ajp.psychiatryonline.org Am J Psychiatry 168:7, July 2011
Adapting Treatment to Patient Problems
Alcoholism is a complex disorder with multifaceted symptoms involving multiple
neural-behavioral systems. Thus, it is not surprising that multiple treatment approach-
es have been reported to improve outcomes. Evidence is accumulating that matching
treatment to patient problems leads to better outcomes. This was shown in a prospective
randomized study (1) in which treatment was applied to specific problems measured
at intake by the Addiction Severity Index (2). Unfortunately, most treatment programs
provide the same treatment to all patients, even though their program advertisements
might say otherwise (3).
Adapting treatment to specific problems can also be approached by selection of med-
ication. Last year in the Journal, Pettinati and colleagues (4) reported on combining
medications for patients suffering from both alcoholism and major depression. This is
a very common combination of problems, and it has been approached with different
kinds of antidepressant medication. In a placebo-controlled trial, Pettinati et al. tried
a combination of two medications, one for
heavy drinking (naltrexone) and the other for
depression (sertraline). The patients receiv-
ing the combination showed significantly
more clinical improvement both in depres-
sion and in drinking behavior than those re-
ceiving either medication alone.
experience and shows that
can indeed be objectively
In this issue, Anton and colleagues (5), again
acknowledging the multifaceted symptoms of
alcoholism, report the effect of adding gaba-
pentin to naltrexone in the postdetoxification
period. The naltrexone-gabapentin combina-
tion makes excellent pharmacological sense, and it is likely to be safe because naltrex-
one has no significant interactions with any class of drugs other than opioids. During the
immediate postdetoxification period, symptoms that can be described as “protracted
withdrawal” are prominent in many patients and may cause treatment dropout or re-
lapse to drinking. Naltrexone has not been found to have any effect on such symptoms.
Clinicians have always been tempted to add other medications for symptomatic treat-
ment of irritability, insomnia, and anxiety early in alcoholism treatment, and gabapentin
seems to be a logical choice. It has already been shown to reduce the symptoms of acute
alcohol withdrawal in a controlled study (6).
But Anton et al. went beyond the usual open clinical experimentation. They tested
their hypothesis in a double-blind trial with the addition of either gabapentin or pla-
cebo to naltrexone. During the first 6 weeks of the study, the addition of gabapentin
to naltrexone produced a longer delay to relapse, fewer drinks per drinking day, and a
decrease in alcohol craving. As expected, the gabapentin group reported fewer sleep
problems than the other two groups, which is consistent with reports of gabapentin’s
benefits for alcohol withdrawal.
The Anton et al. study is a fine example of clinical research guided by clinical experi-
ence and shows that medication combinations can indeed be objectively evaluated.
Their study deserves replication, perhaps adding a gabapentin-alone treatment arm,
as the authors suggest. Another variable to be considered in a replication study is the
dosage of naltrexone. The recommended daily dose of 50 mg was arrived at in 1983 by
“[This] study is a fine
example of clinical
research guided by clinical
Am J Psychiatry 168:7, July 2011 ajp.psychiatryonline.org
convenience, as this was the dosage used in the treatment of heroin addiction. More
recent studies, such as Project COMBINE (7) and the above-cited study using an anti-
depressant and naltrexone (4), have used 100 mg per day.
Most importantly, the Anton et al. study provides guidance to clinicians who are faced
with a patient who has multiple chronic withdrawal complaints during the course of
naltrexone treatment for alcoholism. This is an important problem that often leads to
dropout and relapse to heavy drinking. Clinicians are known to add medications for
symptomatic treatment in the absence of controlled data. While a single study does not
provide adequate proof, the high quality of Anton and colleagues’ study provides sup-
port to desperate clinicians seeking a way to retain the patient in treatment. We can also
hope that a replication study is already in the planning stage.
1. McLellan AT, Grissom GR, Zanis D, Randall M, Brill P, O’Brien CP: Problem-service “matching” in addiction
treatment: a prospective study in 4 programs. Arch Gen Psychiatry 1997; 54:730–735
2. McLellan AT, Luborsky L, Woody GE, O’Brien CP: An improved diagnostic evaluation instrument for substance
abuse patients: the Addiction Severity Index. J Nerv Ment Dis 1980; 168:26–33
3. McLellan AT: The status of the United States treatment system: implications for evidence based treatments,
in Rethinking Substance Abuse: What the Science Shows and What We Should Do About It. Edited by Miller
WR, Carroll KM. New York, Guilford, 2005, pp 146–157
4. Pettinati HM, Oslin DW, Kampman KM, Dundon WD, Xie H, Gallis TL, Dackis C, O’Brien CP: A double-blind,
placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alco-
hol dependence. Am J Psychiatry 2010; 167:668–675
5. Anton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, Randall PK: Gabapentin combined with
naltrexone for the treatment of alcohol dependence. Am J Psychiatry 2011; 168:709–717
6. Myrick H, Malcolm R, Randall PK, Boyle E, Anton RF, Becker HC, Randall CL: A double-blind trial of gaba-
pentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res 2009; 33:1582–1588
7. Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson
BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss
RD, Williams LD, Zweben A; COMBINE Study Research Group: Combined pharmacotherapies and behav-
ioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 2006;
CHArleS P. o’BrieN, M.d., Ph.d.
Address correspondence and reprint requests to Dr. O’Brien (firstname.lastname@example.org). Editorial accepted
for publication April 2011 (doi: 10.1176/appi.ajp.2011.11040594).
Dr. O’Brien has worked as a consultant for Alkermes and Gilead. Dr. Freedman has reviewed this editorial and
found no evidence of influence from these relationships.