Bupropion Plus Zonisamide for Obesity
J Clin Psychiatry 68:8, August 2007
1227
mote weight loss in obese adults in 3 randomized con-
trolled trials.1–3 There is evidence from one randomized
controlled trial that zonisamide, an antiepileptic drug, is
superior to placebo in assisting obese individuals to lose
weight.4 Bupropion is known to enhance the activity of
norepinephrine and dopamine, whereas zonisamide has
similar effects on serotonin and dopamine.1,4 We hypoth-
esized that because all 3 major neurotransmitters that regu-
late appetite and energy homeostasis are targeted with the
combination of zonisamide and bupropion, the combina-
tion therapy might lead to greater weight loss than either
drug alone. Another reason for combining these drugs was
the hope that certain known adverse effects of zonisamide,
such as somnolence, psychomotor slowing, cognitive im-
pairment, fatigue, and depression, could potentially be off-
set by the known side effects of bupropion, such as insom-
nia, activation, and psychomotor agitation, as well as its
antidepressant effect. Further, zonisamide might poten-
tially reduce the seizure risk associated with bupropion.
Therefore, we conducted this preliminary investigation to
examine the effect of the combination therapy on body
weight compared with zonisamide monotherapy.
METHOD
Experimental Design
This was a 12-week, randomized, open-label, parallel-
group comparison of zonisamide versus zonisamide plus
Combination Therapy of Zonisamide and Bupropion
for Weight Reduction in Obese Women:
A Preliminary, Randomized, Open-Label Study
Kishore M. Gadde, M.D.; Gretchen M. Yonish, R.D.;
Mariko S. Foust, R.D.; and H. Ryan Wagner II, Ph.D.
Objective: Zonisamide and bupropion have been
investigated for weight reduction in obese adults. We
conducted a preliminary study comparing the effect
on body weight of the combination of these 2 drugs
versus zonisamide monotherapy.
Method: This was a 12-week, randomized, open-
label, parallel-group comparison of 2 active interven-
tions conducted from