Publications by authors named "Brett D M Jones"

10 Publications

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Targeting Metabolic Dysfunction for the Treatment of Mood Disorders: Review of the Evidence.

Life (Basel) 2021 Aug 11;11(8). Epub 2021 Aug 11.

Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada.

Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition.
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http://dx.doi.org/10.3390/life11080819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401631PMC
August 2021

Metabolic variables associated with response to cognitive behavioural therapy for depression in females: A Canadian biomarker integration network for depression (CAN-BIND) study.

J Psychiatr Res 2021 Oct 21;142:321-327. Epub 2021 Jul 21.

Centre for Addiction and Mental Health and Campbell Family Mental Health Research Institute, 1000 Queen St West, Toronto, Canada; Department of Psychiatry, University of Toronto, 250 College St, Toronto, Canada. Electronic address:

Introduction: Cognitive behavioural therapy (CBT) is an established first-line treatment for depression; however, it remains unclear which factors predict a positive outcome with this approach. Prior work suggests that co-morbid obesity predicts a poorer response to antidepressant medication. The current study examined whether there is an association between weight parameters and improvement of depressive symptoms with CBT.

Methods: This was a secondary analysis of data from the "Clinical and Biological Markers of Response to Cognitive Behavioural Therapy for Depression - 6" (CANBIND-6; https://clinicaltrials.gov/ct2/show/NCT02883257) study. Adult participants (n = 41) with a diagnosis of Major Depressive Disorder (MDD) or Persistent Depressive Disorder (PDD) were recruited from an outpatient tertiary psychiatric centre in Canada. Participants completed 20 individual sessions of CBT over 16 weeks. The primary measure for treatment outcome was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 16.

Results: Thirty-seven participants completed assessments pre and post CBT. Baseline weight parameters were not correlated with treatment response to CBT in the entire group. There was a significant sex*waist circumference (WC) (B:-1.34; p = 0.004) and sex*body mass index (BMI) interaction (B:-2.03; p:0.009). In female participants, baseline waist circumference, but not BMI, significantly predicted week 16 MADRS after controlling for age and baseline MADRS (B:0.422 p:0.049).

Limitations: The major limitation of our preliminary finding is the small sample size.

Conclusion: Our preliminary findings suggest that higher waist circumference may be associated with a better treatment response to CBT for depression in females. This result could be of clinical relevance and warrants further investigation in larger and independent samples.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.031DOI Listing
October 2021

The meaningful change threshold as measured by the 16-item quick inventory of depressive symptomatology in adults with treatment-resistant major depressive and bipolar disorder receiving intravenous ketamine.

J Affect Disord 2021 Nov 20;294:592-596. Epub 2021 Jul 20.

Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Objective: .To identify a meaningful change threshold (MCT) in depression outcomes in adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD) receiving intravenous ketamine treatment at a community-based mood disorders center.

Method: .A triangular approach integrating both anchor-based and distributive methods was used to identify meaningful change on the patient-reported Quick Inventory for Depressive Symptoms Self-Report 16-Item (QIDS-SR16) as associated with the Patient Global Impression - Severity (PGI-S). Both the QIDS-SR16 and the PGI-S are self-report measures, and were collected at five timepoints (timepoints were approximately 2-7 days apart).

Results: .A total of 297 adults with treatment-resistant depression (TRD) as part of either DSM-5-defined MDD or BD were included. The MCT for the QIDS-SR16 revealed that a mean improvement of 3.38 points from baseline was comparable to a 1-point improvement on the PGI-S. Together with an examination of the probability density function, a 3.5-point change is a reasonable MCT (i.e., 1-point PGI-S improvement) for the QIDS-SR16. A 2-point symptomatic improvement on the QIDS-SR16 was associated with no change on the PGI-S.

Conclusion: .A 3.5-point reduction in the QIDS-SR16 represents a MCT based on the PGI-S for adults with treatment-resistant MDD or BD receiving intravenous ketamine treatment at a community-based mood disorders center. These findings are limited by the post-hoc nature of this analysis and open-label case-series design. Measurement-based care decisions by patients, providers and clinicians, as well as cost/reimbursement decisions should include consideration of meaningful change along with conventional objective outcomes.
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http://dx.doi.org/10.1016/j.jad.2021.07.035DOI Listing
November 2021

The use of sequential pharmacotherapy for the treatment of acute major depression: a scoping review.

Expert Opin Pharmacother 2021 Jun 22;22(8):1005-1014. Epub 2021 Feb 22.

Department of Psychiatry, University of Toronto, Toronto, Canada.

Introduction: Major Depressive Disorder (MDD) is a chronic, relapsing, and remitting disorder affecting over 250 million persons each year worldwide. More than 50% of the patients do not respond to their initial antidepressant treatment and may benefit from sequential pharmacotherapy for the acute treatment of their MDD. Although guidelines outline options for next-step treatments, there is a paucity of evidence to select specific second- or third-step treatments.

Areas Covered: This scoping review synthesizes and discusses available evidence for sequential pharmacotherapy for MDD. MEDLINE was searched from inception to 7 July 2020; 4490 studies were identified. We selected meta-analyses and reports on clinical trials that were judged to inform the sequential selection of pharmacotherapy for MDD.

Expert Opinion: Most relevant published trials are focused on, and support, the use of augmentation pharmacotherapy. There is also some support for other strategies such as combining or switching antidepressants. In the future, more studies need to directly compare these sequential options. To provide more personalized treatment within the framework of precision psychiatry, these studies should include an assessment of moderators and mediators ('mechanism') of antidepressant response.
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http://dx.doi.org/10.1080/14656566.2021.1878144DOI Listing
June 2021

Protocol for a systematic review and meta-analysis of the placebo response in treatment-resistant depression: comparison of multiple treatment modalities.

BMJ Open 2021 02 16;11(2):e041349. Epub 2021 Feb 16.

Psychiatry, University of California San Diego, San Diego, California, USA

Introduction: The high placebo response in depression treatment trials is a major contributing factor for randomised control trial failure to establish efficacy of novel or repurposed treatments in treatment-resistant depression (TRD) and major depressive disorder in general. Though there have been a number of meta-analyses and primary research studies evaluating the placebo response in non-TRD, placebo response in TRD is poorly understood. It is important to understand the placebo response of TRD as treatments are only moderately effective and up to 1/3 of patients will experience TRD.

Methods And Analysis: We will conduct a search of electronic databases (MEDLINE and PsychINFO) from inception to 24th January 2020 including randomised, placebo-controlled trials of pharmacological, somatic and psychological interventions for adults with TRD. TRD will be defined as a failure to respond to at least two interventions of adequate dose or duration. We will also search reference lists from review articles. We will perform several meta-analyses to quantify the placebo response for each treatment modality. Regression analysis will explore potential contributing demographic and clinical variables to the placebo response. We will use Cochrane risk of bias tool.

Ethics And Dissemination: There is no research ethics board approval required. The dissemination plan is to publish results in a peer-reviewed academic journal.

Prospero Registration Number: 190 465.
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http://dx.doi.org/10.1136/bmjopen-2020-041349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888315PMC
February 2021

Inflammation as a treatment target in mood disorders: review.

BJPsych Open 2020 Jun 5;6(4):e60. Epub 2020 Jun 5.

Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Canada.

Background: Mood disorders, i.e. major depressive disorder (MDD) and bipolar disorders, are leading sources of disability worldwide. Currently available treatments do not yield remission in approximately a third of patients with a mood disorder. This is in part because these treatments do not target a specific core pathology underlying these heterogeneous disorders. In recent years, abnormal inflammatory processes have been identified as putative pathophysiological mechanisms and treatment targets in mood disorders, particularly among individuals with treatment-resistant conditions.

Aims: In this selective review, we aimed to summarise recent advances in the field of immunopsychiatry, including emerging pathophysiological models and findings from treatment ttrials of immunomodulatory agents for both MDD and bipolar disorders.

Method: We performed a literature review by searching Medline for clinical trials of immunomodulating agents as monotherapy or adjunctive treatments in MDD and bipolar disorders. Included studies are randomised controlled trials (RCTs), cluster RCTs or cross-over trials of immunomodulating agents that had an active comparator or a placebo-arm.

Results: Current evidence shows an association between inflammation and mood symptoms. However, there is conflicting evidence on whether this link is causal.

Conclusions: Future studies should focus on identifying specific neurobiological underpinnings for the putative causal association between an activated inflammatory response and mood disorders. Results of these studies are needed before further treatment trials of immunomodulatory agents can be justified.
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http://dx.doi.org/10.1192/bjo.2020.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345526PMC
June 2020

Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis.

Int Rev Psychiatry 2020 Aug - Sep;32(5-6):477-490. Epub 2020 Jun 5.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation. Of 36 included trials, 27 were suitable for inclusion in NMA, and no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilizers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES = 0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes. This study provides the most comprehensive evidence of augmenters' effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimize treatment choices. Although conclusions are limited by paucity of, and heterogeneity between, trials as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine.
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http://dx.doi.org/10.1080/09540261.2020.1765748DOI Listing
June 2020

Efficacy and acceptability of adjunctive psychological and pharmacological interventions for treatment-resistant depression: protocol for a systematic review and network meta-analysis.

BMJ Open 2019 05 14;9(5):e028538. Epub 2019 May 14.

General Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Introduction: Major depressive disorder (MDD) is a common debilitating illness worldwide. The vast majority of patients with MDD will not achieve remission with first-line treatment and despite the availability of different treatment modalities, at least one-third of patients experience treatment-resistant depression (TRD). There continues to be a paucity of research focused on treatment options for patients with TRD thus treatment decisions are largely based on patient and clinician preference as opposed to evidence-based practice. Herein we propose a systematic review and network meta-analysis (NMA) of available pharmacological and psychological augmentation treatments for TRD, to inform evidence-based management of TRD.

Methods And Analysis: We plan to conduct a search of electronic databases (MEDLINE and ISIWEB) of all dates from inception for randomised controlled trials of pharmacological and psychological augmentation interventions for adults with TRD. Articles for review will be included based upon consensus from two authors. Pharmaceutical companies will be contacted for access to any unpublished data. An NMA will compare the effectiveness pharmacological adjunctive agents for TRD using preanalysis/postanalysis, assuming consistency and transitivity.

Ethics And Dissemination: This project does not require research ethics board approval. The dissemination plan is to present findings at international scientific meetings and publishing results in a peer-reviewed academic journal.

Prospero Registration Number: CRD42019132588.
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http://dx.doi.org/10.1136/bmjopen-2018-028538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530376PMC
May 2019

High reactivity of the cortisol awakening response predicts positive treatment outcome in heterogeneous depressed patients completing an alternate milieu inpatient program.

Gen Hosp Psychiatry 2015 Nov-Dec;37(6):601-5. Epub 2015 Jun 10.

Centre for Addiction and Mental Health, Toronto, Ontario, Canada M6J 1H4; University of Toronto Department of Psychiatry, Toronto, Ontario, Canada M5S 2J7; University of Toronto Department of Physiology, Toronto, Ontario, Canada, M5S 2J7; Institute of Medical Science, Toronto, Ontario, Canada M5S 2J7.

Objective: Delineating clinically meaningful subgroups within heterogeneous depressed populations is a major challenge. As outlined in the Research Domain Criteria Strategy, biomarkers may help to empirically classify such patients. Following this basic strategy, the current pilot study examined whether the cortisol awakening response (CAR) following admission to hospital predicts treatment response in heterogeneous depressed patients completing a 4-week alternate milieu inpatient program.

Methods: The Alternate Inpatient Milieu program at the Centre for Addiction and Mental Health is composed of both individual-based and group-based programming designed to promote a recovery-oriented, collaborative treatment environment. The current sample consisted of 25 consecutive patients with various forms of complex/chronic depression who completed the full program. Saliva samples were collected at 0, 30 and 60 min after awakening on 2 consecutive days following admission. Linear regressions controlling for baseline depression scores were used to assess whether the CAR AUCg (area under the curve ground) and/or AUCi (area under the curve increase) at admission predicted the change in depression scores from admission to discharge based on the Quick Inventory of Depressive Symptoms scale.

Results: The CAR AUCi, but not the CAR AUCg, at admission significantly predicted treatment response over the 4-week hospital stay. In these naturalistic patients with major depressive disorder, high CAR reactivity as assessed using the AUCi was associated with a better treatment response (t=2.20; df=2,24; P=.039). The CAR was easy to implement and well accepted by patients and staff.

Conclusion: This pilot study suggests that CAR reactivity at admission may help to identify a subgroup of depressed patients most likely to respond clinically to a 4-week alternate milieu inpatient program.
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http://dx.doi.org/10.1016/j.genhosppsych.2015.06.006DOI Listing
August 2016

Attachment style at discharge predicts depression status four months following a 28-day alternate-milieu inpatient program.

Asian J Psychiatr 2014 Apr 12;8:104-5. Epub 2013 Nov 12.

Centre for Addiction and Mental Health, Canada; University of Toronto Institute of Medical Science, Canada; University of Toronto Department of Psychiatry, Canada; University of Toronto Department of Physiology, Canada.

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http://dx.doi.org/10.1016/j.ajp.2013.11.002DOI Listing
April 2014
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