Oral naloxone reverses opioid-associated constipation

Opioid-related constipation is one of the most frequent side effects of chr onic pain treatment. Enteral administration of naloxone blocks opioid actio n at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first-pass metabolism. The aim of this study was to exam ine the effects of oral naloxone on opioid-associated constipation in an in traindividually controlled manner. Twenty-two chronic pain patients with or al opioid treatment and constipation were enrolled in this study. Constipat ion was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention ('control period'). Then, oral naloxone was started and titrated individually between 3x3 to 3x12 mg/day depending on laxation and withdrawal symptoms. After the 4-day titration period, pati ents were observed for further 6 days ('naloxone period'). The Wilcoxon sig ned rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patient s did not reach the 'naloxone period' due to death, operation, systemic opi oid withdrawal symptoms, or therapy-resistant vomiting. In the 6 day 'nalox one' compared to the 'control period', the mean number of days with laxatio n increased from 2.1 to 3.5 (P < 0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P < 0.01). The mean naloxone dose in t he 'naloxone period' was 17.5 mg/day. The mean pain intensity did not diffe r between these two periods. Moderate side effects of short duration were o bserved in four patients following naloxone single dose administrations bet ween 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of th e patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5-6 h. This controled study demonstrates that orally administered n aloxone improves symptoms of opioid associated constipation and reduces lax ative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration. (C) 2000 International Association for the Study of Pain. Published by Elsevier Scie nce B.V.