New Lifesaving Medications Buoy Hopes

New discoveries in the research lab are boosting the viability of medication treatment for opioid and alcohol dependence. Buprenorphine, mentioned in this space as far back as September 2003 and examined more closely in recent issues of the magazine, has become more widely used in the treatment of opioid-dependent patients. Some treatment centers are using buprenorphine to retain in treatment those patients who otherwise would check out soon after detox.1


Carlton K. Erickson, PhD

Patients maintained on buprenorphine in a treatment center are clear-minded, stable, and able to participate in the various activities required of inpatients. The idea, then, is to encourage them to discontinue the medication gradually after discharge.

To see how this drug works, one should look first at the other major medication used to treat opioid addiction: methadone. Methadone is known to reduce the craving for heroin and other opioids, to “rebalance” the brain's reward pathway, and to provide stability in the lives of individuals who otherwise may be using dirty injection needles, infecting themselves and others with viruses, and committing crimes to get drugs. Methadone is an opioid agonist, meaning that it activates opioid receptors in the brain to reduce pain and create euphoria. Increasing the dose increases the high.

Buprenorphine has advantages compared with metha-done. It is a partial agonist, meaning that while it will activate opioid receptors up to a point, increasing the dose will not produce greater receptor activation. This means that the drug “shuts itself off” if patients in treatment try to increase the dose to get high. Buprenorphine also antagonizes one form of opioid receptor and therefore can block some of the actions of other opioids.

Any physician (MD or DO) can prescribe buprenorphine for the treatment of pain. Fewer physicians can prescribe buprenorphine for the treatment of opioid dependence, and none can prescribe for this purpose until acquiring eight hours of training on addiction and on the drug's properties. These trained physicians receive a second Drug Enforcement Administration (DEA) number that begins with an X, indicating that they are qualified to prescribe the drug for treating dependence. It is gratifying that so many physicians who knew very little about addiction have been attending buprenorphine training sessions over the past two years.

Physicians typically will initiate dosing of patients with a form of buprenorphine with the trade name Subutex, in the physician's office. Later, the patient may be given a prescription for the maintenance form of the drug, Suboxone (buprenorphine formulated with naloxone, to reduce abuse by users who would grind up the medication, dissolve it in water, and inject it).

Physicians will maintain opioid-dependent patients on buprenorphine for undetermined durations, with decisions depending on patient wishes and physician judgment. Physicians expect that some patients will take the drug for the rest of their lives.

New drug on the horizon

An extended-release formulation of the drug naltrexone is on target for a summer marketing launch by a partnership of manufacturer Alkermes, Inc., and marketer and distributor Cephalon, Inc. Formerly called Vivitrex and now called Vivitrol, this injectable suspension is designed to be given once every 30 days to alcohol-dependent patients receiving counseling. This dosing is seen as potentially far superior to the single daily dosing of oral naltrexone in terms of encouraging patient compliance.

A recent randomized, double-blind, placebo-controlled trial including more than 600 subjects showed a greater effect of the long-acting injectable medication compared with daily administration of oral naltrexone.2 The study found that the long-acting naltrexone was well-tolerated and resulted in reductions in heavy drinking among treatment-seeking, alcohol-dependent patients during six months of therapy.

Just a few years ago, scientists studying medications for chemical dependence treatment could not be sure that pharmaceutical companies would be interested in marketing the drugs. Today we see an entirely new enthusiasm regarding the use of medications either to enhance abstinence or reduce the consequences and severity of uncontrolled drug use. This is possible because of an increased understanding of chemical dependence as a medical disease that responds to many types of treatment, including medications.

It is likely that until physicians learn more about chemical dependence, use of these medications will not be as widespread as use of previous breakthrough drugs such as the selective serotonin reuptake inhibitor (SSRI) antidepressants has been. Medications such as buprenorphine, naltrexone, acamprosate, and bupropion all work to stabilize or correct brain dysregulations that drive the inability to control drug use. Perhaps when we reach the milestone of a dozen antiaddiction drugs that physicians need to know about, all medical schools finally will include alcohol and other drug dependence in their curricula.

References

1. Caldiero RM, Parran TV, Adelman CL, , et al. Inpatient initiation of buprenorphine maintenance vs. detoxification: Can retention of opioid-dependent patients in outpatient counseling be improved ? Amer J Addict 2006; 15:1--7.
2. Garbutt JC, Kranzler HR, O'Malley SS ,. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: A randomized controlled trial. JAMA 2005; 293:1617-25.