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From the Departments of Anesthesiology and Critical Care Medicine (Drs. Raja and Sabeen), Psychiatry and Behavioral Science (Drs. Haythornthwaite and Clark), and Neurology (Dr. Pappagallo), Johns Hopkins University School of Medicine, and Department of Biostatistics (Drs. Royall and Travison), Johns Hopkins University School of Public Health, Baltimore; and Pain and Neurosensory Mechanisms Branch (Dr. Max), National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD.
Address correspondence and reprint requests to Dr. Srinivasa N. Raja, Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Osler 292, 600 N. Wolfe St., Baltimore, MD 21287; e-mail: sraja{at}jhmi.edu
Background: Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial.
Objective: To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN.
Methods: Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks’ duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication.
Results: Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02).
Conclusions: Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.
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