Oral Ketamine vs Placebo in Patients With Cancer-Related Neuropathic Pain

Fallon, Marie; Wilcock, Andrew; Kelly, Caroline; Paul, James; Lewsley, Liz-Anne; Norrie, John; Laird, Barry

doi:10.1001/jamaoncol.2018.0131

Cited by 46 publications

(53 citation statements)

References 6 publications

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“…One randomized controlled trial on the effect of oral ketamine versus placebo in cancer-related neuropathic pain was not included in any of the reviews and deserves mentioning. Fallon et al randomized 214 patients with chemotherapy-induced neuropathic pain [40]. A ketamine or placebo titration phase was followed by pain control maintenance phase.…”

Section: Systematic Reviews and Randomized Trialsmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature

Kamp

Olofsen

et al. 2019

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Chronic neuropathic pain (NP) is an incapacitating illness caused by a lesion of the somatosensory nervous system and is associated with several diseases or syndromes. Since current treatment options lack adequate efficacy in the majority of patients, ketamine is often administered to treat refractory NP. Areas covered: This review gives an overview of new ketamine pharmacokinetic data including data on intranasal and inhaled ketamine. The outcome of seven systematic reviews and meta-analyses, published since 2012, on ketamine efficacy in NP is discussed. The reader will additionally get an understanding of ketamine's complex metabolism with emphasis on the metabolite hydroxynorketamine. Expert opinion: Proof of sustained, large effects of ketamine in the treatment of NP from randomized controlled clinical trials is lacking, although we cannot exclude selective ketamine efficacy in patients with central sensitization, opioid-induced hyperalgesia or opioid tolerance. Interestingly, data from observational trials and case series do suggest the efficacy of ketamine in producing effective pain relief in NP with positive patient-related outcome measures. Additional randomized trials in often illdefined groups of chronic pain patients are not useful and we suggest to conduct future studies in NP patients with central sensitization and/or with opioid refractory severe NP.

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Section: Systematic Reviews and Randomized Trialsmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature

Kamp

Olofsen

et al. 2019

Expert Opinion on Drug Metabolism & Toxicology

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“…There was no statistical difference between the two arms for analgesic benefit ( P = 0.75). [ 49 ] A randomized, double-blind, placebo-controlled study conducted to assess the efficacy of ketamine in patients suffering from cancer pain refractory to opiates did not find benefit of morphine–ketamine combination in refractory pain. [ 50 ]…”

Section: Ethodsmentioning

confidence: 99%

Indian society for study of pain, cancer pain special interest group guidelines on pharmacological management of cancer pain (Part III)

Thota¹,

Ramanjulu²,

Ahmed³

et al. 2020

Indian J Palliat Care

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The Indian Society for Study of Pain (ISSP), Cancer Pain Special Interest Group, guidelines on pharmacological management of cancer pain in adults provide a structured, step-wise approach which will help to improve the management of cancer pain and to provide patients with a minimally acceptable quality of life. The guidelines have been developed based on the available literature and evidence, to suit the needs, patient population, and situations in India. A questionnaire based on the key elements of each sub draft addressing certain inconclusive areas where evidence was lacking, was made available on the ISSP website and circulated by E-mail to all the ISSP and Indian Association of Palliative Care members. Antidepressants and/or anticonvulsants should be used to treat neuropathic cancer pain and the dose should be titrated according to the clinical response and side effects. External beam radiotherapy should be offered to all patients with painful metastatic bone pain. There is evidence on the use of ketamine in cancer neuropathic pain, but with no beneficial effect, thus it is not recommended.

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“…Ketamine and esketamine have demonstrated rapid and robust antidepressant effects in the general population and are currently under investigation in patients with terminal cancer as well (Caddy et al, 2015;Irwin et al, 2013;Irwin and Iglewicz, 2010). Ketamine may have the added benefit of improvements in pain control, which is commonly problematic in palliative care (Bell et al, 2012;Fallon et al, 2018). However, the known risk of ketamine dependence will be a challenge to manage in clinical rollout, especially in non-terminal phases of the illness (Berk et al, 2018).…”

Section: Notable Effectsmentioning

confidence: 99%

Depression in the medically ill

Rosenblat

Kurdyak

Cosci

et al. 2019

Aust N Z J Psychiatry

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Background: Depressive disorders are significantly more common in the medically ill compared to the general population. Depression is associated with worsening of physical symptoms, greater healthcare utilization and poorer treatment adherence. The present paper provides a critical review on the assessment and management of depression in the medically ill. Methods: Relevant articles pertaining to depression in the medically ill were identified, reviewed and synthesized qualitatively. A systematic review was not performed due to the large breadth of this topic, making a meaningful summary of all published and unpublished studies not feasible. Notable studies were reviewed and synthesized by a diverse set of experts to provide a balanced summary. Results: Depression is frequently under-recognized in medical settings. Differential diagnoses include delirium, personality disorders and depressive disorders secondary to substances, medications or another medical condition. Depressive symptoms in the context of an adjustment disorder should be initially managed by supportive psychological approaches. Once a mild to moderate major depressive episode is identified, a stepped care approach should be implemented, starting with general psychoeducation, psychosocial interventions and ongoing monitoring. For moderate to severe symptoms, or mild symptoms that are not responding to low-intensity interventions, the use of antidepressants or higher intensity psychotherapeutic interventions should be considered. Psychotherapeutic interventions have demonstrated benefits with small to moderate effect sizes. Antidepressant medications have also demonstrated benefits with moderate effect sizes; however, special caution is needed in evaluating side effects, drug–drug interactions as well as dose adjustments due to impairment in hepatic metabolism and/or renal clearance. Novel interventions for the treatment of depression and other illness-related psychological symptoms (e.g. death anxiety, loss of dignity) are under investigation. Limitations: Non-systematic review of the literature. Conclusion: Replicated evidence has demonstrated a bidirectional interaction between depression and medical illness. Screening and stepped care using pharmacological and non-pharmacological interventions is merited.

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Oral Ketamine vs Placebo in Patients With Cancer-Related Neuropathic Pain

Abstract: This multicenter randomized clinical trial compares oral ketamine with placebo for treating neuropathic pain in patients with cancer.

Cited by 46 publications

References 6 publications

Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature

Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature

Indian society for study of pain, cancer pain special interest group guidelines on pharmacological management of cancer pain (Part III)

Depression in the medically ill

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