This study aims to assess the effectiveness of new neurostimulation techniques in patients
with eating disorders.
To date, the management of these disorders is still difficult and few treatments have proven
their effectiveness. According to most guidelines, management is typically multidisciplinary.
The best validated and most frequently used treatment is the cognitive behavioral therapy
enanched (CBT-E), a highly individualized psychological treatment designed to treat all
diagnostic categories of eating disorders, addressing the common cognitive-behavioural
mechanisms of maintaining shared and evolving psychopathology of eating disorders.
For Bulimia Nervosa (BN) and Binge Eating Disorder (BED), the serotoninergic antidepressants
are the most frequently used pharmacological option (considering the frequent recurrence of
depressive symptoms in comorbidity in the clinical population with eating disorders), which
may improve symptoms in the medium term, but not allow complete remission. In this context,
the development of alternative therapeutic strategies is crucial. Recently, several studies
have described the important contribution of neurostimulation techniques (such as repetitive
transcranial magnetic stimulation (rTMS), and vagal nerve stimulation (VNS)). Following the
proven effectiveness, both rTMS and VNS have received official approval for the treatment of
depression in Europe and United States. Neuroimaging studies have revealed that both of these
neurostimulation techniques modulate the frontal-vagal network, the one with a top-down
mechanism (rTMS) and the other with a bottom-up mechanism (VNS).
The neuromodulation influencing the functioning of the central nervous system (CNS) and the
emotional/alimentary behavior, would offer an alternative (or complementary) intervention to
psychotropic drugs and different psychological and nutritional approaches. Studies in the
literature, conducted on patients with BN and BED, showed a significant improvement in
symptomatology, in terms of "binge eating", after rTMS stimulation of the left dorsolateral
prefrontal cortex (DLPFC). Instead, the effectiveness of vagal stimulation in the treatment
of ED lies in the fact that the vagus nerve plays a fundamental role in mood and appetite
regulation. Human studies report how tVNS stimulation produces a reduction in the effect of
food cravings. Moreover, currently, in patients with ED, the determined effects of vagal
non-invasive neurostimulation have not been compared with the effects of repetitive
transcranial magnetic stimulation.
Therefore, the primary aim of our proposal is to test a reduction in symptoms of alteration
of eating behaviors, such as always thinking about food or binge eating, in a sample of 30
patients, aged between 18 and 65, with diagnosis of Bulimia Nervosa or Binge Eating Disorder,
according to the diagnostic criteria of DSM-V, and with a psychopathological framework of
depression in comorbidity (cut-off ≥ 8 of the Hamilton Depression Rating Scale, HAM-D). Of
these patients, 10 will undergo to a protocol of vagal transcutaneous stimulation in the ear
(tVNS) and targeted cognitive-behavioral therapy (CBT-E), another 10 to a protocol of
transcranial magnetic stimulation (rtms) and targeted cognitive-behavioral therapy (CBT-E)
and another 10 to a protocol of only tergeted cognitive-behavioral therapy (CBT-E), comparing
the results obtained in the three groups under study. Secondary purposes of this project are
the assessment of the effects of auricular vagal transcutaneous stimulation and of
transcranial magnetic stimulation on depressive symptoms associated with eating disorder, on
the inflammatory profile, on cardiovascular autonomic control, neuronal excitability,
functional connectivity and on the quality of life of these patients.
In order to achieve the objectives of this research project, we will perform a national,
interventional on a medical device, monocentric study, controlled in 3 parallel and
randomized groups with a 1:1:1 allocation ratio. 30 patients will be recruited at the Day
Hospital of the Psychiatry Unit of the Fondazione.
Patients will be assigned by randomization to 3 different groups/treatments:
tVNS+CBT-E group: 10 patients will be instructed to perform tVNS at home for 4
non-consecutive hours per day for 12 weeks with the tVNS VITOS device (already used in
the Fondazione for the study tVNS2019 approved by the Milan Area 2 Ethics Committee on
19.02.2019 and with code 158_2019bis);
rTMS+CBT-E group: 10 patients will participate in a total of 20 rTMS sessions lasting 40
minutes (5 sessions per week for 4 weeks) that will take place at the Day Hospital of
the Psychiatry Unit of the Fondazione;
CBT-E only group: 10 patients will proceed with only targeted cognitive behavioral
therapy (CBT-E), following the CBT-E protocol CG Fairburn - 2010.
During the screening visit, provided by normal clinical practice, the inclusion and exclusion
criteria and the diagnosis of Bulimia Nervosa and Binge Eating Disorder will be verified
through a structured clinical interview planned for DSM-5 and personality disorders (by
administration of the SCID-5 CV and PD scales by the physician). All patients will then be
evaluated during 5 extra standard care visits. At each visit dietary behavior and any
depressive symptoms will be evaluated through scales validated in Italian (Eating Disorder
Examination, Eating Disorder Inventory, Eating Disorder Examination Questionnaire, Hamilton
Depression Rating Scale and Beck Depression Inventory); cardiovascular variables will be
recorded during clinostatism and orthostatism; a resting EEG and a during acute
administration of transcranial magnetic stimulation EEG (TMS-EEG) will be recorded;
participants will be asked to self-compile 2 questionnaires on the quality of life linked to
health; finally a blood sample will be taken for the analysis of the inflammatory profile.
For each patientd an Holter-ECG will be recorded lasting 72h following each visit. All the
devices used in the study have already been purchased with university funds and have been
taken over, labelled and coded by the Clinical Engineering of the Fondazione IRCCS Ca'
Granda, Ospedale Maggiore Policlinico di Milano.