Risk for death higher at start of and immediately after opiate substitution treatment

Patients receiving opiate substitution treatment have a higher risk for death at the beginning of treatment and immediately after it ends, according to a new study.

Researchers in the United Kingdom examined data from primary care patients who had been diagnosed with substance misuse and had received a methadone or buprenorphine prescription during 1990-2005. Main outcome measures were all-cause mortality and rate ratios for periods on and off treatment, adjusted for multiple factors including age, sex, comorbid conditions and calendar year. Mortality rates in opiate users and the general population were also compared. The study results were published online Oct. 26 by BMJ.

Data from 5,577 patients with 267,003 prescriptions for opiate substitution treatment were analyzed. Patients were followed until one year after their last prescription expired, date of death before their last prescription expired, or date at which they transferred out of the primary care practice. The authors found crude mortality rates of 0.7 per 100 person-years when patients were receiving opiate substitution treatment and 1.3 per 100 person-years while patients were not receiving treatment. Corresponding standardized mortality ratios were 5.3 (95% CI, 4.0 to 6.8) and 10.9 (95% CI, 9.0 to 13.1), respectively. Risk for death was approximately twice as high in men using opiates as in women (mortality rate ratio, 2.0 [95% CI, 1.4 to 2.9]).

During the first two weeks of opiate substitution treatment, the crude mortality rate was 1.7 per 100 person-years, or 3.1 times (95% CI, 1.5 to 6.6 times) higher than during the remainder of treatment. Crude mortality rates after treatment stopped were 4.8 per 100 person-years at weeks 1-2, 4.3 per 100 person-years at weeks 3-4, and 0.95 per 100 person-years afterward. These rates were 9 times (95% CI, 5.4 to 14.9 times), 8 times (95% CI, 4.7 to 13.7 times) and 1.9 times (95% CI, 1.3 to 2.8 times) greater than was the baseline mortality risk during treatment.

The authors noted that their study may have overestimated or underestimated mortality rates during and after treatment, and that follow-up was incomplete, among other limitations. However, they concluded that mortality risk is higher when opiate substitution treatment is started and immediately after it is stopped, and that clinicians and patients should be aware of this issue.

“We hypothesize that the raised risk of death in the first month of treatment and especially in the month after the end of treatment may negate any protective effect of opiate substitution treatment, unless treatment is prolonged,” they wrote. They called for additional research to test their hypothesis and to determine how the average duration of opiate substitution treatment affects drug-related mortality rates.