Bulimia Nervosa and Binge Eating Disorder: Comparing Therapeutic Strategies

Bulimia Nervosa Clinical Trial

Official title:

Bulimia Nervosa e Binge Eating Disorder: Strategie Terapeutiche a Confronto

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05296915
• Other study ID #: DIGEST
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: August 31, 2024

Study information

• Verified date: March 2022
• Source: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Contact: Paolo Brambilla, Professor
• Phone: 02 55035982
• Email: paolo.brambilla[@]policlinico.mi.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to assess the effectiveness of new neurostimulation techniques in patients with eating disorders.

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. 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 CBT-E and another 10 to a protocol of only tergeted 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 31, 2024
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria: patients diagnosed with Bulimia Nervosa or Binge Eating Disorder, according to the diagnostic criteria of DSM-V, with a psychopathological framework of depression in comorbidity (cut-off = 8 of the Hamilton Depression Rating Scale, HAM-D), aged between 18 and 65 years.

Exclusion Criteria:

• Previous TMS sessions with significant side effects;

• Conditions leading to an increased risk of epilepsy or side effects in the context of transcranial magnetic stimulation (including personal or family history of epilepsy, cerebral ischemic events, neurological pathologies, neurosurgical interventions, orthopedic or vascular interventions in the head-neck district, major head trauma, migraine or severe headache);

• Presence of pacemakers, defibrillators, infusion pumps, neurostimulation implants (DBS, VNS), endovascular implants in the head-neck district, cochlear implants, cerebrospinal shunts, metal implants in the head-neck area ;

• Exposure to penetration of metal chips in the head-neck area;

• Presence of non-removable metal in the head-neck area (including tattoos, permanent make-up, piercing, excluding dental implants);

• Unstable sinus rhythm at ECG (Pace-Maker rhythm, atrial fibrillation, supra-/ventricular extrasystole);

• Chronic intake of ß-blocker;

• Heart, respiratory, renal or hepatic failure and immunosuppression;

• Current hospitalization;

• State of pregnancy or lactation;

• Vestibular or balance problems;

• Positive personal history of schizophrenia or schizoaffective disorder;

• Substance or alcohol abuse in the last 6 months;

• Positive personal history of intellectual disability ("mental retardation");

• Refusal of informed consent by the patient.

Related Conditions & MeSH terms

• Binge-Eating Disorder
• Bulimia
• Bulimia Nervosa
• Disease
• Feeding and Eating Disorders

Intervention

Device:
• tVNS
An electric current with a frequency of 25 Hz (Figure 2) will be applied to the cymba conca of the left ear through a specific device (VITOS, Cerbomed, Germany; CE marking). The stimulation intensity will be customized between 0.1 and 5 mA according to the sensitivity threshold of each participant. Patients will be instructed to perform tVNS at home for 4 non-consecutive hours per day for 12 weeks, in accordance with the protocol reported in the literature for the treatment of major depression.
• rTMS
The stimulation will be carried out with a TMS STM9000 system (Ates, Medica Device s.r.l., Italy) equipped with a 70 mm "butterfly" cooled coil. The stimulation protocol followed will be the one approved by the FDA for major depression, that is, a stimulation at the level of the left dorsolateral prefrontal cortex at an intensity equal to 120% of the motor threshold, at the frequency of 10hz. Each stimulation session will last 37.5 minutes, and will consist of 75 trains lasting 4 seconds, with a 26-second break between each train. During each session, a total of 3000 stimuli will be administered. The sessions will take place 5 days a week, from Monday to Friday, for 4 weeks, and for a total of 20 sessions of stimulation.

Behavioral:
• CBT-E
Targeted cognitive-behavioral therapy following the CBT-E protocol (CG Fairburn - 2010. La terapia cognitivo-comportamentale dei disturbi dell'alimentazione. Firenze, Eclipsi; 2010.)

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Country where clinical trial is conducted

Italy, 

References & Publications (29)

Arteaga-Henríquez G, Simon MS, Burger B, Weidinger E, Wijkhuijs A, Arolt V, Birkenhager TK, Musil R, Müller N, Drexhage HA. Low-Grade Inflammation as a Predictor of Antidepressant and Anti-Inflammatory Therapy Response in MDD Patients: A Systematic Review of the Literature in Combination With an Analysis of Experimental Data Collected in the EU-MOODINFLAME Consortium. Front Psychiatry. 2019 Jul 9;10:458. doi: 10.3389/fpsyt.2019.00458. eCollection 2019. — View Citation

Bodenlos JS, Kose S, Borckardt JJ, Nahas Z, Shaw, O'Neil PM, Pagoto SL, George MS. Vagus nerve stimulation and emotional responses to food among depressed patients. J Diabetes Sci Technol. 2007 Sep;1(5):771-9. — View Citation

Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000 May 25;405(6785):458-62. — View Citation

Calugi S, Sartirana M, Milanese C, El Ghoch M, Riolfi F, Dalle Grave R. The clinical impairment assessment questionnaire: validation in Italian patients with eating disorders. Eat Weight Disord. 2018 Oct;23(5):685-694. doi: 10.1007/s40519-018-0477-2. Epub 2018 Jan 24. — View Citation

Curcio G, Tempesta D, Scarlata S, Marzano C, Moroni F, Rossini PM, Ferrara M, De Gennaro L. Validity of the Italian version of the Pittsburgh Sleep Quality Index (PSQI). Neurol Sci. 2013 Apr;34(4):511-9. doi: 10.1007/s10072-012-1085-y. Epub 2012 Apr 13. — View Citation

Dalle Grave R, Calugi S, Conti M, Doll H, Fairburn CG. Inpatient cognitive behaviour therapy for anorexia nervosa: a randomized controlled trial. Psychother Psychosom. 2013;82(6):390-8. doi: 10.1159/000350058. Epub 2013 Sep 20. — View Citation

Dalle Grave R, Calugi S, Doll HA, Fairburn CG. Enhanced cognitive behaviour therapy for adolescents with anorexia nervosa: an alternative to family therapy? Behav Res Ther. 2013 Jan;51(1):R9-R12. doi: 10.1016/j.brat.2012.09.008. Epub 2012 Oct 4. — View Citation

Dalle Grave R, Calugi S, El Ghoch M, Conti M, Fairburn CG. Inpatient cognitive behavior therapy for adolescents with anorexia nervosa: immediate and longer-term effects. Front Psychiatry. 2014 Feb 12;5:14. doi: 10.3389/fpsyt.2014.00014. eCollection 2014. — View Citation

De Risio L, Borgi M, Pettorruso M, Miuli A, Ottomana AM, Sociali A, Martinotti G, Nicolò G, Macrì S, di Giannantonio M, Zoratto F. Recovering from depression with repetitive transcranial magnetic stimulation (rTMS): a systematic review and meta-analysis of preclinical studies. Transl Psychiatry. 2020 Nov 10;10(1):393. doi: 10.1038/s41398-020-01055-2. Review. — View Citation

Duriez P, Bou Khalil R, Chamoun Y, Maatoug R, Strumila R, Seneque M, Gorwood P, Courtet P, Guillaume S. Brain Stimulation in Eating Disorders: State of the Art and Future Perspectives. J Clin Med. 2020 Jul 23;9(8). pii: E2358. doi: 10.3390/jcm9082358. Review. — View Citation

Fairburn CG, Cooper Z, Doll HA, O'Connor ME, Bohn K, Hawker DM, Wales JA, Palmer RL. Transdiagnostic cognitive-behavioral therapy for patients with eating disorders: a two-site trial with 60-week follow-up. Am J Psychiatry. 2009 Mar;166(3):311-9. doi: 10.1176/appi.ajp.2008.08040608. Epub 2008 Dec 15. — View Citation

Fairburn CG, Cooper Z, Doll HA, O'Connor ME, Palmer RL, Dalle Grave R. Enhanced cognitive behaviour therapy for adults with anorexia nervosa: a UK-Italy study. Behav Res Ther. 2013 Jan;51(1):R2-8. doi: 10.1016/j.brat.2012.09.010. Epub 2012 Oct 22. — View Citation

Fang J, Egorova N, Rong P, Liu J, Hong Y, Fan Y, Wang X, Wang H, Yu Y, Ma Y, Xu C, Li S, Zhao J, Luo M, Zhu B, Kong J. Early cortical biomarkers of longitudinal transcutaneous vagus nerve stimulation treatment success in depression. Neuroimage Clin. 2016 Dec 18;14:105-111. doi: 10.1016/j.nicl.2016.12.016. eCollection 2017. — View Citation

Hein E, Nowak M, Kiess O, Biermann T, Bayerlein K, Kornhuber J, Kraus T. Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J Neural Transm (Vienna). 2013 May;120(5):821-7. doi: 10.1007/s00702-012-0908-6. Epub 2012 Nov 2. — View Citation

Iseger TA, van Bueren NER, Kenemans JL, Gevirtz R, Arns M. A frontal-vagal network theory for Major Depressive Disorder: Implications for optimizing neuromodulation techniques. Brain Stimul. 2020 Jan - Feb;13(1):1-9. doi: 10.1016/j.brs.2019.10.006. Epub 2019 Oct 10. Review. — View Citation

Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, Stubbs B, Solmi M, Veronese N, Herrmann N, Raison CL, Miller BJ, Lanctôt KL, Carvalho AF. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017 May;135(5):373-387. doi: 10.1111/acps.12698. Epub 2017 Jan 25. — View Citation

Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016 Jan;16(1):22-34. doi: 10.1038/nri.2015.5. Review. — View Citation

Montano N, Porta A, Cogliati C, Costantino G, Tobaldini E, Casali KR, Iellamo F. Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior. Neurosci Biobehav Rev. 2009 Feb;33(2):71-80. doi: 10.1016/j.neubiorev.2008.07.006. Epub 2008 Jul 30. Review. — View Citation

Porta A, Gnecchi-Ruscone T, Tobaldini E, Guzzetti S, Furlan R, Montano N. Progressive decrease of heart period variability entropy-based complexity during graded head-up tilt. J Appl Physiol (1985). 2007 Oct;103(4):1143-9. Epub 2007 Jun 14. — View Citation

Porta A, Guzzetti S, Montano N, Furlan R, Pagani M, Malliani A, Cerutti S. Entropy, entropy rate, and pattern classification as tools to typify complexity in short heart period variability series. IEEE Trans Biomed Eng. 2001 Nov;48(11):1282-91. — View Citation

Poulsen S, Lunn S, Daniel SI, Folke S, Mathiesen BB, Katznelson H, Fairburn CG. A randomized controlled trial of psychoanalytic psychotherapy or cognitive-behavioral therapy for bulimia nervosa. Am J Psychiatry. 2014 Jan;171(1):109-16. doi: 10.1176/appi.ajp.2013.12121511. — View Citation

Reardon C, Murray K, Lomax AE. Neuroimmune Communication in Health and Disease. Physiol Rev. 2018 Oct 1;98(4):2287-2316. doi: 10.1152/physrev.00035.2017. Review. — View Citation

Steenbergen L, Sellaro R, Stock AK, Verkuil B, Beste C, Colzato LS. Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes. Eur Neuropsychopharmacol. 2015 Jun;25(6):773-8. doi: 10.1016/j.euroneuro.2015.03.015. Epub 2015 Mar 30. — View Citation

Thayer JF, Lane RD. Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev. 2009 Feb;33(2):81-8. doi: 10.1016/j.neubiorev.2008.08.004. Epub 2008 Aug 13. Review. — View Citation

Tobaldini E, Carandina A, Toschi-Dias E, Erba L, Furlan L, Sgoifo A, Montano N. Depression and cardiovascular autonomic control: a matter of vagus and sex paradox. Neurosci Biobehav Rev. 2020 Sep;116:154-161. doi: 10.1016/j.neubiorev.2020.06.029. Epub 2020 Jun 26. Review. — View Citation

Treasure J, Duarte TA, Schmidt U. Eating disorders. Lancet. 2020 Mar 14;395(10227):899-911. doi: 10.1016/S0140-6736(20)30059-3. Review. — View Citation

Val-Laillet D, Aarts E, Weber B, Ferrari M, Quaresima V, Stoeckel LE, Alonso-Alonso M, Audette M, Malbert CH, Stice E. Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity. Neuroimage Clin. 2015 Mar 24;8:1-31. doi: 10.1016/j.nicl.2015.03.016. eCollection 2015. Review. — View Citation

Van den Eynde F, Guillaume S. Neuromodulation techniques and eating disorders. Int J Eat Disord. 2013 Jul;46(5):447-50. doi: 10.1002/eat.22100. — View Citation

Zabala MJ, Macdonald P, Treasure J. Appraisal of caregiving burden, expressed emotion and psychological distress in families of people with eating disorders: a systematic review. Eur Eat Disord Rev. 2009 Sep-Oct;17(5):338-49. doi: 10.1002/erv.925. Review. — View Citation

* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changing in dietary behaviour in terms of changes in Eating Disorder Examination scale score at T3	Effectiveness in changing dietary behaviour in terms of the EDE (Eating Disorder Examination) score difference between groups at T3. Great differences mean better clinical outcome.	6 months from the start of treatment
Secondary	Incidence of acute effects of treatments in terms of difference between pre- and post-treatment	Incidence of acute effects of treatment with tVNS+CBT-E, rTMS+CBT-E or only CBT-E in patients with Eating Disorders in terms of difference between pre- and post-treatment for: Variations in EDE-Q (Eating Disorder Examination Questionnaire) validated questionnaire scores.; Depressive symptoms: change in HAM-D and BDI-II scores.; Change in the systemic inflammatory profile: values of inflammatory serum proteins (IL-6, IL-1ß, IL-4, IL-10, TNF-a and PCR) and microvesicles.; Changes in cardiovascular autonomic control: spectral power (ms2) and percentage (normalized units), over 250 beats, of the following frequency classes: very low frequency (VLF), low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.40 Hz). Percentage on 250 beats, of pattern 0V, 2LV and 2UV (symbolic analysis).; For TMS+EEG: variation of neuronal excitability patterns and functional connectivity and changes in quality of life in terms of total score of the CIA 3.0, PSQI validated questionnaires.	After 4 weeks of stimulation (T1)
Secondary	Incidence of acute effects of treatments in terms of difference between pre- and post-treatment	Incidence of acute effects of treatment with tVNS+CBT-E, rTMS+CBT-E or only CBT-E in patients with Eating Disorders in terms of difference between pre- and post-treatment for: Variations in EDE-Q (Eating Disorder Examination Questionnaire) validated questionnaire scores.; Depressive symptoms: change in HAM-D and BDI-II scores.; Change in the systemic inflammatory profile: values of inflammatory serum proteins (IL-6, IL-1ß, IL-4, IL-10, TNF-a and PCR) and microvesicles.; Changes in cardiovascular autonomic control: spectral power (ms2) and percentage (normalized units), over 250 beats, of the following frequency classes: very low frequency (VLF), low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.40 Hz). Percentage on 250 beats, of pattern 0V, 2LV and 2UV (symbolic analysis).; For TMS+EEG: variation of neuronal excitability patterns and functional connectivity and changes in quality of life in terms of total score of the CIA 3.0, PSQI validated questionnaires.	After 12 weeks of stimulation (T2)
Secondary	Incidence of long-term effects in terms of relapses and difference between T0 and T4.	Incidence of long-term effects of the three treatments (tVNS + CBT-E, rtms + CBT-E and CBT-E) in patients with BN and BED in terms of relapses and difference between T0 and T4 for the following indices: Dietary behaviour: change in EDE and EDE-Q scores.; Depressive symptoms: change in HAM-D and BDI-II scores; Change in the systemic inflammatory profile: values of inflammatory serum proteins (IL-6, IL-1ß, IL-4, IL-10, TNF-a and PCR) and microvesicles.; Changes in cardiovascular autonomic control: spectral power (ms2) and percentage (normalized units), over 250 beats, of the following three frequency classes: very low frequency (VLF), low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.40 Hz). Percentage on 250 beats, of pattern 0V, 2LV and 2UV (symbolic analysis).; TMS + EEG: Variation of neuronal excitability patterns and functional connectivity.; Changes in quality of life: total score of PSQI and CIA 3.0 validated questionnaires.	After 12 months (T4) from enrollment

External Links

•   CG Fairburn - 2010. La terapia cognitivo comportamentale dei disturbi dell'alimentazione. Firenze, Eclipsi; 2010.
•   Dalle Grave, R., Sartirana, M., & Calugi, S. La gestione dei casi complessi nei disturbi dell'alimentazione. Verona: Positive Press, 2019
•   Eating Disorders: Recognition and Treatment (NICE Guideline 69).
•   Montano, A. & Flebus, Giovanni Battista. (2006). Presentation of the Beck Depression Inventory - Second edition (BDI-II): Confirmation of bifactorial structure in a sample of the Italian population.