Low-dose ketamine for treatment resistant depression in an academic clinical practice setting

Feifel, David; Malcolm, Benjamin; Boggie, Danielle; Lee, Kelly C.

doi:10.1016/j.jad.2017.06.043

Cited by 25 publications

(15 citation statements)

References 30 publications

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“…Future RCTs should recruit more heterogeneous populations to assess the impact of ketamine treatment on patient subgroups depending on baseline demographic data, comorbidities, and also use of various psychotropic medications. Of note, a recent uncontrolled clinical study confirmed high antidepressant efficacy of single ketamine infusion in patients with TRD who showed significant psychiatric comorbidity, with the 24-h response and remission rates of 54% and 42%, respectively [54].…”

Section: Discussionmentioning

confidence: 93%

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials

Kryst

Kawalec

Mitoraj³

et al. 2020

Pharmacol. Rep

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Background Due to unmet clinical needs for efficient drugs with a rapid onset of antidepressant effects, we aimed to evaluate the efficacy of single-dose ketamine in different subgroups of patients with major depression and establish whether repeated ketamine administration could be a viable strategy to maintain treatment gains. Methods Electronic databases (Medline via PubMed, Embase, Cochrane Library, Trip Database) were systematically searched until February 22, 2019, for published peer-reviewed randomized controlled trials (RCTs) concerning a single and repeated administration of ketamine in patients with major depression. All relevant RCTs were selected and critically appraised, and a meta-analysis of eligible studies was performed. Results A total of 20 studies were included in the meta-analysis. The largest effect of ketamine vs. controls in reducing depressive symptoms was observed at 24 h (SMD = − 0.89; 95% CI − 1.24; − 0.53; p < 0.00001); however, a significant difference was shown for up to 7 days after a single dose. Significant differences compared with controls were observed for up to 7 days in treatment-resistant patients and when ketamine was added to ongoing antidepressant treatment, while there were no significant differences at 7 days when ketamine was used as monotherapy. In patients with major depression, initial antidepressant effects of ketamine were maintained during repeated dosing. At 2-3 weeks of repeated ketamine treatment, significant reduction of depression severity scores was observed: SMD = − 0.70; 95% CI − 1.15; − 0.25 or SMD = − 0.81; 95% CI − 1.41; − 0.20 (depending on the dosing regimen used); p ≤ 0.009 vs placebo. Conclusions Our meta-analysis revealed rapid and robust antidepressant effects of single-dose ketamine in patients with treatment-resistant depression (TRD). By pooling data from RCTs, we showed for the first time that repeated ketamine administration is effective in sustaining initial antidepressant effects observed after single dosing.

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Section: Discussionmentioning

confidence: 93%

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials

Kryst

Kawalec

Mitoraj³

et al. 2020

Pharmacol. Rep

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“…No response was also noted when an intramuscular form of 100 mg was administered TRBD patients [9]. This could be due to different plasma levels of the drug, which depend on the route of administration [16].…”

Section: Ketamine In Major Depressive Disorder (Mdd) and Bipolar Deprmentioning

confidence: 99%

“…Rapid and extensive administrations regimens were described, ranging from 2 to 5 min (i.v.) [16] and up to 100 min, respectively [9]. The FDA and the European Medicines Agency (EMA) established that esketamine intake via intranasal administration takes ca.…”

Section: Ketamine In Major Depressive Disorder (Mdd) and Bipolar Deprmentioning

confidence: 99%

Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis

Włodarczyk

Cubała

2020

Medicina

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The current psychopharmacological treatment approaches for major depression focus on monoaminergic interventions, which are ineffective in a large proportion of patients. Globally, treatment-resistant bipolar depression (TRBD) affects up to 33% of depressive patients receiving treatment. Certain needs are still unmet and require new approaches. Many studies are in favor of treatments with ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, even in single use, whose effects emerge in minutes to hours post administration. However, little data are available on ketamine performance in TRBD patients with somatic comorbidities, including highly prevalent ones, i.e., cardiovascular disease (heart failure, hypertension, post-myocardial infarct, arrhythmias, etc.) diabetes, and obesity, and depression-associated comorbidities such as stroke, epilepsy, as well as in the elderly population. The literature shows that treatment with ketamine is efficacious and safe, and the majority of adverse drug reactions are mild and tend to mostly disappear within 30 min to 2 h of ketamine administration.

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“…In addition, we report that symptoms of dissociation and derealization, as assessed using the CADSS, were highest at the first infusion, followed by a significant attenuation but plateau in subsequent infusions. Extant literature does indicate that symptoms of dissociation do attenuate with repeat doses of IV ketamine [4,9,24]. Contrary to the symptoms of depersonalization and derealization, symptoms of amnesia increased in the third and fourth infusion compared to infusion 2.…”

Section: Discussionmentioning

confidence: 96%

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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Low-dose ketamine for treatment resistant depression in an academic clinical practice setting

Cited by 25 publications

References 30 publications

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials

Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis

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

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