Methadone and Ketamine for Neuropathic Pain Treatment

Study Overview
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Brief Summary
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Methadone and ketamine are effective for neuropathic pain management. However, the benefits of the association of both drugs are uncertain. Here, the investigators conducted a randomized, double-blind, in parallel, active controlled clinical trial to test the hypothesis that methadone combined ketamine (methadone/ketamine) is more effective than methadone or ketamine alone in reducing neuropathic pain.

Detailed Description
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Either oral methadone or ketamine have been used in neuropathic pain management, however, the benefits of the association of both drugs are uncertain. Here, we conducted a randomized, double-blind, in parallel, active controlled clinical trial to test the hypothesis that methadone combined ketamine (methadone/ketamine) is more effective than methadone or ketamine alone in reducing neuropathic pain. Methods: Fourthly two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive during three months oral methadone (n= 13), ketamine (n=13) or methadone combined with ketamine (n=13). The primary outcome was pain score on visual analogical scale (VAS) assessed on baseline, 8, 15, 30, 60 and 90 days throughout the treatment, and the secondary outcomes were symptoms of neuropathic pain such as allodynia, burning or shooting pain as well the side effects.

Official Title
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Management of Neuropathic Chronic Pain With Methadone Combined With Ketamine: Randomized, Double Blind, Active-controlled Clinical Trial

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Drug: Methadone
* Drug: Ketamine
* Drug: Methadone plus Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients complaining of pain for more than 6 months with neuropathic pain poorly responsive to drugs used to treat neuropathic pain (i.e. opioid, non-opioid, anticonvulsants, antidepressants), who were 22 to 77 years old Exclusion Criteria: patients with a history of severe psychiatric disorder, misuse of illegal drugs or hepatic disease

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 77 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methadone<br>Group treated with methadone solution. | Drug: Methadone<br>* The solution of methadone was prepared by mixing 10 ml of methadone (10 mg/ml) and 90 ml of saline 0.9% (Baxter, São Paulo, Brazil)<br>* Other names: Methadone hydrochloride, Cristália® (São Paulo, Brazil);|
| Active Comparator: Ketamine<br>Group treated with ketamine solution | Drug: Ketamine<br>* The solution of ketamine was prepared by mixing 20 ml of S(+)-ketamine hydrochloride (50 mg/ml, Cristália®, São Paulo, Brazil) and 80 ml of saline 0.9% (Baxter, São Paulo, Brazil), obtaining a concentration of 10 mg/ml of ketamine.<br>* Other names: S(+)-ketamine hydrochloride, Cristália®, São Paulo, Brazil;|
| Active Comparator: Methadone plus ketamine<br>Group treated with methadone plus ketamine solution | Drug: Methadone plus Ketamine<br>* the solution of methadone, ketamine was prepared by mixing 10 ml of methadone hydrochloride (10 mg/ml, Cristália®, São Paulo, Brazil), 20 ml of S(+)-ketamine hydrochloride (50 mg/ml, Cristália®, São Paulo, Brazil) and 70 ml of saline 0.9% (Baxter, São Paulo, Brazil), obtaining a concentration of 1 mg/ml of methadone and 10 mg/ml of ketamine.<br>* Other names: methadone and S(+)-ketamine, Cristália®, São Paulo, Brazil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome was pain intensity as assessed by visual analogical scale (VAS) scores |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary outcomes were the presence of burning and/or shooting pain, allodynia and side effects. |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multimodal analgesia, Neuropathic pain, Methadone, Ketamine