Dextromethorphan does not enhance morphine effects

NEW YORK, May 1 (Reuters) Contrary to preliminary findings, the results of a phase III study failed to show that dextromethorphan significantly enhanced the analgesic effects of morphine in terminally ill patients. The findings are published in the Journal of Pain and Symptom Management.

Dr Deborah J Dudgeon of Queen's University in Kingston, Ontario, led a multicenter study of 65 patients with advanced cancer or chronic severe pain requiring 12-hour, slow-release morphine.

Patients were randomly assigned to slow-release morphine plus either placebo or dextromethorphan, 60 milligrams four times a day for seven days. Dextromethorphan was then increased to 120 milligrams four times a day for another seven days, if the patient could tolerate it.

Patients kept records of other medications used, pain scores and symptoms of nausea, drowsiness and insomnia.

Patients in the combination treatment arm had average pain scores of 12.6 compared with 15.8 for patients receiving morphine plus placebo. However, this reduction was not statistically significant, Dudgeon and colleagues report.

Dextromethorphan plus morphine also resulted in a reduction in the number of episodes of pain breakthrough requiring additional medication, in nine instances compared with eleven for morphine plus placebo. However, these differences were also not statistically significant.

The total morphine consumed was 550.9 milligrams in the treatment group compared with 597.1 in the placebo group, which also was not a significant difference.

''We had hoped that the combination would have been helpful in improving pain control,'' Dudgeon acknowledged in an interview with Reuters Health. ''Previous animal and limited human studies had suggested that dextromethorphan should have been helpful.'' The hypothesis was that dextromethorphan's properties would act synergistically with morphine to increase the opioid's analgesic properties while modulating opioid tolerance.

Side effects, primarily dizziness, were more common with combination treatment, although again, the differences were statistically insignificant.

''The usefulness of the addition of dextromethorphan to opioids was limited in part by its toxicity,'' Dudgeon commented. Based on the study findings, she told Reuters Health, ''personally, I would not use it in cases of intractable pain.'' ''Each situation is different and therefore there is no one 'best' approach'' to the treatment of intractable pain in this patient population, Dudgeon concluded. ''Depending on the circumstances, I might try ketamine, methadone or intraspinal opioids'' for the terminally ill patient with severe pain.

Reuters RKM DB0940