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Short- and long-term efficacy of oral ketamine in eight chronic-pain patients

Gifu, Japan

To the Editor:

Ketamine, as a N-methyl-D-aspartate antagonist, has a noticeable analgesic action and can be used for the treatment of neuropathic pain.^1–3 We studied the effect of oral ketamine in eight chronic neuropathic-pain patients.

Patients relieved by the iv infusion of ketamine were entered in the study (Table). After informed consent had been obtained, eight patients were randomly assigned to receive oral ketamine syrup (0.5 mg•kg^–1) or the same volume of a placebo syrup every six hours for a week. After seven days the pain was rated by the patient on a visual analogue scale, and allodynia was rated on a four-point verbal rating scale. The plasma concentration of ketamine was measured at five, ten, 30, 60, 120, and 180 min after its administration in all patients on the seventh day. In this short-term study, the severity of the pain and allodynia was reduced by oral ketamine administration about 15 min after administration, and improvement lasted from six to eight hours. Two of the eight subjects complained of headache relieved by loxoprofen. One patient complained of nightmares reduced by the coadministration of diazepam and of slight dizziness that required no treatment. Ketamine plasma levels were below the limit of detection (0.05 µg•mL^–1) in all patients despite good pain relief.

A subanesthetic dose of oral ketamine proved able to reduce chronic pain. These findings support the idea that norketamine, a metabolite of ketamine, may have played an important part in the analgesia observed in these chronic-pain patients,⁴ although we did not measure the plasma concentration of norketamine. We did not observe serious adverse events or tolerance to oral ketamine in the present study. Oral ketamine may be useful for the long-term treatment of chronic neuropathic pain.

References

1 Eide PK, Jorum E, Stubhaug A, Bremnes J, Breivik H. Relief of post-herpetic neuralgia with the N-methyl- D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo. Pain 1994; 58: 347–54.[Medline]

2 Stannard CF, Porter GE. Ketamine hydrochloride in the treatment of phantom limb pain. Pain 1993; 54: 227–30.[Medline]

3 Nikolajsen L, Hansen PO, Jensen TS. Oral ketamine therapy in the treatment of postamputation stump pain. Acta Anaesthesiol Scand 1997; 41: 427–9.[Medline]

4 Grant IS, Nimmo WS, Clements JA. Pharmacokinetics and analgesic effects of i.m. and oral ketamine. Br J Anaesth 1981; 53: 805–10.[Abstract/Free Full Text]

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