Drug Treatment of Anorexia

I used to work in an eating disorders treatment program.  From
time to time, I give talks on the subject.  When I get to the
part about the use of psychiatric medication, I always start with
something like this: "frankly, the role of medication in the treatment
of eating disorders is extremely limited."



This pessimistic view was amplified this week, by a report in the href="http://jama.ama-assn.org/" rel="tag">Journal
of the American Medical Association (JAMA).
 What is a bit unusual about the report is that it was picked
up in the major news media ( href="http://www.nytimes.com/2006/06/14/health/14prozac.html?ex=1307937600&en=7ae2affea6b1106c&ei=5090&partner=rssuserland&emc=rss">NYT/ href="http://www.washingtonpost.com/wp-dyn/content/article/2006/06/13/AR2006061301034.html">WaPo),
despite the fact that the findings were negative.  That is,
they found that treatment with href="http://en.wikipedia.org/wiki/Fluoxetine" rel="tag">fluoxetine
did not improve the outcome.  



Continue reading below the fold...

href="http://jama.ama-assn.org/cgi/content/full/295/22/2605">Fluoxetine
After Weight Restoration in Anorexia Nervosa



A Randomized Controlled Trial



B. Timothy Walsh, MD; Allan S. Kaplan, MD, FRCPC; Evelyn
Attia, MD; Marion Olmsted, PhD; Michael Parides, PhD; Jacqueline C.
Carter, PhD; Kathleen M. Pike, PhD; Michael J. Devlin, MD; Blake
Woodside, MD, FRCPC; Christina A. Roberto, BA; Wendi Rockert, MEd



JAMA. 2006;295:2605-2612.



Context  Antidepressant medication is frequently
prescribed for patients with anorexia nervosa.



Objective  To determine whether
fluoxetine can promote recovery and prolong time-to-relapse among
patients with anorexia nervosa following weight restoration.



Design, Setting, and Participants 
Randomized, double-blind, placebo-controlled trial. From January 2000
until May 2005, 93 patients with anorexia nervosa received intensive
inpatient or day-program treatment at the New York State Psychiatric
Institute or Toronto General Hospital. Participants regained weight to
a minimum body mass index (calculated as weight in kilograms divided by
the square of height in meters) of 19.0 and were then eligible to
participate in the randomized phase of the trial.



Interventions  Participants were randomly assigned
to receive fluoxetine or placebo and were treated for up to 1 year as
outpatients in double-blind fashion. All patients also received
individual cognitive behavioral therapy.



Main Outcome Measures  The primary
outcome measures were time-to-relapse and the proportion of patients
successfully completing 1 year of treatment.



Results  Forty-nine patients were
assigned to fluoxetine and 44 to placebo. Similar percentages of
patients assigned to fluoxetine and to placebo maintained a body mass
index of at least 18.5 and remained in the study for 52 weeks
(fluoxetine, 26.5%; placebo, 31.5%; P = .57). In a Cox proportional
hazards analysis, with prerandomization body mass index, site, and
diagnostic subtype as covariates, there was no significant difference
between fluoxetine and placebo in time-to-relapse (hazard ratio, 1.12;
95% CI, 0.65-2.01; P = .64).



Conclusions  This study failed to
demonstrate any benefit from fluoxetine in the treatment of patients
with anorexia nervosa following weight restoration. Future efforts
should focus on developing new models to understand the persistence of
this illness and on exploring new psychological and pharmacological
treatment approaches.

In the Introduction, the authors mention two prior studies.
 One found no benefit; the other found some benefit.
 So they decided to do a larger study, in order to settle the
question.  And at this point, I would have to agree that the
question is closer to being settled.



Careful readers, however, will want to know exactly what question it is
that has been settled.  



They authors used 10 different measures to define patient progress or
retrogression, and the analysis was rather complex.
 Consequently, it is difficult to interpret the study
rigorously.



Clearly, one of the most important measures employed was that of body
weight.  Patient in the active treatment group were not more
likely to maintain a healthy weight, compared to those on placebo.
 However, the rationale for the use of antidepressant
medication may not be based upon the intention of maintaining body
weight.  



Often, for patients with anorexia, an antidepressant might be
recommended, not to help maintain weight, but to treat anxiety and/or
depression.  



Could it be that the study showed no benefit in maintaining body
weight, but that patients benefited in other ways?  Maybe they
experienced improvement in depression or anxiety, or overall quality of
life.



It turns out that the authors looked at all of that.  The only
benefit they found was in a reduction of anxiety, as assessed by the
Beck Anxiety Inventory.  Depression did not improve, and
quality of life (as measured by the Quality of Life Enjoyment and
Satisfaction Questionnaire) did not improve.  



So, although anxiety scores declined, if that is the only benefit, and
overall quality of life did not improve, I would have to agree with the
conclusion that the medication simply did not help these people.



As is traditionally done in papers like this, the authors discuss the
limitations of the study.  That is where they include cautions
regarding how generalizable the study is.  

A limitation on the conclusions of the current study
is that we examined the utility of fluoxetine at a particular stage of
illness and in conjunction with a particular form of structured
psychological treatment. We cannot exclude the possibility that
antidepressants might have an effect at other stages of illness, for
example, in patients who have had anorexia nervosa for only a short
time or who maintained a normal weight for a longer period of time
before receiving antidepressant treatment. Similarly, it is conceivable
that fluoxetine might provide benefit if it were the sole treatment
provided or given in association with some other intervention.

Notice that all patients had access to psychotherapy.  Given
the nature of the study, I assume that patients were able to attend
weekly sessions of state-of-the-art cognitive-behavioral therapy, and
all had received expert nutritional counseling.  It is
possible that, if a patient has all that, that the addition of
medication adds nothing.  



However, most patients will not have access to that level of
psychosocial intervention.  Most patients would be lucky to
get 20 sessions of psychotherapy per year.  Many live in areas
where there are not any dietitians with extensive experience with
eating disorder treatment.  



That is why I said earlier that the question is closer
to being settled.  The study shows that patients who get very
good psychosocial treatment do not benefit from the addition of
fluoxetine.  It does not tell us whether patients with
substandard treatment might benefit from medication.  That is
an important distinction, because most patients simply do not have
access to ideal treatment.