Case Report: Ketamine for Pain and Depression in Advanced Cancer

Patients with advanced cancer frequently experience both severe physical pain and depressive symptoms that substantially reduce quality of life. Traditional pharmacologic options have limitations in the end-of-life setting: antidepressants such as SSRIs and SNRIs often require weeks to produce benefit, opioids can cause sedation and respiratory depression and may be less effective for neuropathic pain, and methadone has a complex pharmacology with risks such as QTc prolongation. Ketamine, a rapidly acting dissociative anaesthetic with NMDA-receptor antagonist activity, has been used off-label for both neuropathic pain and treatment-resistant depression and is of interest in the palliative context because of its fast onset of action. Blinderman and colleagues present a single-case report addressing a clinical gap: whether a continuous low-dose intravenous ketamine infusion used for pain might also produce rapid improvement in severe, treatment-naïve depression in a patient with advanced cancer. The report describes the clinical course, dosing rationale, and outcomes for a patient treated at a tertiary academic centre, and situates the case within the sparse literature on ketamine for depression at the end of life.

This is a single-patient case report from a tertiary academic hospital describing evaluation and treatment of pain and depression in a man with advanced cancer. The extracted text does not present a formal methods section beyond the detailed clinical course in the Case Presentation. The patient was a 64-year-old man with metastatic anaplastic thyroid cancer who had previously received surgery, chemotherapy, and radiation. He was admitted for syncope and gastrointestinal bleeding and was found to be hypovolaemic with acute kidney injury and other metabolic abnormalities. Comorbidities included hypertension, hypothyroidism, atrial fibrillation, sleep apnoea, and kidney stones. Performance measures recorded on admission were a Palliative Performance Status of 40% and an Eastern Cooperative Oncology Group (ECOG) grade of 3, suggesting a prognosis of less than six months. His outpatient analgesic regimen included methadone 5 mg twice daily and oxycodone 5 mg every four hours as required; his QTc interval was reported as 605 ms while on methadone and fluconazole. Psychiatry was consulted after the patient expressed a desire to hasten death and scored 24/27 on the Patient Health Questionnaire-9 (PHQ-9), consistent with severe major depressive disorder. The clinical team elected to initiate a continuous intravenous ketamine infusion for pain at 0.2 mg/kg/h, following the institution's guideline for low-dose ketamine for pain; the authors note a separate institutional protocol exists for ketamine in refractory depression that uses different dosing (0.5 mg/kg IV nightly). The infusion was started on hospital day 4 at 17:00. Outcomes were monitored clinically using numeric pain scores, bedside observations of mood and behaviour, and psychiatric reassessment. The team documented responses over the subsequent hospital days, adjusted rescue analgesia as needed, and placed a peripherally inserted central catheter to continue the infusion after discharge to home hospice. Analysis was descriptive and based on serial clinical measurements; no formal statistical testing applies to a single-case report.

Prior to ketamine initiation the patient reported neuropathic odynophagia and right neck pain rated 8/10. After starting a continuous IV infusion of ketamine at 0.2 mg/kg/h, pain decreased to 3/10 by 21:00 on the same day (approximately four hours after initiation) and to 0/10 at 26 hours after initiation. During the infusion he experienced two transient pain spikes up to 7/10 that responded to 0.5 mg intravenous hydromorphone. On psychiatric assessment before treatment the patient had a PHQ-9 score of 24/27, indicating severe depression and expressed wishes to die. During and after the ketamine infusion his affect and behaviour changed markedly: staff and family observed him smiling, engaging in conversation, and dancing with his daughter. The palliative psychiatrist documented an improved mood, congruent affect, and absence of suicidal ideation or plan. The team discontinued methadone—partly because of the previously prolonged QTc—and the patient continued oxycodone 5 mg orally as needed for breakthrough pain. He was discharged to home hospice on hospital day 6 with a peripherally inserted central catheter to continue the ketamine infusion and remained on ketamine until his peaceful death at home approximately two weeks later. The extracted text does not report a follow-up PHQ-9 numeric score, systematic adverse-event surveillance, or formal neurocognitive testing; no serious ketamine-related adverse events were described in this case.

Blinderman and colleagues interpret this case as an example of rapid, clinically meaningful improvement in both neuropathic pain and severe, treatment-naïve depression following a continuous low-dose IV ketamine infusion. They place the case in the context of a variable reported prevalence of major depressive disorder in advanced cancer (15%–48%) and note that symptoms of depression often overlap with cancer-related features, complicating recognition and treatment. The authors argue that the typically delayed onset of conventional antidepressants limits their utility near the end of life, and that alternatives such as methylphenidate, while fast-acting, do not address concomitant pain. The discussion reviews other case reports and small case series that have described rapid antidepressant responses to ketamine administered orally, intramuscularly, or intravenously in patients with advanced cancer; reported benefits have sometimes been sustained for days to weeks but may be short-lived and subject to diminished effect on repeat dosing. The authors emphasise ketamine's dual pharmacologic profile—NMDA-receptor antagonism for neuropathic pain and a putative mechanism relevant to depression—as supportive of its potential utility in palliative care. They acknowledge important limitations: this is a single case report and therefore cannot establish efficacy or safety more generally, objective measurement of caregiver or bereavement outcomes is lacking, and the frequency and clinical significance of tachyphylaxis with prolonged infusion remain unclear. Finally, they call for a well-designed randomised study of continuous IV ketamine for depression in advanced cancer to determine optimal dosing and to better define risks and benefits, and advise clinicians to be familiar with ketamine's mechanisms, dosing regimens, and potential adverse effects before use.