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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.

Objectives: Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6 , and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1 ), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample., Methods: A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0-8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n  = 91), while responders continued ESC (i.e., ESC-Only, n  = 80) from weeks 8-16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0-8 and 8-16, using repeated measures mixed-effects models., Results: In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8-16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F (2,54) = 8.00, p  < 0.001, q  = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF ( r  = -0.42, p  = 0.004, q  = 0.034) and SS ( r  = -0.43, p  = 0.003, q  = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction ( r  = -0.39, p  = 0.009, q  = 0.052)., Conclusions: CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

Background: Repetitive transcranial magnetic stimulation (rTMS) is recommended in Canadian guidelines as a first-line treatment for major depressive disorder. With the shift towards competency-based medical education, it remains unclear how to determine when a resident is considered competent in applying knowledge of rTMS to patient care. Given inconsistencies between postgraduate training programmes with regards to training requirements, defining competencies will improve the standard of care in rTMS delivery., Objective: The goal of this study was to develop competencies for rTMS that can be implemented into a competency-based training curriculum in postgraduate training programmes., Methods: A working group drafted competencies for postgraduate psychiatry trainees. Fourteen rTMS experts from across Canada were invited to participate in the modified Delphi process., Results: Ten experts participated in all three rounds of the modified Delphi process. A total of 20 items reached a consensus. There was improvement in the Cronbach's alpha over the rounds of modified Delphi process (Cronbach's alpha increased from 0.554 to 0.824) suggesting improvement in internal consistency. The intraclass correlation coefficient (ICC) increased from 0.543 to 0.805 suggesting improved interrater agreement., Conclusions: This modified Delphi process resulted in expert consensus on competencies to be acquired during postgraduate medical education programmes where a learner is training to become competent as a consultant and/or practitioner in rTMS treatment. This is a field that still requires development, and it is expected that as more evidence emerges the competencies will be further refined. These results will help the development of other curricula in interventional psychiatry., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Childhood maltreatment is a potent enviromarker of risk for poor response to antidepressant medication (ADM). However, childhood maltreatment is a heterogeneous construct that includes distinct exposures that have distinct neurobiological and psychological correlates. The purpose of the current study is to examine the differential associations of emotional, physical, and sexual maltreatment to ADM outcome and to examine the unique role of anhedonia in driving poor response in patients with specific maltreatment histories., Methods: In a multicentre clinical trial of major depression, 164 individuals were assessed for childhood emotional, physical, and sexual maltreatment with a contextual interview with independent, standardized ratings. All individuals received 8 weeks of escitalopram, with nonresponders subsequently also receiving augmentation with aripiprazole, with outcomes measured with depression rating scales and an anhedonia scale., Results: Greater severity of emotional maltreatment perpetrated by the mother was a significant and direct predictor of lower odds of week 16 remission (odds ratio [OR] = 1.68, P  = 0.02). In contrast, the relations of paternal-perpetrated emotional maltreatment and physical maltreatment to week 16 remission were indirect, mediated through greater severity of anhedonia at week 8., Conclusions: We identify emotional maltreatment as a specific early exposure that places patients at the greatest risk for nonremission following pharmacological treatment. Further, we suggest that anhedonia is a key symptom domain driving nonremission in patients with particular maltreatment histories.

Objective: There is limited data about the impact of mood disorders treatment guidelines on clinical outcomes. The objective of this study was to investigate the impact of prescribers' adherence to the 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) treatment guidelines recommendations on the readmission rates of patients hospitalized for mania., Method: A retrospective cohort of all individuals admitted due to acute mania to Kingston General Hospital, Kingston, ON, from January 2018 to July 2021 was included in this study. Patient variables and data regarding index admission and subsequent hospitalizations were extracted from medical records up to December 31, 2021. Treatment regimens were classified as first-line, second-line, noncompliant, or no treatment. We explored the associations between treatment regimens and the risk of readmissions using univariate, multivariate, and survival analysis., Results: We identified 211 hospitalizations related to 165 patients. The mean time-to-readmission was 211.8 days (standard deviation [SD]  =  247.1); the 30-day rehospitalization rate was 13.7%, and any rehospitalization rate was 40.3%. Compared to no treatment, only first-line treatments were associated with a statistically significant decreased risk of 30-day readmission (odds ratio [OR] = 0.209; 95% CI, 0.058 to 0.670). The risk of any readmission was reduced by first-line (OR = 0.387; 95% CI, 0.173 to 0.848) and noncompliant regimens (OR = 0.414; 95% CI, 0.174 to 0.982) compared to no treatment. On survival analysis, no treatment group was associated with shorter time-to-readmission (log-rank test, p   =  0.014) and increased risk of readmission (hazard ratio = 2.27; 95% CI, 1.30 to 3.96) when compared to first-line medications., Conclusions: Treatment with first-line medications was associated with lower 30-day rehospitalization rates and longer time-to-readmission. Physicians' adherence to treatments with higher-ranked evidence for efficacy, safety, and tolerability may improve bipolar disorder outcomes.

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.

Background: Research has established the independent relationships between depressive symptoms to cognition and functioning in depression; however, little is known about the role of mediators in this relationship. We explored the role of neurocognitive abilities, depressive symptom severity, dysfunctional attitudes, and functional capacity in predicting two dimensions of daily functioning in individuals with major depressive disorder (MDD)., Methods: One hundred and twenty-four participants (mean age  =  46.26, SD  =  12.27; 56% female) with a diagnosis of MDD were assessed on a standard neurocognitive battery, self-reported depressive symptoms, dysfunctional attitudes, and clinician-rated functional impairment. They completed a performance-based assessment of functional competence., Results: Confirmatory path analyses were used to model the independent and mediated effects of variables on two domains of functioning: social (relationships and social engagement) and productive (household and community activities). Cognition and depressive symptoms both predicted productive functioning, and dysfunctional attitudes mediated each of these relationships. Functional competence was a significant mediator in the relationship between neurocognition and productive functioning. Depressive symptoms and cognition were direct predictors of social functioning with no significant mediators., Conclusions: There are divergent pathways to different dimensions of daily functioning in MDD. Measurement implications include the consideration of multiple levels of predicting productive activities and more direct relationships with social outcomes. Treatments that directly target depressive symptoms and cognition might not generalize to improvements in everyday functioning if additional pathways to functioning are not addressed.

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.

Objectives: The COVID-19 pandemic has contributed to a shift from in-person to remote mental health care. While remote care methods have long existed, their widespread use is unprecedented. There is little research about mental health care user and provider experiences with this transition, and no published studies to date have compared satisfaction between these groups., Methods: Canadian mental health care users ( n  = 332) and providers ( n  = 107) completed an online self-report survey from October 2020 to February 2021 hosted by the Canadian Biomarker Integration Network in Depression. Using a mixed-methods approach, participants were asked about their use of remote care, including satisfaction, barriers to use, helpful and unhelpful factors, and suggestions for improvement., Results: Overall, 59% to 63% of health care users and 59% of health care providers were satisfied with remote care. Users reported the greatest satisfaction with the convenience of remote care, while providers were most satisfied with the speed of provision of care; all groups were least satisfied with therapeutic rapport. Health care providers were less satisfied with the user-friendliness of remote care ( P  < 0.001) than users, while health care users were less satisfied than providers with continuity of care ( P  < 0.001). The use of a video-based platform was associated with remote care satisfaction among health care users ( P  < 0.02), and qualitative responses support the importance of visual cues in maintaining therapeutic rapport remotely. The majority of users (55%) and providers (87%) reported a likelihood of using remote care after the pandemic., Conclusions: Remote mental health care is generally accepted by both users and providers, and the majority would consider using remote care following the pandemic. Suggestions for improvement include greater use of video, increased attention to body language and eye contact, consistency with in-person care, as well as increased provider training and administrative support.

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.

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.

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. "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) 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.)

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. 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: 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.)

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.

Objectives: This study investigated the effect of ziprasidone augmentation therapy on sleep architecture in bipolar depression., Methods: We conducted a double-blind, randomized, placebo-controlled clinical pilot trial of ziprasidone versus placebo in Diagnostic and Statistical Manual of Mental Disorders, fourth edition bipolar disorder with current major depressive episode. The effects during acute (2-5 days) and continuation treatment (28-31 days) were measured. Main outcomes were sleep architecture variables including rapid eye movement sleep (REM) and slow wave sleep (SWS) measured by polysomnography. Secondary outcomes included subjective sleep quality measures and illness severity measures including the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAMA) and Clinical Global Illness Severity (CGI-S) scores., Results: The completer analysis comprised of 14 patients (ziprasidone, N = 8 and placebo, N = 6). Latency to REM, duration of SWS, duration of stage 2 sleep, total sleep time, onset to sleep latency, number of awakenings and overall sleep efficiency significantly improved in ziprasidone-treated participants over placebo. CGI-S and HAMA scores also significantly improved. No significant difference between treatment groups was seen on the HAMD-17, MADRS or in self-reported sleep quality. Increase in SWS duration significantly correlated with improvement in CGI-S, however, this finding did not withstand Bonferroni correction., Conclusion: Adjunctive ziprasidone treatment alters sleep architecture in patients with bipolar depression, which may partially explain its mechanism of action and merits further investigation.

Objective: To report the results of the policies and procedures subsection of a nationwide electroconvulsive therapy (ECT) survey: Canadian Electroconvulsive Therapy Survey/Enquête canadienne sur les electrochocs., Method: We contacted 1273 registered health care institutions in Canada and invited the 175 centres identified as providing ECT to complete a comprehensive postal questionnaire. Nonresponding sites were repeatedly reminded and then eventually contacted by telephone., Results: Sixty-one per cent (107/175) of the institutions returned survey questionnaires. Most (84%) of the responding sites have a written general policy for the delivery of ECT. Only 27% of respondents indicated having some written policy for managing concurrent medications during ECT, and practice was quite variable regarding individual psychotropics. Informed consent was usually obtained by the attending physician (88%), and most sites indicated conveying information before ECT by using interdisciplinary and multimodal means. Almost all of the sites (93%) discharged outpatients with accompaniment home by a responsible adult., Conclusions: It is reassuring to note that general ECT policies and procedures do exist in most Canadian ECT centres. Wider variations in practice were observed in several areas, such as the elements of consent provided to patients and families, the use of concurrent medications, and the degree of supervision on discharge home after outpatient ECT. However, adherence to these policies was not captured by the results of the survey. Based on experiences in other countries, establishing a Canadian ECT accreditation service could further improve standards of practice.

Objective: To investigate the frequency of gambling in people who have been diagnosed with major depressive disorder (MDD) or bipolar disorder (BD). Secondary objectives were to examine: sex differences in the rates of gambling behaviour, the temporal relation between onset of mood disorders and problem gambling, psychiatric comorbidities associated with problem gambling, and the influences of problem gambling on quality of life., Method: People (aged 18 years and older) who met criteria for lifetime Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined MDD or BD I or II, and were confirmed by the Mini International Neuropsychiatric Interview, were enrolled. Participants were recruited from 5 sites in Canada and 1 in the United States. Prevalence of past-year problem gambling was assessed with the Canadian Problem Gambling Index. Associated comorbidities with problem gambling are presented., Results: A total of 579 participants were enrolled (female: n = 379, male: n = 200). Prevalence of problem gambling did not differ significantly between the MDD (12.5%) and the BD (12.3%) groups. There was a significant difference in the prevalence of problem gambling between males (19.5%) and females (7.8%) in the BD group (chi-square = 8.695, df = 1, P = 0.003). Among people meeting criteria for problem gambling, the mood disorder was the primary onset condition in 71% of cases. People with a mood disorder with comorbid current panic disorder (OR = 1.96; 95% CI 1.02 to 3.75), obsessive-compulsive disorder (OR = 1.86; 95% CI 1.01 to 3.45), specific phobia (OR = 2.36; 95% CI 1.17 to 4.76), alcohol dependence (OR = 5.73; 95% CI 3.08 to 10.65), or lifetime substance dependence (OR = 2.05; 95% CI 1.17 to 3.58), had significantly increased odds of problem gambling. Problem gambling across MDD and BD populations was also associated with lower quality of life ratings., Conclusion: These results reaffirm a higher prevalence of gambling both in BD and in MDD populations, compared with previously published community samples. Our study also identifies risk factors for gambling behaviours within these populations.

Objectives: Bipolar disorder (BD) is a disabling and often chronic condition. Patients with BD suffer from depression at least one-third of the time, but they do not always respond well to conventional mood stabilizers. Attempts to treat them with antidepressants can provoke a switch to mania or increased cycling. Our open-label trial aimed to assess the long-term response of patients with bipolar depression to the addition of quetiapine to their usual treatment. Our study also sought to assess the safety and tolerability of quetiapine in patients with BD., Method: To meet inclusion criteria for the study, patients had a DSM-IV diagnosis of type I or II BD, were aged 18 years and older, currently suffered from depression with a score of > 18 on the Hamilton Depression Rating Scale (HDRS), and had no change in antidepressant use for at least 3 weeks prior to the study. We added quetiapine to patients' medication and attempted to increase the dosage to at least 400 mg daily. Outcome was measured at baseline and once monthly for 12 months on the HDRS, the Young Mania Rating Scale, the Clinical Global Impression Scale (CGI), and the Abnormal Involuntary Movement Scale., Results: There were 19 patients enrolled in the study (6 men and 13 women), 2 of whom dropped out because they could not tolerate the drug. Seventeen completed at least 2 assessments, and 7 patients completed the full 12-month trial. Data for the 17 patients (that is, last observation carried forward) at 12 months shows HDRS scores reduced from 27.2 to 12.1 and CGI scores reduced from 4.7 to 2.6., Conclusions: Quetiapine seems to be helpful to and relatively well tolerated by patients with bipolar depression when it is added to their usual treatment. There is, however, a need for controlled trials.

Objective: To review the literature for reported cases of mania related to discontinuing antidepressant treatment, as well as for possible explanations of this phenomenon, and to present a case report., Method: We undertook a literature review through the PubMed index, using the key words mania, antidepressant withdrawal, and antidepressants in bipolar disorder. We reviewed 11 articles featuring 23 cases. Where available, we noted and tabulated certain parameters for both bipolar disorder (BD) and unipolar depression. We use a case example to illustrate the phenomenon of mania induced by antidepressant withdrawal., Results: For patients with unipolar depression, we found 17 reported cases of mania induced by antidepressant withdrawal. Antidepressants implicated included tricyclic antidepressants (TCAs) (12/17), monoamine oxidase inhibitors (MAOIs) (2/17), trazodone (1/17), mirtazapine (1/17), and paroxetine (1/17). For patients with BD, we found 19 reported cases of mania induced by antidepressant withdrawal, including our own case example. Of these, selective serotonin reuptake inhibitors (SSRIs) (10/19), TCAs (4/19), MAOIs (2/19), and serotonin norepinephrine reuptake inhibitors (SNRIs) (2/19) were implicated., Conclusion: Our case report supports the observation of antidepressant withdrawal-induced mania in patients with BD. It is distinguishable from antidepressant-induced mania, physiological drug withdrawal, and mania as a natural course of the illness. Many theories have been put forward to explain this occurrence. Noradrenergic hyperactivity and "withdrawal-induced cholinergic overdrive and the cholinergic-monoaminergic system" are the 2 most investigated and supported models. The former is limited by poor clinical correlation and the latter by its applicability only to anticholinergic drugs.