N of 1 randomised controlled trials of oral ketamine in patients with chronic pain

Anecdotal reports suggest that the general anaesthetic drug ketamine, taken orally in low doses, can give rise to some extra analgesia in patients with refractory neuropathic pain. This study was designed to determine the proportion of patients with chronic neuropathic pain responding to oral ketamine, and then to separate the true treatment effect from non-specific effects by means of an n of 1 randomised controlled trial. Twenty-one patients gave informed consent and completed daily pain diaries and continued on their usual treatments (drug and non-drug) for the duration of the study. After a 'baseline' week, oral ketamine was taken once a day for 1 week. The dose of 20 mg was increased each day until an analgesic effect was noticed or adverse effects occurred, or until a maximum of 100 mg was reached. Those patients responding to oral ketamine were then entered into the n of 1 randomised trial which consisted of three treatment/placebo week pairs. Twelve patients did not progress to the n of 1 trial because of no benefit and/or intolerable adverse effects (dizziness, drowsiness etc.). Nine patients completed the n of 1 trial; there was no difference between the ketamine and placebo weeks in six patients; one patient demonstrated effective analgesia with ketamine, but it was of short duration and marred by unpleasant adverse effects; two patients showed some evidence of a beneficial response to ketamine, and continued with the oral ketamine after the trial. We conclude that oral ketamine only gave rise to an extra analgesic response in three out of 21 patients with chronic neuropathic pain (14%). Adverse effects limited the use of the drug in almost half of the patients. The n of 1 trial was useful in demonstrating no true therapeutic effect for the ketamine in two thirds of the patients progressing to that part of the trial.