Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression

Acevedo-Diaz, Elia E.; Cavanaugh, Grace W.; Greenstein, Dede; Kraus, Christoph; Kadriu, Bashkim; Zarate, Carlos A.; Park, Lawrence T.

doi:10.1016/j.jad.2019.11.028

Cited by 73 publications

(45 citation statements)

References 28 publications

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“…diplopia, drowsiness, and confusion. 46,47 Ketamine is also contraindicated in those patients who have underlying conditions such as aortic dissection, uncontrolled hypertension, myocardial infarction or aneurysms, in which increased blood pressure would pose a risk of complications. 48,49 Thus, concerns persist with regard to the safety and feasibility of prolonged use of ketamine.…”

Section: Discussionmentioning

confidence: 99%

<p>BDNF and the Antidepressant Effects of Ketamine and Propofol in Electroconvulsive Therapy: A Preliminary Study</p>

Huang¹,

Xiong²,

He³

et al. 2020

NDT

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Objective: Ketamine and propofol have become increasingly popular in electroconvulsive therapy (ECT) anaesthesia. This study was conducted to examine whether changes in serum levels of brain-derived neurotrophic factor (BDNF) are associated with the antidepressant effects of ketofol, a combination of ketamine and propofol, in ECT for patients with treatment-resistant depression (TRD). Methods: Thirty patients with TRD (18-65 years) were enrolled and underwent eight ECT sessions with ketamine (0.5 mg/kg) plus propofol (0.5 mg/kg) (ketofol). Symptom severity was monitored using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Brief Psychiatric Rating Scale (BPRS), and serum levels of BDNF were examined by enzyme-linked immunosorbent assay (ELISA) at baseline and after 2, 4, and 8 ECT treatments. Serum levels of BDNF were also collected from thirty healthy controls. Results: At baseline, there were no significant differences in serum levels of BDNF between patients with TRD and healthy controls. The response and remission rates in patients with TRD were 100% (30/30) and 53.3% (16/30) after ECT treatment, respectively. Despite a significant reduction in HAMD-17 and BPRS scores after ECT, no changes in serum levels of BDNF were observed after ECT treatment when compared to baseline. No association was found between serum levels of BDNF and changes in illness severity. Conclusion: Serum levels of BDNF did not represent a suitable candidate biomarker for determining the antidepressant effects of ketofol during ECT for patients with TRD.

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Section: Discussionmentioning

confidence: 99%

<p>BDNF and the Antidepressant Effects of Ketamine and Propofol in Electroconvulsive Therapy: A Preliminary Study</p>

Huang¹,

Xiong²,

He³

et al. 2020

NDT

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“…Notwithstanding the relatively well-established antidepressant efficacy of ketamine in TRD, as well as preliminary evidence supporting its anti-suicidality effects, the safety and tolerability of long-term ketamine treatment is insufficiently characterized. Results from short-term (i.e., < 2 weeks) randomized controlled trials indicate that ketamine is generally well tolerated and is safe [8,9]. The most frequently reported treatment-emergent adverse events and safety concerns include dissociation, nausea, blood pressure elevation, tachycardia, and headache [9].…”

Section: Introductionmentioning

confidence: 99%

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

Rodrigues

McIntyre

Lipsitz

et al. 2020

Expert Opinion on Drug Safety

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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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“…We approached the ketamine arm of the treatment cautiously because the patient had struggled with alcohol dependence, substance abuse is common in patients with AN, and ketamine is a drug that is recreationally abused. A recent study, pooling data from 5 clinical trials found no evidence of serious side effects from a single infusion of ketamine for clinical depression, and ketamine was not associated with increased abuse ( 26 ). Many patients reported feeling “loopy” or “dissociative” during the infusion, but this passed rapidly.…”

Section: Discussionmentioning

confidence: 99%

Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report

Scolnick

Zupec‐Kania²,

Calabrese

et al. 2020

Front. Psychiatry

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Background Chronic anorexia nervosa is a tragic disease with no known effective pharmacological or behavioral treatment. We report the case of a 29 year-old woman who struggled with severe and enduring anorexia nervosa for 15 years, and experienced a complete recovery following a novel treatment of adopting a ketogenic diet followed by ketamine infusions. Her remission has persisted for over 6 months. Case Presentation At age 14.5, the patient embarked on an effort to “eat healthy.” She quickly lost control of the dieting, developed associated compulsions and obsessions about food, body dissatisfaction, emotional lability, and lost nearly 13.6 kilograms (30 pounds). She was hospitalized for 6 weeks, and while she regained some weight, she did not attain full weight restoration. For 15 years, she continued to eat in a restrictive manner, exercise compulsively, and have intermittent periods of alcohol dependence. Nevertheless, she always hoped to get well, and at age 29, she began a novel treatment for anorexia nervosa. Conclusions This is the first report of a ketogenic diet used specifically for the treatment of anorexia nervosa, followed by a short series of titrated IV ketamine infusions leading to complete remission of severe and enduring anorexia nervosa, with weight restoration, and sustained cessation of cognitive and behavioral symptoms, for 6 months. Although these treatments were used sequentially the relationship between these modalities, and possible synergy, is unclear, and deserves further study. Complete and sustained remission of chronic anorexia nervosa is quite rare, and the novel use of a ketogenic diet and IV ketamine treatment in this potentially lethal condition suggests avenues for further research, and hope for patients and their families.

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Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression

Cited by 73 publications

References 28 publications

<p>BDNF and the Antidepressant Effects of Ketamine and Propofol in Electroconvulsive Therapy: A Preliminary Study</p>

<p>BDNF and the Antidepressant Effects of Ketamine and Propofol in Electroconvulsive Therapy: A Preliminary Study</p>

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

Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report

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