Publications by authors named "Rodrigo B Mansur"

172 Publications

Validation of the McIntyre And Rosenblat Rapid Response Scale (MARRRS) in Adults with Treatment-Resistant Depression Receiving Intravenous Ketamine Treatment.

J Affect Disord 2021 Mar 26;288:210-216. Epub 2021 Mar 26.

Mood Disorders Psychopharmacology Unit, University Health Network; University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Brain and Cognition Discovery Foundation, Canada; University of Toronto, Toronto, ON, Canada.

Background: Depression severity and efficacy measurement scales employed for rapid-acting treatments (e.g., ketamine) were initially validated in adults receiving conventional monoamine-based antidepressants. The emergence of rapid-acting antidepressants in psychiatry provides the impetus for outcome measures that have been validated as sensitive to change with rapid-acting treatments. Herein, we provide results validating the McIntyre and Rosenblat Rapid Response Scale (MARRRS).

Methods: Adults with treatment-resistant depression (TRD) receiving intravenous (IV) ketamine had depressive symptoms measured with the 16-Item Quick Inventory Depressive Symptoms Self-Report (QIDS-SR-16) and MARRRS at baseline and as a repeated measure across an acute course of four infusions. The MARRRS is a self-report measure assessing depressive symptoms during the past 72 hours.

Results: Sixty-four patients (M = 45.4 ± 13.5) were included. The MARRRS had a high internal consistency across acute infusions as determined by Cronbach's alpha (0.84 to 0.94). There was significant convergent validity between the QIDS-SR-16 and MARRRS total scores across infusions (rs(292) = .87, p < .001); the MARRRS was also sensitive to change (rs(49) = .70, p < .001). Exploratory factor analysis revealed that MARRRS items loaded onto two factors (i.e., dysphoria and psychic anxiety) accounting for 63.4% of the total variance.

Limitations: Heterogenous sample of adults with TRD receiving open-label treatment without placebo comparison.

Conclusion: The MARRRS is a brief validated self-report metric of depression symptom severity that is sensitive to change with the rapid-acting antidepressant ketamine. Measuring outcomes with the MARRRS informs treatment progress and facilitates treatment decisions in persons receiving the rapid-acting antidepressant ketamine. Studies of other rapid-acting antidepressants should incorporate outcome measures that are validated as sensitive to change with rapid-acting antidepressants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.03.053DOI Listing
March 2021

Validation of the McIntyre And Rosenblat Rapid Response Scale (MARRRS) in Adults with Treatment-Resistant Depression Receiving Intravenous Ketamine Treatment.

J Affect Disord 2021 Mar 26;288:210-216. Epub 2021 Mar 26.

Mood Disorders Psychopharmacology Unit, University Health Network; University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Brain and Cognition Discovery Foundation, Canada; University of Toronto, Toronto, ON, Canada.

Background: Depression severity and efficacy measurement scales employed for rapid-acting treatments (e.g., ketamine) were initially validated in adults receiving conventional monoamine-based antidepressants. The emergence of rapid-acting antidepressants in psychiatry provides the impetus for outcome measures that have been validated as sensitive to change with rapid-acting treatments. Herein, we provide results validating the McIntyre and Rosenblat Rapid Response Scale (MARRRS).

Methods: Adults with treatment-resistant depression (TRD) receiving intravenous (IV) ketamine had depressive symptoms measured with the 16-Item Quick Inventory Depressive Symptoms Self-Report (QIDS-SR-16) and MARRRS at baseline and as a repeated measure across an acute course of four infusions. The MARRRS is a self-report measure assessing depressive symptoms during the past 72 hours.

Results: Sixty-four patients (M = 45.4 ± 13.5) were included. The MARRRS had a high internal consistency across acute infusions as determined by Cronbach's alpha (0.84 to 0.94). There was significant convergent validity between the QIDS-SR-16 and MARRRS total scores across infusions (rs(292) = .87, p < .001); the MARRRS was also sensitive to change (rs(49) = .70, p < .001). Exploratory factor analysis revealed that MARRRS items loaded onto two factors (i.e., dysphoria and psychic anxiety) accounting for 63.4% of the total variance.

Limitations: Heterogenous sample of adults with TRD receiving open-label treatment without placebo comparison.

Conclusion: The MARRRS is a brief validated self-report metric of depression symptom severity that is sensitive to change with the rapid-acting antidepressant ketamine. Measuring outcomes with the MARRRS informs treatment progress and facilitates treatment decisions in persons receiving the rapid-acting antidepressant ketamine. Studies of other rapid-acting antidepressants should incorporate outcome measures that are validated as sensitive to change with rapid-acting antidepressants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.03.053DOI Listing
March 2021

The impact of overweight/obesity on monetary reward processing: A systematic review.

J Psychiatr Res 2021 May 18;137:456-464. Epub 2021 Mar 18.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address:

Objective: Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation).

Methods: PsycINFO, Google Scholar and PubMed databases were searched for English-language articles published between database inception to June 6th, 2020. Studies were identified using the following medical search heading (MeSH) terms and search strings: (reward (valuation OR motivation OR anticipation OR learning OR functioning OR decision-making OR reinforcement)) AND ((obesity OR overweight OR obese).

Results: Findings were reviewed from 11 studies evaluating the association between obesity and monetary reward processing. Four studies found significant differences in reward learning in individuals with obesity compared to normal-weight participants. Five studies found body mass index (BMI) to be predictive of willingness to expend effort (i.e., valuation) for a monetary reward. Three studies found changes in neural activations in the ventral striatum during anticipatory phases preceding receipt of a monetary reward in participants with obesity.

Conclusions: Participants with obesity demonstrated significantly poorer performance in task-based measures of reward learning, valuation, and anticipation, resulting in lower monetary reward outcomes across all studies compared to healthy controls. Notably, participants with obesity and comorbid depression performed worse than participants with no comorbid depression.

Limitations: There persists heterogeneity between studies with regards to inclusion of mood disorder populations and exclusion of psychiatric comorbidities in groups with obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2021.03.029DOI Listing
May 2021

Is Obesity A Determinant Of Success With Pharmacological Treatment For Depression? A Systematic Review, Meta-Analysis And Meta-Regression.

J Affect Disord 2021 May 15;287:54-68. Epub 2021 Mar 15.

Mood Disorders Psychopharmacology Unit (MDPU), Toronto Western Hospital, University Health Network, Toronto, ON, Canada.

Background: The bidirectional association between Major Depressive Disorder (MDD) and obesity suggests that body mass index (BMI) at the baseline could influence remission rates (RR) with pharmacological treatment. We evaluated the influence of baseline BMI on the chances of remission among patients with MDD administered antidepressants.

Methods: Based on the guidelines of the PRISMA statement, we conducted a systematic review on PubMed, Cochrane and Embase databases with subsequent meta-analysis and meta-regression. We included only randomized controlled trials evaluating the efficacy of antidepressants of different classes (monotherapy and combined therapies) that evidenced baseline BMI assessment. We created a model to describe the linear relationship between baseline BMI and RR.

Results: Our systematic review yielded 70 studies with a total of 9,779 patients in the active group and 7,136 patients in the placebo group. In placebo controlled studies, BMI influenced the RR of patients randomized to active treatment. The RR for antidepressants in monotherapy was higher in normal weight to overweight patients rather than obese patients (33% vs 12%, respectively). Also in monotherapy, the RR is higher when the study is conducted on patients with a lower baseline BMI (p=0.029). For combined therapies, the pooled RR was higher in obese patients rather than in normal weight to overweight patients (75% vs 17%, respectively).

Limitations: BMI provides no information about body composition and obesity can be related to several potential confounders that potentially influence RR.

Conclusion: The RR with antidepressant therapy seems to be associated with baseline BMI in patients with MDD, although this simple variable was insufficiently explored so far.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.03.032DOI Listing
May 2021

Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation.

Am J Psychiatry 2021 Mar 17:appiajp202020081251. Epub 2021 Mar 17.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto (McIntyre, Rosenblat, Y. Lee, Lui, Mansur); Department of Psychiatry, University of Toronto, Toronto (McIntyre, Rosenblat, Mansur); Department of Pharmacology, University of Toronto, Toronto (McIntyre); Brain and Cognition Discovery Foundation, Toronto (McIntyre, Subramaniapillai); Canadian Rapid Treatment Center of Excellence, Mississauga, Ontario (Rosenblat, Kratiuk); Department of Psychiatry and Behavioral Sciences, Austin Dell Medical School, University of Texas, Austin (Nemeroff); Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. (Sanacora); Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, and Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York (Murrough); Deakin University, Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia (Berk, Dodd); Orygen, National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Melbourne, Australia (Berk); Department of Psychiatry, Queen's University School of Medicine, and Centre for Neuroscience Studies, Queen's University, Kingston, Ontario (Brietzke); Centre for Youth Mental Health and Department of Psychiatry, University of Melbourne, Melbourne, Australia (Dodd); Université de Paris, Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, and GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris (Gorwood); Department of Psychological Medicine, Yong Loo Lin School of Medicine, and Institute of Health Innovation and Technology, National University of Singapore, Singapore (Ho); Department of Psychiatry, NYU School of Medicine, and Clinical Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York (Iosifescu); Department of Psychiatry, Universidad de Antioquia, Medellin, Colombia (Lopez Jaramillo); Center for Brain Research, Medical University of Vienna, Vienna (Kasper); Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan, Poland (Kratiuk); Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Paik Institute for Clinical Research, and Department of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea (J.G. Lee); Institute of Medical Science, University of Toronto, Toronto (Y. Lee); Clinical Trials Network and Institute, Massachusetts General Hospital, Boston (Papakostas); Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, and Corporal Michael J. Crescenz VA Medical Center, Philadelphia (Thase); Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona (Vieta); Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London and South London, and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Beckenham, Kent (Young); Experimental Therapeutics and Pathophysiology Branch and Section on the Neurobiology and Treatment of Mood Disorders, Division of Intramural Research Program, NIMH, Bethesda, Md. (Zarate); Department of Psychiatry and Neuroscience, University of California, Riverside, and University of California, San Diego (Stahl).

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ajp.2020.20081251DOI Listing
March 2021

A Systematic review of the validity of screening depression through Facebook, Twitter, Instagram, and Snapchat.

J Affect Disord 2021 05 8;286:360-369. Epub 2021 Feb 8.

Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore. Electronic address:

Background: The aim of this study was to determine the validity of using social media for depression screening.

Method: Article searches on PubMed and PsycINFO from database inception to August 20, 2019 were completed with a search string and filters.

Results: 15 articles made the inclusion criteria. Facebook, Twitter, and Instagram profiles of depressed people were distinguishable from nondepressed people shown by social media markers. Facebook studies showed that having fewer Facebook friends and mutual friends, posting frequently, and using fewer location tags positively correlated with depressive symptoms. Also, Facebook posts with explicit expression of depressive symptoms, use of personal pronouns, and words related to pain, depressive symptoms, aggressive emotions, and rumination predicted depression. Twitter studies showed that the use of "past focus" words, negative emotions and anger words, and fewer words per Tweet positively correlated with depression. Finally, Instagram studies showed that differences in follower patterns, photo posting and editing, and linguistic features between depressed people and nondepressed people could serve as a marker.

Limitations: The primary articles analyzed had different methods, which constricts the amount of comparisons that can be made. Further, only four social media platforms were explored.

Conclusion: Social media markers like number and content of Facebook messages, linguistic variability in tweets and tweet word count on Twitter, and number of followers, frequency of Instagram use and the content of messages on Instagram differed between depressed people and nondepressed people. Therefore, screening social media profiles on these platforms could be a valid way to detect depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.08.091DOI Listing
May 2021

Peripheral inflammatory biomarkers define biotypes of bipolar depression.

Mol Psychiatry 2021 Mar 3. Epub 2021 Mar 3.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.

We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-021-01051-yDOI Listing
March 2021

Loneliness-based impaired reward system pathway: Theoretical and clinical analysis and application.

Psychiatry Res 2021 Apr 10;298:113800. Epub 2021 Feb 10.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address:

Loneliness is a key determinant in the etiology of mental health disorders such as depression and has profound impacts on health, quality of life, and economic productivity. This narrative review uses extant neurobiology and evolutionary literature to propose a construct through which loneliness may induce depression in adulthood via the reward system (including symptom and treatment aspects). Early childhood (distal) factors were found to be important in influencing adult (proximal) factors, which lead to the formulation of the construct. Due to the heterogenous and comorbid nature of depression, a new subtype known as 'reward depression' was distinguished along with distinct symptoms to aid practitioners when assessing patient treatment options. Furthermore, an evolutionary perspective was applied to the current impaired reward construct to discuss how the ancestral purpose and environment (in terms of reward) clashes with the modern one. Finally, theoretical treatment and prevention ideas were examined and discussed, leading into future work that needs to build upon and confirm the outlined construct.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2021.113800DOI Listing
April 2021

Ecological momentary assessment of depressive symptoms using the mind.me application: Convergence with the Patient Health Questionnaire-9 (PHQ-9).

J Psychiatr Res 2021 03 11;135:311-317. Epub 2021 Jan 11.

Mind Mental Health Technologies Inc., Montreal, QC, Canada.

Ecological momentary assessment (EMA) for mental disorders, using application-based (app) technology capable of passive and ambient data collection, has been insufficiently evaluated and validated with rigorous, adequately-powered, high-quality studies. Herein, we sought to validate the mind.me application for the assessment of depressive symptoms in adults. Adults (ages 18-65) who self-identified as having clinically significant depressive symptoms [i.e. Patient Health Questionnaire 9 (PHQ-9) ≥ 5] utilized the mind.me app-a mobile phone technology that collects data passively and continuously, and is capable of integrating broad multimodal data [e.g., location variance (e.g. GPS), behavioural (e.g. social network activity), and communication data (e.g. SMS texting, phone calls)]. The primary outcome was predictive accuracy (i.e. convergent validity with depressive symptom measurement, as captured by the PHQ-9). 200 subjects were enrolled in the study (mean age 46 ± 12.71). The average PHQ-9 score was 12.8 ± 6.9. The predictive accuracy of the mind.me app was 0.91 ± 0.06. The sensitivity was 0.98 and the specificity was 0.93. The mind.me app was rated by 200 users as highly usable and informative to their illness. The mind.me app exhibits robust predictive accuracy in detecting depressive symptoms in adults with clinically relevant depressive symptoms. The mind.me app more specifically demonstrates convergence with the PHQ-9.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2021.01.012DOI Listing
March 2021

Ketamine-induced urological toxicity: potential mechanisms and translation for adults with mood disorders receiving ketamine treatment.

Psychopharmacology (Berl) 2021 Apr 23;238(4):917-926. Epub 2021 Jan 23.

Mood Disorder Psychopharmacology Unit, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.

Intravenous (IV) ketamine has been shown to have rapid and robust antidepressant effects in adults with treatment-resistant depression (TRD). Urological toxicity has been observed in chronic ketamine abusers as evidenced by dysuria, urgency, and hematuria. The foregoing observation provides the basis for evaluating whether ketamine-induced urological toxicity (KIUT) is associated with sub-anesthetic doses of ketamine (0.5-1.0 mg/kg) in adults with mood disorders. The overarching objective of this article is to identify potential mechanisms of KIUT which appears to be dose and frequency dependent. Available research indicates that high-frequency ketamine is associated with disruption of the urothelial barrier as well as direct ketamine toxicity (i.e., decreased expression of junction proteins) in KIUT of the bladder. Chronic and high-frequency ketamine use is also associated with bladder inflammation mediated via neurogenic and IgE inflammation. Other non-mutually exclusive causes are nerve hyperplasia, hypersensitivity, cell apoptosis, microvascular damage, and overexpression of carcinogenic genes. Notwithstanding the evidence of KIUT in ketamine abusers, there is no evidence that ketamine and/or esketamine treatment in adults with mood disorders is associated with KIUT. However, all patients receiving ketamine/esketamine for mood disorder treatment should be queried about genitourinary symptoms during acute and, where applicable, maintenance dosing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00213-021-05767-1DOI Listing
April 2021

The influence of prescriber and patient gender on the prescription of benzodiazepines: results from the Florida Medicaid Dataset.

CNS Spectr 2021 Jan 19:1-5. Epub 2021 Jan 19.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.

Background: Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.

Methods: Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.

Results: Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.

Conclusions: Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1092852921000055DOI Listing
January 2021

Insulin resistance is associated with deficits in hedonic, self-reported cognitive, and psychosocial functional response to antidepressant treatment in individuals with major depressive disorder.

J Affect Disord 2021 03 24;282:448-453. Epub 2020 Dec 24.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Background: To assess the effect of insulin resistance (IR) on treatment response to the antidepressant, vortioxetine, in patients with Major Depressive Disorder (MDD).

Methods: This is a secondary analysis of an 8-week, open-label clinical trial. Ninety-five adults in a primary care setting experiencing a major depressive episode were included. Response to vortioxetine was measured using the THINC-integrated tool, Montgomery Åsberg Depression Rating Scale (MADRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Perceived Deficits Questionnaire (PDQ-5), and the Sheehan Disability Scale (SDS). Generalized estimating equation models were utilized for data analysis.

Results: When adjusted for age, gender, dose, and BMI, there was a significant baseline IR by time interaction for SHAPS (p = 0.022), PDQ-5 (p = 0.037), and SDS (p = 0.013). Higher baseline IR predicted decreased early improvements in anhedonia. It also predicted poorer subjective assessments of cognition and increased functional impairment at the endpoint of treatment. For functional capacity (i.e. SDS) other covariates including severity of symptoms, illness course, other metabolic factors (e.g. cholesterol), and physical activity were included with no changes to the moderating effect of baseline IR.

Limitations: This was a post-hoc analysis of a primarily non-diabetic sample. Also, only one agent was assessed.

Conclusions: IR was a predictor of response to vortioxetine. This persisted after controlling for other factors including, but not limited to, BMI. These findings strengthen the link between depression and IR and may point to another novel metabolic predictor of response. These findings should be replicated using other antidepressants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.12.074DOI Listing
March 2021

A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions.

J Affect Disord 2021 03 29;282:160-164. Epub 2020 Dec 29.

Mood Disorders Psychopharmacology Unit, University Health Network; University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Brain and Cognition Discovery Foundation, Canada; University of Toronto, Toronto, ON, Canada.

Background: Dissociation is a treatment-emergent adverse event commonly associated with IV ketamine, often measured using the 23-item Clinician-Administered Dissociative States Scale (CADSS). The objective of this study was to develop a short form version of the CADSS for easier clinical use.

Methods: Retrospective data of 260 patients with treatment-resistant depression (TRD) receiving IV ketamine were randomly divided into two datasets. The first dataset (n = 130) was leveraged to develop a brief 6-item version of the CADSS (CADSS-6) based on items most sensitive to ketamine-induced dissociation. The CADSS-6 questions were then applied to the second dataset (n = 130) and the Spearman's correlation between the full-length CADSS and the CADSS-6 were assessed.

Results: The CADSS-6 was developed from questions 1, 2, 6, 7, 15, and 22 from the full length CADSS. There was a strong significant correlation between the CADSS-6 total score and the CADSS total score at infusions 1 (rs(106) = 0.92, p < 0.001), 2 (rs(100) = 0.91, p < 0.001), 3(rs(99) = 0.95, p < 0.001) and 4 (rs(102) = 0.94, p < 0.001).

Limitations: The CADSS-6 was developed using a retrospective data; therefore, the scale remains unvalidated in this population.

Conclusions: The CADSS-6 presented herein was sensitive to dissociation experienced by patients receiving IV ketamine. Overall, the CADSS-6 was strongly correlated at each infusion with the full-length CADSS. While future studies should look to validate the CADSS-6 in a TRD sample, this scale offers clinicians a brief assessment that can be used to characterize symptoms of dissociation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.12.119DOI Listing
March 2021

A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions.

J Affect Disord 2021 03 29;282:160-164. Epub 2020 Dec 29.

Mood Disorders Psychopharmacology Unit, University Health Network; University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Brain and Cognition Discovery Foundation, Canada; University of Toronto, Toronto, ON, Canada.

Background: Dissociation is a treatment-emergent adverse event commonly associated with IV ketamine, often measured using the 23-item Clinician-Administered Dissociative States Scale (CADSS). The objective of this study was to develop a short form version of the CADSS for easier clinical use.

Methods: Retrospective data of 260 patients with treatment-resistant depression (TRD) receiving IV ketamine were randomly divided into two datasets. The first dataset (n = 130) was leveraged to develop a brief 6-item version of the CADSS (CADSS-6) based on items most sensitive to ketamine-induced dissociation. The CADSS-6 questions were then applied to the second dataset (n = 130) and the Spearman's correlation between the full-length CADSS and the CADSS-6 were assessed.

Results: The CADSS-6 was developed from questions 1, 2, 6, 7, 15, and 22 from the full length CADSS. There was a strong significant correlation between the CADSS-6 total score and the CADSS total score at infusions 1 (rs(106) = 0.92, p < 0.001), 2 (rs(100) = 0.91, p < 0.001), 3(rs(99) = 0.95, p < 0.001) and 4 (rs(102) = 0.94, p < 0.001).

Limitations: The CADSS-6 was developed using a retrospective data; therefore, the scale remains unvalidated in this population.

Conclusions: The CADSS-6 presented herein was sensitive to dissociation experienced by patients receiving IV ketamine. Overall, the CADSS-6 was strongly correlated at each infusion with the full-length CADSS. While future studies should look to validate the CADSS-6 in a TRD sample, this scale offers clinicians a brief assessment that can be used to characterize symptoms of dissociation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.12.119DOI Listing
March 2021

Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin.

J Psychiatr Res 2021 01 4;133:82-92. Epub 2020 Dec 4.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855678PMC
January 2021

Effectiveness of intravenous ketamine in mood disorder patients with a history of neurostimulation.

CNS Spectr 2020 Dec 10:1-7. Epub 2020 Dec 10.

Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, Toronto, Ontario, Canada.

Background: Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.

Methods: This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith-Hamilton Pleasure Scale (SHAPS).

Results: Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.

Conclusion: IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1092852920002187DOI Listing
December 2020

Effects of infliximab on brain neurochemistry of adults with bipolar depression.

J Affect Disord 2021 02 3;281:61-66. Epub 2020 Dec 3.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Objectives: To explore the relationship between inflammation and neuronal metabolism in bipolar disorder (BD) by evaluating the neurochemical effects of the tumor necrosis factor-α (TNF-α) antagonist infliximab among individuals with bipolar depression METHODS: This is a post-hoc, exploratory analysis from a 12-week, randomized, double-blind, placebo-controlled trial with infliximab for adults with bipolar depression. We assessed the effects of infliximab on concentration of metabolites in the prefrontal cortex, using proton-magnetic resonance spectroscopy (H-MRS), as well as its association with clinical outcomes (i.e. depressive symptom severity and cognitive function).

Results: Eighteen participants in the placebo and 15 in the infliximab group were included in this analysis. In the pre-specified primary outcome, there were no significant effects of treatment on prefrontal concentrations of N-acetylaspartate (NAA; p = 0.712). In the secondary analyses, there was a significant treatment by time interaction for glutamate (Glx; p = 0.018), indicating that Glx levels decreased in infliximab-treated patients, relative to placebo. Treatment group significantly moderated the association between changes in Glx levels and changes in a neurocognitive test (i.e. Digit Symbol Substitution Test; p = 0.014), indicating that in infliximab-treated participants reductions in Glx were associated with cognitive improvement.

Conclusions: Treatment with infliximab did not affect prefrontal NAA concentration in adults with BD. Exploratory analysis suggested a potential effect of treatment on the glutamate system, a finding that should be confirmed and validated by additional studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.11.128DOI Listing
February 2021

Effects of infliximab on brain neurochemistry of adults with bipolar depression.

J Affect Disord 2021 02 3;281:61-66. Epub 2020 Dec 3.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Objectives: To explore the relationship between inflammation and neuronal metabolism in bipolar disorder (BD) by evaluating the neurochemical effects of the tumor necrosis factor-α (TNF-α) antagonist infliximab among individuals with bipolar depression METHODS: This is a post-hoc, exploratory analysis from a 12-week, randomized, double-blind, placebo-controlled trial with infliximab for adults with bipolar depression. We assessed the effects of infliximab on concentration of metabolites in the prefrontal cortex, using proton-magnetic resonance spectroscopy (H-MRS), as well as its association with clinical outcomes (i.e. depressive symptom severity and cognitive function).

Results: Eighteen participants in the placebo and 15 in the infliximab group were included in this analysis. In the pre-specified primary outcome, there were no significant effects of treatment on prefrontal concentrations of N-acetylaspartate (NAA; p = 0.712). In the secondary analyses, there was a significant treatment by time interaction for glutamate (Glx; p = 0.018), indicating that Glx levels decreased in infliximab-treated patients, relative to placebo. Treatment group significantly moderated the association between changes in Glx levels and changes in a neurocognitive test (i.e. Digit Symbol Substitution Test; p = 0.014), indicating that in infliximab-treated participants reductions in Glx were associated with cognitive improvement.

Conclusions: Treatment with infliximab did not affect prefrontal NAA concentration in adults with BD. Exploratory analysis suggested a potential effect of treatment on the glutamate system, a finding that should be confirmed and validated by additional studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2020.11.128DOI Listing
February 2021

Does body mass index predict response to intravenous ketamine treatment in adults with major depressive and bipolar disorder? Results from the Canadian Rapid Treatment Center of Excellence.

CNS Spectr 2020 Dec 3:1-9. Epub 2020 Dec 3.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.

Background: Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).

Methods: Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith-Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).

Results: Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups.

Conclusions: The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1092852920002102DOI Listing
December 2020

The influence of prescriber and patient gender on the prescription of benzodiazepines: evidence for stereotypes and biases?

Soc Psychiatry Psychiatr Epidemiol 2020 Nov 30. Epub 2020 Nov 30.

Department of Healthcare Administration, Asia University, No. 500, Lioufeng Rd, Wufeng, Taichung, 41354, Taiwan.

Purpose: Benzodiazepines are commonly prescribed globally. We hypothesize that gender stereotypes influence benzodiazepine prescriptions insofar as male prescribers are more likely to prescribe benzodiazepines to female patients.

Methods: Our nationwide cohort study included 2,127,441 patients with a psychiatric disorder (ICD-9 codes 290-319) and 38,932 prescribers as part of the Taiwan National Health Insurance Research Database (1997-2013). We evaluated the effects of patient and prescriber gender on the proportion of patients prescribed benzodiazepines and the cumulative dosage of benzodiazepine prescription (mg) using generalized estimating equation and general linear models.

Results: The proportion of patients prescribed benzodiazepines was higher among male (vs. female) prescribers [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.05-1.07] and among female (vs. male) patients (OR = 1.08, 95% CI = 1.08-1.09). Similarly, male prescriber gender (β = 10,292.2, SE = 1265.5, p < 0.001) and female patient gender (β = 7913.7, SE = 627.1, p < 0.001) predicted higher cumulative dosages of benzodiazepine prescription. Mean cumulative dosage was highest among female patients seen by male prescribers (β = 4283.7, SE = 717.6, p < 0.001). The results were consistent in sensitivity analyses of patients with anxiety disorder (n = 1,632,363), major depression (n = 1,122,796), or chronic administration (n = 1,981,819), and prescribers with psychiatrists (n = 1276), and non-psychiatrists (n = 33,268).

Conclusions: Male prescribers were more likely to prescribe benzodiazepines to female patients relative to male patients. This gender bias in prescription is significant and warrants careful attention at point of care. We hypothesize that internalized societal biases and stereotypes affect benzodiazepine prescribing behaviour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00127-020-01989-4DOI Listing
November 2020

The Effects of Ketamine on Cognition in Treatment-Resistant Depression: A Systematic Review and Priority Avenues for Future Research.

Neurosci Biobehav Rev 2021 01 23;120:78-85. Epub 2020 Nov 23.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address:

Replicated evidence has documented cognitive deficits in populations with treatment-resistant depression (TRD). Approximately 40 % of patients with MDD present with impairment of one or more cognitive domains. As such, there is an unmet need to discover treatments that have pro-cognitive effects in TRD patients. Ketamine has demonstrated efficacy as a rapid-onset intervention for the treatment of depression. The objective of the current review was to assess the effects of ketamine on cognition in TRD patients. We systematically searched PubMed, Google Scholar and PsycINFO between database inception to March 24th, 2020. We identified five studies that evaluated cognition in TRD populations following ketamine treatment. All studies included a 0.5 mg/kg subanesthetic intravenous (IV) administration of ketamine. One study found significant improvements in complex (p = .008) and simple (p = .027) working memory and one study found improvements in visual learning memory following IV ketamine infusions (p = .014). Improvements in speed of processing and verbal learning memory were observed in anxious TRD participants only. Importantly, a subanesthetic dose of IV ketamine does not worsen cognitive function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2020.11.020DOI Listing
January 2021

Development and implementation of guidelines for the management of depression: a systematic review.

Bull World Health Organ 2020 Oct 27;98(10):683-697H. Epub 2020 Aug 27.

School of Clinical Medicine, The University of Queensland, Brisbane, Australia.

Objective: To evaluate the development and implementation of clinical practice guidelines for the management of depression globally.

Methods: We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries.

Findings: We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence.

Conclusion: Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2471/BLT.20.251405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652558PMC
October 2020

The Effect of Loneliness on Distinct Health Outcomes: A Comprehensive Review and Meta-Analysis.

Psychiatry Res 2020 12 19;294:113514. Epub 2020 Oct 19.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address:

The primary objective was to evaluate the comparative effects of loneliness on multiple distinct health outcomes. The literature was qualitatively reviewed to identify loneliness risk factors, explore mechanisms, and discuss potential evidence-based interventions for targeting loneliness. 114 identified studies were systematically reviewed and analyzed to examine for associations between loneliness (as measured by the UCLA Loneliness or de Jong Gierveld Loneliness Scales) and one or more health outcome(s). Health outcomes were broadly defined to include measures of mental health (i.e., depression, anxiety, suicidality, general mental health), general health (i.e., overall self-rated health), well-being (i.e., quality of life, life satisfaction), physical health (i.e., functional disability), sleep, and cognition. Loneliness had medium to large effects on all health outcomes, with the largest effects on mental health and overall well-being; however, this result may have been confounded by the breadth of studies exploring the association between loneliness and mental health, as opposed to other health outcomes. A significant effect of gender on the association between loneliness and cognition (i.e., more pronounced in studies with a greater proportion of males) was also observed. The adequate training of health care providers to perceive and respond to loneliness among patients should be prioritized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2020.113514DOI Listing
December 2020

The effectiveness of intravenous ketamine in adults with treatment-resistant major depressive disorder and bipolar disorder presenting with prominent anxiety: Results from the Canadian Rapid Treatment Center of Excellence.

J Psychopharmacol 2021 Feb 11;35(2):128-136. Epub 2020 Oct 11.

Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada.

Background: Individuals meeting criteria for treatment-resistant depression (TRD) are differentially affected by high levels of anxiety symptoms.

Aims: There is a need to identify the efficacy of novel rapid-onset treatments in adults with mood disorders and comorbid anxious-distress.

Methods: This study included patients with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD) who were receiving intravenous (IV) ketamine treatment at a community-based clinic.Anxious-distress was proxied using items from the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS-SR) and Generalized Anxiety Disorder 7-item (GAD7) scales. The difference in QIDS-SR total score, QIDS-SR suicidal ideation (SI) item and GAD7 score were analyzed between groups.

Results: A total of 209 adults with MDD ( = 177) and BD ( = 26) were included in this analysis. From this sample, 94 patients (mean = 45 ± 13.9 years) met the criteria for anxious-distress. Individuals meeting the criteria for anxious-distress exhibited a significantly greater reduction in QIDS-SR total score following four infusions ( = 0.02) when compared with patients not meeting the anxious-distress criteria. Both anxious-distressed and low-anxiety patients exhibited a significant reduction in SI ( < 0.0001) following four infusions.Finally, there was a significantly greater reduction in anxiety symptoms in the anxious-distress group compared with the non-anxious distress group following three ( = 0.02) and four infusions ( < 0.001).

Conclusion: Patients with TRD and prominent anxiety receiving IV ketamine exhibited a significant reduction in depressive, SI and anxiety symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0269881120954048DOI Listing
February 2021

Early symptomatic improvements as a predictor of response to repeated-dose intravenous ketamine: Results from the Canadian Rapid Treatment Center of Excellence.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Mar 5;105:110126. Epub 2020 Oct 5.

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; Brain and Cognition Discovery Foundation, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Background: Early symptomatic improvement with monoamine-based antidepressants is predictive of treatment response. The objective of this study was to determine if early symptomatic improvements with intravenous (IV) ketamine predicted treatment response to an acute course of four infusions.

Method: 134 adults with treatment resistant depression (TRD) received four ketamine infusions over one to two weeks. Depressive symptoms were measured using the Quick Inventory for Depressive Symptomatology Self-Report (QIDS-SR) at baseline and post-infusions 1, 2, 3, and 4. Early improvement was defined as ≥20% reduction in QIDS-SR scores after the first or second infusion. Linear models were used to determine whether early improvement was associated with post-infusion 4 QIDS-SR scores after controlling for baseline characteristics.

Results: Early improvement post-infusion 1 (β = -3.52, 95% BCa CI [-5.40, -1.78]) and 2 (β = -3.16, 95% BCa CI [-5.75, -1.59]) both significantly predicted QIDS-SR scores post-infusion 4. Early improvers had significantly lower QIDS-SR scores at post-infusion 4 (post-infusion 1 improvers: M = 9.8, SD = 4.5; post-infusion 2 improvers: M = 10.6, SD = 5.7) compared to non-early improvers (post-infusion 1 non-improvers: M = 13.7, SD = 5.8; post-infusion 2 non-improvers: M = 14.1, SD = 5.3) when controlling for baseline characteristics. The majority (58%) of individuals who did not improve post-infusions 1 or 2 still experienced an antidepressant response or partial response (≥20% reduction in QIDS-SR) post-infusion 4.

Limitations: This is a post-hoc analysis of an open-label study.

Conclusion: Early improvement was associated with greater antidepressant effects following a course of four ketamine infusions. However, individuals who did not show early improvements still had a high likelihood of experiencing clinically significant symptom reduction after the fourth infusion, suggesting that completing four infusions, regardless of early symptom changes, is appropriate and merited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pnpbp.2020.110126DOI Listing
March 2021

Antidepressant Medications and Weight Change: A Narrative Review.

Obesity (Silver Spring) 2020 11 6;28(11):2064-2072. Epub 2020 Oct 6.

Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network, Toronto, Ontario, Canada.

Antidepressant medications are the first-line treatment option for moderate to severe major depressive disorder. However, most antidepressants have numerous documented adverse events, including cardiometabolic effects and weight gain, which are major public health concerns. Antidepressant agents provide varying risk of associated weight gain, including significant within-class differences. Some agents, such as mirtazapine, show significant levels of weight gain, while others, such as bupropion, demonstrate weight-loss effects. Current findings suggest the role of histamine and serotonin off-target appetite-promoting pathways in adverse weight-gain effects. Therefore, controlling for undesired weight effects is an important consideration for the selection of antidepressants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/oby.22969DOI Listing
November 2020

The emerging role of psilocybin and MDMA in the treatment of mental illness.

Expert Rev Neurother 2020 12 30;20(12):1263-1273. Epub 2020 Sep 30.

Mood Disorders Psychopharmacology Unit, University Health Network , Toronto, ON, Canada.

Introduction: Mental illness has a chronic course of illness with a number of clinical manifestations. Affected individuals experience significant functional, emotional, cognitive, and/or behavioral impairments. The growing prevalence of mental illness has been associated with significant social and economic costs. Indeed, the economic burden of mental illness is estimated to exceed $1.8 trillion USD over the next 30 years. A significant number of individuals affected by mental illness fail to respond to first-line treatment options. Therefore, there remains an unmet need for rapidly attenuating therapeutic options for mental health disorders with minimal social and economic burden.

Areas Covered: The paucity of novel treatment options warrants a renewed investigation of psychedelic-based psychotherapy. Herein, the authors will evaluate the therapeutic potential of traditional psychedelics, psilocybin, and MDMA, in the treatment of mental illness with a narrative review of available literature.

Expert Opinion: Psychedelics, such as psilocybin and MDMA, offer an alternative avenue of therapy for many mental health disorders. Available evidence indicates that psychedelics may offer a single-dose, rapid effect model that have robust effects with treatment-resistant mental disorders and a unique advantage as a possible monotherapy for mental illness. Novel clinical trials that evaluate the safety, tolerability, and efficacy in clinically representative populations are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14737175.2020.1826931DOI Listing
December 2020

Intravenous ketamine for postmenopausal women with treatment-resistant depression: Results from the Canadian Rapid Treatment Center of Excellence.

J Psychiatr Res 2021 04 8;136:444-451. Epub 2020 Aug 8.

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; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Women are disproportionately represented amongst samples of adults with treatment-resistant depression (TRD). Ketamine has demonstrated rapid and robust efficacy in adults with TRD. Herein, we sought to determine whether the effectiveness of intravenous (IV) ketamine was influenced by menopausal status in women with TRD. We defined premenopausal women as those under the age of 45 (n = 52), while postmenopausal women (n = 54) were those over the age of 51. Participants received four IV ketamine infusions over one-to-two weeks at a community-based center for adults with TRD. The primary outcome of interest was the change in depressive symptom severity as measured by the Quick Inventory of Depressive Symptomatology Self-Report 16 (QIDS-SR) following four infusions, compared to pretreatment. The secondary outcomes were improvements in suicidal ideation (SI; i.e., QIDS-SR SI item), anxiety (i.e., Generalized Anxiety Disorder-7 scale), anhedonic severity (i.e., Snaith-Hamilton Pleasure Scale), and workplace and psychosocial function (i.e., Sheehan Disability Scale). Menopausal status did not influence overall treatment response, F (4, 280) = 1.83, p = .123, η = 0.025. Both premenopausal and postmenopausal participants demonstrated similar response rates (30% and 26%, respectively) and remission rates (both 13%) to IV ketamine treatment following four infusions. Premenopausal women experienced improvements in social function more rapidly than postmenopausal women, F (2, 174) = 1.65, p = .047, η = 0.019. Postmenopausal women experienced reduction in SI more rapidly than premenopausal women, F (4, 280) = 2.72, p = .030, η = 0.037. These preliminary post-hoc findings provide the impetus for future studies to investigate the moderational role of menopausal status, as defined by hormone levels, on response to IV ketamine for TRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2020.08.002DOI Listing
April 2021

Intravenous ketamine for postmenopausal women with treatment-resistant depression: Results from the Canadian Rapid Treatment Center of Excellence.

J Psychiatr Res 2021 04 8;136:444-451. Epub 2020 Aug 8.

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; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Women are disproportionately represented amongst samples of adults with treatment-resistant depression (TRD). Ketamine has demonstrated rapid and robust efficacy in adults with TRD. Herein, we sought to determine whether the effectiveness of intravenous (IV) ketamine was influenced by menopausal status in women with TRD. We defined premenopausal women as those under the age of 45 (n = 52), while postmenopausal women (n = 54) were those over the age of 51. Participants received four IV ketamine infusions over one-to-two weeks at a community-based center for adults with TRD. The primary outcome of interest was the change in depressive symptom severity as measured by the Quick Inventory of Depressive Symptomatology Self-Report 16 (QIDS-SR) following four infusions, compared to pretreatment. The secondary outcomes were improvements in suicidal ideation (SI; i.e., QIDS-SR SI item), anxiety (i.e., Generalized Anxiety Disorder-7 scale), anhedonic severity (i.e., Snaith-Hamilton Pleasure Scale), and workplace and psychosocial function (i.e., Sheehan Disability Scale). Menopausal status did not influence overall treatment response, F (4, 280) = 1.83, p = .123, η = 0.025. Both premenopausal and postmenopausal participants demonstrated similar response rates (30% and 26%, respectively) and remission rates (both 13%) to IV ketamine treatment following four infusions. Premenopausal women experienced improvements in social function more rapidly than postmenopausal women, F (2, 174) = 1.65, p = .047, η = 0.019. Postmenopausal women experienced reduction in SI more rapidly than premenopausal women, F (4, 280) = 2.72, p = .030, η = 0.037. These preliminary post-hoc findings provide the impetus for future studies to investigate the moderational role of menopausal status, as defined by hormone levels, on response to IV ketamine for TRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2020.08.002DOI Listing
April 2021

Intravenous ketamine for postmenopausal women with treatment-resistant depression: Results from the Canadian Rapid Treatment Center of Excellence.

J Psychiatr Res 2021 04 8;136:444-451. Epub 2020 Aug 8.

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; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Women are disproportionately represented amongst samples of adults with treatment-resistant depression (TRD). Ketamine has demonstrated rapid and robust efficacy in adults with TRD. Herein, we sought to determine whether the effectiveness of intravenous (IV) ketamine was influenced by menopausal status in women with TRD. We defined premenopausal women as those under the age of 45 (n = 52), while postmenopausal women (n = 54) were those over the age of 51. Participants received four IV ketamine infusions over one-to-two weeks at a community-based center for adults with TRD. The primary outcome of interest was the change in depressive symptom severity as measured by the Quick Inventory of Depressive Symptomatology Self-Report 16 (QIDS-SR) following four infusions, compared to pretreatment. The secondary outcomes were improvements in suicidal ideation (SI; i.e., QIDS-SR SI item), anxiety (i.e., Generalized Anxiety Disorder-7 scale), anhedonic severity (i.e., Snaith-Hamilton Pleasure Scale), and workplace and psychosocial function (i.e., Sheehan Disability Scale). Menopausal status did not influence overall treatment response, F (4, 280) = 1.83, p = .123, η = 0.025. Both premenopausal and postmenopausal participants demonstrated similar response rates (30% and 26%, respectively) and remission rates (both 13%) to IV ketamine treatment following four infusions. Premenopausal women experienced improvements in social function more rapidly than postmenopausal women, F (2, 174) = 1.65, p = .047, η = 0.019. Postmenopausal women experienced reduction in SI more rapidly than premenopausal women, F (4, 280) = 2.72, p = .030, η = 0.037. These preliminary post-hoc findings provide the impetus for future studies to investigate the moderational role of menopausal status, as defined by hormone levels, on response to IV ketamine for TRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2020.08.002DOI Listing
April 2021