There is currently no easy way to prevent weight gain caused by
second-generation antipsychotics such as olanzapine, clozapine, and
risperidone. But researchers may have identified a drug that may halt
antipsychotic-provoked weight gain after it has started. The drug is
Amantadine is a dopamine agonist approved for treatment of influenza A
virus, idiopathic parkinsonism, and the extrapyramidal side effects of
antipsychotic medications. Since previous studies have shown that weight loss
is a side effect of amantadine, Karen Graham, M.D., an assistant professor of
psychiatry at the University of North Carolina, and colleagues decided to
undertake a small pilot trial to determine whether amantadine could halt
weight gain in subjects who had gained weight while using a second-generation
Twenty-one adults who had taken the second-generation antipsychotic
olanzapine for one to 44 months and who had gained between five and 58 pounds
while on it were randomly assigned to receive up to 300 mg/day of amantadine
or a placebo in addition to olanzapine for 12 weeks. Subjects' body mass
indices and positive and negative symptoms were assessed at baseline and at 12
Twelve subjects were taking the amantadine, and eight of them either
stabilized their weight or lost weight, whereas only two of the nine placebo
The amantadine group lost an average of 0.8 pounds and reduced their body
mass index by an average of 0.07 kg/m2, whereas the placebo group
gained an average of 8.7 pounds and increased their body mass index by an
average of 1.24 kg/m2.
Moreover, the positive and negative symptoms of subjects taking amantadine
did not worsen over the course of the study, suggesting that the drug was not
aggravating their psychosis.
Thus, it looks as if amantadine might be able to halt weight gain in some
patients taking a second-generation antipsychotic and may do so without
causing adverse psychological effects, Graham and her team concluded in the
September American Journal of Psychiatry.
The challenge now, Graham told Psychiatric News, is to see whether
amantadine can keep individuals placed on a second-generation antipsychotic
from gaining weight in the first place. She and her group are currently
conducting such a study.
Yet even if their results are positive, she cautioned, amantadine will
probably not be a "magic bullet" to prevent weight gain in
patients on second-generation antipsychotics.
The reason, she explained, is that "the causes of weight gain will be
varied and will depend on the medication in question and characteristics of
the individual patient. The second-generation antipsychotics act on a number
of neurotransmitters, which influence appetite, satiety, spontaneous and
volitional activity, and the ability of our bodies to store or burn energy.
For any given combination of patient and medication, one or more of these may
promote weight gain."
Moreover, she added, "Obesity is steadily increasing in the United
States and many other countries and has reached alarming rates. Our patients
are living in a sedentary culture, where access to cheap calorie-dense,
nutrient-poor food is much greater than it is to fresh fruits and vegetables.
We need to address these societal issues as well as look for pharmacologic
means to help people reach and maintain a healthy weight."
The mechanism by which amantadine thwarts weight gain is unknown. But it
may decrease appetite through its dopaminergic anorexic effects.
The study was financed by the National Institute of Diabetes and Digestive
and Kidney Diseases and an unrestricted gift from Eli Lilly and Co., maker of
"Double-Blind, Placebo-Controlled Investigation of Amantadine
for Weight Loss in Subjects Who Gained Weight With Olanzapine" is posted
Am J Psychiatry