This comprehensive review (2019) compared the efficacy of ketamine treatment for pain and depression within palliative care across administration route and dosing regimen. Efficacy of pain treatment exhibited generally inconclusive and mixed results, but studies that administered ketamine either epidurally or intrathecally demonstrated significant analgesia, in contrast, to subcutaneously or intravenous administration routes. Depression was improved across all relevant studies and was sustained the longest during a daily dosing regimen, whereas a single or a multidose did not exert effects beyond 7 days after administration.
Abstract
“Background: Previous literature suggests that ketamine may be an effective drug in the palliative care population as this drug has been shown to treat multiple conditions that are common in these patients.
Objective: This review examines the efficacy of ketamine for the treatment of depression and physical pain in palliative care patients.
Methods: Eleven studies were included on the topic of ketamine as an antidepressant in the palliative care population. Additionally, 5 RCT studies were included on the topic of physical pain in this population.
Results: All 11 studies, including one RCT, found antidepressant effects of ketamine in this patient population. Ketamine’s effect on treating physical pain was mixed with the largest and most recent RCTs suggesting no significant analgesic effect.
Discussion: This review suggests that starting qualified patients on intravenous (IV) ketamine and switching to oral or intranasal administration may be the most effective and convenient for treating depression, especially for patients who wish to receive treatment at home. Significant analgesia was found in patients who received epidural or intrathecal ketamine as well as in one study using intravenous administration. More research is necessary to determine which palliative care patients may benefit from ketamine treatment.”
Authors: Nathaniel Goldman, Michael Frankenthaler & Lidia Klepacz
Notes
This paper is included in our ‘Top 12 Articles on on Ketamine for Mental Health‘
Ketamine has been shown to be effective in treating depression and physical pain in palliative care patients.
Background
Palliative medicine patients with life-threatening illness have a high prevalence of depression, with varying levels reported among noncancer patients.
As challenging as accurately diagnosing depression among palliative care patients is developing an effective treatment strategy, standard antidepressants require additional time to reach therapeutic dose and are often ineffective before death.
Using psychostimulants with monoaminergic treatment can help treat depression more rapidly in terminally ill patients, but they carry possible side effects.
Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, is being studied for its off-label use in treating refractory depression. It is thought to work by modulating the glutamatergic system through inhibition of the NMDA receptor.
Ketamine has been shown to be safe when administered intravenously or orally and has shown positive results in the treatment of chronic and opioid-resistant pain outside of palliative care patients.
Purpose
This review discusses the efficacy of ketamine for the treatment of depression and physical pain in the palliative care population.
Depression
A search was conducted to find articles on depression in palliative care patients. 11 articles were found, including 1 RCT, 1 retrospective chart review, 1 open label trial, and 8 case reports.
Physical pain
A review of RCTs on ketamine use in palliative care patients was conducted. Five studies were included after assessing the relevant patient population and treatment protocol.
Depression studies
Two larger studies using ketamine to treat depression in palliative care patients reported positive results. The only RCT for ketamine use in cancer patients with depression recorded significant lower suicidal ideation and an antidepressant effect already on day 1.
In Iglewicz et al., hospice patients given ketamine for depression showed positive results on days 0 – 1 and 2 – 3 and 4 – 7.
In a smaller case study, Irwin and Iglewicz reported positive results using ketamine to treat depression in two hospice patients.
Irwin et al. conducted a study in which 14 terminally ill patients received 0.5 mg/kg of ketamine every night for 28 days. Overall, 57% of the subjects experienced an improvement in depressive symptoms.
Five small case studies examined multiple-dose ketamine use for depression in this patient population. All of these case studies reported positive results, with the most recent report showing a 38% decrease in depression on the Hospital Anxiety and Depression Scale (HADS-D) scale after 48 hours.
Physical pain studies
In a randomized, double-blind, placebo-controlled study, 48 terminally-ill cancer patients with chronic pain received epidural ketamine, neostigmine, or midazolam. The ketamine group maintained a pain score below 4/10 for significantly longer than the control group.
10 patients with opioid-resistant cancer pain received ketamine as an IV bolus at 0.25 and 0.5 mg/kg. Adverse psychological effects resolved with administration of 1 mg IV diazepam.
In a double-blind crossover study, patients with advanced cancer and chronic pain received intrathecal ketamine and morphine. The M + K group required a lower dose of morphine to achieve acceptable analgesia and had lower pain scores compared with the M phase.
In a double-blind, placebo-controlled study, 185 palliative care patients with refractory cancer pain received either subcutaneous ketamine (100 – 500 mg/day) or saline (control). No significant difference in pain outcomes was found between the ketamine and control groups.
Salas et al. found no significant analgesic effect for ketamine when used as an adjuvant to opioids in 20 palliative care patients with opioid refractory cancer pain.
Discussion
Every study that used ketamine to treat depression in palliative care patients reported positive results. The most sustained alleviation of depression was observed in the studies that administered ketamine on a daily dosing regimen.
Ketamine’s efficacy was influenced by its speed of onset, and ketamine injection showed rapid onset. Ketamine oral administration showed variations in time of onset, but may prove useful for hospice patients who wish to remain at home instead of receiving treatment in the hospital.
Ketamine was used in multiple studies for depression and anxiety in palliative care patients. Long-term safety and efficacy was not extensively assessed, and caution should be taken when considering long-term use of ketamine in palliative care patients.
In this review of five RCTs on ketamine use in palliative care patients, the analgesic effect of ketamine was inconclusive. Older studies reported positive analgesic effects, whereas two newer studies did not see this effect.
Ketamine analgesia was demonstrated when administered epidurally or intrathecally. Subcutaneous or intravenously administered ketamine had no significant analgesic effect.
Ketamine may not have been given a sufficient dose in some studies, which may have explained the lack of analgesic effects.
Ketamine may be useful in treating multiple comorbid aspects of pain in the palliative care setting. It is possible that an ideal ketamine dose exists, and a screening method may be useful for determining which patients will most benefit from ketamine.