Methadone

McPherson, Mary Lynn; Costantino, Ryan C.; McPherson, Alexandra

doi:10.1016/j.hoc.2018.01.004

Cited by 13 publications

(9 citation statements)

References 14 publications

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“…As it is well-known, methadone is characterized by unique and diverse pharmacologic properties, including NMDA receptor antagonism, inhibition of serotonin and noradrenaline uptake and affinity for DOR in addition to MOR (28,87). The possible role of these different mechanisms in the mild immunomodulation induced by methadone has never been assessed.…”

Section: Discussionmentioning

confidence: 99%

“…It primarily acts at the MOR but also activates kappa (KOR) and delta (DOR) receptors. Moreover, it also binds N-methyl-D-aspartate receptor as a weak antagonist (28). Methadone is a potent and long-acting opioid and its PK and PD characteristics have made it the most used opioid for substitution therapy in opioid dependence (29).…”

Section: Methadonementioning

confidence: 99%

“…However, methadone is also a valuable drug in the management of chronic pain especially in cancer pain. Its efficacy as an NMDA antagonist suggests its use in neuropathic pain as well (28).…”

Section: Methadonementioning

confidence: 99%

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Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies

et al. 2019

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Suppression of the immune system has been constantly reported in the last years as a classical side effect of opioid drugs. Most of the studies on the immunological properties of opioids refer to morphine. Although morphine remains the "reference molecule," other semisynthetic and synthetic opioids are frequently used in the clinical practice. The primary objective of this review is to analyze the available literature on the immunomodulating properties of opioid drugs different from morphine in preclinical models and in the human. A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms "immunosuppression," "immune system," "opioids," "Natural killer cells," "cytokines," and "lymphocytes." The results achieved concerning the effects of fentanyl, methadone, oxycodone, buprenorphine, remifentanil, tramadol, and tapentadol on immune responses in animal studies, in healthy volunteers and in patients are reported. With some limitations due to the different methods used to measure immune system parameters, the large range of opioid doses and the relatively scarce number of participants in the available studies, we conclude that it is not correct to generalize immunosuppression as a common side effect of all opioid molecules.

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Section: Discussionmentioning

confidence: 99%

Section: Methadonementioning

confidence: 99%

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Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies

et al. 2019

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“…In fact, the ED 50 of methadone alone was 0.50 mg/kg while the equieffective dose of the MgSO 4 /methadone combination only contained 0.16 mg/kg methadone, which means that the addition of MgSO 4 allowed the methadone content of the dose to be reduced to less than one third. If extrapolated to humans, this might be an important finding because the side-effects of methadone in clinical settings are related to dosing and treatment duration, both for cancer (McPherson et al, 2018) and non-cancer (Els et al, 2017) pains. Indeed, according to the guidelines from the American Pain Society (Chou et al, 2014) and from the experts group of the Hospice and Palliative Care (McPherson, 2016), rotation to methadone of opioid-tolerant patients with cancer pain should be based on dose calculations, as exact opioid/ methadone ratios.…”

Section: Discussionmentioning

confidence: 99%

“…Although these drawbacks may discourage the use of methadone for chronic non-cancer pain, therapeutic methadone use has increased 167.0% from 2000 to 2014 globally and 205.2% in the United States (Manchikanti et al, 2018). The drawbacks of chronic methadone administration are clearly related to dosing and treatment duration both for cancer (McPherson et al, 2018) and non-cancer (Els et al, 2017) pain. Consequently, the possibility of enhancing the analgesic effect of methadone (and therefore of reducing its dose) by combining it with other nonopioid antinociceptive drugs could significantly help to reduce the side effects and risks associated with the therapeutic use of this drug.…”

Section: Introductionmentioning

confidence: 99%

Magnesium Salt, a Simple Strategy to Improve Methadone Analgesia in Chronic Pain: An Isobolographic Preclinical Study in Neuropathic Mice

et al. 2020

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Analgesic efficacy of methadone in cancer and chronic non-cancer pains is greater than that of other opioids, probably because of its unique pharmacokinetics properties and also because it targets glutamatergic receptors in addition to µ-opioid receptors. However, methadone has drawbacks which are clearly related to dosing and treatment duration. The authors hypothesized that the antinociceptive efficacy of methadone could be synergistically potentiated by magnesium and copper salts in a preclinical mouse model of chronic pain, using the intraplantar formalin test as algesimetric tool. The spared nerve injury mice model was used to generate mononeuropathy. A low dose (0.25%) formalin was injected in the neuropathic limb in order to give rise only to Phase I response, resulting from direct activation by formalin of nociceptive primary afferents. Licking/biting of the formalin-injected limb was evaluated as nociceptive behavior during a 35-min observation period. Dose-response curves for intraperitoneal magnesium sulfate (10, 30, 100, and 300 mg/kg i.p.), copper sulfate (0.1, 0.3, 1, and 3 mg/kg i.p.) and methadone (0.1, 0.3, 1, and 3 mg/kg i.p.) allowed to combine them in equieffective doses and to determine their interaction by isobolographic analysis. Magnesium sulfate, copper sulfate and methadone dose-dependently decreased the nociceptive response evoked by formalin injection, the respective ED 50 being 76.38, 1.18, and 0.50 mg/kg i.p. Isobolographic analysis showed a superadditive interaction for magnesium and methadone. Indeed, despite that both ED 50 are obviously equieffective, the ED 50 for the MgSO4/methadone combination contained less than one third of the methadone having the ED 50 for methadone alone. For the CuSO 4 /methadone combination, the interaction was only additive. Extrapolated to clinical settings, the results suggest that magnesium salts might be used to improve synergistically the efficacy of methadone in neuropathy, which would allow to reduce the dose of methadone and its associated side effects.

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First-line methadone for cancer pain: titration time analysis

Mammana¹,

Bertolino²,

Bruera

et al. 2021

Support Care Cancer

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Background. Methadone is a low-cost, strong opioid that is increasingly used as a rst-line treatment for pain in palliative care (PC). Its long and unpredictable half-life and slow elimination phase can make titration challenging. Evidence for titration modalities is scarce.Objective. To describe the titration phase of the treatment with low dose rst-line methadone and the use of methadone for breakthrough pain.Methods. Prospective study with strong opioid-naïve patients with moderate to severe cancer pain followed at a tertiary PC unit in Argentina. Starting methadone dose was 2.5-5 mg/day every 8, 12, or 24 hours. Titration allowed daily dose increases from Day 1, and prescription of oral methadone 2.5 mg every 2 hours with a maximum of 3 rescue doses/day for breakthrough pain. Pain control, methadone stabilization dose, and adverse effects, among other variables, were daily assessed over the rst 7 days (T0 -T7).Results. 62 patients were included. Initial median (IQR) methadone dose was 5(2.5) mg/day. Pain intensity decreased from a median (IQR) of 8(2.3) at T0 to 4(2.3) at T1 and remained ≤4 until T7 (all p<0.0001 compared to T0). Similar results were obtained through the categorical and tolerability scales for pain. Fifty patients (81%) reached pain control, 66% in the rst 48 hours. Methadone daily dose at T2 and T7 were higher than that at T0: 7.5(3) and 6.7(5.5) versus 5(2.5); respectively (all p<0.05). The opioid escalation index at T7 was 1.7%. The median (IQR) number of rescues, stabilization dose and time for stabilization were 0 (1), 5(4.5) mg and 3(2) days, respectively. Two patients were discontinued due to delirium. All the other side effects were mild.Conclusions. First-line, low-dose methadone using rescue methadone resulted in a pronounced and rapid decrease in pain, with minimal need for titration and for breakthrough doses, and no evidence of accumulation or sedation by the end of the week.

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Methadone

Cited by 13 publications

References 14 publications

Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies

Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies

Magnesium Salt, a Simple Strategy to Improve Methadone Analgesia in Chronic Pain: An Isobolographic Preclinical Study in Neuropathic Mice

First-line methadone for cancer pain: titration time analysis

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