Publications by authors named "Kevin Kratiuk"

23 Publications

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Ketamine monotherapy versus adjunctive ketamine in adults with treatment-resistant depression: Results from the Canadian Rapid Treatment Centre of Excellence.

J Psychiatr Res 2021 Sep 3;143:209-214. Epub 2021 Sep 3.

Mood Disorder 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.

A proportion of individuals with major depressive disorder (MDD) do not receive adequate therapeutic benefit from conventional monoaminergic antidepressant drugs, leading to treatment-resistant depression (TRD). Ketamine has been shown to provide rapid and significant efficacy in treating patients with TRD. The majority of published studies have investigated the adjunctive efficacy of ketamine with one or more monoaminergic antidepressants. There remains a clinical need to ascertain the relative effectiveness of ketamine monotherapy versus adjunctive ketamine treatment in adults with TRD. In this retrospective study, we investigate multidimensional, self-reported outcomes (i.e., antidepressant, anti-suicidality, antianxiety, and anti-functional impairment) of 220 patients to compare monotherapy (n = 39) and adjunctive (n = 181) ketamine treatment for TRD at a community-based clinic. Both groups had clinically and statistically significant antidepressant effects (p < 0.05). Individuals receiving ketamine monotherapy exhibited a significantly greater reduction on the suicidal ideation (SI) item of the Quick Inventory for Depressive Symptomatology-Self Report 16-Item (QIDS-SR) than the adjunctive group, with a small effect size [F (1, 265) = 4.73; p = 0.03*; partial η = 0.02], and a significantly higher proportion of partial responders at post-infusion 4 (p = 0.034*). No other between-group differences were significant. Limitations include the small sample, single-centred, open-label, non-randomized, uncontrolled, retrospective nature of this study and indication bias. Our real-world evidence suggests that ketamine may be effective as monotherapy or adjunct to monoamine-based treatments. A priority research and clinical vista is to identify subsets of individuals with TRD who are most likely to have a desired therapeutic outcome with monotherapy versus adjunctive ketamine treatment.
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http://dx.doi.org/10.1016/j.jpsychires.2021.09.002DOI Listing
September 2021

Ketamine monotherapy versus adjunctive ketamine in adults with treatment-resistant depression: Results from the Canadian Rapid Treatment Centre of Excellence.

J Psychiatr Res 2021 Sep 3;143:209-214. Epub 2021 Sep 3.

Mood Disorder 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.

A proportion of individuals with major depressive disorder (MDD) do not receive adequate therapeutic benefit from conventional monoaminergic antidepressant drugs, leading to treatment-resistant depression (TRD). Ketamine has been shown to provide rapid and significant efficacy in treating patients with TRD. The majority of published studies have investigated the adjunctive efficacy of ketamine with one or more monoaminergic antidepressants. There remains a clinical need to ascertain the relative effectiveness of ketamine monotherapy versus adjunctive ketamine treatment in adults with TRD. In this retrospective study, we investigate multidimensional, self-reported outcomes (i.e., antidepressant, anti-suicidality, antianxiety, and anti-functional impairment) of 220 patients to compare monotherapy (n = 39) and adjunctive (n = 181) ketamine treatment for TRD at a community-based clinic. Both groups had clinically and statistically significant antidepressant effects (p < 0.05). Individuals receiving ketamine monotherapy exhibited a significantly greater reduction on the suicidal ideation (SI) item of the Quick Inventory for Depressive Symptomatology-Self Report 16-Item (QIDS-SR) than the adjunctive group, with a small effect size [F (1, 265) = 4.73; p = 0.03*; partial η = 0.02], and a significantly higher proportion of partial responders at post-infusion 4 (p = 0.034*). No other between-group differences were significant. Limitations include the small sample, single-centred, open-label, non-randomized, uncontrolled, retrospective nature of this study and indication bias. Our real-world evidence suggests that ketamine may be effective as monotherapy or adjunct to monoamine-based treatments. A priority research and clinical vista is to identify subsets of individuals with TRD who are most likely to have a desired therapeutic outcome with monotherapy versus adjunctive ketamine treatment.
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http://dx.doi.org/10.1016/j.jpsychires.2021.09.002DOI Listing
September 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 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

Does pre-treatment functioning influence response to intravenous ketamine in adults with treatment-resistant depression?

J Affect Disord 2021 09 20;292:714-719. Epub 2021 Jun 20.

Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Background: The efficacy of monoamine-based antidepressants in adults with major depressive disorder (MDD) is attenuated in persons with greater pre-treatment functional impairment. Herein, we investigated whether pre-treatment functioning in outpatients with treatment-resistant depression (TRD) moderates response to intravenous (IV) ketamine.

Methods: Adults (N= 326; M = 45) with DSM-5-defined MDD or bipolar disorder and TRD received repeat-dose IV ketamine at a community-based clinic. Function was evaluated with the Sheehan Disability Scale (SDS), using total scores as well as scores on the subdomains of workplace/school, social life, and family life/home responsibilities. The primary dependent measure was change in depressive symptoms from pre-treatment to post-infusion 4, as measured by the Quick Inventory for Depressive Symptomatology-Self Report-16.

Results: Total functional disability, as well as the subdomains of social life and family life/home responsibilities, significantly moderated response to IV ketamine (p = .003; p = .008; p = .008). Follow-up simple slopes analyses indicated a significant improvement in depressive symptoms across the functional domain spectrum (ps < .001). Above average functional disability (i.e., 1 SD > mean functional impairment within the sample) was associated with a greater change in depressive symptoms. Workplace function did not significantly moderate response to IV ketamine (p = .307), suggesting that individuals with significantly impaired workplace functioning may expect a similar response to ketamine as those with less workplace impairment.

Conclusions: Symptomatic benefit with IV ketamine was observed in patients with TRD and significant pre-treatment functional impairment. The foregoing result has implications for mechanism of action, cost-effectiveness, and patient selection in adults with TRD receiving IV ketamine.
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http://dx.doi.org/10.1016/j.jad.2021.05.090DOI Listing
September 2021

Does pre-treatment functioning influence response to intravenous ketamine in adults with treatment-resistant depression?

J Affect Disord 2021 09 20;292:714-719. Epub 2021 Jun 20.

Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Background: The efficacy of monoamine-based antidepressants in adults with major depressive disorder (MDD) is attenuated in persons with greater pre-treatment functional impairment. Herein, we investigated whether pre-treatment functioning in outpatients with treatment-resistant depression (TRD) moderates response to intravenous (IV) ketamine.

Methods: Adults (N= 326; M = 45) with DSM-5-defined MDD or bipolar disorder and TRD received repeat-dose IV ketamine at a community-based clinic. Function was evaluated with the Sheehan Disability Scale (SDS), using total scores as well as scores on the subdomains of workplace/school, social life, and family life/home responsibilities. The primary dependent measure was change in depressive symptoms from pre-treatment to post-infusion 4, as measured by the Quick Inventory for Depressive Symptomatology-Self Report-16.

Results: Total functional disability, as well as the subdomains of social life and family life/home responsibilities, significantly moderated response to IV ketamine (p = .003; p = .008; p = .008). Follow-up simple slopes analyses indicated a significant improvement in depressive symptoms across the functional domain spectrum (ps < .001). Above average functional disability (i.e., 1 SD > mean functional impairment within the sample) was associated with a greater change in depressive symptoms. Workplace function did not significantly moderate response to IV ketamine (p = .307), suggesting that individuals with significantly impaired workplace functioning may expect a similar response to ketamine as those with less workplace impairment.

Conclusions: Symptomatic benefit with IV ketamine was observed in patients with TRD and significant pre-treatment functional impairment. The foregoing result has implications for mechanism of action, cost-effectiveness, and patient selection in adults with TRD receiving IV ketamine.
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http://dx.doi.org/10.1016/j.jad.2021.05.090DOI Listing
September 2021

The effect of intravenous ketamine on cognitive functions in adults with treatment-resistant major depressive or bipolar disorders: Results from the Canadian rapid treatment center of excellence (CRTCE).

Psychiatry Res 2021 Aug 13;302:113993. Epub 2021 May 13.

Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Ketamine may exert pro-cognitive effects on select measures of cognition in adults with mood disorders. We evaluated the effectiveness of intravenous (IV) ketamine on cognition in 68 adult outpatients with treatment-resistant depression (TRD) at the Canadian Rapid Treatment Center of Excellence between July 3, 2018 and April 16, 2020 (NCT04209296). Eligibility criteria for the present retrospective study included: primary diagnosis of major depressive or bipolar disorder; currently depressed; and insufficient response to two or more prior treatments. Participants received four infusions of ketamine hydrochloride (0.5-0.75 mg/kg) over 1-2 weeks. We assessed objective and subjective measures of cognition before and after two infusions, i.e., Digit Symbol Substitution Test (DSST), Trail Making Test-B (TMT-B), Patient Deficits Questionnaire, 5-item (PDQ-5-D). Ketamine significantly improved DSST (effect size [ES]=0.60), TMT-B (ES=0.84), as well as PDQ-5-D scores (ES=0.63), indicative of a moderate-to-large effect size. Improvements in DSST and PDQ-5-D with ketamine were mediated by reductions in depressive symptoms, whereas improvements in TMT-B were independent of changes in depressive symptoms. Our results support the independent, rapid-onset, pro-cognitive effects with IV ketamine in adults with TRD. Larger, randomized, controlled trials with ketamine wherein cognition is the primary outcome measure in mood and non-mood disorder samples are warranted.
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http://dx.doi.org/10.1016/j.psychres.2021.113993DOI Listing
August 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 06 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.
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http://dx.doi.org/10.1016/j.jad.2021.03.053DOI Listing
June 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 06 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.
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http://dx.doi.org/10.1016/j.jad.2021.03.053DOI Listing
June 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 05 17;178(5):383-399. 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.
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http://dx.doi.org/10.1176/appi.ajp.2020.20081251DOI Listing
May 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.
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http://dx.doi.org/10.1007/s00213-021-05767-1DOI Listing
April 2021

Safety, Tolerability, and Real-World Effectiveness of Intravenous Ketamine in Older Adults With Treatment-Resistant Depression: A Case Series.

Am J Geriatr Psychiatry 2021 09 9;29(9):899-913. Epub 2021 Jan 9.

Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, University Health Network (OL, JDV, NBR, DSC, YL, MS, RSM, JDR), Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence (OL, NBR, YL, DG, KMT, MS, KK RSM, JDR), Mississauga, ON, Canada; Department of Psychiatry, University of Toronto (AJF, RSM, JDR), Toronto, ON, Canada.

Objective: To evaluate the safety, tolerability, and effectiveness of repeated doses of intravenous (IV) ketamine in older adults (i.e., ≥60 years of age) with treatment-resistant depression.

Method: In this case series, fifty-three older adults (M = 67, SD = 6; 57% female [n = 30]) received 4 IV ketamine infusions, administered over 1-2 weeks. Effectiveness of IV ketamine was measured using the Quick Inventory for Depressive Symptomatology-Self Report 16 (QIDS-SR16) approximately 2 days after infusions 1-3, and 1-2 weeks after infusion 4. Safety was measured as hemodynamic changes before, during, immediately after, and 20 minutes after each infusion. Tolerability was assessed via systematic reporting of treatment-emergent adverse events during and after each infusion, in addition to symptoms of dissociation measured using the Clinician Administered Dissociative States Scale. Partial response (25%-50% symptomatic improvement from baseline), response (≥50% symptomatic improvement from baseline), clinically significant improvements (≥25% symptomatic improvement from baseline), and remission rates (QIDS-SR16 ≤5) were also calculated.

Results: Participants reported significant decreases in depressive symptoms (i.e., as measured by the QIDS-SR16) with repeated ketamine infusions (F(4, 92) = 7.412, p <0.001). The mean QIDS-SR16 score was 17.12 (SD = 5.33) at baseline and decreased to 12.52 (SD = 5.79) following 4 infusions. After 4 infusions, 31% (n = 8) of participants partially responded to IV ketamine, 27% (n = 7) responded, 58% (n = 15) experienced clinically significant improvements, and 10% (n = 3) met remission criteria. Thirty-six participants (69%) experienced treatment-emergent hypertension during at least 1 infusion, and 10 (19%) required intervention with an antihypertensive. Drowsiness was the most commonly reported adverse event (50% of infusions; n = 73).

Conclusion: Ketamine was associated with transient treatment-emergent hypertension. Response and remission rates were comparable to those reported in general adult samples. Findings are limited by the open-label, chart review nature of this study.
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http://dx.doi.org/10.1016/j.jagp.2020.12.032DOI Listing
September 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.
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http://dx.doi.org/10.1016/j.jad.2020.12.119DOI Listing
March 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.
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http://dx.doi.org/10.1017/S1092852920002187DOI Listing
December 2020

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.
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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 02 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.
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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 03 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.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110126DOI Listing
March 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.
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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.
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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.
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April 2021

Safety and tolerability of IV ketamine in adults with major depressive or bipolar disorder: results from the Canadian rapid treatment center of excellence.

Expert Opin Drug Saf 2020 Aug 15;19(8):1031-1040. Epub 2020 Jun 15.

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

Objectives: Rigorous clinical trials suggest ketamine is safe and well-tolerated in patients with treatment-resistant depression (TRD). There is a paucity of data on the safety and tolerability of ketamine in community-based clinics treating patients with TRD.

Methods: Retrospective data was analyzed from 203 patients with TRD who received repeat-dose IV ketamine. Safety was operationalized as hemodynamic changes. Tolerability was evaluated through the reporting of adverse events and dissociation symptom severity, as measured by the Clinician-Administered Dissociative States Scale.

Results: Ketamine was well-tolerated, with less than 5% of patients withdrawing due to tolerability concerns. Blood pressure significantly increased during infusion, with 44.3% meeting criteria for treatment-emergent hypertension (i.e., blood pressure ≥ 165/100 mmHg). 12% of patients exhibiting hypertension required pharmacological intervention. The most frequently reported adverse events included drowsiness (56.4%), dizziness (45.2%), dissociation (35.6%), and nausea (13.3%). Dissociation severity significantly attenuated after the first infusion, but plateaued for subsequent infusions.

Conclusion: Intravenous ketamine was safe and well-tolerated. Hypertension was commonly observed and was often transient. Dissociation was most frequently reported after the first infusion but remained a consistent but not treatment-limiting adverse event thereafter. No patients exhibited psychosis, mania, or new onset suicidality with IV ketamine.
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http://dx.doi.org/10.1080/14740338.2020.1776699DOI Listing
August 2020

Safety and tolerability of IV ketamine in adults with major depressive or bipolar disorder: results from the Canadian rapid treatment center of excellence.

Expert Opin Drug Saf 2020 Aug 15;19(8):1031-1040. Epub 2020 Jun 15.

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

Objectives: Rigorous clinical trials suggest ketamine is safe and well-tolerated in patients with treatment-resistant depression (TRD). There is a paucity of data on the safety and tolerability of ketamine in community-based clinics treating patients with TRD.

Methods: Retrospective data was analyzed from 203 patients with TRD who received repeat-dose IV ketamine. Safety was operationalized as hemodynamic changes. Tolerability was evaluated through the reporting of adverse events and dissociation symptom severity, as measured by the Clinician-Administered Dissociative States Scale.

Results: Ketamine was well-tolerated, with less than 5% of patients withdrawing due to tolerability concerns. Blood pressure significantly increased during infusion, with 44.3% meeting criteria for treatment-emergent hypertension (i.e., blood pressure ≥ 165/100 mmHg). 12% of patients exhibiting hypertension required pharmacological intervention. The most frequently reported adverse events included drowsiness (56.4%), dizziness (45.2%), dissociation (35.6%), and nausea (13.3%). Dissociation severity significantly attenuated after the first infusion, but plateaued for subsequent infusions.

Conclusion: Intravenous ketamine was safe and well-tolerated. Hypertension was commonly observed and was often transient. Dissociation was most frequently reported after the first infusion but remained a consistent but not treatment-limiting adverse event thereafter. No patients exhibited psychosis, mania, or new onset suicidality with IV ketamine.
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August 2020

Rapastinel - an investigational NMDA-R modulator for major depressive disorder: evidence to date.

Expert Opin Investig Drugs 2019 Feb 26;28(2):113-119. Epub 2018 Dec 26.

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

Introduction: Major depressive disorder (MDD) is a debilitating disorder with increasing prevalence globally. Despite the development of novel treatments for MDD, many patients present with treatment resistant depression (TRD), identified by treatment non-response following one or more adequate trials of an antidepressant. Rapastinel may prove to be a viable treatment for TRD; it has the potential to produce a rapid antidepressant response without serious adverse events and improve functional symptoms. Areas covered: We review the efficacy of rapastinel via completed and on-going clinical trials. The online databases Pubmed, clinicaltrials.gov and clinicaltrialsregister.eu were searched for rapastinel (GLYX-13) treatment in subjects with MDD. Nine clinical trials were identified. Expert opinion: Rapastinel is a novel and potentially transformative treatment for individuals with TRD. There is a limited number of clinical studies so far, but this compound has the potential to provide rapid, reliable and robust antidepressant effects without psychotomimetic and other unwanted side effects. Alternative formulations such as the oral formulation, provide the opportunity for rapastinel to be administered less frequently, i.e. once weekly. Furthermore, the beneficial effects on measures of cognition and suicidality so far, represent a tremendous advantage.
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http://dx.doi.org/10.1080/13543784.2019.1559295DOI Listing
February 2019
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