So how can abstinence based programs not inform patients about these studies and the alternatives to abstinence? In any other branch of medicine this is called negligence and the Supreme Court has clearly ruled that to not inform a patient of alternative therapies and relative rates of recovery is unethical and negligent practice. Why do state licensing agencies allow this to happen? As noted below, although this new study adds to the literature, many other studies have shown reduced mortality from maintenance as opposed to either detox, stabilize and taper or simply abstinence-based treatments. In my view, programs that are based on an ideological belief in abstinence but who do not inform patients of the relative risks, benefits and likelihood of recovery are risking a lawsuit because they are not providing basic informed consent for patients and families.
From Medscape Medical News
Opiate Replacement Treatment Reduces Mortality in Addicted Patients
October 29, 2010 — Year-long treatment with either buprenorphine or methadone can substantially decrease the number of drug-related deaths in opiate misusers, suggests new findings from British researchers.
In fact, results from this large cohort study showed that patients given "opiate substitution treatment" for 12 months or more had a greater than 85% reduced overall mortality risk.
"This treatment reduces the risk of death — but treatment duration matters," investigative team member Matt Hickman, professor in public health and epidemiology at the School of Social and Community Medicine at the University of Bristol in the United Kingdom, told Medscape Medical News.
In addition, the investigators write that "closer supervision is needed" because significant mortality risks were found for these patients during both the first 28 days after beginning and the first month after ending treatment compared with other times.
"We found that the risk of death in the first month leaving...was about 4 times higher than rest of time off treatment, which is very similar to difference in risk of death after leaving prison," said Professor Hickman.
The investigators write that although "the difference in mortality between opiate users in and out of treatment is stark and well known," few studies have looked at this risk at specific time points.
"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 add.
The study was published online October 27 in the British Medical Journal.
Opiate Use Continues to Increase
For opiate users, "systematic reviews estimate annual death rates of about 1%, which is more than 10 times that of the general population and contributes more than 10% of adult mortality," write the study authors. Most of these deaths are due to overdose.
"Estimates of the prevalence of opiate use in the UK suggest 30-fold increases between 1970 and 2000, but more recent estimates are stable at around 250,000 opiate users," they add, noting that opiate substitution therapy in their country is given mainly within primary care.
For this study, the investigators pulled information from the United Kingdom's General Practice Research Database. They then evaluated data on 5577 primary care patients between the ages of 16 and 59 years (58% younger than 30 at start of treatment, 69% male) diagnosed as having "substance misuse" and prescribed noninjectible methadone or buprenorphine between 1990 and 2005.
A total of 267,003 prescriptions were written for these patients. A total of 57% of the patients were prescribed methadone only; 19% were prescribed methadone and dihydrocodeine; 9% were prescribed methadone and buprenorphine; 8% were prescribed buprenorphine only; 4% were prescribed buprenorphine and dihydrocodeine; and 4% were prescribed methadone, buprenorphine, and dihydrocodeine.
All patients were followed up "until 1 year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice," report the investigators. The median length of follow-up was 2 years.
The main outcome measure was all-cause mortality. Secondary measures included risk for death at different periods during and after treatment.
They also estimated "the probability that opiate substitution treatment reduces average mortality for patients exposed to different durations of treatment compared with if they had been unexposed."
Mortality Doubled When Not Receiving Treatment
Results of the analysis showed that 178 of the patients died (62 while undergoing treatment, 116 within 1 year of their last prescription).
The overall crude mortality rates were 0.7 per 100 person-years while receiving opiate replacement treatment and 1.3 while not receiving treatment.
"The crude mortality rate off treatment was almost double that on treatment, and after adjustment (for age, sex, calendar period, and comorbidity) the mortality rate ratio was more than twice as high" (2.3; 95% confidence interval [CI], 1.7 – 3.1), write the investigators.
Standardized mortality ratios, "comparing death rates among study patients with the population of England and Wales," were 5.3 (95% CI, 4.0 – 6.8) while undergoing treatment and 10.9 (95% CI, 9.0 –13.1) while not undergoing treatment.
In addition, men using opiates almost doubled the risk for death of women users (mortality rate ratio, 1.97; 95% CI, 1.4 – 2.9). However, the standardized mortality ratios were similar between men and women when both receiving and not receiving treatment.
Also, "mortality increased with age and was positively associated with comorbidity score," report the researchers.
When looking at treatment duration, the crude mortality rate was highest during the first 2 weeks at 1.7 per 100 person-years. After adjustment, this was 3.1 (95% CI, 1.5 – 6.6) times higher than the rate during the remainder of time receiving treatment.
The crude mortality rate during weeks 3 and 4 of treatment was 1.3, and the adjusted mortality rate ratio was 2.4 (95% CI, 0.95 – 6.0).
The mortality rates and ratios during the first month after stopping treatment were even higher:
Table. Mortality Rates and Ratios
Time Not Receiving Treatment Crude MR Adjusted MR Ratio (95% CI)
1-2 weeks 4.8 9.0 (5.4 – 14.9)
3-4 weeks 4.3 8.0 (4.7 – 13.7)
Remainder of time 0.95 1.9 (1.3 – 2.8)
CI = confidence interval; MR = mortality rate
"We found no evidence of any difference in the risk of death between buprenorphine and methadone when we compared the whole period on and off treatment," the study authors write.
Finally, short treatment durations of between 20 to 30 weeks reduced the overall risk for death by less than 25%. However, that rate increased to 65% at 40 weeks' duration and to more than 85% at durations "approaching or exceeding a year.
"The overall risk of death, standardized mortality ratios, and overall difference in mortality between time on and off treatment for opiate users in UK primary care in this study are consistent with international literature," report the investigators.
"Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality," they write.
"We hope that others also will examine further what interventions might reduce risk of relapse following treatment," added Professor Hickman.
Twice as Likely to Live If in Treatment
"This study is based on the British concepts of treatment, which are different from the US," Mary Jeanne Kreek, MD, professor and head of the Laboratory of the Biology of Addictive Diseases at Rockefeller University in New York City, told Medscape Medical News.
"They simply took all comers over a protracted period of 15 years who were labeled as receiving prescriptions for opiate substitution treatment. So their data will not look like US, Swedish, Norwegian data. Any place where they carefully follow up their people with more oversight," said Dr. Kreek.
She said that the British do not have tight control regarding this treatment "because individual doctors can do the prescribing."
Also, she noted that the word "substitution" is not used in the United States. "That's not allowed. Instead, we call it 'replacement treatment' or simply 'maintenance treatment.'"
Dr. Kreek, who was not involved with this study, has served on the National Institute on Drug Abuse National Advisory Council and is a past president of the College on Problems of Drug Dependence.
She said that "the most important result" from this study is the substantial crude mortality rate difference between people receiving and not receiving treatment. "That's the critical thing."
However, this finding isn't new. Dr. Kreek noted that Dr. Lars Gunne wrote that heroin addicts untreated had a death rate that was "multifold higher, based on a randomized study of methadone treatment in Sweden in the late 70s" (Drug Alcohol Depend. 1981;7:249-256).
She also noted that "there isn't really an end-of-treatment phase" for these types of patients in the United States.
"There is only about 5% to 10% who've been successfully treated and request to have their medication dose reduced and eliminated," said Dr. Kreek. "To take people off treatment is, to us, unethical unless they really ask and will work with you as a care provider to be followed up in a medication-free state.
"So why are these people [in this study] coming off treatment? The [investigators] don't really get into that, but in Britain there is more of a casual entry to and exit from treatment."
Another big difference is that "we've never seen a death in this country at the induction of this treatment," reported Dr. Kreek. "With buprenorphine, we don't watch people, but we have a very tight induction schedule that's well regulated, starting low and going on up."
Overall, Dr. Kreek said that this study is interesting to look at but "isn't really relevant to US practice" — except for the crude mortality rate difference.
"It doesn't matter what kind of program you have, people are twice as apt to live if they're in treatment than if they're not in treatment. That's what's important. Methadone and buprenorphine both can be very effective if properly used," she summarized.
This study was funded in part by a grant from the National Institute of Health Research (NIHR) for the Center for Research on Drugs and Health Behavior, a career scientist fellowship award from the NIHR, and an Medical Research Council new investigator award. The study authors and Dr. Kreek have disclosed no relevant financial relationships.
BMJ. Published online October 27, 2010.