Methadone and Ketamine for Neuropathic Pain Treatment

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

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.

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Methadone; Drug: Ketamine; Drug: Methadone plus Ketamine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Santa Maria, Rio Grande do Sul, Brazil, 97105-900
      • University Hospital in Santa Maria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methadone; Group treated with methadone solution.	Drug: Methadone; 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); Other Names: Methadone hydrochloride, Cristália® (São Paulo, Brazil)
Active Comparator: Ketamine; Group treated with ketamine solution	Drug: Ketamine; 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.; Other Names: S(+)-ketamine hydrochloride, Cristália®, São Paulo, Brazil
Active Comparator: Methadone plus ketamine; Group treated with methadone plus ketamine solution	Drug: Methadone plus Ketamine; 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.; Other Names: methadone and S(+)-ketamine, Cristália®, São Paulo, Brazil

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Universidade Federal de Santa Maria
• Collaborators: Hospital de Clinicas de Porto Alegre; Santa Casa de Misericórdia de Belo Horizonte

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: August 22, 2014
• First Submitted That Met QC Criteria: September 5, 2014
• First Posted (Estimate): September 8, 2014

Study Record Updates

• Last Update Posted (Estimate): September 8, 2014
• Last Update Submitted That Met QC Criteria: September 5, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Ketamine; Neuropathic pain; Methadone; Multimodal analgesia
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Ketamine; Methadone
• Other Study ID Numbers: Methadone plus ketamine