments (light therapy, sleep deprivation, exercise, yoga, and acupuncture) and 2) natural health products (St. John's wort, omega-3 fatty acids; S-adenosyl-L-methionine [SAM-e], dehydroepiandrosterone, folate, Crocus sativus, and others). Recommendations were based on available data on efficacy, tolerability, and safety.Conclusions: For MDD of mild to moderate severity, exercise, light therapy, St. John's wort, omega-3 fatty acids, SAM-e, and yoga are recommended as first- or second-line treatments. Adjunctive exercise and adjunctive St. John's wort are second-line recommendations for moderate to severe MDD. Other physical treatments and natural health products have less evidence but may be considered as third-line treatments. CAM treatments are generally well tolerated. Caveats include methodological limitations of studies and paucity of data on long-term outcomes and drug interactions. [ABSTRACT FROM AUTHOR]

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Pharmacological Treatments" is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants.Results: Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents.Conclusions: Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient. [ABSTRACT FROM AUTHOR]

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) has revised its 2009 guidelines for the management of major depressive disorder (MDD) in adults by updating the evidence and recommendations. The target audiences for these 2016 guidelines are psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Psychological Treatments" is the second of six sections of the 2016 guidelines.Results: Evidence-informed responses were developed for 25 questions under 5 broad categories: 1) patient characteristics relevant to using psychological interventions; 2) therapist and health system characteristics associated with optimizing outcomes; 3) descriptions of major psychotherapies and their efficacy; 4) additional psychological interventions, such as peer interventions and computer- and technology-delivered interventions; and 5) combining and/or sequencing psychological and pharmacological interventions.Conclusions: First-line psychological treatment recommendations for acute MDD include cognitive-behavioural therapy (CBT), interpersonal therapy (IPT), and behavioural activation (BA). Second-line recommendations include computer-based and telephone-delivered psychotherapy. Where feasible, combining psychological treatment (CBT or IPT) with antidepressant treatment is recommended because combined treatment is superior to either treatment alone. First-line psychological treatments for maintenance include CBT and mindfulness-based cognitive therapy (MBCT). Patient preference, in combination with evidence-based treatments and clinician/system capacity, will yield the optimal treatment strategies for improving individual outcomes in MDD. [ABSTRACT FROM AUTHOR]

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. This section is the first of six guidelines articles.Results: In Canada, the annual and lifetime prevalence of MDD was 4.7% and 11.3%, respectively. MDD represents the second leading cause of global disability, with high occupational and economic impact mainly attributable to indirect costs. DSM-5 criteria for depressive disorders remain relatively unchanged, but other clinical dimensions (sleep, cognition, physical symptoms) may have implications for depression management. e-Mental health is increasingly used to support clinical and self-management of MDD. In the 2-phase (acute and maintenance) treatment model, specific goals address symptom remission, functional recovery, improved quality of life, and prevention of recurrence.Conclusions: The burden attributed to MDD remains high, whether from individual distress, functional and relationship impairment, reduced quality of life, or societal economic cost. Applying core principles of care, including comprehensive assessment, therapeutic alliance, support of self-management, evidence-informed treatment, and measurement-based care, will optimize clinical, quality of life, and functional outcomes in MDD. [ABSTRACT FROM AUTHOR]

An introduction is presented to 2016 guidelines for the treatment of major depressive disorder in adults from the organization Canadian Network for Mood and Anxiety Treatments (CANMAT), noting the methodology used in creating the guidelines from research results.

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. This section on "Special Populations" is the sixth of six guidelines articles.Results: Recent studies inform the treatment of MDD in children and adolescents, pregnant and breastfeeding women, women in perimenopause or menopause, and the elderly. Evidence for efficacy of treatments in these populations is more limited than for the general adult population, however, and risks of treatment in these groups are often poorly studied and reported.Conclusions: Despite the limited evidence base, extant data and clinical experience suggest that each of these special populations can benefit from the systematic application of treatment guidelines for treatment of MDD. [ABSTRACT FROM AUTHOR]

Background: Social restrictions to curb COVID-19's spread have had adverse effects on population mental health. Rumination is one mechanism through which pandemic stress (PS) might translate into psychopathology. In particular, intrusive rumination (IR) is believed to be problematic. In this study, we investigated whether IR and deliberate rumination (DR) mediated the associations between PS and both depression and anxiety severity.Methods: 1090 participants recruited online and from an undergraduate psychology participation pool completed an assessment of COVID-19 PS, as well as the Event-Related Rumination Inventory, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Total scores for PS, IR, DR, depression, and anxiety severity were tested in a parallel mediation model.Results: PS positively predicted IR, DR, depression, and anxiety severity. IR positively predicted 1depression and anxiety severity, whereas DR did not. Indirect effects of PS on depression and anxiety severity were significant for IR, but not DR. Direct effects of PS on anxiety and depression severity were significant. Taken together, IR partially mediated the association between PS and both measures of psychopathology, and DR did not.Limitations: This study was limited by its cross-sectional design and the lack of assessment of when PS exposure occurred.Conclusions: Regarding PS that is unrelated to infection by COVID-19, IR is one mechanism through which psychopathology may emerge, whereas DR appears to be benign. Promoting a shift from IR to DR may therefore be one strategy for mitigating the negative effects of PS and other stressors on mental health. [ABSTRACT FROM AUTHOR]

Preclinical research implicates stress-induced upregulation of the enzyme, serum- and glucocorticoid-regulated kinase 1 (SGK1), in reduced hippocampal volume. In the current study, we tested the hypothesis that greater SGK1 mRNA expression in humans would be associated with lower hippocampal volume, but only among those with a history of prolonged stress exposure, operationalized as childhood maltreatment (physical, sexual, and/or emotional abuse). Further, we examined whether baseline levels of SGK1 and hippocampal volume, or changes in these markers over the course of antidepressant treatment, would predict treatment outcomes in adults with major depression [MDD]. We assessed SGK1 mRNA expression from peripheral blood, and left and right hippocampal volume at baseline, as well as change in these markers over the first 8 weeks of a 16-week open-label trial of escitalopram as part of the Canadian Biomarker Integration Network in Depression program (MDD [ n = 161] and healthy comparison participants [ n = 91]). Childhood maltreatment was assessed via contextual interview with standardized ratings. In the full sample at baseline, greater SGK1 expression was associated with lower hippocampal volume, but only among those with more severe childhood maltreatment. In individuals with MDD, decreases in SGK1 expression predicted lower remission rates at week 16, again only among those with more severe maltreatment. Decreases in hippocampal volume predicted lower week 16 remission for those with low childhood maltreatment. These results suggest that both glucocorticoid-related neurobiological mechanisms of the stress response and history of childhood stress exposure may be critical to understanding differential treatment outcomes in MDD. ClinicalTrials.gov: NCT01655706 Canadian Biomarker Integration Network for Depression Study [ABSTRACT FROM AUTHOR]

Background: In treatment studies of major depressive disorder (MDD), exposure to major life events predicts less symptom improvement and greater likelihood of relapse. In contrast, the impact of minor life events has received less attention. We hypothesized that the impact of minor events on symptom improvement and risk of relapse would be heightened in the presence of concurrent chronic stress. We also hypothesized that major events would predict less symptom improvement and greater risk of relapse independently of chronic stress.Methods: Adult patients experiencing an episode of MDD were enrolled into a 16-week trial with antidepressant treatments (n = 156). Forty-three fully remitted patients agreed to participate in a naturalistic 18-month follow-up, and 30 had full data for analyses. Life events and chronic stressors were assessed using a contextual life stress interview.Results: Greater exposure to minor events predicted greater improvement in symptoms during acute treatment, but this relation was specific to those who reported greater severity of chronic stress. During follow-up, however, major life events predicted increased risk of relapse, and this effect was not moderated by chronic stress.Limitation: High attrition rates led to a small sample size for the follow-up analyses.Conclusions: Exposure to minor events may provide an opportunity to practice problem-solving skills, thereby facilitating symptom improvement. Nevertheless, acute treatment did not protect patients from relapse when they subsequently faced major events during follow-up. Therefore, adjunctive strategies may be needed to enhance outcomes during pharmacotherapy, consolidating benefits from acute treatment and providing skills to prevent relapse. [ABSTRACT FROM AUTHOR]

Objective: To report side effect frequency and severity in patients with major depressive disorder (MDD) receiving escitalopram and aripiprazole adjunctive therapy and to examine whether pretreatment anxious depression is associated with the number and presence of specific side effects. Methods: 188 of the 211 trial participants provided information on side effects during treatment with escitalopram (10–20 mg) for 8 weeks, and nonresponders received further augmentation on aripiprazole (2–10 mg) adjunctive therapy for another 8 weeks, whereas responders remained on escitalopram. Participants completed the Toronto Side Effects Scale at weeks 2, 4, 10, and 12. Covariate‐adjusted negative binomial regression and Wilcoxon tests examined the association between anxious depression (GAD‐7 ≥ 10) and number of side effects. Covariate‐adjusted logistic regression and chi‐square tests explored the association between anxious depression and specific side effects. Results: For both therapies, the most frequent side effects were also the most severe. They mostly related to the central nervous system (CNS) (i.e., drowsiness and nervousness). Between baseline and week 2, the number of side effects participants experienced (incidence rate ratio [IRR] = 1.38, p =.010) or had trouble with (IRR = 1.34, p =.026) was significantly higher among those with anxious depression for escitalopram but not adjunctive aripiprazole. Further, odds of experiencing and having trouble with nervousness and agitation were also significantly higher in anxious depression for escitalopram only (p <.05). Conclusion: Patients on escitalopram and aripiprazole adjunctive therapy may experience and have trouble with CNS side effects. Pretreatment anxious depression may predispose escitalopram recipients with MDD to developing side effects, especially those related to anxiety. This study demonstrates the utility of a standardized side effects questionnaire (TSES) and advances our understanding of the association between pretreatment anxious depression and an increased number of side effects. Patients with anxious depression have significantly more side effects in the first weeks of escitalopram therapy than patients with nonanxious depression, particularly those related to anxiety (i.e., nervousness, agitation). [ABSTRACT FROM AUTHOR]

Introduction: Although anxiety symptoms frequently co-occur with major depressive disorder, few studies examined the prediction of treatment outcomes among participants with anxious depression receiving antidepressants. We investigated whether baseline anxiety, and early improvements in anxiety and depression symptoms predict eventual treatment outcomes.Methods: 111 participants with anxious depression, defined using ≥ 10 on GAD-7, received escitalopram (10-20 mg) for 8 weeks. Covariate-adjusted logistic regression was conducted to examine the impact of baseline anxiety, and to assess the extent week 2 anxiety (GAD-7) and depression (QIDS-SR) percentage improvement associates with week 8 anxiety (GAD-7) and depression (MADRS) response/remission. Optimum improvement thresholds were identified using receiving-operating-curve analysis and their predictive values assessed.Results: Greater percentage improvement in anxiety and depression after the first 2 weeks of treatment significantly increased odds of achieving week 8 anxiety and depression response/remission (OR:1.01-1.04, p<0.05). Early anxiety (68.4%/87.2%) and depression (52.2%/83.0%) improvement thresholds around 30 and 40% provided moderate to high positive predictive value (PPV) for predicting week 8 anxiety response/remission, as well as moderate to high negative predictive value (NPV) for predicting week 8 depression response/remission (anxiety:70.8%/91.7%; depression:72.2%/90.1%). Baseline anxiety severity predicted anxiety outcomes at weeks 2 and 8.Limitations: Trial lacked placebo group.Conclusion: In anxious depression, early improvement in anxiety may be better than depression in predicting anxiety outcomes, with similar or higher PPVs. Both improvement types perform similarly in predicting depression outcomes, with the lack of improvement predictive of non-response and non-remission. Finally, baseline anxiety predicts eventual anxiety but not depression outcomes. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) is characterized by objective and subjective cognitive deficits. Discrepancies between objective and subjective cognitive performance can reflect under- to over-estimations of cognitive abilities, and these discrepancies are referred to as cognitive self-appraisals. Despite evidence that low self-appraisals are associated with depression, the modifiability of self-appraisals and their association with treatment outcome remains unclear. The current study examined whether self-appraisals change following antidepressant treatment. Furthermore, we investigated the association of self-appraisals with treatment outcome.Methods: As part of the CAN-BIND-1 clinical trial, 154 patients with MDD completed measures of objective and subjective cognitive abilities, depressive symptoms, and functional outcomes (work productivity, psychosocial functioning, and quality of life) at baseline and post-escitalopram treatment. Self-appraisals were calculated based on discrepancies between objective and subjective cognitive abilities, with higher scores indicating overestimation of cognitive abilities.Results: Baseline self-appraisals were not predictive of treatment outcomes. However, self-appraisals increased from pre- to post-treatment. Moreover, pre-post treatment increases in self-appraisals were associated with positive treatment response and remission, decreases in depressive symptoms, and improvements in work productivity, psychosocial functioning, and quality of life.Limitations: The pre-post intervention design precluded examining the temporal precedence of change in self-appraisals versus depressive symptoms and functional outcomes.Conclusions: Findings are the first to demonstrate that self-appraisals are treatment-sensitive and are associated with treatment outcomes and recovery from MDD. Cognitive self-appraisals may represent a key marker of treatment response and a valuable target for assessment and intervention, as well as a potential mechanism underlying risk and recovery. [ABSTRACT FROM AUTHOR]

Depression is associated with blunted reactivity to acute stress, as well as blunted responsivity to rewards. However, the extent to which responses to stress are associated with responses to reward in individuals meeting criteria for a depressive disorder is unknown. The goal of this study was to examine the relation of responses to stress and reward, and to determine if this relation is moderated by depression diagnosis, anhedonia, and sex. Participants included 114 adults (68 depressed, 46 non-depressed; 75% women) recruited from the community. Stress reactivity was operationalized as the total salivary cortisol output to the Trier Social Stress Test (TSST; Kirschbaum et al., 1993). Response bias to monetary reward was assessed following the TSST recovery period with a probabilistic reward task (PRT; Pizzagalli et al., 2005). In men only, total cortisol output during the TSST was more strongly positively associated with response bias to reward across the three blocks of the PRT. In addition, among depressed participants with high levels of anhedonia, higher cortisol output during the TSST was significantly associated with higher overall response bias to reward. We suggest that in men, the stress and reward systems may both respond quickly, and resolve rapidly, in the face of acute stress. Further, in depression, our findings suggest that anhedonia may represent a specific phenotype in which the stress and reward systems are particularly tuned together. [ABSTRACT FROM AUTHOR]

Childhood maltreatment is widely implicated as the strongest developmental risk factor for depression onset. The current research is novel in examining the fine-grained associations of childhood emotional versus physical versus sexual maltreatment to indices of the severity, course, and presence of anxiety and trauma-related psychopathology in depression. An amalgamation across 6 previous investigations resulted in a sample of 575 adolescents and adults (76% female; age range 12-70, M = 27.88, SD = 13.58). All participants were in a current episode of a unipolar depressive disorder. Retrospective reports of childhood maltreatment were assessed using a rigorous contextual interview with independent, standardized ratings. Higher levels of emotional maltreatment and/or sexual maltreatment emerged as significantly associated with greater depression severity, number of previous episodes, and risk for posttraumatic stress disorder (PTSD), and were significantly more strongly associated with these characteristics than was physical maltreatment. Further, emotional maltreatment perpetrated by mothers was significantly associated with depression severity and history, whereas emotional maltreatment perpetrated by fathers was significantly associated with a greater risk of PTSD. These latter results suggest that prevention and intervention efforts may need to focus on the unique roles of mothers versus fathers on the development of depressive- versus threat-related psychopathology, respectively. (PsycInfo Database Record (c) 2020 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

• Limited research on changes in insomnia symptoms with antidepressant pharmacotherapy. • We investigated the course of insomnia symptoms during acute treatment of MDD. • MDD patients were treated with open-label escitalopram (10–20 mg/day) for 8-weeks. • Remitters had lower QIDS-SR sleep-onset and mid-nocturnal insomnia scores. • Remitters also had lower PSQI sleep quality score than non-remitters. Despite considerable efforts to study the relationship between insomnia and depression, there is minimal research investigating whether insomnia symptoms change over time during a course of antidepressant pharmacotherapy. This study investigated the course of insomnia symptoms during the acute treatment of major depressive disorder (MDD) using a secondary analysis of data from MDD patients (N = 180) who were treated with open-label escitalopram (10–20 mg/day) for 8-weeks. Montgomery-Asberg Depression Rating Scale without sleep item (modified-MADRS) assessed depression and Self-reported Quick Inventory Depressive Scale (QIDS-SR) measured subjective sleep-onset, mid-nocturnal, and early-morning insomnia throughout 8-weeks of treatment. Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality, duration, onset latency, and efficiency throughout 8-weeks of treatment. Remission of depression was defined as modified-MADRS ≤10 at week-8. Mixed model repeated measures (MMRMs) were conducted with remission status as an independent variable and each sleep variable as a dependent variable. MMRMs demonstrated that remitters had significantly lower QIDS-SR sleep-onset and mid-nocturnal insomnia scores as well as a significantly lower PSQI sleep quality score than non-remitters throughout 8-weeks of treatment. Monitoring subjective sleep-onset and mid-nocturnal insomnia during the course of treatment with serotonergic antidepressants may be useful for predicting acute remission of depression. [ABSTRACT FROM AUTHOR]

• Escitalopram treatment improved self-reported pain severity and interference scores • Clinical response to escitalopram was associated with greater improvements in pain • Adjunctive aripiprazole was not associated with changes in pain scores Escitalopram may have pain-alleviating effects for patients with comorbid pain and depression. This study aimed to quantify improvements in pain for patients on escitalopram and adjunctive aripiprazole. A secondary analysis of the CAN-BIND-1 trial was conducted which only included participants with a current depressive episode and pain. Participants received escitalopram (10–20mg) for eight weeks and treatment response was defined as a reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) of at least 50% from baseline. Non-responders at week 8 received adjunctive aripiprazole (2–10mg) for another eight weeks. The Brief Pain Inventory's pain severity (PSC) and pain interference (PIC) composite scores were measured at baseline, week 8, and week 16. Linear regression was used to determine how PSC and PIC differed between treatment responders and non-responders. Eighty-two participants with pain and depression received escitalopram. PSC and PIC decreased significantly regardless of treatment response at week 8, although responders had significantly lower PSC and PIC than non-responders. For the group receiving aripiprazole after week 8, neither PSC nor PIC improved further. Further research is needed to identify interventions that might treat both pain and depression symptoms. [ABSTRACT FROM AUTHOR]