When "virtual" works and when it doesn't: A survey of physician and patient experiences with virtual care during the COVID-19 pandemic.

Objective: To assess the experience of virtual care among both patients and physicians across a range of clinical scenarios during the COVID-19 pandemic. Methods: A web-based survey was disseminated to patients and physicians through a variety of media and healthcare communications from May 2020 to July 2021. Demographic details and attitudes across a range of virtual care domains were collected. Quantitative responses were analyzed descriptively. Open-text responses were gathered to contrast when a virtual visit was superior or inferior to an in-person one, and a thematic content analysis was used. Results: There were 197 patients and 93 physician respondents, representing a range of demographic and practice characteristics. Patients noted several benefits of virtual care and felt it should continue to be available. Physicians felt they could do a lot of their care virtually. Common themes related to the superiority of virtual care were for "quick" visits, reviewing test results, chronic disease monitoring, and medication needs. Virtual care was less ideal when a physical exam was needed, and was not perceived as a good fit for an individual's cultural, language, or emotional needs. Certain conditions were identified as both ideal and non-ideal for the virtual format (e.g. mental healthcare). Discussion: Certain situations are more amenable to virtual care with personal preferences among both patients and physicians. Future priorities should ensure that virtual care is effective across the range of clinical situations in which it may be used and that both virtual and in-person options are equally available to those who want them.

Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Prognostic factors in major depressive disorder: comparing responders and non-responders to Repetitive Transcranial Magnetic Stimulation (rTMS), a naturalistic retrospective chart review.

AIM: Repetitive transcranial magnetic stimulation (rTMS) is widely utilized as an effective treatment for major depressive disorder (MDD) with varying response rates. Factors associated with better treatment outcome remain scarce. This naturalistic retrospective chart review hopes to shed light on easily obtainable and measurable predictive factors for patients referred to rTMS. METHODS: Protocol parameters, medication, rated scales, rTMS protocols, and treatment outcomes were reviewed for 196 patients with MDD who received rTMS at Saint Boniface Hospital between 2013 and 2019. Logistic regression and marginal effects were used to assess the different predictor variables for response (50% reduction or more on the Hamilton Depression Rating Scale (Ham-D)) and remission (Ham-D of ≤7 by the last session). RESULTS: HamD at 10 sessions was predictive of remission, and Sheehan Disability Scale (SDS) at 10 sessions was predictive of response to rTMS. Ham-D, SDS, and Beck Anxiety Inventory were predictive of remission and response by Beck Anxiety Inventory 20 sessions. High frequency rTMS had a similar response and remission rate to low frequency, but higher response rate to intermittent Theta Burst Stimulation with no difference in remission rate. Positive predictive factors of response were lower age and bupropion use. Negative predictive factors were antipsychotics, anticonvulsants, or benzodiazepine use. For remission, antipsychotics or anticonvulsants use were negative predictors; bupropion use and higher resting motor threshold were positive predictors. Severity of depression as measured by baseline HamD was not associated with different probabilities of treatment success.

Neuropsychiatry's Role in the Postacute Sequelae of COVID-19: Report From the American Neuropsychiatric Association Committee on Research.

Postacute sequelae of COVID-19 can occur in patients who had only mild acute disease. A comprehensive neuropsychiatric approach reviews historical factors, provides objective assessment of symptoms, considers potential etiologies, and offers a therapeutic approach aimed at restoring premorbid functioning.

Determining affected memory domains in patients with amnestic mild cognitive impairment using computerized and interactive tests.

This study explores different episodic memory domains, namely object, temporal and spatial memory, affected in patients with a clinical diagnosis of single domain amnestic mild cognitive impairment (aMCI). 15 aMCI patients and 25 healthy controls were recruited and tested. Object, spatial, and temporal memory were tested using computerized tasks and again in interactive, real-world tasks. Controls outperformed patients on the object computerized task and showed a trend toward significance for the computerized spatial and temporal tasks, but there was no difference in spatial and temporal memory when using the interactive tasks, indicating the employment of compensatory mechanisms in patients to overcome some of the memory impairments associated with aMCI. These findings highlight that aMCI patients might delay seeking help due to compensatory mechanisms which mask their deficits in real-world situations.

Alzheimer's Disease-Related Metabolic Pattern in Diverse Forms of Neurodegenerative Diseases.

Dementia is broadly characterized by cognitive and psychological dysfunction that significantly impairs daily functioning. Dementia has many causes including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). Detection and differential diagnosis in the early stages of dementia remains challenging. Fueled by AD Neuroimaging Initiatives (ADNI) (Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.), a number of neuroimaging biomarkers for AD have been proposed, yet it remains to be seen whether these markers are also sensitive to other types of dementia. We assessed AD-related metabolic patterns in 27 patients with diverse forms of dementia (five had probable/possible AD while others had atypical cases) and 20 non-demented individuals. All participants had positron emission tomography (PET) scans on file. We used a pre-trained machine learning-based AD designation (MAD) framework to investigate the AD-related metabolic pattern among the participants under study. The MAD algorithm showed a sensitivity of 0.67 and specificity of 0.90 for distinguishing dementia patients from non-dementia participants. A total of 18/27 dementia patients and 2/20 non-dementia patients were identified as having AD-like patterns of metabolism. These results highlight that many underlying causes of dementia have similar hypometabolic pattern as AD and this similarity is an interesting avenue for future research.

Improvements in error-monitoring and symptoms following low-frequency rTMS of dorsal anterior cingulate cortex in obsessive compulsive disorder; a randomized, sham-controlled study.

Action monitoring deficit is a core underlying characteristic and endophenotype of Obsessive Compulsive Disorder (OCD). Dorsal anterior cingulate cortex (dACC) is heavily involved in error monitoring and cognitive control, and the hyperactivity in this region is associated with OCD symptom severity. This study aimed to test whether low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) targeting dACC improves both error-monitoring performance and OCD symptoms in a randomized, sham-controlled, double-blind trial design. 20 OCD patients were randomly assigned to receive 20 sessions of Active (n = 10) or Sham (n = 10) rTMS administered twice-daily. Error-monitoring performance and symptom severity were measured pre- and post-treatment using Erikson Flanker tasks and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with three month symptom follow-up. Following active-but not sham-rTMS, patients showed improved response time for incongruent stimuli, trials following a correct response, and for reporting and correcting errors. Significant OCD symptom improvement was observed at one-month follow-up for patients who received Active (28.0% reduction) but not Sham (11.7% reduction) stimulation. In OCD patients, LF rTMS of the dACC can simultaneously improve on-line adjustment of behaviour-by enhancing the capacity for rapid error monitoring-and clinical symptoms, suggesting a link between error monitoring impairment and OCD pathophysiology.

Neuroimaging in Functional Neurological Disorder: State of the Field and Research Agenda.

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using "rule-in" examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

Oxolipidomics profile in major depressive disorder: Comparing remitters and non-remitters to repetitive transcranial magnetic stimulation treatment.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation [rTMS] is increasingly being used to treat Major Depressive Disorder [MDD]. Given that not all patients respond to rTMS, it would be clinically useful to have reliable biomarkers that predict treatment response. Oxidized phosphatidylcholine [OxPC] and some oxylipins are important plasma biomarkers of oxidative stress and inflammation. Not only is depression associated with oxidative stress, but rTMS has been shown to have anti-oxidative effects. OBJECTIVES: To investigate whether plasma oxolipidomics profiles could predict treatment response in patients with treatment resistant MDD. METHODS: Fourty-eight patients undergoing rTMS treatment for MDD were recruited along with nine healthy control subjects. Plasma OxPCs and oxylipins were extracted and analyzed through high performance liquid chromatography coupled with mass spectrometry. Patients with a Hamilton Depression Rating Scale score [Ham-D] ≤7 post-treatment were defined as having entered remission. RESULTS: Fifty-seven OxPC and 32 oxylipin species were identified in our subjects. MDD patients who entered remission following rTMS had significantly higher pre-rTMS levels of total and fragmented OxPCs compared to non-remitters and controls [one-way ANOVA, p<0.05]. However, no significant changes in OxPC levels were found as a result of rTMS, regardless of treatment response [p>0.05]. No differences in plasma oxylipins were found between remitters and non-remitters at baseline. CONCLUSION: Certain categories of OxPCs may be useful predictive biomarkers for response to rTMS treatment in MDD. Given that elevated oxidized lipids may indicate higher levels of oxidative stress and inflammation in the brain, patients with this phenotype of depression may be more receptive to rTMS treatment.

Repeated Transcranial Magnetic Stimulation for Improving Cognition in Patients With Alzheimer Disease: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Alzheimer disease has no known cure. As existing pharmacologic interventions only modestly slow cognitive decline, there is a need for new treatments. Recent trials of repetitive transcranial magnetic stimulation (rTMS) have reported encouraging results for improving or stabilizing cognition in patients diagnosed with Alzheimer dementia. However, owing to small samples and lack of a well-controlled double-blind design, the results to date are inconclusive. This paper presents the protocol for a large placebo-controlled double-blind study designed with sufficient statistical rigor to measure the efficacy of rTMS treatment in patients with Alzheimer dementia. OBJECTIVE: The objectives are to (1) recruit and enroll up to 200 eligible participants, (2) estimate the difference in treatment effects between active treatment and sham treatment, (3) estimate the difference in treatment effects between two doses of rTMS applications, (4) estimate the duration of treatment effects among responders to active rTMS treatment, and (5) estimate the effect of dementia severity on treatment outcomes among patients receiving active rTMS treatment. METHODS: We have designed our study to be a double-blind, randomized, placebo-controlled clinical trial investigating the short- and long-term (up to 6 months) benefits of active rTMS treatment at two doses (10 sessions over 2 weeks and 20 sessions over 4 weeks) compared with sham rTMS treatment. The study will include patients aged ≥55 years who are diagnosed with Alzheimer disease at an early to moderate stage and have no history of seizures and no major depression. The primary outcome measure is the change in the Alzheimer Disease Assessment Scale-Cognitive Subscale score from pretreatment to posttreatment. Secondary outcomes are changes in performance on tests of frontal lobe functioning (Stroop test and verbal fluency), changes in neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), and changes in activities of daily living (Alzheimer Disease Co-operative Study-Activities of Daily Living Inventory). Tolerability of the intervention will be assessed using a modification of the Treatment Satisfaction Questionnaire for Medication. We assess participants at baseline and 3, 5, 8, 16, and 24 weeks after the intervention. RESULTS: As of November 1, 2020, we have screened 523 individuals, out of which 133 were eligible and have been enrolled. Out of the 133 individuals, 104 have completed the study. Moreover, as of November 1, 2020, there has been no serious adverse event. We anticipate that rTMS will considerably improve cognitive function, with effects lasting up to 3 months. Moreover, we expect rTMS to be a well-tolerated treatment with no serious side effect. CONCLUSIONS: This protocol design will allow to address both the rTMS active treatment dose and its short- and long-term effects compared with sham treatment in large samples. TRIAL REGISTRATION: ClinicalTrials.gov NCT02908815; https://clinicaltrials.gov/ct2/show/NCT02908815. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25144.

Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures: A Report From the American Neuropsychiatric Association Committee on Research.

The American Neuropsychiatric Association's Committee on Research assigned the task of defining the most helpful clinical factors and tests in establishing the diagnosis of psychogenic nonepileptic seizures (PNES) during a neuropsychiatric assessment. A systematic review of the literature was conducted using three search engines and specified search terms for PNES and the predetermined clinical factors and diagnostic tests, followed by a selection process with specific criteria. Data extraction results from selected articles are presented for clinical factors (semiology, psychiatric comorbidities, medical comorbidities, psychological traits) and diagnostic tests (EEG, psychometric and neuropsychological measures, prolactin level, clinical neuroimaging, autonomic testing). Semiology with video EEG (vEEG) remains the most valuable tool to determine the diagnosis of PNES. With the exception of semiology, very few studies revealed the predictive value of a clinical factor for PNES, and such findings were isolated and not replicated in most cases. Induction techniques, especially when coupled with vEEG, can lead to a captured event, which then confirms the diagnosis. In the absence of a captured event, postevent prolactin level and personality assessment can support the diagnosis but need to be carefully contextualized with other clinical factors. A comprehensive clinical assessment in patients with suspected PNES can identify several clinical factors and may include a number of tests that can support the diagnosis of PNES. This is especially relevant when the gold standard of a captured event with typical semiology on vEEG cannot be obtained.

Accelerated repetitive transcranial magnetic stimulation in the treatment of post-concussion symptoms due to mild traumatic brain injury: a pilot study.

Objective: To investigate the feasibility, tolerability, and efficacy of twice-daily, low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (DLPFC) in the reduction of chronic post-concussion symptoms (PCS) in patients who have suffered a mild traumatic brain injury (mTBI).Methods: 15 patients with mTBI received 30 sessions of twice-daily LF rTMS (1 Hz) over the right DLPFC. Post-concussion symptoms, pain, disability, fatigue, apathy, agitation, and mood were assessed by a psychiatrist pre- and post-treatment. Cognitive testing was also performed pre-, mid-, and post-rTMS.Results: All participants completed treatment with no serious adverse events. Significant improvements were observed in overall post-concussion symptoms, disability and pain ratings, as well as depression and anxiety symptoms. There was no significant change in overall executive functioning, fatigue severity, apathy, or agitation. Cognitive testing revealed improvements in verbal fluency, working memory, selective attention, and cognitive processing speed.Conclusions: This small-sample pilot study suggests that twice-daily, LF rTMS over the right DLPFC can be safely and tolerably applied and has the potential to improve post-concussion symptoms as well as elements of mood and cognition in patients with mTBI. Larger, sham-controlled studies will be important to confirm these observations.

Elevated caudate connectivity in cognitively normal Parkinson's disease patients.

Mild cognitive impairment (MCI) is common in Parkinson's disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson's patients. We recruited 18 Parkinson's disease patients-10 PDNC [normal cognition Parkinson's disease; Montreal Cognitive Assessment (MoCA) ≥ 26], 8 PDLC (low cognition Parkinson's disease; MoCA < 26) -and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer's disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson's patient groups, but not in healthy control subjects. Interestingly, PDNC's functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer's disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson's disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson's disease. Our findings support and complement the dual syndrome hypothesis.

Attitudes of Psychiatry Residents in Canadian Universities toward Neuroscience and Its Implication in Psychiatric Practice.

OBJECTIVE: Despite recent advances in neuroscience highlighting its potential applications in the assessment and treatment of psychiatric disorders, the training of psychiatrists in neuroscience is lacking. However, it is not clear to what extent Canadian trainees are interested in further learning and using neuroscience in their daily clinical practice. This study explored the attitudes of Canadian psychiatry trainees with regard to neuroscience education and training by asking them to assess their own understanding of neuroscience and the perceived relevance of neuroscience knowledge to effective psychiatric practice. METHODS: An online questionnaire was sent to psychiatry residents at Canadian universities. This questionnaire consisted of self-assessments of neuroscience knowledge, attitudes toward neuroscience education, preferences in learning modalities, and interest in specific neuroscience topics. RESULTS: One hundred and eleven psychiatry residents from psychiatry residency programs at Canadian universities responded to this survey. Participants represented trainees from all 5 years of residency. Almost half of all trainees (49.0%) reported their knowledge of neuroscience to be either "inadequate" or "less than adequate," and only 14.7% of trainees reported that they feel "comfortable" or "very comfortable" discussing neuroscience findings with their patients. 63.7% of Canadian trainees rated the quantity of neuroscience education in their residency program as either less than adequate or inadequate, and 46.1% rated the quality of their neuroscience education as "poor" or "very poor." The vast majority of participants (>70%) felt that additional neuroscience education would be moderately-to-hugely helpful in finding personalized treatments, discovering future treatments, destigmatizing patients with psychiatric illness, and understanding mental illness. CONCLUSIONS: Canadian trainees generally feel that their neuroscience knowledge and the neuroscience education they receive during their psychiatry residencies is inadequate. However, as the first step for any change, the majority of future Canadian psychiatrists are very motivated and have a positive attitude toward neuroscience learning.

Cognitive profiles in major depressive disorder: Comparing remitters and non-remitters to rTMS treatment.

Major Depressive Disorder (MDD) is typically accompanied by cognitive impairment. Repetitive Transcranial Magnetic Stimulation (rTMS) treatment for MDD involves stimulation of the dorsolateral prefrontal cortex which plays an important role in cognition. This study aimed to identify differences in cognitive profiles between remitters and non-remitters to rTMS at baseline and across treatment. 25 patients with MDD performed cognitive tasks at baseline and after 6, 12 and 30 sessions of rTMS. At baseline, there was no difference in simple reaction time (RT) between groups, but remitters (n = 13) showed faster RTs than non-remitters (n = 12) in the Switch and No-Switch conditions of Task Switching. Across sessions, remitters showed a decrease in 3-Back omission errors and RTs to 3-Back, Stroop's Congruent and Incongruent, and Task Switching's Switch and No-Switch conditions, whereas non-remitters only showed improvements in Stroop Congruent and Incongruent RTs. Baseline and final scores on the Hamilton Depression Rating Scale were positively correlated with Switch and No-Switch RTs. This study demonstrates that eventual remitters to rTMS treatment for MDD perform better in cognitive tasks requiring shifting attention, and this difference is observable prior to the start of treatment. Remitters also show improvement in both their mood and cognitive performance.

Efficacy of twice-daily vs once-daily sessions of repetitive transcranial magnetic stimulation in the treatment of major depressive disorder: a retrospective study.

PURPOSE: There is no clinical consensus on the optimal protocol for the treatment of major depressive disorder (MDD) using repetitive transcranial magnetic stimulation (rTMS). Accelerated protocols using more than a single session of treatment per day have been suggested as a means to reduce the overall length of time required for rTMS therapy. The objective of this study is to compare the treatment outcomes of patients with MDD who received two sessions of rTMS per day vs those who received one session per day, keeping the overall number of delivered pulses constant. PATIENTS AND METHODS: In a retrospective study, we compared treatment outcomes of 36 patients with MDD who received 30 sessions of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. Patients received 3,000 pulses per session (5 s trains, 25 s intertrain interval) at 110% of resting motor threshold using a figure-eight coil. Patients received either two rTMS sessions per day (n=17) or one session per day (n=19). Depression symptoms were assessed by a psychiatrist using the Hamilton Rating Scale for Depression at baseline and after every 10 sessions of rTMS. RESULTS: The majority of patients in both groups responded to treatment, and there was a trend toward greater response rate in the twice-daily (TD) group (82.4%) compared to the once-daily (OD) group (52.6%). TD stimulation was tolerable for patients and produced no adverse side effects. Patients in the TD group experienced an improvement in symptoms faster than the OD group due to the accelerated therapy period. CONCLUSION: Administration of two rTMS treatment sessions per day is tolerable for patients and does not seem to be inferior in efficacy to a OD protocol. TD administration has the benefit of producing symptom improvement over a shorter time span and requires fewer visits to the clinic.

Beyond anxiety and agitation: A clinical approach to akathisia.

BACKGROUND: When patients suddenly become restless and are unable to sit or stand still, especially in general medical settings, anxiety is often the topmost differential on every clinician's mind. However, the possibility of the very subjectively distressing condition called 'akathisia' should always be considered. OBJECTIVE: The aim of this article is to discuss a clinical approach to the management of akathisia, drawing on the presentation of a patient who was admitted to a general medical ward. DISCUSSION: Akathisia, a subjective and very distressing feeling of restlessness, has been found to be caused by a wide range of medications used in general medical settings, such as azithromycin, antiemetics and antipsychotics. Despite its high incidence and association with an increase in suicidal thoughts, it often goes unrecognised. This paper highlights the need for its early recognition, provides a diagnostic guide and an approach to its management.

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.