The opioid antagonist naltrexone is the first new drug approved for use in the treatment of alcoholism in nearly 50 years. Croop and associates performed a nonrandomized open-label study to evaluate the safety profile of naltrexone.
The study was performed before approval of naltrexone and was sponsored by the manufacturer of the drug. The 12-week study was conducted at 40 alcoholism treatment centers throughout the United States. Patients in the study included 865 men and women over the age of 18 (age range: 18 to 73 years; mean age: 38.9 years) who had not ingested alcohol for one to six weeks. A total of 570 study subjects received naltrexone, and 295 served as the reference group. Both groups underwent the same evaluations during the study and participated in a psychosocial treatment program for alcoholism. The majority of the patients in the naltrexone group (69.9 percent) received 50 mg per day (dosage range: 25 mg every third day to 200 mg daily). Blood samples for hematologic evaluation and liver function studies were obtained at baseline and every four weeks for 12 weeks. All adverse clinical events were recorded at two-week intervals.
Approximately 80 percent of the patients in each group received concomitant medications during the study, including antidepressants, benzodiazepines and antipsychotic agents. After 12 weeks, 220 patients treated with naltrexone and 145 reference patients had completed the study.
Data on adverse events were available for 238 reference patients and 500 patients who received naltrexone. Of these patients, 37.6 percent of the naltrexone group and 17.6 percent of the reference group reported at least one adverse event during the study. Fifteen percent of the group that received naltrexone withdrew from the study because of adverse side effects, most commonly nausea, headache and dizziness. Serious adverse events were reported in 53 patients in the naltrexone group and in 12 patients in the reference group. However, most of the adverse events represented hospitalization because of relapse or depression, and none were believed to be related to naltrexone.
No significant laboratory abnormalities were noted. A significant decrease from baseline occurred in alanine aminotransferase levels (a very sensitive indicator of drug-induced hepatocellular injury) in both the naltrexone group and the reference group.
The authors conclude that naltrexone has a very broad safety profile for the treatment of alchoholism. No previously unreported adverse events were identified during this study.