Management of chronic neuropathic pain of different causes with the combination of oral methadone along with ketamine

Godoy, Maria de Mello de Celoni; Dalmolin, Gerusa Duarte; Rigo, Flávia Karine; Rossato, Mateus; Menezes, Miriam Seligman; Alvarez, Manuel Antônio; Hernandes, Juan José Galard; Moreno, L.; Sinche, M.; Ferreira, Juliano

doi:10.1097/eja.0b013e32835f9a3b

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…Oral ketamine has been prescribed fairly commonly for home use in patients with chronic pain, following guidelines for dosing, 19 safety, and efficacy. 20,21 However, such data are not yet available in the setting of MDD.…”

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confidence: 99%

Oral Ketamine in Treatment-Resistant Depression

Shirawi¹,

Kennedy²,

Ho³

et al. 2017

J Clin Psychopharmacol

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PurposeThe aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.MethodsWe reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.FindingsOver the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.ConclusionsAlthough this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.

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confidence: 99%

Oral Ketamine in Treatment-Resistant Depression

Shirawi¹,

Kennedy²,

Ho³

et al. 2017

J Clin Psychopharmacol

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“…Despite these similarities, the drugs present the following different selectivity: methadone presents a higher affinity for the opioid receptor (activator), while ketamine presents a higher affinity for the NMDA receptor (inhibitor) (6,9). It is well known that these systems present a synergistic effect, eliciting a better and safer analgesic effect even in patients with pain refractory to analgesics (16,(22)(23)(24). Ketamine is an arylcyclohexylamine derivative, with dissociative, analgesic, and anesthetic properties, due to several mechanisms, mainly the blockade of the NMDA receptor and activation of the opioid system.…”

Section: Discussionmentioning

confidence: 99%

“…To avoid these therapeutic limitations and to increase analgesic efficacy, multimodal analgesia (drug combination therapy) has been successfully used in pain therapy (15). In our previous report, we demonstrated that oral methadone plus ketamine was efficient to treat refractory neuropathic pain, reducing pain and decreasing several side effects (16).…”

Section: Randomization and Maskingmentioning

confidence: 97%

Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial

Rigo¹,

Trevisan

Godoy

et al. 2017

Pain Phys

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Background: Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Objective: Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. Study Design: We conducted a randomized, double blind, active-controlled parallelgroup clinical trial. Methods: Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. Results: During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Limitations: Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. Conclusion: This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain. Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid

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“…Combination of methadone with tricyclic antidepressants (Banks et al, 2010;Schreiber et al, 2014), methylph enidate (Schreiber et a l., 2017), delta9tetrahydrocannabinol (Cichewicz et al, 1999) and ketamine (Pelissier et al, 2003) have already been reported, but almost in acute preclinical pain models. Methadone/ketamine (de Godoy et al, 2013) and methadone/ibuprofen (Ferrer-Brechner and Ganz, 1984) combinations have been used as antinociceptive agents in the clinic, but controlled studies reported that ketamine alone is more effective than the methadone/ketamine combination (Rigo et al, 2017) and that at the long-term nonsteroidal anti-inflammatory drugs (NSAIDs) can result in increased risk of gastrointestinal and cardiovascular side-effects (Wehling, 2014;Ho et al, 2018).…”

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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Management of chronic neuropathic pain of different causes with the combination of oral methadone along with ketamine

Cited by 5 publications

References 6 publications

Oral Ketamine in Treatment-Resistant Depression

Oral Ketamine in Treatment-Resistant Depression

Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial

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

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