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
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
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
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
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." ▪