Low-Dose Morphine Puts Damper on Chronic Cough

HULL, England, Feb. 15 -- Low-dose slow-release morphine sulfate reduces the severity and frequency of chronic intractable cough by 40%, researchers found here.

The results of a small study give physicians evidence for another option when the cough is refractory to antitussives, reported Alyn H. Morice, M.D., of the University of Hull and Castle Hill Hospital, and colleagues, in the Feb. 15 issue of the American Journal of Respiratory and Critical Care Medicine.

The double-blind crossover study included 27 patients recruited from a cough clinic and randomized to four weeks of 5 mg extended-release morphine sulfate twice daily and four weeks of matched placebo.

The patients all had chronic, persistent cough for greater than three months that had failed to respond to trials of specific antitussive therapies. None had significant lung disease or used any other cough remedies during the study. Eighteen of the patients were women and the average age was 55.

The researchers found significant improvements in the morphine group on Leicester Cough Questionnaire scores, reflecting impact on activities of daily living. The findings were:

• Significant improvement in overall scores for morphine compared with baseline and placebo (15.5 versus 12.3 baseline, P

They also noted that the mechanism of morphine in suppressing cough does not appear to be due to sedation because sedation found in the study -- drowsiness was one of the most common side effects at 25% -- was transitory and mild whereas the antitussive effect was not.

"Opiates have long been advocated for the suppression of cough, but there are few trial data to support this recommendation," the authors wrote.

Although only a small percentage of chronic cough patients do not have an obvious cause or a treatable precipitant for their condition, previous studies have shown that their quality of life resembles severe chronic obstructive pulmonary disease (COPD). For these patients, there had been no evidence supporting antitussive use, the researchers said.

"Thus, in patients with chronic refractory cough, there is a pressing need for symptomatic treatment," Dr. Morice and colleagues said.

Another opiate, codeine, is more widely used as an antitussive compared with morphine, the researchers said, "but this probably arises from ease of prescribing due to its noncontrolled drug status rather than any unique pharmacological properties."

Liquid preparations of codeine used as cough suppressants are classified as Schedule V products by the Drug Enforcement Agency while morphine is Schedule II.

In addition, they wrote "consistent therapeutic response to codeine is unlikely because it is a prodrug metabolized to morphine by cytochrome P450-2D6, and so plasma levels depend on the acetylator status, which varies widely in the population."

In addition to drowsiness noted in 25%, 40% of patients receiving morphine had constipation.

"Side effects and dependence are obvious concerns with opiate therapy for what is a disabling but non-life-threatening condition," Dr. Morice and colleagues wrote but added: "We believe that the risk-benefit risk ratio makes low-dose morphine sulfate a credible therapeutic option in patients with chronic cough who fail with specific treatment."

They cautioned though that the study was limited in its inability to completely blind patients to the effects of a psychoactive drug and the need to study the long-term effects of low-dose morphine to see if it can be administered without causing addiction as is the case with chronic pain.