Depression is common among seriously ill patients. Pharmacotherapy has been psychostimulants for those with a shorter prognosis (days to weeks) and selective serotonin reuptake inhibitors (SSRIs) for those with a longer prognosis (weeks to months), however the efficacy of these medications has been mixed in palliative care populations
Ketamine has the potential to offer rapid relief in treatment-resistant depression (TRD – which has not responded to at least two adequate trials of antidepressants).
It can be given for depression intravenously (IV) or orally (usually the IV solution mixed into a palatable liquid). However, oral ketamine poor bioavailability (only 20%). Intranasal ketamine or esketamine has a bioavailability of 45%. Ketamine has not been well studied in seriously ill adults with depression, and there is poor evidence to support its use for TRD in children.

Intravenous. Ketamine for TRD have examined healthy patients receiving one-time IV infusions of 0.5 mg/kg over 40 minutes as an adjuvant therapy with a follow-up of less than two weeks. A single administration of IV ketamine significantly reduced depressive symptoms and suicidal thinking within one week. Response rates for a single infusion are 50-70%; the time to relapse is 1-3 weeks, necessitating repeat infusions. Reported side effects are short lived (commonly four hours) and include dizziness, euphoria, perceptual disturbances, confusion, blood pressure elevation.

Oral. A study of oral ketamine in hospice patients demonstrated some improvement in a validated, patient-reported depression scale when dosed at 0.5 mg/kg for 28 days; the time to response was 1-2 weeks; lack of response was 30 %. Side effects were dizziness, delirium, hallucinations, nausea, vomiting, and headache.

Intranasal. Esketamine (an S-isomer) is used as a nasal spray for TRD in conjunction with oral antidepressants; a study showed a 44% response rate to a single dose of 50 mg intranasal ketamine; onset was 40 minutes and lasted less than 3 days. Common side effects are “feeling unreal,” fatigue, and poor memory for up to four hours.

Ketamine’s effect on depression outlasts the side effect of euphoria. As needed benzodiazepines such as midazolam 1-5 mg IV or lorazepam 0.5 mg-2 mg IV are recommended for ketamine-induced delirium and hallucinations, the most common adverse drug reactions

There is concern for its potential to produce urinary, hepatobiliary, and neuropsychiatric side effects if used more than two weeks consecutively.
Its risk of misuse or addiction is relatively unknown.

See reference for more information.

Adapted from Christensen A, Pruskowski J.The role of ketamine in depression. Palliative Care Network of Wisconsin. Fast facts and concepts #384. Internet. Accessed on Sep 10, 2019.