Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial.
Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain.



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.



We conducted a randomized, double blind, active-controlled parallel-group clinical trial.



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.



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.



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.



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.
Graduation Core of Santa Casa de Belo Horizonte, Department of Biomedicin and Medicin, Belo Horizonte, MG, Brazil; Department of Health, University of South of Santa Catarina - UNESC, Criciuma - SC, Brazil.
Flavia Karine
FK
Rigo
Department of Health, University of South of Santa Catarina - UNESC, Criciuma - SC, Brazil.
Gabriela
G
Trevisan
Department of Surgery and Anesthesia, Center of Health Science, University Hospital of Santa Maria, Federal University of Santa Maria, RS, Brazil.
Maria C
MC
Godoy
Center of Innovation and Preclinical Studies - CIEnP, Florianopolis - SC, Brazil.
Mateus Fortes
MF
Rossato
Department of Pharmacology, Federal University of Santa Caratina, Florianopolis - SC, Brazil.
Gerusa D
GD
Dalmolin
Departament of Health, Course of Biomedicine University of Education and Culture of Vilhena, Vilhena, RO, Brazil.
Mariane A
MA
Silva
Department of Surgery and Anesthesia, Center of Health Science, University Hospital of Santa Maria, Federal University of Santa Maria, RS, Brazil.
Mirian S
MS
Menezes
Service of pain and palliative care and pain and Neuromodulation Laboratory, Hospital de Clinicas de Porto Alegre, Brazil.
Wolnei
W
Caumo
Department of Pharmacology, Federal University of Santa Caratina, Florianopolis - SC, Brazil.
Juliano
J
Ferreira
D000328:Adult; D000368:Aged; D059350:Chronic Pain / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement
D007649:Ketamine; D008691:Methadone