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Efficacy of ketamine for comorbid depression and acute or chronic pain: A systematic review.

Aksharra Balachandran, Vanessa K Tassone, Fathima Adamsahib, Anne-Marie Di Passa, Sarah Kuburi, Ilya Demchenko, Karim S Ladha, Venkat Bhat

Frontiers in Pain Research 2022 DOI: 10.3389/fpain.2022.1022767 (opens in new tab)

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Characteristics Systematic review Placebo-controlled Longitudinal Peer reviewed
Population Individuals with comorbid depression and chronic pain (CDCP) or comorbid depression and acute pain (CDAP)
Intervention Ketamine
Dose sub-anesthetic doses
Topics Ketamine Depression Esketamine
Keywords Comorbidity Dissociative anesthetics Glutamate Mood disorders Pain
Key findings Across 7 chronic pain trials, 3 reported reductions in both depression and pain, 3 in only one, and 1 in neither; across 7 acute pain trials, 4 reported improvements in both and 3 in only one. Ten of 12 case studies and 2 of 3 observational studies reported improvements in pain and depression scores after treatment, with variable duration. The authors conclude preliminary evidence supports ketamine for these comorbid conditions, but heterogeneous, mixed results prevent comprehensive conclusions.

Abstract

Pain and depression frequently co-occur. Due to its antidepressant and analgesic properties, ketamine has been used for the management of treatment-resistant depression and pain. This systematic review examined the literature on the efficacy of sub-anesthetic doses of ketamine in individuals experiencing comorbid depression and chronic pain (CDCP), as well as comorbid depression and acute pain (CDAP). A secondary objective was to provide an assessment of dosage, route, and adverse effects of ketamine treatment for CDCP and CDAP. A literature search was conducted on MEDLINE, PsycINFO, and Embase databases, coupled with a manual screening of the bibliography sections of included articles. In addition, registered ongoing and planned trials were searched on Clinicaltrials.gov. The end date of the search was April 9th, 2022. Included studies assessed changes in depression and pain in patients receiving at least one sub-anesthetic dose of ketamine. Assessment of quality was conducted using the GRADE checklist. Of the 7 CDCP clinical trials, 3 reported a reduction in depression and pain, 3 reported a reduction in depression or pain only, and 1 reported no improvement in either comorbidity. Among the 7 CDAP clinical trials, 4 studies found improvements in depression and pain while the remaining 3 reported improvements in only one parameter. Ten of the 12 case studies and 2 of the 3 observational studies assessing CDCP and CDAP found improvements in pain and depression scores post-treatment with effects of variable duration. The planned methodologies of the registered clinical trials are in line with those of the published research. Preliminary evidence supports the efficacy of ketamine in treating CDCP and CDAP. However, the current review identified a small number of heterogeneous studies with mixed results, preventing comprehensive conclusions. More longitudinal placebo-controlled studies are needed to identify the effects of ketamine for patients with CDCP and CDAP.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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