Public Release:  Slow-release morphine reduces level of intractable cough

American Thoracic Society

Slow-release morphine helped a group of patients with long-term, treatment-resistant chronic cough reduce their daily cough score levels by 40 percent.

The research results appear in the second issue for February 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Alyn H. Morice, M.D., of the Department of Academic Medicine at the University of Hull and Castle Hill Hospital in East Yorkshire, United Kingdom, and six associates enrolled 27 patients with intractable cough in an eight-week, randomized, double-blind, placebo-controlled study to test the use of slow-release morphine sulfate versus a placebo on their cough. Each phase lasted four weeks.

Morphine, derived from opium, is used in medicine as an analgesic, light anesthetic or a sedative. Although opiates have been long advocated for the suppression of cough, there are few trial data to support this recommendation. In fact, prior to this research, the use of opiates in intractable chronic cough had never been studied.

"Although acute cough is benign and self-limiting, chronic persistent cough can have a devastating effect on the quality of life of sufferers," said Dr. Morice. "This research provides evidence for the use of opiates in chronic cough."

The investigators found a "rapid and highly significant reduction by 40 percent in daily cough scores was noted by patients on slow-release morphine sulfate."

Patients responded quickly to treatment starting at five milligrams twice daily. The researchers found patients benefited the most by day five of treatment, and that this response was sustained through the remainder of the four-week period. The authors noted that the rapid response to morphine was in contrast to the absence of any effect of placebo.

The 27 participants, 18 of whom were female, were recruited from a hospital cough clinic. All had endured a chronic, persistent cough for more than three months. Their average age was 55.

During each four-week interval, patients made three visits to a clinical trial center, where they filled out a quality-of-life questionnaire on the impact of chronic cough on activities of daily living. A spirometric lung test was performed at the first visit, and lung function was measured on each subsequent visit.

In addition, each participant assessed their cough severity daily, rating it from 0 to 9 on a record card. Participants could not use other cough remedies, including over-the-counter products, during the eight-week study period.

According to the authors, one-third of the participants increased their dose of morphine sulfate from 5 mg to 10 mg twice daily during the first month; 11 percent did so in the second month; and a further 22 percent joined them in the third month. By the end of the study, two-thirds of the patients had increased their dose to 10 milligrams.

"The optimum dose in the suppression of chronic cough lies between 5 and 10 mg twice daily," said Dr. Morice, who added that the most common side effects were constipation (40 percent) and drowsiness (25 percent).

The investigators believe that the risk-benefit ratio makes low-dose morphine sulfate a credible therapeutic option for patients with chronic cough who fail other specific treatments.

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Contact: Alyn H. Morice, Department of Academic Medicine, University of Hull, Castle Hill Hospital, Cottingham, East Yorkshire HU 165JQ, United Kingdom
Phone: +44 (0) 148 262 4067
E-mail: a.h.morice@hull.ac.uk

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