Search

Studies of clinical populations that combine MRI data generated at multiple sites are increasingly common. The Canadian Biomarker Integration Network in Depression (CAN-BIND; www.canbind.ca) is a national depression research program that includes multimodal neuroimaging collected at several sites across Canada. The purpose of the current paper is to provide detailed information on the imaging protocols used in a number of CAN-BIND studies. The CAN-BIND program implemented a series of platform-specific MRI protocols, including a suite of prescribed structural and functional MRI sequences supported by real-time monitoring for adherence and quality control. The imaging data are retained in an established informatics and databasing platform. Approximately 1300 participants are being recruited, including almost 1000 with depression. These include participants treated with antidepressant medications, transcranial magnetic stimulation, cognitive behavioural therapy and cognitive remediation therapy. Our ability to analyze the large number of imaging variables available may be limited by the sample size of the substudies. The CAN-BIND program includes a multimodal imaging database supported by extensive clinical, demographic, neuropsychological and biological data from people with major depression. It is a resource for Canadian investigators who are interested in understanding whether aspects of neuroimaging--alone or in combination with other variables--can predict the outcomes of various treatment modalities., Introduction Treatment of major depressive disorder (MDD) is evidence-based, but treatment selection is not personalized to the features of an individual's illness. (1) The discovery of biomarkers --or predictors--of treatment [...]

Background: In an effort to optimize patient outcomes, considerable attention is being devoted to identifying patient characteristics associated with major depressive disorder (MDD) and its responsiveness to treatment. In the current study, we extend this work by evaluating whether early change in these sensitivities is associated with response to antidepressant treatment for MDD. Methods: Participants included 210 patients with MDD who were treated with 8 weeks of escitalopram and 112 healthy comparison participants. Of the original 210 patients, 90 non-responders received adjunctive aripiprazole for an additional 8 weeks. Symptoms of depression and anhedonia were assessed at the beginning of treatment and 8 weeks later in both samples. Reward and punishment sensitivity were assessed using the BIS/BAS scales measured at the initiation of treatment and 2 weeks later. Results: Individuals with MDD exhibited higher punishment sensitivity and lower reward sensitivity compared with healthy comparison participants. Change in reward sensitivity during the first 2 weeks of treatment was associated with improved depressive symptoms and anhedonia following 8 weeks of treatment with escitalopram. Similarly, improvement in reward responsiveness during the first 2 weeks of adjunctive therapy with aripiprazole was associated with fewer symptoms of depression at post-treatment. Conclusions: Findings highlight the predictive utility of early change in reward sensitivity during antidepressant treatment for major depression. In a clinical setting, a lack of change in early reward processing may signal a need to modify a patient's treatment plan with alternative or augmented treatment approaches. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Patients suffering from depression experience significant mood, anxiety, and cognitive symptoms. Currently, most antidepressants work by altering neurotransmitter activity in the brain to improve these symptoms. However, in the last decade, research has revealed an extensive bidirectional communication network between the gastrointestinal tract and the central nervous system, referred to as the "gut-brain axis." Advances in this field have linked psychiatric disorders to changes in the microbiome, making it a potential target for novel antidepressant treatments. The aim of this review is to analyze the current body of research assessing the effects of probiotics, on symptoms of depression in humans. Methods: A systematic search of five databases was performed and study selection was completed using the preferred reporting items for systematic reviews and meta-analyses process. Results: Ten studies met criteria and were analyzed for effects on mood, anxiety, and cognition. Five studies assessed mood symptoms, seven studies assessed anxiety symptoms, and three studies assessed cognition. The majority of the studies found positive results on all measures of depressive symptoms; however, the strain of probiotic, the dosing, and duration of treatment varied widely and no studies assessed sleep. Conclusion: The evidence for probiotics alleviating depressive symptoms is compelling but additional double-blind randomized control trials in clinical populations are warranted to further assess efficacy. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

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

Treatment-resistant depression (TRD) refers to a condition where individuals with major depressive disorder have inadequate or no response to treatment. Although functional disability is a prominent and costly feature of treatment resistance, very little is known about the factors that contribute to and maintain functional impairment in TRD. This is the first study to report the neurocognitive profile of TRD and the relationships among neurocognition, symptoms, and functioning in this syndrome. Results indicated that patients with TRD (N = 33) exhibit mildly reduced performance across all neurocognitive domains with a superimposed moderate impairment in verbal working memory. Neurocognition was associated with functional competence (what one can do), whereas depressive symptoms were associated with functional performance (what one actually does). Understanding the psychological mechanisms related to functioning may help us move toward recovery in this chronically ill group. [ABSTRACT FROM PUBLISHER]

The management of depression remains a constant challenge in clinical practice. This is largely due to the fact that initial treatments frequently do not lead to remission and recovery. The current treatment approach involves lengthy trial-and-error periods. It would be beneficial to have early reliable predictors to determine whether patients will respond to treatment or not. Electroencephalography (EEG) derived biomarkers namely change in the activity of EEG frequency bands, hemispheric alpha asymmetry, theta cordance, the antidepressant treatment response index (ATR) and evoked potentials have all been shown to predict response to a variety of antidepressant medications. However, the neurobiology in support of this association has been largely unexplored. In this review, we discuss biological mechanisms for each EEG derived biomarker predictive of treatment response. Validating such biomarkers will not only greatly aid clinicians in selecting antidepressant treatment for individual patients but will also provide a critical step in drug discovery. [ABSTRACT FROM AUTHOR]

The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events. Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients’ lives. This update provides an expanded look at bipolar II disorder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, MacQueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI. The evolution of CANMAT Bipolar Disorder Guidelines: past, present, and future. Bipolar Disord 2013: 15: 58-60. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd. [ABSTRACT FROM AUTHOR]

A response is presented in regards to two letters to the editor concerning the establishment of ratings concerning short-term psychodynamic psychotherapy for treatment of major depressive disorders in the Canadian Network for Mood and Anxiety Treatment guidelines.

The author analyzes a study on the role of agitation as predictor of response of major depressive disorder (MDD) to botulinum toxin treatment. Topics discussed include an overview of MDD, other treatments available for MDD, including psychotherapy, pharmacotherapy and neurostimulation, and the use of the Montgomery-Asberg Depression Rating Scale as the primary outcome measure for the study.

A letter to the editor is presented concerning the Canadian Network for Mood and Anxiety Treatments/International Society for Bipolar Disorders (CANMAT/ISBD) Collaborative 2013 Update of Guidelines for the Management of Patients with Bipolar Disorder.

Background: This study aims to compare the effectiveness of EEG frequency band activity including interhemispheric asymmetry and prefrontal theta cordance in predicting response to escitalopram therapy at 8-weeks post-treatment, in a multi-site initiative.Methods: Resting state 64-channel EEG data were recorded from 44 patients with a diagnosis of major depressive disorder (MDD) as part of a larger, multisite discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). Clinical response was measured at 8-weeks post-treatment as change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 50% or more. EEG measures were analyzed at (1) pre-treatment baseline (2) 2 weeks post-treatment and (3) as an ''early change" variable defined as change in EEG from baseline to 2 weeks post-treatment.Results: At baseline, treatment responders showed elevated absolute alpha power in the left hemisphere while non-responders showed the opposite. Responders further exhibited a cortical asymmetry in the parietal region. Groups also differed in pre-treatment relative delta power with responders showing greater power in the right hemisphere over the left while non-responders showed the opposite. At 2 weeks post-treatment, responders exhibited greater absolute beta power in the left hemisphere relative to the right and the opposite was noted for non-responders. A reverse pattern was noted for absolute and relative delta power at 2 weeks post-treatment. Responders exhibited early reductions in relative alpha power and early increments in relative theta power. Non-responders showed a significant early increase in prefrontal theta cordance.Conclusions: Hemispheric asymmetries in the alpha and delta bands at baseline and at 2 weeks post-treatment have moderately strong predictive utility in predicting response to antidepressant treatment. [ABSTRACT FROM AUTHOR]

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

Background: Psychostimulants have been used in the treatment of depression, with mixed results. This meta-analysis examines the efficacy and tolerability of the stimulant Lisdexamfetamine (LDX) as an add-on strategy in those with MDD who have failed to respond to an antidepressant.Method: Randomized control trials were identified and extracted from Pubmed; Web of Science; PsychINFO; and Cochrane Library. The efficacy of LDX was evaluated using Hedges' g and Odds Ratio, whereas Risk Difference was used to assess the safety and tolerability of LDX.Results: Four studies met inclusion criteria. LDX did not demonstrate superiority in efficacy relative to placebo as indicated by a Hedges' g score of 0.126 (95% CI -0.040-0.291; p = 0.136) for mean change in Montgomery-Asberg Depression Rating Scale. Odds ratios of 1.206 (95% CI 0.745-1.954; p = 0.446) and 1.244 (95% CI 0.959-1.614; p = 0.1) were found for remission and response rates respectively. Risk differences of -0.1 (95% CI -0.155-(-0.045); p < 0.001) indicated a 10% increase chance of developing treatment-emergent adverse events (TEAE) in the LDX group. There was no significant difference in risk for developing serious or severe TEAE and discontinuing treatment due to TEAE.Limitations: The number of included studies was small and only one metric was available for analysis of antidepressant efficacy of LDX.Conclusions: LDX when used as antidepressant augmentation produced a small effect in improving depressive symptoms that approached trend-level significance and demonstrated comparable tolerability to placebo. Further studies are needed to determine the optimal clinical subset of depressive symptoms responsive to LDX augmentation. [ABSTRACT FROM AUTHOR]

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