As misuse of prescription drugs increases, treating addiction to these drugs has become as crucial as preventing it. Yet best practice in this area remains elusive. David Holmes reports.

Last June, the UN flagship World Drug Report 2011 launched by Ban Ki-moon outlined the scale of the problem - declining world markets for cocaine, heroin, and cannabis, almost entirely offset by increases in the misuse of prescription opioid drugs. Then, in November, the European Monitoring Centre for Drugs and Drug Addiction annual report for 2011 painted a similar picture, showing that although drug misuse is fairly stable in Europe, there has been a striking increase in the misuse of synthetic opioid drugs. But, as the most recent figures from the US Substance Abuse and Mental Health Services Administration (SAMHSA) showed in December, it is the USA that is the epicentre of the world’s problems with prescription drugs.

The SAMHSA data, which are taken from the nationwide Treatment Episode Data Set, show that although the overall rate of treatment admissions for substance misuse among people aged 12 years and older in the USA was stable from 1999 to 2009, there was a huge 430% increase in the rate of treatment admissions for the misuse of prescription opioid drugs in the same period—from ten per 100 000 people in 1999 to 53 per 100 000 people in 2009. And these are just the latest in a long list of numbers released in 2011 that were so stark the US Centers for Disease Control and Prevention has classified prescription drug misuse as an epidemic; the White House calls it “the Nation’s fastest-growing drug problem”.

Frank Falco agrees. Falco is the incoming President of The American Society of Interventional Pain Physicians (ASIPP) and Clinical Assistant Professor at Temple University Medical School, Philadelphia, PA, USA. “Opioids are now abused more than any other illicit drug or controlled prescription drug, passing marijuana for the first time”, he says, before reeling off the kind of statistics that have forced policy makers to sit up and take notice: “80% of Americans between the ages of 12 and 20 have used a controlled drug that was prescribed for someone else at least once for an unintended prescribed indication. The state of Florida consumes 80% of the world’s supply of oxycodone [a powerful analgesic drug]. More Americans die from an opioid overdose than those that die from motor vehicle accidents. In Florida, 10 people per day die from an overdose of opioids or benzodiazepines. In Delaware, where I practice, one person dies every other day from an overdose of opioids.”

After initially facing criticism for being too slow to react to the growing crisis, the Obama administration has made the 2011 Prescription Drug Abuse Prevention Plan a central plank of its National Drug Control Strategy. As part of the plan, the Drug Enforcement Administration is working on implementing Risk Evaluation and Mitigation Strategies to reduce the misuse and diversion of opioid drugs and other prescription controlled drugs, at the same time as developing mandatory education requirements for physicians who prescribe and pharmacies that dispense opioid analgesic drugs. There will also be a renewed commitment to prescription drug monitoring programmes. Despite being signed into law in 2005, the National All Schedules Prescription Electronic Reporting Act (NASPER) has often failed to get funding from the US Congress because it costs too much. “If consistently funded on an annual basis, [NASPER] would significantly prevent doctor shopping and drug diversion by allowing physicians and pharmacists to access patient records showing what prescribed controlled drugs have been prescribed and dispensed to a patient anywhere in the US”, says ASIPP’s Falco, whose organisation’s founder and CEO Laxmaiah Manchikanti first introduced the Act to Congress.

The magnitude of the problem means that prevention can now only be part of the solution - the SAMHSA data show that improving the efficacy of treatment is absolutely crucial. SAMHSA Administrator Pamela Hyde advises that “concerned family members or friends who think a substance abuse problem may exist should seek help. Treatment is effective and people recover”, whereas the White House asserts that “thousands of individuals who have struggled with addiction are now living healthy and happy lives with the help of treatment and recovery services”; but both statements belie the fact that research into the treatment for prescription opioid drug addiction has been chronically neglected. As a result, the evidence base that informs best practice is thin. “The ‘standard treatment’ for prescription opioid dependence is evolving, and I can’t say that there is a single current standard at this time”, says Roger Weiss, of Harvard Medical School in Boston, MA, USA.

Weiss was the lead author of the first - and so far only - large- scale study of the treatment of prescription opioid addiction, which was published recently in the Archives of General Psychiatry, and which posed as many questions as it answered. The investigators assessed the efficacy of brief (phase 1: 2- week stabilisation, 2- week taper, and 8- week postmedication follow- up) and extended (phase 2: 12- week treatment, 4- week taper, and 8- week postmedication follow- up) treatment with a combination of the opioid substitute buprenorphine and the opioid antagonist naloxone (which causes withdrawal if the combination is taken by any route other than orally, as intended), with or without intensive opioid dependence counselling in addition to standard weekly medical management during which physicians recommend abstinence and self- help therapy participation.

653 outpatients were randomly assigned treatment at ten sites throughout the USA. Of these, only 43 (6·6%) had a successful urine- test - confirmed outcome of no opioid use after phase 1 of treatment, and there was no difference between those who were assigned intensive counselling and those who received standard medical management. 177 (49·2%) of the 360 patients who underwent phase 2 treatment had a successful outcome at week 12 of treatment, but this fell to just 31 (8·6%) 8 weeks after completing the taper, with no difference between those who received adjunct counselling and those who did not.

At present, many patients who are addicted to opioid drugs and who seek treatment are tapered off opioid drugs and given behavioural treatment alone, or are otherwise maintained on buprenorphine or methadone. “In our study, even those who were maintained on buprenorphine for 12 weeks had successful outcomes in only approximately half of the cases”, says Weiss, while behavioural treatment after tapering off opioid drugs “did not result in good outcomes”. “Most patients who tapered off of buprenorphine did return to opioid use”, Weiss explains. “I believe that this shows that for many such patients, ongoing pharmacotherapy may be highly beneficial in sustaining recovery. We are currently conducting a longer- term follow up study of this patient population, which should give us greater insight into the types of treatments that would be necessary to sustain longer- term recovery.” One such option could be naltrexone, an opioid receptor antagonist. Although poor adherence to oral naltrexone has limited its success in the past, an injectable extended release formulation is available. “We will see what role long- lasting injectable naltrexone has in the treatment of this population”, Weiss affirms.

Getting behavioural treatment right is also a huge challenge. Adding intensive counselling had no affect on outcomes in Weiss’s study. “We don’t know whether more intensive counselling would have been helpful”, he says. “Moreover, the weekly medical counselling that all patients received was both more frequent and perhaps of higher quality than they might receive in the community; it was delivered more often than is typically done, and the study physicians were carefully chosen because of their deep interest in the treatment of opioid dependence.” However, says ASIPP’s Falco, “as with any addiction, cognitive behavioural therapy and supportive group therapy are key to prevent relapse”.

What is increasingly clear is that, in some respects, treating prescription drug dependency presents an even more complex problem than the treatment of addiction to illicit drugs. “It all depends on the patient, their problem”, and what is meant by dependent, says Falco. Although many people who become dependent on prescription pain killers obtain them illicitly as they would illicit opioid drugs such as heroin, many people do have a legitimate prescription and are highly likely to have co- occurring chronic pain, “and this becomes an important clinical issue when treating these patients”, says Weiss. “Moreover”, he adds, “many such patients don’t want to stop using opioids, but just want to reduce their dose”. Identifying and treating psychiatric disorders is also an important step in preventing and treating drug abuse, says Falco. “I think that recovery from prescription opioid dependence is likely best achieved through a combination of pharmacotherapy and counselling”, concludes Weiss; “determining the optimal combination of these two treatment approaches is an evolving field”.

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The Lancet, Volume 379, Issue 9810, Pages 17 - 18, 7 January 2012
doi:10.1016/S0140-6736(12)60007-5