Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

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.

The Differential Relation of Emotional, Physical, and Sexual Abuse Histories to Antidepressant Treatment Remission and Persistence of Anhedonia in Major Depression: A CAN-BIND-1 Report.

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.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations.

OBJECTIVES: The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address. METHOD: Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion. RESULTS: No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options. CONCLUSION: The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.

Impacts on Quality of Life with Escitalopram Monotherapy and Aripiprazole Augmentation in Patients with Major Depressive Disorder: A CAN-BIND Report.

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

Cognition and Its Association with Psychosocial and Occupational Functioning during Treatment with Escitalopram in Patients with Major Depressive Disorder: A CAN-BIND-1 Report: La Cognition Et Son Association Avec Le Fonctionnement Psychosocial Et Professionnel Durant Le Traitement Par Escitalopram Chez Des Patients Souffrant De Trouble Dépressif Majeur: Une Étude Can-Bind-1.

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 (ß = -0.17; P = 0.03) and LEAPS productivity subscale (ß = -0.17; P = 0.05), but not SDS total (ß = 0.19; P = 0.12) or LEAPS total (ß = 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.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur.

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.

Childhood maltreatment and cognitive functioning in patients with major depressive disorder: a CAN-BIND-1 report.

BACKGROUND: Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission. METHODS: Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM-, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM-, n = 80). Separate analyses in MDD participants who remitted were conducted. RESULTS: DM+ had lower baseline global cognition, processing speed, and memory v. HM-, with no significant baseline differences amongst DM-, HM+, and HM- groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM-, scored significantly lower than HM- in working memory and processing speed. CONCLUSIONS: Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.

The Effects of Probiotics on Symptoms of Depression: Protocol for a Double-Blind Randomized Placebo-Controlled Trial.

BACKGROUND: A growing body of evidence has linked mental health outcomes to the gut microbiome. This has led to the investigation of the GI tract as a target for novel treatments and interventions for depression, including probiotic supplementation. Our recent pilot study provided the first evidence of probiotics improving symptoms of depression in treatment-naive depressed patients. To further support and expand upon this evidence, data from the pilot study were used to plan a 16-week, double-blind, randomized, placebo-controlled trial to assess the effects of probiotics on depression. Here, we report the protocol for this trial. METHODS: Participants diagnosed with depression will orally consume a probiotic supplement containing Lactobacillus helveticus and Bifidobacterium longum or placebo once daily. Participants will undergo assessments measuring clinical outcomes using a battery of validated clinical scales and questionnaires. Sleep architecture and quality will be measured using polysomnography. Neuroimaging data will be collected using magnetic resonance imaging to examine functional and structural neurophysiological changes. Molecular data will be collected from blood, stool, and urine samples to examine cytokine levels and explore potential genes and proteins that may predict outcomes in depression. RESULTS: We expect results to replicate and expand on our pilot data demonstrating that probiotics may be effective in alleviating symptoms of depression, and to find biomarkers that will predict these outcomes. CONCLUSIONS: The findings from this study will add to the growing body of research in this emerging field, which eventually may provide evidence for probiotics having a role in alleviating symptoms of depression.

Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient.

Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly.

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.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 1. Disease Burden and Principles of Care.

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.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments.

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.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 2. Psychological Treatments.

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.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 4. Neurostimulation Treatments.

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.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments.

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.

Functional neuroimaging biomarkers of anhedonia response to escitalopram plus adjunct aripiprazole treatment for major depressive disorder.

BACKGROUND: Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine. AIMS: To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram. METHOD: Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole. RESULTS: Anhedonia severity significantly improved after treatment with adjunct aripiprazole.There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus. CONCLUSIONS: Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.

Relation of hippocampal volume and SGK1 gene expression to treatment remission in major depression is moderated by childhood maltreatment: A CAN-BIND-1 report.

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

Data and alternative models describing the associations among non-infection pandemic stress, event-related rumination, depression, and anxiety.

Here we present cross-sectional data collected from 1507 participants through the Qualtrics online survey platform. Participants were recruited from Reddit, Facebook, and the Queen's University undergraduate participant pool, and were instructed to complete a pandemic stress survey, the Beck Depression Inventory-II (BDI-II) [1], the Beck Anxiety Inventory (BAI) [2], a modified version of Event-Related Rumination Inventory (ERRI) [3], and a demographics questionnaire. For the 1069 participants who were not exposed to COVID-19 infection, we calculated the sum of each scale/subscale and performed a multiple mediation analysis using MPlus. The results indicated that three models (one primary model and two alternative models) had comparable statistical power to explain the variance as we tested different configurations of predictor, mediator, and outcome variables. Given the cross-sectional nature of the present study, we could not conclude which model was most valid. Therefore, we share our original data and tested models here for others to use. They are useful for researchers who wish to replicate our results, conduct new analyses with these data, or design future studies.

The course of insomnia symptoms during the acute treatment of major depressive disorder: A CAN-BIND-1 report.

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.