Oral Ketamine and Transdermal Nitroglycerin as Analgesic Adjuvants to Oral Morphine Therapy for Cancer Pain Management

Lauretti, Gabriela Rocha; Lima, Izabel C. P. R.; Reis, Marlene Paulino dos; Prado, Wiliam A.; Pereira, Newton Lindolfo

doi:10.1097/00000542-199906000-00005

Cited by 191 publications

(97 citation statements)

References 29 publications

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“…Ketamine, administered by intravenous infusion or orally, is effective in relieving cancer pain [79][80][81][82] and reducing opioid requirements [83]. Clinicians who are experienced in the use of parenteral ketamine may, therefore, consider this option in patients with refractory pain.…”

Section: N-methyl-d-aspartate Receptor Blockersmentioning

confidence: 99%

Adjuvant Analgesics in Cancer Pain Management

2004

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Adjuvant analgesics are defined as drugs with a primary indication other than pain that have analgesic properties in some painful conditions. The group includes numerous drugs in diverse classes. Although the widespread use of these drugs as first-line agents in chronic nonmalignant pain syndromes suggests that the term "adjuvant" is a misnomer, they usually are combined with a less-than-satisfactory opioid regimen when administered for cancer pain. Some adjuvant analgesics are useful in several painful conditions and are described as multipurpose adjuvant analgesics (antidepressants, corticosteroids, α α 2 -adrenergic agonists, neuroleptics), whereas others are specific for neuropathic pain (anticonvulsants, local anesthetics, N-methyl-D-aspartate receptor antagonists), bone pain (calcitonin, bisphosphonates, radiopharmaceuticals), musculoskeletal pain (muscle relaxants), or pain from bowel obstruction (octreotide, anticholinergics). This article reviews the evidence supporting the use of each class of adjuvant analgesic for the treatment of pain in cancer patients and provides a comprehensive outline of dosing recommendations, side effects, and drug interactions. The Oncologist 2004;9:571-591

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Section: N-methyl-d-aspartate Receptor Blockersmentioning

confidence: 99%

Adjuvant Analgesics in Cancer Pain Management

2004

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“…In subanesthetic doses it can also be given as an adjuvant to opiates for the treatment of cancer pain, particularly when opiates alone are ineffective. [35][36][37][38][39][40][41][42] In addition to being a potent NMDA receptor channel blocker, ketamine has other actions, which may contribute to its analgesic and antidepressant effects. These include its interactions with other calcium and sodium channels, cholinergic transmission, noradrenergic and serotonergic reuptake inhibition, glutamate transmission, synapse formation, and l, d, , opioid-like effects.…”

Section: Introductionmentioning

confidence: 99%

“…50 Significant literature supports its safe use in hospice patients for other symptoms, including pain. 36,37,40,41,[51][52][53][54][55][56] Presented are data from a 28-day, open-label, proof-ofconcept trial of daily oral ketamine administration with the objectives of evaluating and assessing the tolerability, potential efficacy, and time to potential efficacy in the treatment of depression and anxiety in patients receiving hospice care.…”

Section: Introductionmentioning

confidence: 99%

Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Irwin

Iglewicz

Nelesen

et al. 2013

Journal of Palliative Medicine

132

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Background: Depression and anxiety are prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine has many properties that make it an interesting candidate for rapidly treating depression and anxiety in patients receiving hospice care. To test this hypothesis, a 28-day, open-label, proof-of-concept trial of daily oral ketamine administration was conducted in order to evaluate the tolerability, potential efficacy, and time to potential efficacy in treating depression and anxiety in patients receiving hospice care. Methods:In this open-label study, 14 subjects with symptoms of depression or depression mixed with anxiety warranting psychopharmacological intervention received daily oral doses of ketamine hydrochloride (0.5 mg/ kg) over a 28-day period. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS), which was used to rate overall depression and anxiety symptoms at baseline, and on days 3, 7, 14, 21, and 28. Results: Over the 28-day trial there was significant improvement in both depressive symptoms (F 5,35 = 8.03, p = 0.002, g 2 = 0.534) and symptoms of anxiety (F 5,35 = 14.275, p < 0.001, g 2 = 0.67) for the eight subjects that completed the trial. One hundred percent of subjects completing the trial responded to ketamine for both anxiety and depression. A significant response in depressive symptoms occurred by day 14 for depression (mean D = 3.5, d = 1.14, 95% CI = 1.09-5.9, p = 0.01) and day 3 for anxiety (mean D = 2.4, d = 0.67, 95% CI = 1.0-3.7, p = 0.004). These improvements remained significant through day 28 for both depression (mean D = 4.0, d = 1.34, 95% CI = 2.3-5.9, p = 0.001) and anxiety (mean D = 6.09, d = 1.34, 95% CI = 3.6-8.6, p < 0.001). Side effects were rare, the most common being diarrhea, trouble sleeping, and trouble sitting still. Conclusions: Patients who received daily oral ketamine experienced a robust antidepressant and anxiolytic response with few adverse events. The response rate for depression is similar to those found with IV ketamine; however, the time to response is more protracted. The findings of the potential efficacy of oral ketamine for depression and the response of anxiety symptoms are novel. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the efficacy and safety of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care or other subject populations.

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“…22 Significant literature supports its safe use in hospice patients for other symptoms, including pain. [23][24][25][26][27][28][29][30][31][32] The cases presented here involved subjects in an on-going open label study that is approved by both the Institute for Palliative Medicine Institutional Review Board and the University of California, San Diego Human Research Protection Program.…”

Section: Introductionmentioning

confidence: 99%

Oral Ketamine for the Rapid Treatment of Depression and Anxiety in Patients Receiving Hospice Care

Irwin

Iglewicz

2010

Journal of Palliative Medicine

101

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Depression is prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Here, two cases are reported in which a single oral dose of ketamine provided rapid and moderately sustained symptom relief for both depression and anxiety. In addition, no adverse effects were noted. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the effectiveness of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care. Ketamine may be a promising safe, effective, and cost-effective rapid treatment for depression and anxiety in this population.

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Oral Ketamine and Transdermal Nitroglycerin as Analgesic Adjuvants to Oral Morphine Therapy for Cancer Pain Management

Abstract: Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management.

Cited by 191 publications

References 29 publications

Adjuvant Analgesics in Cancer Pain Management

Adjuvant Analgesics in Cancer Pain Management

Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Oral Ketamine for the Rapid Treatment of Depression and Anxiety in Patients Receiving Hospice Care

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