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Add-On Deep Transcranial Magnetic Stimulation (Dtms) in Patients with Dysthymic Disorder Comorbid with Alcohol Use Disorder: a Comparison with Standard Treatment

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Add-On Deep Transcranial Magnetic Stimulation (Dtms) in Patients with Dysthymic Disorder Comorbid with Alcohol Use Disorder: a Comparison with Standard Treatment The World Journal of Biological Psychiatry ISSN: 1562-2975 (Print) 1814-1412 (Online) Journal homepage: http://www.tandfonline.com/loi/iwbp20 Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: A comparison with standard treatment Paolo Girardi, Chiara Rapinesi, Flavia Chiarotti, Georgios D. Kotzalidis, Daria Piacentino, Daniele Serata, Antonio Del Casale, Paola Scatena, Flavia Mascioli, Ruggero N. Raccah, Roberto Brugnoli, Vittorio Digiacomantonio, Vittoria Rachele Ferri, Stefano Ferracuti, Abraham Zangen & Gloria Angeletti To cite this article: Paolo Girardi, Chiara Rapinesi, Flavia Chiarotti, Georgios D. Kotzalidis, Daria Piacentino, Daniele Serata, Antonio Del Casale, Paola Scatena, Flavia Mascioli, Ruggero N. Raccah, Roberto Brugnoli, Vittorio Digiacomantonio, Vittoria Rachele Ferri, Stefano Ferracuti, Abraham Zangen & Gloria Angeletti (2015) Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: A comparison with standard treatment, The World Journal of Biological Psychiatry, 16:1, 66-73, DOI: 10.3109/15622975.2014.925583 To link to this article: https://doi.org/10.3109/15622975.2014.925583 Published online: 20 Aug 2014. Submit your article to this journal Article views: 182 View related articles View Crossmark data Citing articles: 9 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iwbp20 The World Journal of Biological Psychiatry, 2015; 16: 66–73 BRIEF REPORT Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: A comparison with standard treatment PAOLO GIRARDI 1,2 , CHIARA RAPINESI 1,2 , FLAVIA CHIAROTTI 3 , GEORGIOS D. KOTZALIDIS 1 , DARIA PIACENTINO 1 , DANIELE SERATA1,2 , ANTONIO DEL CASALE 1,4 , PAOLA SCATENA2 , FLAVIA MASCIOLI 2 , RUGGERO N. RACCAH 5 , ROBERTO BRUGNOLI 1 , VITTORIO DIGIACOMANTONIO 2 , VITTORIA RACHELE FERRI 1,2 , STEFANO FERRACUTI 1 , ABRAHAM ZANGEN 6 & GLORIA ANGELETTI 1 1 NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University of Rome, School of Medicine and Psychology, Sant ’ Andrea Hospital, Rome, Italy, 2 Alcohology Service, Villa Rosa, Suore Hospitaliere of the Sacred Heart of Jesus, Viterbo, Italy, 3 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit à , Rome, Italy, 4 Department of Psychiatric Rehabilitation, Fondazione P. Alberto Mileno Onlus, Vasto, CH, Italy, 5 ATID Ltd Advanced Technology Innovation Distribution, Rome, Italy, and 6 Department of Life Sciences, Ben Gurion University of the Negev, Be ’ er Sheva, Israel Abstract Objectives. Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and substance use disorders. We predicted higher effi cacy for add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), com- pared with standard drug treatment (SDT) in patients with dysthymic disorder (DD)/alcohol use disorder (AUD) comorbidity. Methods. We carried-out a 6-month open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with previously developed DD. Ten patients received SDT for AUD with add-on bilateral dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression with the Hamilton Depression Rating Scale (HDRS), clinical status with the Clinical Global Impressions scale (CGI), and global functioning with the Global Assessment of Functioning (GAF). Results. At the end of the 20-session dTMS period (or an equivalent period in the SDT group), craving scores and depressive symptoms in the dTMS-AO group dropped signifi cantly more than in the SDT group ( P Ͻ 0.001 and P Ͻ 0.02, respectively). Conclusions. High frequency bilateral DLPFC dTMS with left preference was well tolerated and found to be effective as add-on in AUD. The potential of dTMS for reducing craving in substance use disorder patients deserves to be further investigated. Key words: alcohol , dysthymia, depression, dorsolateral pre-frontal cortex (DLPFC), deep Transcranial magnetic stimulation (dTMS) Introduction to drink or intense thoughts about alcohol (World Health Organization 1992), and its development Alcohol use disorder (AUD), currently the most common psychiatric disorder, represents a wide- plays a major role in maintaining alcohol intake and spread and serious personal and public health prob- dependence and may promote relapse (Drummond lem in the United States (Kessler et al. 1994; Hasin 2001). The development of craving is correlated et al. 2007). Alcohol craving is an irresistible urge with changes in the brain reward circuitry, which Correspondence: Georgios D. Kotzalidis, MD, NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University, School of Medicine and Psychology, Psychiatry Unit, Sant ’ Andrea Hospital, Rome, Italy. Tel: ϩ 39 0633775951. Fax: ϩ 39 0633775342. E-mail: [email protected] (Received 30 July 2013 ; accepted 14 May 2014 ) ISSN 1562-2975 print/ISSN 1814-1412 online © 2015 Informa Healthcare DOI: 10.3109/15622975.2014.925583 dTMS in dysthymia plus alcoholism 67 includes the medial forebrain bundle and the meso- Materials and methods cortical and meso-limbic dopamine pathways (Park Patients et al. 2007). Prefrontal abnormalities have been documented The study was conducted at the Alcoholism in many substance abuse disorders (Lang et al. Service, Villa Rosa, Viterbo, Italy. We admitted to 2008; Moreno-L ó pez et al. 2012; Bosch et al. the Alcoholism Service ’ s day hospital 10 consecu- 2013) and the dorsolateral prefrontal cortex tive patients with comorbid long-term DSM-IV-TR (DLPFC) is a major component of the neural sub- DD and AUD (American Psychiatric Association strate of craving for several psychoactive substances, 2000) in their detoxifi cation phase (i.e., abstaining including alcohol (Olbrich et al. 2006). DLPFC for at least 1 month), from December 2011 to June abnormalities have been demonstrated in alcohol 2012. Patients agreed to undergo dTMS as an use disorder (AUD) using different methodologies, add-on to their current treatment, which was left including functional near-infrared spectroscopy unmodifi ed, and did not use their abuse substance (Ernst et al. 2014), functional magnetic resonance throughout the study period. imaging (Park et al. 2010), structural magnetic Inclusion criteria, besides the above-mentioned resonance imaging (Makris et al. 2008), and post- DSM-IV-TR diagnoses, were age between 16 and mortem proteomic analysis (Alexander-Kaufman 65 years; at least 5-year duration of illness; avail- et al. 2007). Functional and structural DLPFC ability of reliable informants; wish to participate in alterations have also been reported in mood disor- the study; and providing consent for undergoing ders, namely bipolar (Townsend et al. 2010), major dTMS. Exclusion criteria were other concurrent depressive (Chang et al. 2011; Oh et al. 2012; Ye substance use except nicotine; specifi c contraindica- et al. 2012), and dysthymic disorders (DD; Ravin- tions to dTMS (history of seizures and carrying a dran et al. 2009). Indeed, alcohol dependence and pacemaker); and having received dTMS in the past mood disorders often co-occur and complicate the 12 months. course and outcome of one another (Grant et al. DSM-IV-TR diagnoses were established after 2004). structured interviews with all patients (Structured The effectiveness of available anticraving drugs for Clinical Interviews for DSM-IV Axis I and II Dis- alcohol dependence is limited (O ’ Brien 2005). Inter- orders; SCID-1 and SCID-2, respectively) (First estingly, transcranial magnetic stimulation (TMS) et al. 1997, 2002). All patients met also criteria for techniques are increasingly employed and reported DSM-5 Persistent Depressive Disorder (Dysthy- to benefi t several psychiatric conditions, including mia) (American Psychiatric Association 2013). cocaine (Politi et al. 2008) and alcohol abuse in The rating scales used to assess patient status abstinent patients (Mishra et al. 2010; Rapinesi et al. were the Obsessive Compulsive Drinking Scale 2013), nicotine abuse (Amiaz et al. 2009), and mood (OCDS; Anton et al. 1995), the Hamilton Depres- disorders (Wassermann and Zimmermann 2012). sion Rating Scale (HDRS; Hamilton 1960), the Several studies have shown the potential anti- Clinical Global Impressions scale, severity (CGIs; craving effects of repetitive transcranial magnetic Guy 1976), and the Global Assessment of Func- stimulation (rTMS; Politi et al. 2008; Amiaz et al. tioning Scale (GAF; Endicott et al. 1976). The 2009; Mishra et al. 2010) and deep TMS (dTMS) OCDS is a 14-item self-rated scale; individual or in substance dependence (Rapinesi et al. 2013), combined items are Likert-like scales ranging from hence TMS may be effective for treating addictive 0 to 4, with higher scores refl ecting worse alcohol behaviours (Feil and Zangen 2010). dTMS, in consumption attitude. Its score ranges from 0 to 40, contrast to standard rTMS, by using a specially with 0 – 20 ranges on each of the Obsessive and constructed H-coil, is able to stimulate neural tis- Compulsive subscales; there are no explicit cut-off sue beyond 1.5 cm from the scalp and allows for scores, but the tool is able to assess severity, clinical better precision. course, and treatment outcome (Anton et al. 1996).
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