more of the following: consumption of
peculiar forms of food or toxic substances,
insomnia related to sleep disruption with
daytime fatigue or sleepiness, sleep-related
injury, dangerous behaviors performed
while in pursuit of food or while cooking
food, morning anorexia, and adverse health
consequences from recurrent binge eating
of high-caloric foods.
1
Because our patient
exhibited recurrent episodes of binge and
uncontrollable eating after arousal from
sleep, she could not remember her ab-
normal eating behavior; her symptoms
met the diagnostic criteria for SRED. Sev-
eral drugs, such as zolpidem, triazolam,
olanzapine, risperidone, and quetiapine
related to SRED,
3Y9
and topiramate, clo-
nazepam, and dopaminergics showed ther-
apeutic benefits through case reports and
small uncontrolled studies.
10Y12
Mirtazapine enhances serotonin re-
lease by blocking >-2 autoreceptors and
heteroreceptors, selectively antagonizing
the serotonin 5-HT2 and 5-HT3 receptors
in the central and peripheral nervous sys-
tem. Blockade of 5-HT2 and 5-HT3 re-
ceptors may produce antidepressant effects
by relieving sleep disturbance or increasing
appetite. Mirtazapine also has a potent an-
tagonist effect on histamine 1 receptors,
which may augment the sedative and
appetite-increasing effects.
The pathophysiology of SRED is still
unclear. However, because SRED is prev-
alent in patients with RLS and PLMD,
there is evidence that SRED may be related
to dopaminergic dysfunction.
2,10,13,14
Some
investigators have reported that combined
selective >-2 adrenoceptor antagonists and
norepinephrine transporter inhibitors caused
a marked and selective increase of extracel-
lular dopamine in prefrontal cortex.
15,16
However, second-generation antide-
pressants alone may cause RLS in 9% of
patients, and mirtazapine induced or ex-
acerbated RLS in 28% of patients.
17
More-
over, recent reports showed an association
of mirtazapine with PLMD-like symp-
toms.
18
Although serotonin-mediated do-
pamine inhibition might be a mechanism,
19
it
is uncertain which mechanism of mirtazapine
causes SRED.
Here, we report the first case of
mirtazapine-related SRED. The use of
mirtazapine should, therefore, be consid-
ered a possible precipitating factor for
developing SRED, and it will not neces-
sarily have an immediate onset.
AUTHOR DISCLOSURE
INFORMATION
The authors declare no conflicts of
interest.
This is an open access article dis-
tributed under the terms of the Creative
Commons Attribution-NonCommercial-
NoDerivatives 3.0 License, where it is
permissible to download and share the
work provided it is properly cited. The
work cannot be changed in any way or
used commercially.
Jong-Hyun Jeong, MD, PhD
Department of Psychiatry
St Vincent’s Hospital
College of Medicine
The Catholic University of Korea
Suwon, Korea
Won-Myong Bahk, MD, PhD
Department of Psychiatry
St Mary’s Hospital
College of Medicine
The Catholic University of Korea
Seoul, Korea
wmbahk@catholic.ac.kr
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Donepezil-Associated Mania
in Two Patients Who Were
Using Donepezil Without
a Prescription
To the Editors:
M
ore than 40 years ago, it was pos-
tulated that excess acetylcholine
was associated with depression and de-
creased acetylcholine was associated with
mania.
1
Although the prevailing notion
that increased cholinergic status is asso-
ciated with depression, to date, there are
7 case reports of mania related to the use
of donepezil in subjects with dementia.
2Y7
Donepezil is a reversible acetylcholines-
terase inhibitor, which acts on the nervous
system when used in the treatment of de-
mentia of the Alzheimer type. We report
the first 2 cases of mania associated with
donepezil use in healthy men who took
donepezil that was not originally pre-
scribed for them.
Journal of Clinical Psychopharmacology & Volume 34, Number 6, December 2014 Letters to the Editors
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