Publications by authors named "Lakshmi N Yatham"

233 Publications

Metacognitive knowledge and experience across multiple cognitive domains in euthymic bipolar disorder.

Eur Psychiatry 2021 Jun 4;64(1):e36. Epub 2021 Jun 4.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Metacognitive knowledge (MK; general awareness of cognitive functioning) and metacognitive experience (ME; awareness of cognitive performance on a specific cognitive task) represent two facets of metacognition that are critical for daily functioning, but are understudied in bipolar disorder. This study was conducted to evaluate MK and ME across multiple cognitive domains in individuals diagnosed with bipolar disorder and unaffected volunteers, and to investigate the association between metacognition and quality of life (QoL).

Methods: Fifty-seven euthymic participants with bipolar disorder and 55 demographically similar unaffected volunteers provided prediction and postdiction ratings of cognitive task performance across multiple cognitive domains. Self-ratings were compared to objective task performance, and indices of MK and ME accuracy were generated and compared between groups. Participants rated QoL on the Quality of Life in Bipolar Disorder Scale (QoL.BD).

Results: Metacognitive inaccuracies in both MK and ME were observed in participants with bipolar disorder, but only in select cognitive domains. Furthermore, most metacognitive inaccuracies involved underestimation of cognitive ability. Metacognitive indices were minimally associated with medication variables and mood symptoms, but several indices were related to QoL.

Conclusions: Individuals with bipolar disorder demonstrate inaccuracies in rating their cognitive functioning and in rating their online cognitive task performance, but only on select cognitive functions. The tendency to underestimate performance may reflect a negative information processing bias characteristic of mood disorders. Metacognitive variables were also predictive of QoL, indicating that further understanding of cognitive self-appraisals in persons with bipolar disorder has significant clinical relevance.
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http://dx.doi.org/10.1192/j.eurpsy.2021.31DOI Listing
June 2021

Longitudinal grey matter changes following first episode mania in bipolar I disorder: A systematic review.

J Affect Disord 2021 May 7;291:198-208. Epub 2021 May 7.

Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 2A1. Electronic address:

Background: While widespread grey matter (GM) changes are seen in bipolar I disorder (BD-I), it is unclear how early in the illness such changes emerge. To date there has been little synthesis of findings regarding longitudinal grey matter changes early in the course of BD-I. We conducted a systematic review to examine the evolution of GM changes in BD-I patients following the first episode of mania (FEM).

Methods: Following PRISMA guidelines, we conducted a systematic review of studies examining longitudinal changes in GM volume (GMV), cortical thickness and/or surface area in BD-I patients following FEM. We qualitatively synthesized results regarding longitudinal GM changes in BD-I patients.

Results: Fifteen studies met inclusion criteria, all examining GMV changes. Longitudinal ACC volume decrease following FEM was the most replicated finding, but was only reported in 4 out of 7 studies that examined this region as part of a whole brain/region of interest analysis, with 2 of these positive studies using an overlapping patient sample. The impact of episode recurrence, medications, and other clinical factors was inconsistently examined.

Limitations: The literature regarding GM changes early in BD-I is highly inconsistent, likely due to heterogeneity in participant characteristics, imaging methodology/analysis and duration of follow up.

Conclusions: Though there was some suggestion that structural ACC changes may represent a marker for neuroprogression following FEM, results were too inconsistent to draw any conclusions. Larger longitudinal studies examining cortical thickness/surface area, and the influence of relevant clinical factors, are needed to better understand neuroprogression in early BD-I.
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http://dx.doi.org/10.1016/j.jad.2021.04.051DOI Listing
May 2021

Intermittent Theta-Burst Stimulation Transcranial Magnetic Stimulation Increases GABA in the Medial Prefrontal Cortex: A Preliminary Sham-Controlled Magnetic Resonance Spectroscopy Study in Acute Bipolar Depression.

Front Psychiatry 2021 11;12:665402. Epub 2021 May 11.

Department of Psychiatry, University of Calgary, Calgary, AB, Canada.

Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric acid (GABA) alterations in mood disorders, particularly in the medial prefrontal cortex (mPFC) where decreased concentrations have been associated with anhedonia. In major depressive disorder (MDD), prior work suggests that repetitive transcranial magnetic stimulation (rTMS) increases mPFC GABA concentrations proportional to antidepressant response. To our knowledge, this has not been examined in acute bipolar depression. As part of a multicentre 4-week randomized, double-blind, sham-controlled trial using intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex (DLPFC) in individuals with acute bipolar depression, we quantified mPFC GABA and Glx (glutamate+glutamine) concentrations using a 3T MRS scan at baseline and after the intervention. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale-17 (HRDS-17), and anhedonia was measured using the Snaith-Hamilton Pleasure Scale (SHAPS). The trial was terminated for futility and magnetic resonance spectroscopy data was acquired for 18 participants. At baseline, there were no associations between GABA or Glx concentrations and anhedonia, however GABA was negative correlated with depressive symptom severity on the HRDS-17. Compared to the sham-iTBS group, participants receiving active-iTBS had a significant increase in mPFC GABA concentrations. This was unrelated to antidepressant outcomes or improvements in anhedonia. Our data suggests that iTBS targeting the DLPFC is associated with physiological changes in the mPFC. In acute bipolar depression, our preliminary data suggests that mPFC GABA is dissociated from antidepressant iTBS treatment outcomes and anhedonia.
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http://dx.doi.org/10.3389/fpsyt.2021.665402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144302PMC
May 2021

New Developments in the Use of Atypical Antipsychotics in the Treatment of Bipolar Disorder: a Systematic Review of Recent Randomized Controlled Trials.

Curr Psychiatry Rep 2021 05 8;23(7):39. Epub 2021 May 8.

Department of Psychiatry, Detwiller Pavilion, University of British Columbia, 2255 Wesbrook mall, Vancouver, BC, V6T 2A1, Canada.

Purpose Of Review: Atypical antipsychotics are increasingly used in the treatment of bipolar disorder (BD). This systematic review provides an overview of recently published randomized controlled trials (RCTs) on the efficacy and safety of atypical antipsychotics in BD.

Recent Findings: Several studies supported efficacy of quetiapine monotherapy in acute bipolar I (BDI) and bipolar II (BDII) depression. Moreover, quetiapine adjunctive therapy showed superior efficacy to placebo in treatment-resistant bipolar depression. Cariprazine 1.5 mg was effective in treating bipolar I depression. Aripiprazole 400 mg IM once monthly was effective in preventing manic episodes with minimal metabolic effects. In youth with BD, lurasidone was effective and well-tolerated for acute depression while asenapine showed efficacy in treating acute manic and mixed episodes. Recently published RCTs generally support the efficacy of atypical antipsychotics in different phases of BD. Future studies should focus on understudied populations including pediatric BD and geriatric BD and BDII, as well as a focus on cognitive functioning and quality of life measures.
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http://dx.doi.org/10.1007/s11920-021-01252-wDOI Listing
May 2021

Response to Commentary on "Grey Matter Abnormalities in First Episode Mania: A Systematic Review and Meta-analysis of Voxel-Based Morphometry Studies".

Bipolar Disord 2021 May 3. Epub 2021 May 3.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

We appreciate the comments by Sheng and colleagues on our manuscript titled "Grey matter abnormalities in first-episode mania: A systematic review and meta-analysis of voxel-based morphometry studies " and would like to take this opportunity to clarify our methodology and share the findings of additional analyses we have performed.
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http://dx.doi.org/10.1111/bdi.13091DOI Listing
May 2021

Cariprazine and akathisia, restlessness, and extrapyramidal symptoms in patients with bipolar depression.

J Affect Disord 2021 Jun 31;288:191-198. Epub 2021 Mar 31.

Clinical Development, AbbVie, Madison, NJ, United States.

Background: Akathisia is a neuropsychiatric syndrome that is commonly related to the use of dopamine receptor antagonists/partial agonists. The characteristics of cariprazine-related akathisia, restlessness, and extrapyramidal symptoms (EPS) were investigated in patients with bipolar I depression.

Methods: Akathisia-related data from 3 fixed-dose clinical studies of cariprazine 1.5 mg/d and 3 mg/d in bipolar depression were evaluated in pooled post hoc analyses. Outcomes related to treatment-emergent adverse events (TEAEs) included incidence, time to onset, time to resolution, severity, discontinuations, and rescue medication use.

Results: The incidence of akathisia was 7.6% for overall cariprazine (1.5 mg/d=5.5%; 3 mg/d=9.6%) and 2.1% for placebo; acute EPS occurred in 4.5% of cariprazine-treated (1.5 mg/d=3.8%; 3 mg/d=5.1%) and 2.1% of placebo-treated patients. Findings were similar for restlessness. Most TEAEs were mild/moderate (>95%), occurred during the first 3 weeks of cariprazine initiation or dose increase, and resulted in few discontinuations (<3%); median time to resolution of an akathisia or EPS TEAE after the last dose of cariprazine was ~1 week. Rescue medication was used by <3% of patients to manage akathisia/EPS events.

Limitations: Post hoc analyses; no active comparator.

Conclusions: In patients with bipolar depression, the incidence of cariprazine-related akathisia was higher than acute EPS or restlessness, with lower cariprazine doses associated with lower incidences of events. Akathisia and EPS TEAEs occurred early in treatment and were mild/moderate in severity. Few patients with akathisia or acute EPS discontinued treatment. Cariprazine-related akathisia and EPS can be minimized with conservative dosing and titration strategies.

Trial Registration: ClinicalTrials.gov Identifiers: NCT01396447, NCT02670538, NCT02670551.
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http://dx.doi.org/10.1016/j.jad.2021.03.076DOI Listing
June 2021

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.

Mol Psychiatry 2021 Apr 16. Epub 2021 Apr 16.

Unit for Psychosomatics / CL Outpatient Clinic for Adults, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
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http://dx.doi.org/10.1038/s41380-021-01098-xDOI Listing
April 2021

What impact does bipolar disorder staging have on the use of pharmacotherapy?

Expert Opin Pharmacother 2021 Apr 16:1-4. Epub 2021 Apr 16.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

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http://dx.doi.org/10.1080/14656566.2021.1915988DOI Listing
April 2021

Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial.

JAMA Netw Open 2021 03 1;4(3):e210963. Epub 2021 Mar 1.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

Importance: Major depressive episodes in bipolar disorder are common and debilitating. Repetitive transcranial magnetic stimulation is well established in the treatment of major depressive disorder, and the intermittent theta burst stimulation (iTBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, iTBS has not been adequately studied in bipolar disorder and, therefore, its efficacy is uncertain.

Objective: To determine whether iTBS to the left dorsolateral prefrontal cortex (LDLPFC) is safe and efficacious in the treatment of acute bipolar depression.

Design, Setting, And Participants: This study was a double-blind, 4-week, randomized clinical trial of iTBS targeting the LDLPFC. Two Canadian academic centers recruited patients between 2016 and 2020. Adults with bipolar disorder type I or type II experiencing an acute major depressive episode were eligible if they had not benefited from a first-line treatment for acute bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments and were currently treated with a mood stabilizer, an atypical antipsychotic, or their combination. Seventy-one participants were assessed for eligibility, and 37 were randomized to daily sham iTBS or active iTBS using a random number sequence, stratified according to current pharmacotherapy. Data analysis was performed from April to September 2020.

Interventions: Four weeks of daily active iTBS (120% resting motor threshold) or sham iTBS to the LDLPFC. Nonresponders were eligible for 4 weeks of open-label iTBS.

Main Outcomes And Measures: The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. Secondary outcomes included clinical response, remission, and treatment-emergent mania or hypomania.

Results: The trial was terminated for futility after 37 participants (23 women [62%]; mean [SD] age, 43.86 [13.87] years; age range, 20-68 years) were randomized, 19 to sham iTBS and 18 to active iTBS. There were no significant differences in Montgomery-Asberg Depression Rating Scale score changes (least squares mean difference between groups, -1.36 [95% CI, -8.92 to 6.19; P = .91] in favor of sham iTBS), and rates of clinical response were low in both the double-blind phase (3 of 19 participants [15.8%] in the sham iTBS group and 3 of 18 participants [16.7%] in the active iTBS group) and open-label phase (5 of 21 participants [23.8%]). One active iTBS participant had a treatment emergent hypomania, and a second episode occurred during open-label treatment.

Conclusions And Relevance: iTBS targeting the LDLPFC is not efficacious in the treatment of acute bipolar depression in patients receiving antimanic or mood stabilizing agents. Additional research is required to understand how transcranial magnetic stimulation treatment protocols differ in efficacy between unipolar and bipolar depression.

Trial Registration: ClinicalTrials.gov Identifier: NCT02749006.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955269PMC
March 2021

Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients: a longitudinal magnetic resonance spectroscopy study.

Psychol Med 2021 Mar 12:1-9. Epub 2021 Mar 12.

Mood Disorders Centre, University of British Columbia, Vancouver, BC, Canada.

Background: We previously reported that bipolar disorder (BD) patients with clinically significant weight gain (CSWG; ⩾7% of baseline weight) in the 12 months after their first manic episode experienced greater limbic brain volume loss than patients without CSWG. It is unknown whether CSWG is also a risk factor for progressive neurochemical abnormalities.

Methods: We investigated whether 12-month CSWG predicted greater 12-month decreases in hippocampal N-acetylaspartate (NAA) and greater increases in glutamate + glutamine (Glx) following a first manic episode. In BD patients (n = 58) and healthy comparator subjects (HS; n = 34), we measured baseline and 12-month hippocampal NAA and Glx using bilateral 3-Tesla single-voxel proton magnetic resonance spectroscopy. We used general linear models for repeated measures to investigate whether CSWG predicted neurochemical changes.

Results: Thirty-three percent of patients and 18% of HS experienced CSWG. After correcting for multiple comparisons, CSWG in patients predicted a greater decrease in left hippocampal NAA (effect size = -0.52, p = 0.005). CSWG also predicted a greater decrease in left hippocampal NAA in HS with a similar effect size (-0.53). A model including patients and HS found an effect of CSWG on Δleft NAA (p = 0.007), but no diagnosis effect and no diagnosis × CSWG interaction, confirming that CSWG had similar effects in patients and HS.

Conclusion: CSWG is a risk factor for decreasing hippocampal NAA in BD patients and HS. These results suggest that the well-known finding of reduced NAA in BD may result from higher body mass index in patients rather than BD diagnosis.
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http://dx.doi.org/10.1017/S0033291721000544DOI Listing
March 2021

Plant-based Medicines (Phytoceuticals) in the Treatment of Psychiatric Disorders: A Meta-review of Meta-analyses of Randomized Controlled Trials: Les médicaments à base de plantes (phytoceutiques) dans le traitement des troubles psychiatriques: une méta-revue des méta-analyses d'essais randomisés contrôlés.

Can J Psychiatry 2021 Feb 18:706743720979917. Epub 2021 Feb 18.

Deakin University, IMPACT-the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.

Objectives: Plant-based medicines have had a long-standing history of use in psychiatric disorders. Highly quantified and standardized extracts or isolates may be termed "phytoceuticals," in a similar way that medicinal nutrients are termed as "nutraceuticals." Over the past 2 decades, several meta-analyses have examined the data for a range of plant-based medicines in the treatment of psychiatric disorders. The aim of this international project is to provide a "meta-review" of this top-tier evidence.

Methods: We identified, synthesized, and appraised all available up to date meta-analyses... of randomized controlled trials (RCTs) reporting on the efficacy and effectiveness of individual phytoceuticals across all major psychiatric disorders.

Results: Our systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 individuals. Supportive meta-analytic evidence was found for St John's wort for major depressive disorder (MDD); curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders. We also provide details on 22 traditional Chinese herbal medicine formulas' meta-analyses (primarily for depression studies), all of which revealed highly significant and large effect sizes. Their methodology, reporting, and potential publication bias were, however, of marked concern. The same caveat was noted for the curcumin, ginkgo, and saffron meta-analyses, which may also have significant publication bias.

Conclusions: More rigorous international studies are required to validate the efficacy of these phytoceuticals before treatment recommendations can be made. In conclusion, the breadth of data tentatively supports several phytoceuticals which may be effective for mental disorders alongside pharmaceutical, psychological therapies, and standard lifestyle recommendations.
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http://dx.doi.org/10.1177/0706743720979917DOI Listing
February 2021

Implementing Measurement-Based Care for Depression: Practical Solutions for Psychiatrists and Primary Care Physicians.

Neuropsychiatr Dis Treat 2021 14;17:79-90. Epub 2021 Jan 14.

Shanghai Mental Health Center, Shanghai, People's Republic of China.

Measurement-based care (MBC) can be defined as the clinical practice in which care providers collect patient data through validated outcome scales and use the results to guide their decision-making processes. Despite growing evidence supporting the effectiveness of MBC for depression and other mental health conditions, many physicians and mental health clinicians have yet to adopt MBC practice. In part, this is due to individual and organizational barriers to implementing MBC in busy clinical settings. In this paper, we briefly review the evidence for the efficacy of MBC focusing on pharmacological management of depression and provide example clinical scenarios to illustrate its potential clinical utility in psychiatric settings. We discuss the barriers and challenges for MBC adoption and then address these by suggesting simple solutions to implement MBC for depression care, including recommended outcome scales, monitoring tools, and technology solutions such as cloud-based MBC services and mobile health apps for mood tracking. The availability of MBC tools, ranging from paper-pencil questionnaires to mobile health technology, can allow psychiatrists and clinicians in all types of practice settings to easily incorporate MBC into their practices and improve outcomes for their patients with depression.
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http://dx.doi.org/10.2147/NDT.S283731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813452PMC
January 2021

Probing the clinical and brain structural boundaries of bipolar and major depressive disorder.

Transl Psychiatry 2021 01 14;11(1):48. Epub 2021 Jan 14.

Clinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Bipolar disorder (BD) and major depressive disorder (MDD) have both common and distinct clinical features, that pose both conceptual challenges in terms of their diagnostic boundaries and practical difficulties in optimizing treatment. Multivariate machine learning techniques offer new avenues for exploring these boundaries based on clinical neuroanatomical features. Brain structural data were obtained at 3 T from a sample of 90 patients with BD, 189 patients with MDD, and 162 healthy individuals. We applied sparse partial least squares discriminant analysis (s-PLS-DA) to identify clinical and brain structural features that may discriminate between the two clinical groups, and heterogeneity through discriminative analysis (HYDRA) to detect patient subgroups with reference to healthy individuals. Two clinical dimensions differentiated BD from MDD (area under the curve: 0.76, P < 0.001); one dimension emphasized disease severity as well as irritability, agitation, anxiety and flight of ideas and the other emphasized mostly elevated mood. Brain structural features could not distinguish between the two disorders. HYDRA classified patients in two clusters that differed in global and regional cortical thickness, the distribution proportion of BD and MDD and positive family history of psychiatric disorders. Clinical features remain the most reliable discriminant attributed of BD and MDD depression. The brain structural findings suggests that biological partitions of patients with mood disorders are likely to lead to the identification of subgroups, that transcend current diagnostic divisions into BD and MDD and are more likely to be aligned with underlying genetic variation. These results set the foundation for future studies to enhance our understanding of brain-behavior relationships in mood disorders.
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http://dx.doi.org/10.1038/s41398-020-01169-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809029PMC
January 2021

The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: Major depression summary.

Bipolar Disord 2020 12;22(8):788-804

Centre for Mental Health, Swinburne University of Technology, Hawthorn, VIC, Australia.

Objectives: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg ).

Methods: To develop the MDcpg , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on major depression. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of major depression.

Results: The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non-response.

Conclusions: The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg . The recommendations are informed by research evidence in conjunction with clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians, but will be of interest to all clinicians and carers involved in the management of patients with depressive disorders.
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http://dx.doi.org/10.1111/bdi.13035DOI Listing
December 2020

The 2020 Royal Australian and New Zealand College of psychiatrists clinical practice guidelines for mood disorders: Bipolar disorder summary.

Bipolar Disord 2020 12;22(8):805-821

Centre for Mental Health, Swinburne University of Technology, Hawthorn, VIC, Australia.

Objectives: To provide a succinct, clinically useful summary of the management of bipolar disorder, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg ).

Methods: To develop the MDcpg , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on bipolar disorder. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of bipolar disorder.

Results: The bipolar disorder summary provides a systematic approach to diagnosis, and a logical clinical framework for management. It addresses the acute phases of bipolar disorder (mania, depression and mixed states) and its longer-term management (maintenance and prophylaxis). For each phase it begins with Actions, which include important strategies that should be implemented from the outset wherever possible. These include for example, lifestyle changes, psychoeducation and psychological interventions. In each phase, the summary advocates the use of Choice medications for pharmacotherapy, which are then used in combinations along with additional Alternatives to manage acute symptoms or maintain mood stability and provide prophylaxis. The summary also recommends the use of electroconvulsive therapy (ECT) for each of the acute phases but not for maintenance therapy. Finally, it briefly considers bipolar disorder in children and its overlap in adults with borderline personality disorder.

Conclusions: The bipolar disorder summary provides up to date guidance regarding the management of bipolar disorder, as set out in the MDcpg . The recommendations are informed by evidence and clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians but will be of interest to anyone involved in the management of patients with bipolar disorder.
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http://dx.doi.org/10.1111/bdi.13036DOI Listing
December 2020

A clinical approach to treatment resistance in depressed patients: What to do when the usual treatments don't work well enough?

World J Biol Psychiatry 2020 Dec 8:1-20. Epub 2020 Dec 8.

IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Australia.

Background: Major depressive disorder is a common, recurrent, disabling and costly disorder that is often severe and/or chronic, and for which non-remission on guideline concordant first-line antidepressant treatment is the norm. A sizeable percentage of patients diagnosed with MDD do not achieve full remission after receiving antidepressant treatment. How to understand or approach these 'refractory', 'TRD' or 'difficult to treat' patients need to be revisited. Treatment resistant depression (TRD) has been described elsewhere as failure to respond to adequate treatment by two different antidepressants. This definition is problematic as it suggests that TRD is a subtype of major depressive disorder (MDD), inferring a boundary between TRD and depression that is not treatment resistant. However, there is scant evidence to suggest that a discrete TRD entity exists as a distinct subtype of MDD, which itself is not a discrete or homogeneous entity. Similarly, the boundary between TRD and other forms of depression is predicated at least in part on regulatory and research requirements rather than biological evidence or clinical utility.

Aim: This paper aims to investigate the notion of treatment failure in order to understand (i) what is TRD in the context of a broader formulation based on the understanding of depression, (ii) what factors make an individual patient difficult to treat, and (iii) what is the appropriate and individualised treatment strategy, predicated on an individual with refractory forms of depression?

Method: Expert contributors to this paper were sought internationally by contacting representatives of key professional societies in the treatment of MDD - World Federation of Societies for Biological Psychiatry, Australasian Society for Bipolar and Depressive Disorders, International Society for Affective Disorders, Collegium Internationale Neuro-Psychopharmacologium and the Canadian Network for Mood and Anxiety Treatments. The manuscript was prepared through iterative editing.

Outcomes: The concept of TRD as a discrete subtype of MDD, defined by failure to respond to pharmacotherapy, is not supported by evidence. Between 15 and 30% of depressive episodes fail to respond to adequate trials of 2 antidepressants, and 68% of individuals do not achieve remission from depression after a first-line course of antidepressant treatment. Failure to respond to antidepressant treatment, somatic therapies or psychotherapies may often reflect other factors including; biological resistance, diagnostic error, limitations of current therapies, psychosocial variables, a past history of exposure to childhood maltreatment or abuse, job satisfaction, personality disorders, co-morbid mental and physical disorders, substance use or non-adherence to treatment. Only a subset of patients not responding to antidepressant treatment can be explained through pharmacokinetic or pharmacodynamics mechanisms. We propose that non remitting MDD should be personalised, and propose a strategy of 'deconstructing depression'. By this approach, the clinician considers which factors contribute to making this individual both depressed and 'resistant' to previous therapeutic approaches. Clinical formulation is required to understand the nature of the depression. Many predictors of response are not biological, and reflect a confluence of biological, psychological, and sociocultural factors, which may influence the illness in a particular individual. After deconstructing depression at a personalised level, a personalised treatment plan can be constructed. The treatment plan needs to address the factors that have contributed to the individual's hard to treat depression. In addition, an individual with a history of illness may have a lot of accumulated life issues due to consequences of their illness, and these should be addressed in a recovery plan.

Limitations: A 'deconstructing depression' qualitative rubric does not easily provide clear inclusion and exclusion criteria for researchers wanting to investigate TRD.

Conclusions: MDD is a polymorphic disorder and many individuals who fail to respond to standard pharmacotherapy and are considered hard to treat. These patients are best served by personalised approaches that deconstruct the factors that have contributed to the patient's depression and implementing a treatment plan that adequately addresses these factors. The existence of TRD as a discrete and distinct subtype of MDD, defined by two treatment failures, is not supported by evidence.
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http://dx.doi.org/10.1080/15622975.2020.1851052DOI Listing
December 2020

Efficacy of cariprazine in bipolar I depression across patient characteristics: a post hoc analysis of pooled randomized, placebo-controlled studies.

Int Clin Psychopharmacol 2021 Mar;36(2):76-83

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

Patients who experience bipolar depression have diverse demographic and clinical characteristics that have the potential to impact treatment. The efficacy of cariprazine in bipolar I depression was evaluated in patient subgroups defined by baseline demographic and clinical characteristics. Post hoc analyses of data from three randomized, double-blind, placebo-controlled trials in bipolar I depression (NCT01396447, NCT02670538 and NCT02670551) evaluated mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores for pooled cariprazine 1.5-3 mg/d versus placebo in subgroups defined by demographic and clinical characteristics. The least-squares mean difference in MADRS total score change from baseline was statistically significant for cariprazine 1.5-3 mg/d versus placebo in all patient subgroups analyzed (P < 0.05 all subgroups): demographic characteristics (age, sex, white or black race and obese/nonobese BMI); episode characteristics (defined by current episode duration, number of previous manic/mixed and depressive episodes, and prior bipolar disorder medication use) and disease severity (groups above and below Clinical Global Impressions-Severity and MADRS cutoff scores). Cariprazine 1.5-3 mg/d consistently improved depressive symptoms in all patient subgroups without regard to differences in baseline demographic and clinical characteristics, suggesting broad efficacy across a spectrum of patients with bipolar I depression.
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http://dx.doi.org/10.1097/YIC.0000000000000344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846289PMC
March 2021

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.

Can J Psychiatry 2021 Feb 11;66(2):113-125. Epub 2020 Nov 11.

Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.

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 -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.
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http://dx.doi.org/10.1177/0706743720970860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918868PMC
February 2021

Cognitive subgroups in first episode bipolar I disorder: Relation to clinical and brain volumetric variables.

Acta Psychiatr Scand 2021 02 28;143(2):151-161. Epub 2020 Nov 28.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Objective: Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by 'early neurodevelopmental' (low premorbid IQ and intracranial volume) versus 'later neurodevelopmental' (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology.

Methods: Recently recovered first manic episode BDI patients (n = 91) and healthy controls (HC, n = 63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non-verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes.

Results: Three cognitive subgroups emerged: (i) globally impaired (GI, n = 31), scoring 0.5-1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n = 47), with predominant processing speed deficits and (iii) high performing (HP, n = 13), with above-average cognitive performance. GI patients showed a 'later neurodevelopmental' pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p = 0.003). GI patients had higher left frontal pole GM versus HC (p < 0.05, FWE corrected).

Conclusions: A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset.
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http://dx.doi.org/10.1111/acps.13245DOI Listing
February 2021

Grey matter abnormalities in first-episode mania: A systematic review and meta-analysis of voxel-based morphometry studies.

Bipolar Disord 2021 May 8;23(3):228-240. Epub 2020 Oct 8.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Objectives: It has been proposed that different stages of bipolar disorder may be underpinned by distinct neurobiological substrates. However, structural neuroimaging studies in early stages of the illness are limited by small sample sizes yielding inconsistent findings. The purpose of this systematic review and meta-analysis, therefore, was to identify regional grey matter volume (GMV) changes that are consistently associated with first episode of mania (FEM).

Methods: Following PRISMA guidelines, we conducted a systematic search of the literature to identify Voxel-Based Morphometry (VBM) studies in FEM patients compared with healthy individuals. We then conducted a voxel-wise meta-analysis using Seed-based d-Mapping technique. Finally, we performed univariate meta-regression analyses to explore the potential effects of moderator variables including age, gender, and percentage of lithium users on GMV alterations.

Results: We identified 15 VBM studies and included 12 studies in the meta-analysis. Four studies found no regional differences in GM volumes while other 11 studies reported volume changes in frontal and temporal regions as well as anterior cingulate cortex (ACC), cerebellum and basal ganglia. The meta-analysis revealed a single cluster of GMV reduction in bilateral pregenual ACC in patients with FEM compared to healthy individuals (P < .001). The Egger's test showed no evidence of publication bias at peak voxel level (P = .447). Meta-regression analyses revealed no significant effects of moderators evaluated.

Conclusions: Structural brain changes are evident in the early stages of bipolar disorder. GMV reduction in bilateral pregenual ACC is the most consistent finding in VBM studies of FEM.
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http://dx.doi.org/10.1111/bdi.12995DOI Listing
May 2021

The Quality of Life in Bipolar Disorder (QoL.BD) questionnaire a decade on - A systematic review of the measurement of condition-specific aspects of quality of life in bipolar-disorder.

J Affect Disord 2021 01 7;278:33-45. Epub 2020 Sep 7.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Background: Condition-specific quality of life (QoL) instruments are more representative of the priorities of people with lived experience. As such, the development of the first and only bipolar disorder (BD) specific measurement instrument, the Quality of Life in Bipolar Disorder (QoL.BD) questionnaire, marked an important step forward for the literature. The present systematic review aims to characterise applications of the QoL.BD in the BD literature and review empirical findings obtained from studies using this measure.

Methods: A systematic search identified 37 peer-reviewed publications which reported original empirical data using the QoL.BD in a BD population. No restrictions were placed on language/study type.

Results: Adaptations to the QoL.BD displayed appropriate psychometric properties. Although clinical trials were typically underpowered, promising effect sizes for a number of treatment modalities were reported. QoL.BD scores were moderately correlated with depressive symptoms; a number of candidate predictors were identified.

Limitations: Due to resource limitations, the present review used one database (Google Scholar), and a single author reviewed articles for eligibility. On balance the risks of missing relevant studies were deemed minimal.

Conclusion: A sizeable, international body of evidence now exists regarding the measurement, presentation, and treatment of condition-specific aspects of QoL in BD. Key avenues for future research include large scale, randomized control clinical trials using the QoL.BD as a primary outcome, and granular exploration of potential correlates of QoL.BD domain scores. Finally, longer follow-up periods are required to inform understanding of the dynamic relationship between clinical variables and condition-specific aspects of QoL in BD.
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http://dx.doi.org/10.1016/j.jad.2020.09.017DOI Listing
January 2021

Broad Efficacy of Cariprazine on Depressive Symptoms in Bipolar Disorder and the Clinical Implications.

Prim Care Companion CNS Disord 2020 Sep 17;22(5). Epub 2020 Sep 17.

Clinical Development, AbbVie, Madison, New Jersey, USA.

Introduction: Bipolar disorder is a complex mood disorder characterized by a chronic and subtle course of fluctuating manic/hypomanic and depressive symptoms. Cariprazine, a dopamine D₃-preferring D₃/D₂ receptor partial agonist with serotonin 5-HT1A receptor partial agonist and serotonin 5-HT2A antagonist properties, is approved to treat manic and depressive episodes of bipolar disorder. Post hoc analyses evaluated efficacy across symptoms in bipolar depression.

Methods: Pooled data were analyzed from 3 phase 2 or 3, randomized, double-blind, placebo-controlled studies of adults with bipolar disorder and a major depressive episode. Mean change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score and individual item scores were analyzed in individual dose groups (1.5 mg/d, 3 mg/d) and overall cariprazine (1.5-3 mg/d). Pooled safety was evaluated via adverse events.

Results: A significantly greater difference in mean change from baseline in MADRS total score was seen for each cariprazine dose group versus placebo (least squares mean difference vs placebo: 1.5-3 mg/d = -2.6, 1.5 mg/d = -2.8, 3 mg/d = -2.4) (P < .001 all). Significant differences versus placebo were seen on all individual MADRS items except inner tension for the overall cariprazine group (P < .05). Cariprazine was generally well tolerated.

Conclusions: Cariprazine demonstrated broad efficacy across symptoms of depression in bipolar disorder. In previous post hoc analyses, cariprazine also demonstrated broad efficacy across manic symptoms, suggesting that it is effective across the wide range of symptoms on the bipolar spectrum. A 1.5-mg/d starting dose and slow titration resulted in lower rates of some adverse events in the bipolar depression studies versus the mania studies.

Trial Registration: ClinicalTrials.gov identifiers: NCT01396447, NCT02670538, NCT02670551.
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http://dx.doi.org/10.4088/PCC.20m02611DOI Listing
September 2020

Early intervention for people at high risk of developing bipolar disorder: a systematic review of clinical trials.

Lancet Psychiatry 2021 01 25;8(1):64-75. Epub 2020 Aug 25.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Early intervention approaches are built on the premise of preventing disability, burden, and cognitive sequelae caused by bipolar disorder. The objective of this systematic review was to characterise the effectiveness of all the available psychological and pharmacological treatments for early intervention in people at high risk of developing bipolar disorder. The study was registered with PROSPERO (CRD42019133420). We did a systematic search to identify studies published in ten databases up to March 27, 2020. Randomised controlled trials and cohort studies that assessed the effect of pharmacological or psychological interventions in people at high risk of developing bipolar disorder were included. Studies of first episodes of mania were excluded. Eligible papers were assessed for quality and data were extracted. The primary outcomes were change in manic and depressive symptoms from baseline to endpoint. Of the 2856 citations retrieved by our search, 16 studies were included; five evaluated pharmacotherapeutic strategies (three randomised controlled trials and two open-label studies), ten assessed psychotherapeutic strategies (four randomised controlled trials and six open-label studies), and one randomised controlled trial assessed combination therapy; these 16 trials included a total of 755 participants at high risk of developing bipolar disorder. Quality assessment indicated fair to good quality for open-label studies, and a high risk of bias in four randomised controlled trials. Among the pharmacotherapeutic interventions, there is preliminary support for the efficacy of aripiprazole in reducing mood symptoms in people at high risk of developing bipolar disorder. Psychological interventions were effective for various outcomes. There was substantial methodological heterogeneity across studies. This systematic review underscores the need for multicentre, prospective, methodologically homogeneous studies evaluating conversion to bipolar disorder as an outcome measure.
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http://dx.doi.org/10.1016/S2215-0366(20)30188-7DOI Listing
January 2021

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group.

Hum Brain Mapp 2020 Jul 29. Epub 2020 Jul 29.

Division of Mental Health and Addicition, Oslo University Hospital, Oslo, Norway.

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
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http://dx.doi.org/10.1002/hbm.25098DOI Listing
July 2020

Increasing the power of randomized trials comparing different treatment durations.

Contemp Clin Trials Commun 2020 Sep 10;19:100588. Epub 2020 Jun 10.

School of Population and Public Health, University of British Columbia, 2206 East Mall, Vancouver, BC, V6T 1Z3, Canada.

When the optimal treatment duration is uncertain, a randomized trial may allocate patients to receive active treatment for different durations. We use an example where patients receive treatment for 0, 24, or 52 weeks. In this trial, patients in the 24-weeks and 52-weeks arms receive the same treatment during the first 24 weeks. This overlap allows for more powerful analyses than conventional pair-wise comparisons of arms. When the outcome is the time-to-event, the power for the 0-weeks versus 24-weeks comparison can be increased by including patients in the 52-weeks arm as patients in the 24-weeks arm for the first 24 weeks and censoring at 24 weeks. Furthermore, differences observed between the 24-weeks and 52-weeks arms during the first 24 weeks can only reflect noise. Hence, the comparison of these two arms should be restricted to only patients who remain on the study at 24 weeks and include only the events after 24 weeks. Through simulation, we show that modified analyses accounting for these considerations increase study power substantially. Moreover, if patients were allocated equally to the arms, then events or discontinuations during the first 24 weeks will reduce the number of patients available for the 24-weeks versus 52-weeks comparison, and hence the power of this analysis will be lower than that for the 0-weeks versus 24-weeks comparison. We present a sample size calculation procedure for equalizing the power of these two analyses. Typically, this allocation requires much larger sample sizes in the 24-weeks and 52-weeks arms than in the 0-week arm.
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http://dx.doi.org/10.1016/j.conctc.2020.100588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322686PMC
September 2020

Our Digital Moment: Innovations and Opportunities in Digital Mental Health Care.

Can J Psychiatry 2021 Jan 30;66(1):5-8. Epub 2020 Jun 30.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1177/0706743720937833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890581PMC
January 2021

Quality of Life Impacts of Bright Light Treatment, Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

Can J Psychiatry 2021 Mar 23;66(3):289-297. Epub 2020 Jun 23.

Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome.

Methods: This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy ( = 32), fluoxetine monotherapy ( = 30), and the combination of these ( = 27) to placebo ( = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression.

Results: Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores.

Conclusion: The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.
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http://dx.doi.org/10.1177/0706743720936470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958199PMC
March 2021

Preservation of Gray Matter Volume in Early Stage of Bipolar Disorder: A Case for Early Intervention: Préservation du volume de matière grise au stade précoce du trouble bipolaire: un cas pour intervention précoce.

Can J Psychiatry 2021 Feb 18;66(2):139-146. Epub 2020 May 18.

Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.

Objective: It has been proposed that different stages of the bipolar disorder might have distinct neurobiological changes. However, the evidence for this has not been consistent, as the studies in early stages of the illness are limited by small sample sizes. The purpose of this study was to investigate the gray matter volume changes in bipolar patients who recently recovered from their first episode of mania (FEM).

Methods: Using a whole-brain voxel-based analysis, we compared the regional gray matter volumes of 61 bipolar patients who have recovered from their FEM in the past 3 months with 43 age- and gender-matched healthy participants. We also performed a series of subgroup analyses to determine the effects of hospitalization during the FEM, history of depressive episodes, and exposure to lithium.

Results: No statistically significant difference was found between gray matter volumes of FEM patients and healthy participants, even at a more liberal threshold ( < 0.001, uncorrected for multiple comparisons). Voxel-based subgroup analyses did not reveal significant gray matter differences except for a trend toward decreased gray matter volume in left lateral occipital cortex ( < 0.001, uncorrected) in patients with a previous history of depression.

Conclusion: This study represents the largest structural neuroimaging investigation of FEM published to date. Early stage of bipolar disorder was not found to be associated with significant gray matter volume changes. Our findings suggest that there might be a window of opportunity for early intervention strategies to prevent or delay neuroprogression in bipolar disorder.
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http://dx.doi.org/10.1177/0706743720927827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918870PMC
February 2021

Mental Health of Communities during the COVID-19 Pandemic.

Can J Psychiatry 2020 10 11;65(10):681-687. Epub 2020 May 11.

Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1177/0706743720926676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502878PMC
October 2020