Medical Hypotheses (2005) 65, 1176–1178

http://intl.elsevierhealth.com/journals/mehy

Repetitive transcranial magnetic stimulation:

A possible novel therapeutic approach to
eating disorders
Shih-Jen Tsai *

Department of Psychiatry, Taipei Veterans General Hospital, Taiwan Division of Psychiatry,

School of Medicine, National Yang-Ming University, No. 201 Shih-Pai Road, Sec. 2, 11217 Taipei, Taiwan

Received 15 May 2005; accepted 19 May 2005

Summary The two most common eating disorders, anorexia nervosa and bulimia nervosa, are characterized by
aberrant eating patterns and disturbances in body image. Treatment involves combining individual, behavioural,
group, and family therapies, possibly with medications. Studies have found that medication, chiefly antidepressants,
could be of help in bulimia nervosa but the evidence is weaker for use in anorexia nervosa. Repetitive transcranial
magnetic stimulation (rTMS) is a non-invasive technique that briefly stimulates or depresses cortical areas within the
brain. It has been used in the treatment of various psychiatric disorders, especially major depression, which is a
condition that patients with eating disorders often experience as a significant comorbidity. Given that both disorders
may share a common pathogenesis, this report proposes that rTMS may represent an alternative strategy for the
treatment of eating disorders. Other evidence that supports this notion comes from animal studies that show that rTMS
can change feeding behaviours and central neurotransmitters related to the regulation of eating behaviours. Further
investigation into the dose, duration and type of rTMS stimulus is needed to verify the efficacy of this intervention in
eating disorders.
c 2005 Elsevier Ltd. All rights reserved.

Eating disorders such as anorexia nervosa (AN)
and bulimia nervosa (BN) are a group of serious
conditions that are becoming increasingly preva-
lent among children and adolescents in industrial-
ized nations [1]. Both AN and BN are
characterized by abnormal patterns in eating
behaviour and weight regulation, and by distur-
bances in body image. Early treatments of eating
disorders focus on the restoration of nutritional
* Tel.: +886 2 28757027x276; fax: +886 2 28725643.
E-mail address: sjtsai@vghtpe.gov.tw.
status and somatic health, and support is offered
to the patient and his/her family [2]. Once this is
achieved, a wide variety of medical and psycho-
logical approaches are available to the clinician
to address the disease itself. These include
medications and psychodynamic, behavioural,
cognitive-behavioural, family, and group psycho-
therapies [3–5]. Antidepressants are the most
commonly used medication in eating disorders.
Antidepressant medication has been shown to
be of benefit in BN, but the evidence is weaker
for most AN patients [6,7].


0306-9877/$ - see front matter c 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2005.05.020
Repetitive transcranial magnetic stimulation
Repetitive transcranial magnetic stimulation
(rTMS) is a non-invasive technique that briefly stim-
ulates or depresses cortical brain areas. It has been
previously assessed and used in the treatment of
various psychiatric disorders including major
depression, mania, obsessive-compulsive disorder,
post-traumatic stress disorder, and schizophrenia
[8,9] and recently it has also been suggested to
have therapeutic potential for autistic disorders
[10]. Here, this report proposes that rTMS could
be a potential strategy for the treatment of eating
disorders.
Firstly, rTMS has been reported to be effective
in the treatment of major depression [11]. The
intricate link between major depression and eating
disorders (the increased prevalence of depressive
episodes in patients with eating disorders and some
common biochemical changes in both disorders
[12]) suggests that rTMS could be effective for cer-
tain types of eating disorders.
Secondly, it has been suggested that distur-
bances in the serotonin system may underlie the
pathogenesis to eating disorders [13]. In one partic-
ular animal study, chronic rTMS was shown to in-
duce sub-sensitivity of presynaptic serotonergic
autoreceptor activity in rat brain and such sub-sen-
sitivity has been demonstrated after other antide-
pressant treatments [14]. Therefore, rTMS
treatment in eating disorders may help to normal-
ize serotonergic dysfunction.
Thirdly, brain-derived neurotrophic factor
(BDNF) is a protein that belongs to the neurotro-
phin subfamily. Body of evidences indicates that
BDNF may be involved in the regulation of eating
behaviours and may be implicated in the pathogen-
esis of eating disorders [15]. BDNF and the tyrosine
kinase receptor (TrkB) are expressed in hypotha-
lamic nuclei associated with satiety [15]. In BDNF
heterozygous (±) mice, basal BDNF concentration
is reduced and it was found they also exhibit abnor-
malities in eating behaviours [15]. The association
between BDNF and eating disorders in humans
was demonstrated by the findings that serum BDNF
in patients with AN or BN was significantly lower
than that in control subjects [16]. Furthermore,
in all of these subjects, there was a significant po-
sitive correlation between serum BDNF levels and
body mass index and eating-related psychopathol-
ogy [16]. The role of BDNF in eating disorders is
further implicated by genetic studies that demon-
strate an association between BDNF genetic poly-
morphisms and eating disorders [17–20].
A study by Muller and colleagues [21] demon-
strated that long-term rTMS stimulation increases
BDNF mRNA expression in specific areas of rat
brain. Given that the low levels of BDNF in patients
1177
with eating disorders [16] has already been de-
scribed, using rTMS to increase central BDNF levels
may improve these disorders.
Fourthly, cholecystokinin (CCK) can inhibit food
intake in animals as well as human subjects [22],
and is localized within the hypothalamus in inte-
grative centres of feeding regulation. Study in rats
has demonstrated that rTMS stimulation increases
the central CCK mRNA expression [21]. BN is char-
acterized by binge eating, and is defined as eating
more food than most persons in similar circum-
stances, accompanied by a strong sense of losing
control. The potential effect of rTMS treatment
in BN is that rTMS stimulation may increase cen-
tral CCK and therefore inhibit these compulsive
eating behaviours.
Finally, the positive effect of rTMS stimulation
on eating behaviours has been demonstrated by
Godlevskii and Kobolev [23] in animal models.
Treatment with rTMS (20 impulses with induction,
peak 1.5 T) was accompanied by increases in mea-
sures of feeding behaviour [23], suggesting rTMS
may help to increase eating behaviour in AN.
Eating disorders are a type of psychological dis-
ease, where relapses are common and success
often comes only after several therapeutic ap-
proaches have been tried. Therefore, different
strategies for patients are needed to achieve max-
imum therapeutic effect. RTMS is, a non-invasive
intervention that could be used in the treatment
of eating disorders to change feeding behaviours
or neurotransmitters such as serotonin related to
their regulation. However, the dose, duration and
type of rTMS stimulus to be implemented in such
an intervention require further investigation. This
report has focused on discussing the potential ther-
apeutic effect of rTMS in eating disorders. Obesity
is a condition that is also related to deranged feed-
ing behaviours. Whether rTMS would also be of use
here is worth exploration.
References
[1] Kohn M, Golden NH. Eating disorders in children and
adolescents: epidemiology, diagnosis and treatment. Pae-
diatr Drugs 2001;3:91–9.
[2] Ebeling H, Tapanainen P, Joutsenoja A, Koskinen M, Morin-
Papunen L, Jarvi L, et al. A practice guideline for treat-
ment of eating disorders in children and adolescents. Ann
Med 2003;35:488–501.
[3] Carter WP, Hudson JI, Lalonde JK, Pindyck L, McElroy SL,
Pope Jr HG. Pharmacologic treatment of binge eating
disorder. Int J Eat Disord 2003;34(Suppl.):S74–88.
[4] Mitchell JE, Peterson CB, Myers T, Wonderlich S. Combining
pharmacotherapy and psychotherapy in the treatment of
patients with eating disorders. Psychiatr Clin North Am
2001;24:315–23.
1178
[5] Peterson CB, Mitchell JE. Psychosocial and pharmacological
treatment of eating disorders: a review of research
findings. J Clin Psychol 1999;55:685–97.
[6] Walsh BT, Devlin MJ. The pharmacologic treatment of
eating disorders. Psychiatr Clin North Am 1992;15:
149–60.
[7] Zhu AJ, Walsh BT. Pharmacologic treatment of eating
disorders. Can J Psychiat 2002;47:227–34.
[8] Lisanby SH, Kinnunen LH, Crupain MJ. Applications of TMS
to therapy in psychiatry. J Clin Neurophysiol 2002;19:
344–60.
[9] Burt T, Lisanby SH, Sackeim HA. Neuropsychiatric applica-
tions of transcranial magnetic stimulation: a meta analysis.
Int J Neuropsychopharmacol 2002;5:73–103.
[10] Tsai SJ. Could repetitive transcranial magnetic stimu-
lation be effective in autism? Med Hypotheses
2005;64:1070–1.
[11] McNamara B, Ray JL, Arthurs OJ, Boniface S. Transcranial
magnetic stimulation for depression and other psychiatric
disorders. Psychol Med 2001;31:1141–6.
[12] Jimerson DC, Lesem MD, Kaye WH, Hegg AP, Brewerton TD.
Eating disorders and depression: is there a serotonin
connection? Biol Psychiat 1990;28:443–54.
[13] Steiger H. Eating disorders and the serotonin connection:
state, trait and developmental effects. J Psychiat Neurosci
2004;29:20–9.
[14] Gur E, Lerer B, Dremencov E, Newman ME. Chronic
repetitive transcranial magnetic stimulation induces sub-
sensitivity of presynaptic serotonergic autoreceptor activ-
ity in rat brain. Neuroreport 2000;11:2925–9.
[15] Kernie SG, Liebl DJ, Parada LF. BDNF regulates eating
behavior and locomotor activity in mice. Embo J
2000;19:1290–300.
[16] Nakazato M, Hashimoto K, Shimizu E, Kumakiri C, Koizumi
H, et al. Decreased levels of serum brain-derived neuro-
Tsai
trophic factor in female patients with eating disorders. Biol
Psychiat 2003;54:485–90.
[17] Koizumi H, Hashimoto K, Itoh K, Nakazato M, Shimizu E,
Ohgake S, et al. Association between the brain-derived
neurotrophic factor 196G/A polymorphism and eating
disorders. Am J Med Genet B Neuropsychiatr Genet
2004;127:125–7.
[18] Ribases M, Gratacos M, Armengol L, de Cid R, Badia
A, Jimenez A, et al. Met66 in the brain-derived
neurotrophic factor (BDNF) precursor is associated with
anorexia nervosa restrictive type. Mol Psychiat
2003;8:745–51.
[19] Ribases M, Gratacos M, Fernandez-Aranda F, Bellodi L,
Boni C, Anderluh M, et al. Association of BDNF with
anorexia, bulimia and age of onset of weight loss in
six European populations. Hum Mol Genet 2004;13:
1205–12.
[20] Ribases M, Gratacos M, Fernandez-Aranda F, Bellodi
L, Boni C, Anderluh M, et al. Association of BDNF
with restricting anorexia nervosa and minimum body
mass index: a family-based association study of eight
European populations. Eur J Hum Genet 2005;13:
428–434.
[21] Muller MB, Toschi N, Kresse AE, Post A, Keck ME. Long-term
repetitive transcranial magnetic stimulation increases the
expression of brain-derived neurotrophic factor and chole-
cystokinin mRNA, but not neuropeptide tyrosine mRNA in
specific areas of rat brain. Neuropsychopharmacology
2000;23:205–15.
[22] Moran TH. Cholecystokinin and satiety: current perspec-
tives. Nutrition 2000;16:858–65.
[23] Godlevskii LS, Kobolev EV. The effects of L-DOPA and
transcranial magnetic stimulation on behavioral reac-
tions in kindled rats. Neurosci Behav Physiol 2005;
35:313–7.