Search

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults., Methods: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process., Results: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted., Conclusions: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Camelia Adams has nothing to disclose. Anees Bahji has nothing to disclose. Serge Beaulieu reports research grants, personal fees, and/or nonfinancial support from Abbvie, Boehringer-Ingelheim, Canadian Institutes for Health Research (CIHR), DiaMentis, Idorsia, Eisai, Janssen, and Otsuka-Lundbeck. Venkat Bhat reports research grants from the American Foundation for Suicide Prevention, AMS, Brain and Behaviour Research Foundation, CIHR, Department of Defense, Eisai, New Frontiers in Research Fund, Novartis, Ontario Ministry of Health, Roche, Royal College of Physicians and Surgeons of Canada, and the University of Toronto. Pierre Blier received research grants and/or personal fees from Abbvie, Allergan, CIHR, Janssen, Lundbeck, Merck, Ontario Brain Institute (OBI), Otsuka, Pfizer, University of Ottawa Medical Research Fund, and VilaNova. Daniel M. Blumberger reports research grants, nonfinancial support, and/or other support from Brain Canada, CIHR, Magventure, National Institutes of Health (NIH), and Welcony Inc. Elisa Brietzke reports research grants from Queen’s University Centre for Neuroscience and the PSI Foundation. Trisha Chakrabarty has nothing to disclose. Dr. André Do reports research grants and/or personal fees from AbbVie, CIHR, Janssen, and Otsuka. Benicio N. Frey has nothing to disclose. Dr. Peter Giacobbe reports research grants from CIHR and salary support from the Academic Scholars Fund, Department of Psychiatry, University of Toronto. David David Gratzer has nothing to disclose. Dr. Sophie Grigoriadis reports personal fees from the Canadian Pharmacists Association, Norton, and UptoDate. Jeffrey Habert reports research grants, personal fees and/or other support from Abbvie, Amgen, Astra-Zeneca, Bausch, Bayer, BMS, Boehringer-Ingelheim, Eisai, Eli-Lilly, Elvium, GSK, HLS, Idorsia, Janssen, Lundbeck, Novartis, Novo-Nordisk, Otsuka, Pfizer, and Valeo. M. Ishrat Husain reports research grants and/or other support from the Centre for Addiction and Mental Health (CAMH) Foundation, CIHR, COMPASS Pathfinder, MindSet Pharma, Psyched Therapeutics, University of Toronto, and Wake Network. Zahinoor Ismail reports personal fees from Lundbeck and Otsuka. Sidney H. Kennedy reports research grants, personal fees and/or other support from Abbott, Abbvie, Boehringer-Ingelheim, Brain Canada, Canada’s Strategy for Patient-Oriented Research (SPOR), CIHR, -, Janssen, Lundbeck, Merck, -, OBI, Otsuka, - Servier, and Sunovion. Raymond W. Lam reports research grants, personal fees and/or other support from AbbVie, Asia-Pacific Economic Cooperation (APEC), Bausch, BC Leading Edge Endowment Fund, Brain Canada, CANMAT, Carnot, CIHR, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Michael Smith Health Research BC, MITACS, Neurotorium, OBI, Otsuka, Pfizer/Viatris, Unity Health, and VGH-UBCH Foundation. Alexander McGirr reports other support from Allergan Canada; he holds a patent 63/193,643 pending. Roger S. McIntyre reports research grants and/or personal fees from Abbvie, Alkermes, Atai Life Sciences, Axsome, Bausch, Biogen, Boehringer Ingelheim, Braxia Scientific Corp., CIHR, Eisai, Global Alliance for Chronic Diseases, Intra-Cellular, Janssen, Kris, Lundbeck, Milken Institute, Mitsubishi Tanabe, National Natural Science Foundation of China, Neumora Therapeutics, Neurocrine, NewBridge Pharmaceuticals, Novo Nordisk, Otsuka, Pfizer, Purdue, Sage, Sanofi, Sunovion, Takeda, and Viatris. Erin E. Michalak reports research grants from the Otsuka-Lundbeck Alliance. Roumen V. Milev reports research grants and/or personal fees from AbbVie, Allergan, Canadian Biomarker Integration Network in Depression (CAN-BIND), CIHR, Eisai, Janssen, KYE, Lallemand, Lundbeck, Neonmind, Nubiyota, OBI, Ontario Mental Health Foundation, Otsuka, and Sunovion. Daniel J. Müller reports research grants or personal fees from CAMH AFP Innovation Fund, CAMH Foundation, CIHR, Novagenic, Nubiyota, and OBI. Sagar V. Parikh is the Medical Director for the National Network of Depression Centers and reports research grants, honoraria and/or personal fees from Aifred, Boehringer Ingelheim, Janssen, Medscape, Mensante, Merck, Myriad/Assurex, Otsuka, and Sage; and private shares in Mensante. Lena S. Quilty has nothing to disclose. Arun V. Ravindran has nothing to disclose. Nisha Ravindran has nothing to disclose. Johanne Renaud has nothing to disclose. Joshua D. Rosenblat reports research grants and/or personal fees from Academic Scholars Award, Allergan, American Psychiatric Association, American Society of Psychopharmacology, Boehringer Ingelheim, Braxia Health (Chief Medical and Scientific Officer of Braxia Scientific; Medical Director of the Canadian Rapid Treatment Centre of Excellence [Braxia Health]), Brain and Cognition Discovery Foundation, Canadian Cancer Society, Canadian Psychiatric Association, CIHR, COMPASS, iGan, Janssen, Joseph M. West Family Memorial Fund, Labatt Brain Health Network, Lundbeck, Physician Services Inc. (PSI) Foundation, Sunovion, Timeposters Fellowship, University Health Network Centre for Mental Health, and University of Toronto. Zainab Samaan has nothing to disclose. Gayatri Saraf has nothing to disclose. Kathryn Schade has nothing to disclose. Ayal Schaffer reports personal fees from AbbVie, Lundbeck, and Otsuka. Mark Sinyor has nothing to disclose. Claudio N. Soares reports research grants and/or personal fees from Bayer, Boehinger-Ingelheim, Clairvoyant Therapeutics, Diamond Therapeutics, Eisai, OBI, and Otsuka, Jennifer Swainson reports personal fees, nonfinancial support, and/or other support from AbbVie, Bausch, Eisai, Idorsia, Janssen, Lundbeck, Newly Institute, and Otsuka. Valerie H. Taylor has nothing to disclose. Smadar V. Tourjman reports personal fees from AbbVie, Elvium, Esai, Idorsia, Janssen, Lundbeck, Otsuka, Pfizer, Sunovion, and Takeda. Rudolf Uher has nothing to disclose. Michael van Ameringen reports research grants, personal fees, and/or other support from Abbvie, Bausch Health, Biohaven, Boehringer Ingelheim, CIHR, Elvium (Purdue), Jazz, Lundbeck, Michael G. DeGroote Centre for Medicinal Cannabis Research, Otsuka, Sunovion, Takeda, UptoDate, and Vistagen. Gustavo Vazquez reports personal fees for Abbvie, Allergan, Asofarma, Elea/Phoenix, Eurofarma, Gador, Janssen, Lundbeck/Otsuka, NeonMind Biosciences, Psicofarma, Raffo, Sunovion, and Tecnofarma. Simone Vigod reports royalties from UpToDate. Daphne Voineskos holds the Labatt Family Professorship in Depression Biology, a University Named Professorship at the University of Toronto; she reports research grants from CIHR, CAMH, Centre for Mental Health at University Health Network, Department of Psychiatry at the University of Toronto, and the National Institute of Mental Health. Lakshmi N. Yatham reports research grants and/or personal fees from Abbvie, Alkermes, Allergan, Dainippon Sumitomo, Gedeon Richter, GSK, Intracellular Therapies, Merck, Sanofi, and Sunovion.

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., Competing Interests: Declaration of Competing Interest MD, MW, VKT, ID, and WL do not have any disclosures. BNF has received grant/research support from Alternative Funding Plan Innovations Award, Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Hamilton Health Sciences Foundation, J.P. Bickell Foundation, Ontario Brain Institute, Ontario Mental Health Foundation, Society for Women's Health Research, Teresa Cascioli Charitable Foundation, Eli Lilly and Pfizer, and has received consultant and/or speaker fees from AstraZeneca, Bristol-Myers Squibb, Canadian Psychiatric Association, CANMAT, Daiichi Sankyo, Lundbeck, Pfizer, Servier and Sunovion. RVM has received consulting and speaking honoraria from AbbVie, Allergan, Janssen, KYE, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF. AVR has received speaker and consultant honoraria or research funds from Bristol Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer and Sunovion. SVP has been a consultant to Takeda, Bristol Myers Squibb, Lundbeck; has had a research contract with Assurex; has equity in Mensante. SR holds a patent ‘Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof.’ Inventors: David Lovejoy, R.B. Chewpoy, Dalia Barsyte, Susan Rotzinger. RWL has received speaker and consultant honoraria or research funds from AstraZeneca, Brain Canada, Bristol-Myers Squibb, the Canadian Institutes of Health Research (CIHR), the Canadian Network for Mood and Anxiety Treatments, the Canadian Psychiatric Association, Eli Lilly, Janssen, Lundbeck, Lundbeck Institute, Medscape, Otsuka, Pfizer, Servier, St. Jude Medical, Takeda, the University Health Network Foundation, and Vancouver Coastal Health Research Institute. SHK has received honoraria or research funds from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, CIHR, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, Sun Pharmaceuticals, and holds stock in Field Trip Health. VB is supported by an Academic Scholar Award from the University of Toronto Department of Psychiatry and has received research support from the Canadian Institutes of Health Research, Brain & Behavior Foundation, Ontario Ministry of Health Innovation Funds, Royal College of Physicians and Surgeons of Canada, Department of National Defence (Government of Canada), New Frontiers in Research Fund, Associated Medical Services Inc. Healthcare, American Foundation for Suicide Prevention, Roche Canada, Novartis, and Eisai., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: The primary objectives of these international guidelines were to provide a global audience of clinicians with (a) a series of evidence-based recommendations for the provision of lifestyle-based mental health care in clinical practice for adults with Major Depressive Disorder (MDD) and (b) a series of implementation considerations that may be applicable across a range of settings., Methods: Recommendations and associated evidence-based gradings were based on a series of systematic literature searches of published research as well as the clinical expertise of taskforce members. The focus of the guidelines was eight lifestyle domains: physical activity and exercise, smoking cessation, work-directed interventions, mindfulness-based and stress management therapies, diet, sleep, loneliness and social support, and green space interaction. The following electronic bibliographic databases were searched for articles published prior to June 2020: PubMed, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), CINAHL, PsycINFO. Evidence grading was based on the level of evidence specific to MDD and risk of bias, in accordance with the World Federation of Societies for Biological Psychiatry criteria., Results: Nine recommendations were formed. The recommendations with the highest ratings to improve MDD were the use of physical activity and exercise, relaxation techniques, work-directed interventions, sleep, and mindfulness-based therapies (Grade 2). Interventions related to diet and green space were recommended, but with a lower strength of evidence (Grade 3). Recommendations regarding smoking cessation and loneliness and social support were based on expert opinion. Key implementation considerations included the need for input from allied health professionals and support networks to implement this type of approach, the importance of partnering such recommendations with behaviour change support, and the need to deliver interventions using a biopsychosocial-cultural framework., Conclusions: Lifestyle-based interventions are recommended as a foundational component of mental health care in clinical practice for adults with Major Depressive Disorder, where other evidence-based therapies can be added or used in combination. The findings and recommendations of these guidelines support the need for further research to address existing gaps in efficacy and implementation research, especially for emerging lifestyle-based approaches (e.g. green space, loneliness and social support interventions) where data are limited. Further work is also needed to develop innovative approaches for delivery and models of care, and to support the training of health professionals regarding lifestyle-based mental health care.

Background: Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders., Objective: The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder., Methods: We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations., Results: Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results., Conclusion: The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.

Objective: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder., Methods: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria., Results: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient., Conclusions: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.

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., (Copyright © 2022. Published by Elsevier B.V.)

Background: Antidepressant use for major depressive disorder (MDD) is frequently associated with sexual dysfunction., Aims: Cross-sectional and longitudinal relationships between antidepressant treatment outcomes and sexual functioning (SF) were evaluated separately for males and females receiving escitalopram. We further assessed the association between pre- and posttreatment SF., Methods: In all, 208 of the 211 CAN-BIND-1 trial participants (77 males and 131 females) with MDD and detectable drug blood levels were eligible for the analyses. All received escitalopram (10-20 mg) for 8 weeks. At baseline and Week 8, participants completed the Montgomery-Åsberg Depression Rating Scale (MADRS) and the SexFx scale, which measures sexual satisfaction and SF frequency. Mixed-model repeated measures assessed baseline to Week 8 SF changes among participants with different response/remission statuses. Multiple linear regression analyses examined SF differences between treatment outcomes at Week 8 as well as associations between pretreatment and eventual SF., Results: For both sexes, overall sexual satisfaction improved among responders but not among nonresponders ( p  < 0.05). For females, overall SF frequency did not change significantly over time regardless of response status. For males, overall SF decreased significantly among nonresponders; orgasm decreased significantly among nonresponders and, to a lesser extent, among responders ( p  < 0.05). For both sexes, pretreatment SF was significantly associated with SF at Week 8 across all domains ( p  < 0.05)., Conclusion: For both sexes, sexual satisfaction improves with response to escitalopram. For females, the response does not correspond to improvements in SF frequency. For males, SF frequency, particularly that of orgasm, declines regardless of response/nonresponse.ClinicalTrials.gov identifier: NCT01655706.

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., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: Quetiapine is approved as an adjunctive treatment for major depressive disorder (MDD) and as monotherapy for bipolar depression. It is often used off-label for treating anxiety conditions and as an augmentation agent for treatment-resistant depression. However, its benefit in depression with comorbid anxiety disorders has not been systematically evaluated. The current study evaluated the benefit and tolerability of quetiapine as augmentation to first-line antidepressants for MDD comorbid with anxiety disorders., Methods: In this multicenter trial (June 2008-June 2013), 76 adults (aged 18-65 years) with a primary diagnosis of unipolar depression comorbid with at least 1 anxiety disorder (per DSM-IV-TR criteria) received flexible-dose quetiapine extended-release (XR) 50-300 mg/d or placebo as add-on for 12 weeks in a 2:1 ratio. Depression, anxiety, life satisfaction, and adverse events were assessed., Results: Depression, anxiety, and function improved significantly in both groups. On primary outcome measures, quetiapine was superior to placebo in improving depression (17-item Hamilton Depression Rating Scale score: mean difference = -3.64; 95% CI, -7.01 to -0.27) and anxiety symptoms (Hamilton Anxiety Rating Scale score: mean difference = -4.02; 95% CI, -7.41 to -0.64), as well as Clinical Global Impressions-Severity of Illness scale score (mean difference = -0.64; 95% CI, -1.13 to -0.15). On secondary measures including the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Penn State Worry Questionnaire, and Quality of Life Satisfaction and Enjoyment Questionnaire, quetiapine produced a greater degree of improvement compared to placebo, but group differences were not statistically significant. Quetiapine was well tolerated, with mostly minor and no serious adverse effects., Conclusions: Quetiapine augmentation may be a useful intervention for MDD with comorbid anxiety., Trial Registration: ClinicalTrials.gov Identifier: NCT00688818., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

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., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: Plant-based medicines have had a long-standing history of use in psychiatric disorders. Highly quantified and standardized extracts or isolates may be termed "phytoceuticals," in a similar way that medicinal nutrients are termed as "nutraceuticals." Over the past 2 decades, several meta-analyses have examined the data for a range of plant-based medicines in the treatment of psychiatric disorders. The aim of this international project is to provide a "meta-review" of this top-tier evidence., Methods: We identified, synthesized, and appraised all available up to date meta-analyses... of randomized controlled trials (RCTs) reporting on the efficacy and effectiveness of individual phytoceuticals across all major psychiatric disorders., Results: Our systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 individuals. Supportive meta-analytic evidence was found for St John's wort for major depressive disorder (MDD); curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders. We also provide details on 22 traditional Chinese herbal medicine formulas' meta-analyses (primarily for depression studies), all of which revealed highly significant and large effect sizes. Their methodology, reporting, and potential publication bias were, however, of marked concern. The same caveat was noted for the curcumin, ginkgo, and saffron meta-analyses, which may also have significant publication bias., Conclusions: More rigorous international studies are required to validate the efficacy of these phytoceuticals before treatment recommendations can be made. In conclusion, the breadth of data tentatively supports several phytoceuticals which may be effective for mental disorders alongside pharmaceutical, psychological therapies, and standard lifestyle recommendations.

Objectives: Major depressive disorder (MDD) is associated with impairments in both cognition and functioning. However, whether cognitive deficits significantly contribute to impaired psychosocial and occupational functioning, independent of other depressive symptoms, is not well established. We examined the relationship between cognitive performance and functioning in depressed patients before and after antidepressant treatment using secondary data from the first Canadian Biomarker Integration Network in Depression-1 study., Methods: Cognition was assessed at baseline in unmedicated, depressed participants with MDD ( n = 207) using the Central Nervous System Vital Signs computerized battery, psychosocial functioning with the Sheehan Disability Scale (SDS), and occupational functioning with the Lam Employment Absence and Productivity Scale (LEAPS). Cognition ( n = 181), SDS ( n = 175), and LEAPS ( n = 118) were reassessed after participants received 8 weeks of open-label escitalopram monotherapy. A series of linear regressions were conducted to determine (1) whether cognitive functioning was associated with psychosocial and occupational functioning prior to treatment, after adjusting for overall depressive symptom severity and (2) whether changes in cognitive functioning after an 8-week treatment phase were associated with changes in psychosocial and occupational functioning, after adjusting for changes in overall symptom severity., Results: Baseline global cognitive functioning, after adjusting for depression symptom severity and demographic variables, was associated with the SDS work/study subscale (β = -0.17; P = 0.03) and LEAPS productivity subscale (β = -0.17; P = 0.05), but not SDS total (β = 0.19; P = 0.12) or LEAPS total (β = 0.41; P = 0.17) scores. Although LEAPS and SDS scores showed significant improvements after 8 weeks of treatment ( P < 0.001), there were no significant associations between changes in cognitive domain scores and functional improvements., Conclusion: Cognition was associated with occupational functioning at baseline, but changes in cognition were not associated with psychosocial or occupational functional improvements following escitalopram treatment. We recommend the use of more comprehensive functional assessments to determine the impact of cognitive change on functional outcomes in future research.

Purpose: Cancer is a growing public health issue in low- and lower-middle-income countries (LLMICs), but the mental health consequences in this setting have not been well-characterized. We aimed to systematically evaluate the available literature on the prevalence, associates, and treatment of mental disorders in patients with cancer in LLMICs., Methods: We systematically searched Medline, PsycINFO, EMBASE, and CINAHL. We performed a random effects meta-analysis to determine the pooled prevalence of major depression or anxiety disorders in this population, defined by Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria. We qualitatively reviewed studies that examined the prevalence of depressive or anxiety disorders defined by self-report tools, the prevalence of other mental disorders, associated factors of depressive and anxiety symptoms, and the treatment of mental disorders in this population., Results: Forty studies spanning a 15-year period were included in the review. The pooled prevalence defined by Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria was 21% for major depression (95% CI, 15 to 28) and 18% for anxiety disorders (95% CI, 8 to 30). Depressive and anxiety symptoms were most frequently associated with advanced disease and low levels of education. Among the four studies evaluating treatment, three evaluated the effectiveness of psychotherapy and one evaluated a yoga program., Conclusion: The prevalence of depression and anxiety in patients with cancer generally appears higher in LLMICs than in upper-income countries. Our findings demonstrate the existence of a significant and underappreciated disease burden. We suggest that clinicians remain vigilant to psychiatric symptoms. Improved screening and treatment are likely to improve quality of life and reduce both morbidity and mortality., Competing Interests: Zoe J. WalkerStock and Other Ownership Interests: Noxopharm, ResMed Michael P. JonesEmployment: Icon Cancer CareStock and Other Ownership Interests: Noxopharm, ResMed Arun V. RavindranHonoraria: Empower Pharm, Toronto CanadaConsulting or Advisory Role: Empower PharmResearch Funding: Grand Challenges Canada, Canadian Institute of Health Research, Templeton FoundationNo other potential conflicts of interest were reported.

Objective: Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N -methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice., Methods: A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question-answer format., Results: Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response., Conclusions: Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.

Objective: To evaluate the development and implementation of clinical practice guidelines for the management of depression globally., Methods: We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries., Findings: We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence., Conclusion: Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes., ((c) 2020 The authors; licensee World Health Organization.)

Objective: Differential predictors of response to alternative treatment options are needed to improve the outcomes in major depressive disorder. The symptom dimension comprising loss of interest and reduced activity has been reported as a predictor of poor outcome of treatment with antidepressants. We hypothesized that augmentation with partial dopamine agonist aripiprazole will be effective for individuals with pronounced interest-activity symptoms., Methods: We tested the hypothesis in the 2-phase Canadian Biomarker Integration Network in Depression trial 1 (CAN-BIND-1). All participants had a primary diagnosis of major depressive disorder confirmed with the Mini-International Neuropsychiatric Interview. In phase 1, 188 individuals received escitalopram monotherapy 10-20 mg daily for 8 weeks. In phase 2, nonresponders received augmentation with aripiprazole 2-10 mg daily while responders continued escitalopram monotherapy for another 8 weeks. Outcomes were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) every 2 weeks. Effects of baseline interest-activity symptoms on outcomes were tested in repeated-measures mixed-effects models., Results: Higher baseline interest-activity score (indicative of more severe loss of interest and reduction in activity) predicted worse outcome of escitalopram monotherapy in phase 1 (b = 1.75; 95% CI, 0.45 to 3.05; P = .009), but the association disappeared with the augmentation option in phase 2 (b = -0.19; 95% CI, -1.30 to 0.92; P = .739). A significant interaction between the baseline interest-activity score and aripiprazole reflected the opposite direction of the relationship between baseline interest-activity score and degree of improvement with escitalopram monotherapy versus aripiprazole augmentation (b = -1.60; 95% CI, -2.35 to -0.84; P < .001)., Conclusions: Individuals with prominent loss of interest and reduction in activity benefit less from escitalopram monotherapy and more from aripiprazole augmentation. Future trials may test the benefits of early prodopaminergic augmentation guided by interest-activity symptoms., Trial Registration: ClinicalTrials.gov identifier: NCT01655706., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Background: Identifying objective biomarkers can assist in predicting remission/non-remission to treatment, improving remission rates, and reducing illness burden in major depressive disorder (MDD)., Methods: Sixteen MDD 8-week remitters (MDD-8), twelve 16-week remitters (MDD-16), 14 non-remitters (MDD-NR) and 30 healthy comparison participants (HC) completed a functional magnetic resonance imaging emotional conflict task at baseline, prior to treatment with escitalopram, and 8 weeks after treatment initiation. Patients were followed 16 weeks to assess remitter status., Results: All groups demonstrated emotional Stroop in reaction time (RT) at baseline and Week 8. There were no baseline differences between HC and MDD-8, MDD-16, or MDD-NR in RT or accuracy. By Week 8, MDD-8 demonstrated poorer accuracy compared to HC. Compared to HC, the baseline blood-oxygen level dependent (BOLD) signal was decreased in MDD-8 in brain-stem and thalamus; in MDD-16 in lateral occipital cortex, middle temporal gyrus, and cuneal cortex; in MDD-NR in lingual and occipital fusiform gyri, thalamus, putamen, caudate, cingulate gyrus, insula, cuneal cortex, and middle temporal gyrus. By Week 8, there were no BOLD activity differences between MDD groups and HC., Limitations: The Emotional Conflict Task lacks a neutral (non-emotional) condition, restricting interpretation of how mood may influence perception of non-emotionally valenced stimuli., Conclusions: The Emotional Conflict Task is not an objective biomarker for remission trajectory in patients with MDD receiving escitalopram treatment. Escitalopram may have influenced emotion recognition in MDD groups in terms of augmented accuracy and BOLD signal in response to an Emotional Conflict Task, following 8 weeks of escitalopram treatment., Competing Interests: Declaration of Competing Interest All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2019. Published by Elsevier B.V.)

Methods: We studied 48 MDD and 30 HC who performed an emotional conflict task in a functional magnetic resonance imaging (fMRI) scanner., Results: On the emotional conflict task, MDD and HC demonstrated a robust emotional Stroop effect in reaction time and accuracy. Overall, accuracy was lower in MDD compared to HC with no significant reaction time differences. The fMRI data indicated lower BOLD activation in MDD compared to HC on comparisons of all trials, congruent, incongruent, and incongruent > congruent trials in regions including right inferior temporal gyrus, lateral occipital cortex, and occipital fusiform gyrus. Behavioural and neuroimaging data indicated no group differences in fearful versus happy face processing., Limitations: Inclusion of a neutral condition may have provided a valuable contrast to how MDD and HC process stimuli without emotional valence compared to stimuli with a strong emotional valence., Conclusions: MDD and HC demonstrated a robust emotional Stroop effect. Compared to HC, MDD demonstrated an overall reduced accuracy on the emotional conflict task and reduced BOLD activity in regions important for face perception and emotion information processing, with no differences in responding to fearful versus happy faces. These findings provide support for the theory of emotion context insensitivity in individuals with depression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism-particularly the polyunsaturated fatty acids metabolism, and purine metabolism-that were associated with MDD in these young patients. In addition, inosine was shown as a potential independent diagnostic biomarker for MDD, achieving an area under the ROC curve of 0.999 in discriminating drug-naive MDD patients and 0.866 in discriminating drug-treated MDD from healthy controls. Moreover, we found evidence for differences in the pathophysiology of MDD in children and adolescents to that of adult MDD, specifically with tryptophan metabolism. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and the pathophysiology and diagnostic biomarker of child and adolescent MDD.

Background: Chronic Major Depressive Disorder (CMDD) is a common, disabling illness that is often complicated by high reactivity to social stress. To further elucidate the nature of this reactivity, the current study evaluated whether the personality dimensions of neuroticism and extraversion influenced cortisol responses to a social challenge in CMDD patients vs. controls., Methods: Fifty participants with CMDD and 58 healthy controls completed the Trier Social Stress Test (TSST) using a standard protocol. Neuroticism and extraversion were measured using the Revised NEO Personality Inventory. Hierarchical linear regressions assessed associations between independent variables neuroticism and extraversion and dependent variable cortisol area-under-the-curve increase (AUCi) in response to the TSST in the two study groups., Results: The extraversion-by-group interaction was a significant predictor of cortisol AUCi, while no significant findings related to neuroticism were found. Simple slopes analysis revealed a significant negative association between extraversion and AUCi in the CMDD group, but not in healthy controls. Post-hoc analysis of the raw cortisol data over time found that CMDD participants with higher extraversion scores had significantly higher pre-challenge cortisol levels than did other study participants, however this did not explain or confound the AUCi results., Conclusions: In participants with CMDD but not in controls, higher levels of extraversion were associated with higher pre-challenge cortisol levels and decreased cortisol reactivity during the TSST, however these two findings were statistically independent. These findings underline the importance of considering personality factors when studying stress biology in CMDD patients. Extraversion may prove to be an important intermediate target for both research and clinical work in this complex, heterogenous and often treatment-resistant population., (Copyright © 2019. Published by Elsevier Ltd.)

The ability to use feedback to guide optimal decision-making is essential for goal-directed behaviour. While impairments in feedback-driven decision-making have been associated with schizophrenia and depression, this has been examined primarily in the context of binary probabilistic choice paradigms. In real-world decision-making, however, individuals must make choices when there are more than two competing options that vary in the frequency and magnitude of potential rewards and losses. Thus, the current study examined win-stay/lose-shift (WSLS) behaviour on the Iowa Gambling Task (IGT) in order to evaluate the influence of immediate rewards and losses in guiding real-world decision-making in patients with schizophrenia and major depressive disorder. Fifty-one patients with schizophrenia, 43 patients with major depressive disorder, and 51 healthy controls completed the IGT, as well as a series of clinical and cognitive measures. WSLS was assessed by quantifying trial-by-trial behaviour following rewards and losses on the IGT. Multivariate analyses of variance revealed that patients with schizophrenia demonstrated intact lose-shift behaviour, but significantly reduced win-stay rates compared to healthy controls. In contrast, no WSLS impairments emerged in the depressed group. Win-stay impairments in the schizophrenia group were significantly related to deficits in motivation and cognition. Patients with schizophrenia exhibit impaired reward-driven decision-making in the context of multiple choices with concurrent rewards and losses, and this appears to be driven by a reduced propensity for advantageous win-stay behaviour. With the importance of reward learning and decision-making in generating goal-directed behaviour, these findings suggest a potential mechanism contributing to the motivation deficits seen in schizophrenia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To report the symptomatic and functional outcomes in patients with major depressive disorder (MDD) during a 2-phase treatment trial and to estimate the value of early improvement after 2 weeks in predicting clinical response to escitalopram and subsequently to adjunctive treatment with aripiprazole., Methods: Participants with MDD (N = 211) identified with the Montgomery-Asberg Depression Rating Scale (MADRS) and confirmed with the Mini-International Neuropsychiatric Interview were recruited from 6 outpatient centers across Canada (August 2013 through December 2016) and treated with open-label escitalopram (10-20 mg) for 8 weeks (Phase 1). Clinical and functional outcomes were evaluated using the MADRS, Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR), Sheehan Disability Scale (SDS), and Lam Employment Absence and Productivity Scale (LEAPS). Participants were evaluated at 8 and 16 weeks for clinical and functional response and remission. Phase 1 responders continued escitalopram while nonresponders received adjunctive aripiprazole (2-10 mg) for a further 8 weeks (Phase 2)., Results: After Phase 1, MADRS response (≥ 50% decrease from baseline) and remission (score ≤ 10) were, respectively, 47% and 31%, and SDS response (score ≤ 12) and remission (score ≤ 6) were, respectively, 53% and 24%. Response to escitalopram was maintained in 91% of participants at week 16, while 61% of the adjunctive aripiprazole group achieved MADRS response during Phase 2. Response and remission rates with the QIDS-SR were lower than with the MADRS. The LEAPS demonstrated significant occupational improvement (P < .05). Early symptomatic improvement predicted outcomes with modest accuracy., Conclusions: This study demonstrates comparable symptomatic and functional outcomes to those of other large practical-design studies. There was a high response rate with the adjunctive use of aripiprazole in escitalopram nonresponders. Given the limited value of early clinical improvement to predict outcome, integration of clinical and biological markers deserves further exploration., Trial Registration: ClinicalTrials.gov identifier: NCT01655706., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

Objective: Both Mindfulness Based Cognitive Therapy (MBCT) and Cognitive Therapy (CT) enhance self-management of prodromal symptoms associated with depressive relapse, albeit through divergent therapeutic procedures. We evaluated rates of relapse in remitted depressed patients receiving MBCT and CT. Decentering and dysfunctional attitudes were assessed as treatment-specific process markers., Method: Participants in remission from Major Depressive Disorder (MDD; N = 166) were randomized to 8 weeks of either MBCT (N = 82) or CT (N = 84) and were followed for 24 months, with process markers measured every 3 months. Attendance in both treatments was high (6.3/8 session) and treatment fidelity and competence were evaluated. Relapse was defined as a return of symptoms meeting the criteria for major depression on Module A of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID)., Results: Intention-to-treat analyses indicated no differences between MBCT and CT in either rates of relapse to MDD or time to relapse across 24 months of follow up. Both groups experienced significant increases in decentering and participants in CT reported greater reductions in dysfunctional attitudes. Within both treatments, participants who relapsed evidenced lower decentering scores than those who stayed well over the follow up., Conclusions: This is the first study to directly compare relapse prophylaxis following MBCT and CT directly. The lack of group differences in time to relapse supports the view that both interventions are equally effective and that increases in decentering achieved via either treatment are associated with greater protection. These findings lend credence to Teasdale et al.'s (2002) contention that, even though they may be taught through dissimilar methods, CT and MBCT help participants develop similar metacognitive skills for the regulation of distressing thoughts and emotions. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RVM has received speaker and consultant honoraria or research funds from Allergan, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Eli Lilly, Johnson & Johnson, Lallemand, Lundbeck, Merck, Ontario Brain Institute, Ontario Mental Health Foundation, Otsuka, Paladin, Pfizer, Queen’s University, Sunovion, Takeda, the University Health Network Foundation, and Valeant. PG has received speaker and consultant honoraria or research funds from Brain & Behavior Research Foundation, Bristol-Myers Squibb, Canadian Institutes of Health Research, Lundbeck, National Institute of Health, and St. Jude Medical. SHK has received honoraria for ad hoc speaking or advising/consulting or research funds from Allergan, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Janssen, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion, and Takeda. DMB has received research funds/support from Brain Canada, Brain Research and Development Ltd., Brainsway Inc., CAMH Foundation, Campbell Institute, Canadian Institutes of Health Research, National Institutes of Health, Tonika/Magventure, and Invidior. ZJD has received honoraria for ad hoc speaking or advising/consulting or received research funds from Brain and Behavior Research Foundation, Brainsway Inc., CAMH Foundation, Campbell Institute, Canadian Institutes of Health Research, Eli Lilly, Hoffmann-La Roche Limited, Merck, Ontario Mental Health Foundation, and Sunovion, JD has received research support or honoraria from ANT Neuro, Canadian Institutes of Health Research, Brain Canada, Edgestone Foundation, Klarman Family Foundation, Lundbeck, MagVenture, National Institutes of Health, and Toronto General and Western Hospital Foundation. MM and SP have no disclosures. FVR has received grant funding from Brain Canada and the Canadian Institutes of Health Research. RWL has received honoraria for ad hoc speaking or advising/consulting or received research funds from Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute. GMM has been on advisory board or speaker for Janssen, Lilly, Lundbeck, and Pfizer. SVP has been a consultant to Bristol Myers Squibb, Lundbeck, and Takeda; has had a research contract with Assurex; and has equity in Mensante. AVR has received speaker and consultant honoraria or research funds from Bristol-Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer, and Sunovion., (© The Author(s) 2016.)

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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SHK has received honoraria for ad hoc speaking or advising/consulting or received research funds from Allergan, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion, and Takeda. RWL has received honoraria for ad hoc speaking or advising/consulting or received research funds from Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute. RSM has received research grants and/or personal fees and/or nonfinancial support from AstraZeneca, Bristol Myers Squibb, CME Outfitters, Eli Lilly, France Foundation, GlaxoSmithKline, I3CME, Janssen-Ortho, Lundbeck, Merck, National Alliance for Research on Schizophrenia and Depression, National Institutes of Mental Health, Optum Health, Organon, Pfizer, Physicians’ Postgraduate Press, Shire, and Stanley Medical Research Institute, SVT has received honoraria for ad hoc speaking or advising/consulting or received research funds from Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck, Otsuka, Pfizer, Purdue, Shire, Sunovion, and Valeant. VB has no disclosures. PB has received research grants, personal fees, and/or nonfinancial support from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Forest, Euthymics, Janssen, Lundbeck, Merck, Otsuka, Pfizer, Pierre Fabre, Servier, Shire, Takeda, and Valeant. MH has no disclosures. FJ has no disclosures. AJL has received research grants, personal fees, and/or nonfinancial support from Eli Lilly, Janssen, Lundbeck, and Sanofi-Aventis, GMM has received honoraria for ad hoc speaking or advisory/consulting from Janssen, Lilly, Lundbeck, and Pfizer. SJM has received fellowship funding from Pfizer. DM has received honoraria for ad hoc speaking or advising/consulting or received research funds from Allergan, Bristol Myers Squibb, Lundbeck, Janssen-Ortho, Otsuka, Pfizer, Shire, and Sunovion. RVM has received honoraria for ad hoc speaking or advising/consulting or received research funds from Allergan, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Eli Lilly, Johnson & Johnson, Lallemand, Lundbeck, Merck, Ontario Brain Institute, Ontario Mental Health Foundation, Otsuka, Paladin, Pfizer, Queen’s University, Sunovion, Takeda, the University Health Network Foundation, and Valeant. DJM has received research funds from Canadian Institutes of Health Research, Canadian Foundations for Innovation, National Alliance for Research in Schizophrenia and Depression, Ontario Mental Health Foundation, National Institutes of Health, and the University of Toronto. SVP has been a consultant to Bristol Myers Squibb, Lundbeck, and Takeda; has had a research contract with Assurex; and has equity in Mensante. NLP has no disclosures. AVR has received honoraria for ad hoc speaking or advising/consulting or received research funds from Bristol Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer, and Sunovion. RU has received research funds from European Commission Framework 6., (© The Author(s) 2016.)

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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SVP has been a consultant to Bristol Myers Squibb, Lundbeck, and Takeda; has had a research contract with Assurex; and has equity in Mensante. LCQ, PR, BP, VV, and RU have nothing to disclose. MR received honoraria from AstraZeneca, Bristol-Myers Squibb, Canadian Psychiatric Association, Eli Lilly, Lundbeck, Otsuka, Pfizer, and Sunovion. SG has received honoraria as a consultant, member of an advisory committee, or for lectures from Actavis, Bristol Myers Squibb, Eli Lilly Canada, and Pfizer, as well as research grant support from Canadian Institutes of Health Research, CR Younger Foundation, Ontario Mental Health Foundation, and Ontario Ministry of Health and Long-Term Care. SHK has received honoraria for ad hoc speaking or advising/consulting or received research funds from Allergan, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Janssen, Lundbeck, Ontario Brain Institute, Pfizer, St. Jude Medical, Servier, and Sunovion. RWL has received honoraria for ad hoc speaking or advising/consulting or received research funds from Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute. GMM has been on advisory board or speaker for Janssen, Lilly, Lundbeck, and Pfizer. RVM has received speaker and consultant honoraria or research funds from Allergan, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Eli Lilly, Johnson & Johnson, Lallemand, Lundbeck, Merck, Ontario Brain Institute, Ontario Mental Health Foundation, Otsuka, Paladin, Pfizer, Queen’s University, Sunovion, Takeda, the University Health Network Foundation, and Valeant. AVR has received speaker and consultant honoraria or research funds from Bristol-Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer, and Sunovion., (© The Author(s) 2016.)

Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds from the Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute. SHK has received honoraria for ad hoc speaking, or advising/consulting or research funds from Allergan, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Janssen, Lundbeck, Ontario Brain Institute, St. Jude Medical, Servier, Sunovion, and Pfizer. SVP has been a consultant to Bristol Myers Squibb, Lundbeck, and Takeda; has had a research contract with Assurex; and has equity in Mensante. GMM has been on advisory board or speaker for Janssen, Lilly, Lundbeck, and Pfizer. RVM has received speaker and consultant honoraria or research funds from Allergan, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Eli Lilly, Johnson & Johnson, Lallemand, Lundbeck, Merck, Ontario Brain Institute, Ontario Mental Health Foundation, Otsuka, Paladin, Pfizer, Queen's University, Sunovion, Takeda, the University Health Network Foundation, and Valeant. AVR has received speaker and consultant honoraria or research funds from Bristol-Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer, and Sunovion.

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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RWL has received honoraria for ad hoc speaking or advising/consulting or received research funds from Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute. DM has received honoraria for ad hoc speaking or advising/consulting or received research funds from Allergan, Bristol-Myers Squibb, Lundbeck, Janssen-Ortho, Otsuka, Pfizer, Shire, and Sunovion. JLW has no disclosures. MWE has no disclosures. TK has received speaker and/or advisory honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly Canada, Lundbeck, Lundbeck-Otsuka, Janssen-Ortho, Pfizer, and Sunovion. EEM has received advisory honoraria from Lundbeck. JS has no disclosures. WYS has received honoraria for ad hoc speaking or advising/consulting or research funds from AstraZeneca, Bristol-Myers Squibb, Canadian Psychiatric Association, Eli Lilly, Forrest Laboratories, Lundbeck, Ortho-Janssen, Pfizer, and Sunovion. SHK has received honoraria for ad hoc speaking or advising/consulting or research funds from Allergan, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Janssen, Lundbeck, Ontario Brain Institute, Pfizer, St. Jude Medical, Servier, and Sunovion. GMM has been on advisory board or speaker for Janssen, Lilly, Lundbeck, and Pfizer. RVM has received speaker and consultant honoraria or research funds from Allergan, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Eli Lilly, Johnson & Johnson, Lallemand, Lundbeck, Merck, Ontario Brain Institute, Ontario Mental Health Foundation, Otsuka, Paladin, Pfizer, Queen’s University, Sunovion, Takeda, the University Health Network Foundation, and Valeant. SVP has been a consultant to Bristol Myers Squibb, Lundbeck, and Takeda; has had a research contract with Assurex; and has equity in Mensante. AVR has received speaker and consultant honoraria or research funds from Bristol-Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer, and Sunovion., (© The Author(s) 2016.)

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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AVR has received speaker and consultant honoraria or research funds from Bristol-Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer, and Sunovion. LB, GF, AO, RLM, and LR have no disclosures. DM has received honoraria for ad hoc speaking or received advising/consulting or research funds from Allergan, Bristol-Myers Squibb, Lundbeck, Janssen-Ortho, Otsuka, Pfizer, Shire, and Sunovion. LNY has received honoraria for ad hoc speaking or received advising/consulting or research funds from AstraZeneca, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Psychiatric Foundation, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, National Alliance for Research on Schizophrenia and Depression, Novartis, Pfizer, Abbott, Servier, Stanley Foundation, and Wyeth. SHK has received honoraria for ad hoc speaking or received advising/consulting or research funds from Allergan, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Janssen, Lundbeck, Ontario Brain Institute, Pfizer, St. Jude Medical, Servier, and Sunovion. RWL has received honoraria for ad hoc speaking or advising/consulting or received research funds from Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute. GMM has been on advisory board or speaker for Janssen, Lilly, Lundbeck, and Pfizer. RVM has received speaker and consultant honoraria or research funds from Allergan, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Eli Lilly, Johnson & Johnson, Lallemand, Lundbeck, Merck, Ontario Brain Institute, Ontario Mental Health Foundation, Otsuka, Paladin, Pfizer, Queen’s University, Sunovion, Takeda, the University Health Network Foundation, and Valeant. SVP has been a consultant to Bristol Myers Squibb, Lundbeck, and Takeda; has had a research contract with Assurex; and has equity in Mensante., (© The Author(s) 2016.)

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., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GMM has been on advisory boards or a speaker for Janssen, Lilly, Lundbeck, and Pfizer. BNF has received honoraria for ad hoc speaking or advising/consulting or received research funds from Alternative Funding Plan Innovations Award, AstraZeneca, Brain & Behavioral Foundation, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Daiichi Sankyo, Eli Lilly, Hamilton Health Sciences Foundation, J. P. Bickell Foundation, Lundbeck, Lundbeck International Neuroscience Foundation, Ontario Brain Institute, OMHF, Ontario Ministry of Research and Innovation, NSERC, Pfizer, Servier, Society for Women’s Health Research, Sunovion, and the Teresa Cascioli Charitable Foundation. ZI has received honoraria for ad hoc speaking or advising/consulting or received research funds from Canadian Biomarker Integration Network for Depression, Canadian Consortium for Neurodegeneration and Aging, Canadian Institutes of Health Research, Janssen, Joan and Clifford Hatch Foundation, Katthy Taylor Chair in Vascular Dementia, Lundbeck, National Institute of Aging, Ontario AFP Innovation Fund, Otsuka, Pfizer, and Sunovion. NJ has no financial conflicts to declare. MS has no financial conflicts to declare. RJV has no financial conflicts to declare. SHK has received honoraria for ad hoc speaking or advising/consulting or received research funds from Allergan, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Janssen, Lundbeck, Ontario Brain Institute, Pfizer, St. Jude Medical, Servier, and Sunovion. RWL has received honoraria for ad hoc speaking or advising/consulting or received research funds from Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute. RVM has received speaker and consultant honoraria or research funds from Allergan, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association Eli Lilly, Johnson & Johnson, Lallemand, Lundbeck, Merck, Ontario Brain Institute, Ontario Mental Health Foundation, Otsuka, Paladin, Pfizer, Queen’s University, Sunovion, Takeda, the University Health Network Foundation, and Valeant. SVP has been a consultant to Bristol Myers Squibb, Lundbeck, and Takeda; has had a research contract with Assurex; and has equity in Mensante. AVR has received speaker and consultant honoraria or research funds from Bristol-Myers Squibb, Canadian Depression Research and Intervention Network, Canadian Foundation for Innovation and the Ministry of Economic Development and Innovation, Canadian Institutes of Health Research, Grand Challenges Canada, Janssen, Lundbeck, Ontario Mental Health Foundation, Pfizer, and Sunovion., (© The Author(s) 2016.)

Background: Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people., Methods: We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023., Findings: We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference -0·51, 95% credible interval [CrI] -0·99 to -0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I(2) values were 33·21% for efficacy and 0% for tolerability., Interpretation: When considering the risk-benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated., Funding: National Basic Research Program of China (973 Program)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD., Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response., Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research., Trial Registration: ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.

Objective: To comparatively analyze the efficacy, acceptability, and tolerability of various augmentation agents in adult patients with treatment-resistant depression., Data Sources: An electronic literature search of PubMed, EMBASE, the Cochrane Library, Web of Science, EBSCO, PsycINFO, EAGLE, and NTIS for trials published up to December 2013 was conducted. Several clinical trial registry agencies and US Food and Drug Administration reports were also reviewed. No language, publication date, or publication status restrictions were imposed., Study Selection: Randomized controlled trials comparing 11 augmentation agents (aripiprazole, bupropion, buspirone, lamotrigine, lithium, methylphenidate, olanzapine, pindolol, quetiapine, risperidone, and thyroid hormone) with each other and with placebo for adult treatment-resistant depression were included., Data Extraction: The proportion of patients who responded to treatment was defined as primary efficacy, and the proportion of all-cause discontinuation and side-effects discontinuation were respectively defined as acceptability and tolerability, which were assessed with odds ratios (ORs) and a Bayesian random-effects model with 95% credible intervals (CrIs)., Results: A total of 48 trials consisting of 6,654 participants were eligible. In terms of the primary efficacy, quetiapine (OR = 1.92; 95% CrI, 1.39-3.13), aripiprazole (OR = 1.85; 95% CrI, 1.27-2.27), thyroid hormone (OR = 1.84; 95% CrI, 1.06-3.56), and lithium (OR = 1.56; 95% CrI, 1.05-2.55) were significantly more effective than placebo. Sensitivity analyses indicated that efficacy estimates for aripiprazole and quetiapine were more robust than those for thyroid hormone and lithium. In terms of acceptability, no significant difference was found between active agents and placebo. In terms of tolerability, compared to placebo, quetiapine (OR = 3.85; 95% CrI, 1.92-8.33), olanzapine (OR = 3.36; 95% CrI, 1.60-8.61), aripiprazole (OR = 2.51; 95% CrI, 1.11-7.69), and lithium (OR = 2.30; 95% CrI, 1.04-6.03) were significantly less well tolerated., Conclusions: Quetiapine and aripiprazole appear to be the most robust evidence-based options for augmentation therapy in patients with treatment-resistant depression, but clinicians should interpret these findings cautiously in light of the evidence of potential treatment-related side effects., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Objectives: High frequency left-sided (HFL) and low frequency right-sided (LFR) unilateral repetitive transcranial magnetic stimulation (rTMS) are efficacious in treatment-resistant major depression (TRD). Similar benefit has been suggested for sequential bilateral rTMS (LFR then HFL). There are few published reports on the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS. Therefore, this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD., Methods: Subjects between the ages of 18 and 85 were recruited from a tertiary care university hospital. Seventy-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS) greater than 21 were randomized to receive unilateral, bilateral, or sham rTMS. The rates of remission were compared among the three treatment groups., Results: The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not respond to electroconvulsive therapy (ECT) during the current episode. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the unilateral group did not differ from either group., Conclusion: These findings warrant larger controlled studies that compare the efficacy of sequential bilateral rTMS and HFL rTMS in TRD.

Objective: While a significant body of research has demonstrated high comorbidity rates between depression and obesity, the vast majority of this work has considered depression as a unitary diagnosis. Given that increased appetite and weight gain are highly characteristic of the "atypical" subtype of depression, while classic depression is characterized by decreased appetite and weight loss, it would be important to examine whether increased obesity risk is consistent across the major vegetative subtypes of depression or is limited to the atypical subtype., Method: Using data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we identified 5,092 US adults with past or current major depression based on DSM-IV-TR criteria and 1,500 gender-matched controls. Each depressed subject was designated as having classic, atypical, or undifferentiated depression based on core vegetative symptoms. Logistic regression models examined rates of current obesity (defined as a current body mass index [kg/m2] > 30) across the 3 depressive subgroups and nondepressed controls, adjusting for demographic differences. To limit the possible effect of current depressive symptoms on observed obesity rates, secondary analyses were completed in individuals with past depression only., Results: Subjects with atypical depression had markedly elevated obesity rates compared to population controls and to other depressed subjects, with corresponding pairwise odds ratios consistently greater than 2.0 (P < .001). In contrast, obesity rates were not significantly different in subjects with classic depression and nondepressed controls. These results were manifest in individuals with either current or past depression and were independent of gender and age., Conclusions: While many individuals with classic depression will present with obesity due to the high prevalence of both disorders, only atypical depression is associated with an elevated risk of obesity relative to the population at large. Refining the target phenotype(s) for future work on depression and obesity might improve our understanding, prevention, and treatment of this complex clinical problem., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Background: In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is renewed interest in refined approaches to brain stimulation, particularly for treatment resistant major depressive disorder (MDD)., Methods: The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support. This section on "Neurostimulation Therapies" is one of 5 guidelines articles., Results: Among the four forms of neurostimulation reviewed in this section, electroconvulsive therapy (ECT) has the most extensive evidence, spanning seven decades. Repetitive transcranial magnetic (rTMS) and vagus nerve stimulation (VNS) have been approved to treat depressed adults in both Canada and the United States with a much smaller evidence base. There is also emerging evidence that deep brain stimulation (DBS) is effective for otherwise treatment resistant depression, but this is an investigational approach in 2009., Limitations: Compared to other modalities for the treatment of MDD, the data based is limited by the relatively small numbers of randomized controlled trials (RCTs) and small sample sizes., Conclusions: There is most evidence to support ECT as a first-line treatment under specific circumstances and rTMS as a second-line treatment. Evidence to support VNS is less robust and DBS remains an investigational treatment.

Background: In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field., Methods: The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included Levels of Evidence and expert clinical support. This section on "Pharmacotherapy" is one of 5 guideline articles., Results: Despite emerging data on efficacy and tolerability differences amongst newer antidepressants, variability in patient response precludes identification of specific first choice medications for all patients. All second-generation antidepressants have Level 1 evidence to support efficacy and tolerability and most are considered first-line treatments for MDD. First-generation tricyclic and monoamine oxidase inhibitor antidepressants are not the focus of these guidelines but generally are considered second- or third-line treatments. For inadequate or incomplete response, there is Level 1 evidence for switching strategies and for add-on strategies including lithium and atypical antipsychotics., Limitations: Most of the evidence is based on trials for registration and may not reflect real-world effectiveness., Conclusions: Second-generation antidepressants are safe, effective and well tolerated treatments for MDD in adults. Evidence-based switching and add-on strategies can be used to optimize response in MDD that is inadequately responsive to monotherapy.

Background: Major depressive disorder (MDD) is one of the most burdensome illnesses in Canada. The purpose of this introductory section of the 2009 revised CANMAT guidelines is to provide definitions of the depressive disorders (with an emphasis on MDD), summarize Canadian data concerning their epidemiology and describe overarching principles of managing these conditions. This section on "Classification, Burden and Principles of Management" is one of 5 guideline articles in the 2009 CANMAT guidelines., Methods: The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to the Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support., Results: Epidemiologic data indicate that MDD afflicts 11% of Canadians at some time in their lives, and approximately 4% during any given year. MDD has a detrimental impact on overall health, role functioning and quality of life. Detection of MDD, accurate diagnosis and provision of evidence-based treatment are challenging tasks for both clinicians and for the health systems in which they work., Limitations: Epidemiologic and clinical data cannot be seamlessly linked due to heterogeneity of syndromes within the population., Conclusions: In the eight years since the last CANMAT Guidelines for Treatment of Depressive Disorders were published, progress has been made in understanding the epidemiology and treatment of these disorders. Evidence supporting specific therapeutic interventions is summarized and evaluated in subsequent sections.

Background: In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is widespread interest in complementary and alternative medicine (CAM) therapies in the treatment of major depressive disorder (MDD)., Methods: The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support. This section on "Complementary and Alternative Medicine Treatments" is one of 5 guideline articles., Results: There is Level 1 evidence to support light therapy in seasonal MDD and St. John's wort in mild to moderate MDD. There is also some evidence for the use of exercise, yoga and sleep deprivation, as well as for omega-3 fatty acids and SAM-e . Support for other natural health products and therapies is still limited., Limitations: The evidence base remains limited and studies often have methodological problems, including small samples, variability in dose, short duration of treatment, unknown quality of the agent and limited long-term data. Safety data are also sparse with little information about drug interactions., Conclusions: Some CAM treatments have evidence of benefit in MDD. However, problems with standardization and safety concerns may limit their applicability in clinical practice.

Background: In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. This article, one of five in the series, reviews new studies of psychotherapy in the acute and maintenance phase of MDD, including computer-based and telephone-delivered psychotherapy., Methods: The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. Evidence-based responses are based on updated systematic reviews of the literature and recommendations are graded according to the Level of Evidence, using pre-defined criteria. Lines of Treatment are identified based on criteria that included evidence and expert clinical support., Results: Cognitive-Behavioural Therapy (CBT) and Interpersonal Therapy (IPT) continue to have the most evidence for efficacy, both in acute and maintenance phases of MDD, and have been studied in combination with antidepressants. CBT is well studied in conjunction with computer-delivered methods and bibliotherapy. Behavioural Activation and Cognitive-Behavioural Analysis System of Psychotherapy have significant evidence, but need replication. Newer psychotherapies including Acceptance and Commitment Therapy, Motivational Interviewing, and Mindfulness-Based Cognitive Therapy do not yet have significant evidence as acute treatments; nor does psychodynamic therapy., Limitations: Although many forms of psychotherapy have been studied, relatively few types have been evaluated for MDD in randomized controlled trials. Evidence about the combination of different types of psychotherapy and antidepressant medication is also limited despite widespread use of these therapies concomitantly., Conclusions: CBT and IPT are the only first-line treatment recommendations for acute MDD and remain highly recommended for maintenance. Both computer-based and telephone-delivered psychotherapy--primarily studied with CBT and IPT--are useful second-line recommendations. Where feasible, combined antidepressant and CBT or IPT are recommended as first-line treatments for acute MDD.

Background: Acute depression has been associated with increased hypothalamic-pituitary-adrenal (HPA) reactivity. While chronicity of depressive illness influences symptoms, course and outcome, its effect on the HPA axis has not been extensively evaluated. The current study evaluated cortisol stress responses to a social challenge in chronic major depressive disorder (CMDD)., Methods: Cortisol stress responses to the Trier Social Stress Test (TSST) were compared in 26 participants with CMDD and 28 healthy controls using repeated measures analysis of variance (RANOVA). In addition, group differences in area under the curve (AUC) and peak percentage change in cortisol were examined., Results: The RANOVA indicated a significant sex by condition interaction in cortisol responses to the social challenge. Post-hoc testing of pair-wise group differences revealed that in females, CMDD subjects had greater cortisol levels in response to the TSST than did controls. Similarly, AUC was greater in females with CMDD than in female controls. Neither of these differences was significant in males. However, male CMDD subjects exhibited a significantly decreased peak percentage change in cortisol in response to the TSST than did male controls., Conclusions: Males and females with CMDD exhibited unique differences in cortisol responses to the social challenge relative to controls. In females, CMDD subjects had greater overall secretion of cortisol whereas in males, CMDD subjects had a blunted peak response to the social stressor. Sex differences are an important consideration in future work in this population.

Objective: To evaluate the efficacy, safety, and tolerability of adjunctive osmotic-release oral system (OROS) methylphenidate in outpatients with major depressive disorder (MDD) receiving a stable oral antidepressant regimen., Method: This multicenter, double-blind, randomized, placebo-controlled, parallel-group, 5-week trial enrolled 145 subjects who met DSM-IV-TR criteria for MDD and who had failed 1 to 3 previous antidepressant monotherapies (including current antidepressant) of adequate dose and duration. Augmentation therapy was initiated with 18 mg of OROS methylphenidate and increased to a maximum dose of 54 mg of OROS methylphenidate until an optimal dose was achieved. Efficacy scales included the Montgomery-Asberg Depression Rating Scale (MADRS), 7 atypical items from the 31-item Hamilton Rating Scale for Depression, the Clinical Global Impressions-Severity of Illness (CGI-S) scale, the CGI-Improvement scale (CGI-I), the Sex Effects scale, the Multidimensional Assessment of Fatigue (MAF) scale, and the Apathy Evaluation Scale (AES). Subjects were recruited at 17 community and academic centers across Canada. The study was conducted from June 8, 2005, to April 18, 2006., Results: There was no statistically significant difference between the groups at endpoint on the MADRS. OROS methylphenidate was superior to placebo in improving apathy and fatigue as measured by the AES and the MAF. Statistically significant differences using mixed-model analysis were observed on the AES at all visits and at endpoint (p = .01) and on the MAF (p < .01). No differences were observed on other secondary measures, including the CGI-I and CGI-S. There were no clinically significant findings on electrocardiogram., Conclusions: OROS methylphenidate did not demonstrate statistical significance on the MADRS at endpoint. Apathy and fatigue were significantly improved with OROS methylphenidate treatment, which was well tolerated with minimal side effects., Clinical Trials Registration: ClinicalTrials.gov identifier NCT00246233.

Recurrent brief depression is a well-recognized subtype of depressive illness with brief episodes of depression alternating with periods of euthymia. The symptoms are often severe, with frequent association to suicidal ideation. Literature suggests frequent nonresponse to first-line antidepressants. Lamotrigine is an anticonvulsant with antidepressant properties, and reported effectiveness in bipolar depression. We report on two patients with recurrent brief depression, nonresponsive to selective serotonin reuptake inhibitors and venlafaxine, and who responded to therapeutic doses of lamotrigine.

The current study addresses the relationship of personality and atypical depression using the Five-Factor Model (FFM), a dimensional approach to personality. The aim of the study was to help clarify which personality traits are more characteristic of atypical depression than of other depressive subtypes. Outpatients (n=160) with non-psychotic major depression were characterized as having atypical (n=26), or non-atypical depression (n=134) based on DSM-IV criteria. To limit the effect of state depression, personality was assessed after subjects received a minimum of 14 weeks of antidepressant treatment. The Revised NEO Personality Inventory, which generates data based on the FFM, was the primary assessment measure. Post-treatment, relative to the non-atypical comparison group, the atypical group had significantly higher scores on the dimension of Neuroticism, the facets of Impulsivity and Anger-Hostility, and a significantly lower score on the facet of Deliberation. In sum, the FFM provides a new understanding of which unique personality characteristics may be associated with atypical depression.