`Harm Reduction' Controversial in Alcohol Treatment

Seemingly one of the most significant issues facing addiction specialists is the debate between those who favor complete abstinence as a treatment goal and those who favor “harm reduction” as a valid treatment target.

During last month's annual meeting of the American Academy of Addiction Psychiatry (AAAP), several sessions explored the apparent disconnect between traditional addiction treatment trials and clinicians' real-world experience with their patients. Clinical trials for addiction treatments have commonly used dichotomous outcome measures such as “drinking alcohol” versus “not drinking alcohol.” Few patients in these trials were able to achieve complete abstinence, and the medications being studied were deemed not very effective.

Yet in the “real world” many addiction specialists clinically use a more continuous outcome measure: they simply aim to help patients reduce the amount they drink on any given day and/or reduce the number of days a month when the patient does drink. If the traditional clinical trials had used more continuous outcomes measures, the available medications would have looked significantly better, some researchers say.

“Requiring complete abstinence isn't realistic,” said Richard Rosenthal, M.D., who chaired a symposium at the AAAP meeting on emerging concepts in the pharmacotherapy of alcoholism. Rosenthal is a professor of psychiatry at Columbia University and St. Luke's Roosevelt Hospital Center in New York City and former president of AAAP.

“Using a continuous model of treatment outcomes opens up new potential targets for therapy,” Rosenthal explained. “You can target reducing heavy drinking days, for example, or you could target reducing alcohol intake—from heavy down to moderate. Might these outcomes, which result in a reduction in harm, have clinical value?”

Recently, Rosenthal detailed, clinical trials have been published using outcomes such as the reduction of heavy drinking compared with traditional abstinence measures. These trials, he added, may impact treatment planning and patient selection. In addition, he said, recent data using the continuous model “suggest potential targets for pharmacological intervention beyond categorical alcohol dependence.”

In the future, Rosenthal said, “as new medications for alcoholism become available and new research opens broader opportunities to document positive treatment effects, clinicians may need to adjust their therapeutic approach and consideration of what is a successful intervention.”

“The big question, though,” added Henry Kranzler, M.D., a professor of psychiatry at the University of Connecticut School of Medicine,“ is how do you differentiate folks who need total abstinence versus those who could be appropriate for a goal of reduced number of heavy drinking days?”

Clinically that is a difficult question, Kranzler said, but a look at the three currently approved medications for the treatment of alcohol abuse may help clinicians decide on which drug treatment to use to promote which treatment goal.

Disulfiram (Antabuse) is approved “for the prevention of any alcohol intake,” Kranzler explained. “When taken in combination with alcohol, the drug reacts violently and makes the patient very ill.”

In clinical trials disulfiram has been effective at cutting in half the number of heavy drinking days when the 250 mg dose was compared with placebo, said Kranzler. Yet disulfiram was not statistically significantly better than placebo at promoting complete abstinence.

Acamprosate (Campral), also approved for the maintenance of abstinence from alcohol, has been effective in clinical trials at promoting abstinence. After one year of treatment, clinical trial data suggest abstinence is doubled in those taking acamprosate compared with those taking placebo. The effect, Kranzler added, appears to persist for as long as one year after acamprosate treatment was stopped. In addition, for those taking acamprosate who did not achieve complete abstinence, there was a noted significant effect on harm reduction through reduced alcohol intake.

The third approved medication for alcohol abuse and dependence is naltrexone (ReVia). In 14 clinical trials with more than 2,000 patients, Kranzler said, the drug has been shown to have a “clear effect on reducing risk of relapse in those patients who are abstinent when they start naltrexone. However, naltrexone has a negligible effect on increasing abstinence.”

The FDA recently issued an approvable letter for a monthly injectable formulation of naltrexone (Vivitrol) (see MedCheck on page 30). Researchers hope the once-a-month injection may help increase compliance in patients with alcohol dependence who do not regularly take their daily medication.

“Clearly, all of the approved medications reduce drinking,” Kranzler concluded, but the data on increasing abstinence are not clear.“ We need to develop and determine predictors for the reduced harm versus abstinence treatment pathways.” ▪