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      Both active and sham low-frequency rTMS single sessions over the right DLPFC decrease cue-induced cravings among pathological gamblers seeking treatment: A randomized, double-blind, sham-controlled crossover trial

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          Abstract

          Background

          Craving is a core symptom of addictive disorders, such as pathological gambling for example. Over the last decade, several studies have assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the addiction field, which triggers the dorsolateral prefrontal cortex (DLPFC) to decrease craving. The STIMJEU study investigated whether a single session of low-frequency (LF, i.e., 1 Hz) rTMS applied to the right DLPFC reduced cue-induced gambling craving in a sample of treatment-seeking pathological gamblers.

          Methods

          Thirty patients received both active and sham rTMS in random order and were blinded to the condition in a within-subject crossover design. Outcome measures included self-reported gambling craving (Visual Analog Scale and Gambling Craving Scale) and physiological measures (heart rate and blood pressure).

          Results

          The rTMS sessions were associated with a significant decrease in the gambling urge, regardless of whether the session was active or sham. When controlling cue-induced craving levels, no effects were observed on craving for active rTMS. Overall, rTMS was well-tolerated, and the credibility of the sham procedure was assessed and appeared to be appropriate.

          Conclusions

          We failed to demonstrate the specific efficacy of one session of LF rTMS to decrease cue-induced craving in pathological gamblers. A strong placebo-effect and rTMS parameters may partly explain these results. Yet, we are convinced that rTMS remains a promising therapeutic method. Further studies are required to examine its potential effect.

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          Most cited references55

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          Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research.

          This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.
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            Neurocircuitry of addiction.

            Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: 'binge/intoxication', 'withdrawal/negative affect', and 'preoccupation/anticipation' (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex-dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.
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              The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI

              The Mini International Neuropsychiatric Interview (MINI) is a short diagnostic structured interview (DSI) developed in France and the United States to explore 17 disorders according to Diagnostic and Statistical Manual (DSM)-III-R diagnostic criteria. It is fully structured to allow administration by non-specialized interviewers. In order to keep it short it focuses on the existence of current disorders. For each disorder, one or two screening questions rule out the diagnosis when answered negatively. Probes for severity, disability or medically explained symptoms are not explored symptom-by-symptom. Two joint papers present the inter-rater and test-retest reliability of the MINI the validity versus the Composite International Diagnostic Interview (CIDI) (this paper) and the Structured Clinical Interview for DSM-III-R patients (SCID) (joint paper). Three-hundred and forty-six patients (296 psychiatric and 50 non-psychiatric) were administered the MINI and the CIDI ‘gold standard’. Forty two were interviewed by two investigators and 42 interviewed subsequently within two days. Interviewers were trained to use both instruments. The mean duration of the interview was 21 min with the MINI and 92 for corresponding sections of the CIDI. Kappa coefficient, sensitivity and specificity were good or very good for all diagnoses with the exception of generalized anxiety disorder (GAD) (kappa = 0.36), agoraphobia (sensitivity = 0.59) and bulimia (kappa = 0.53). Interrater and test-retest reliability were good. The main reasons for discrepancies were identified. The MINI provided reliable DSM-III-R diagnoses within a short time frame, The study permitted improvements in the formulations for GAD and agoraphobia in the current DSM-IV version of the MINI.
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                Author and article information

                Journal
                jba
                2006
                Journal of Behavioral Addictions
                J Behav Addict
                Akadémiai Kiadó (Budapest )
                2062-5871
                2063-5303
                20 February 2018
                March 2018
                : 7
                : 1
                : 126-136
                Affiliations
                [ 1 ]Psychiatry Neuromodulation Unit, Addictology and Liaison Psychiatry Department, CHU Nantes , Nantes, France
                [ 2 ]Faculty of Sport Sciences, Laboratory “Movement, Interactions, Performance” (E.A. 4334), University of Nantes , Nantes, France
                [ 3 ] SPHERE MethodS in Patients-centered outcomes and HEalth ResEarch, Université de Nantes, Université de Tours , Nantes, France
                [ 4 ]Pathological Gambling Treatment Unit, Addictology and Liaison Psychiatry Department, CHU Nantes , Nantes, France
                Author notes
                [* ]Corresponding author: Marie Grall-Bronnec; Pathological Gambling Unit, Addictology and Liaison Psychiatry Department, Centre Hospitalier Universitaire, 85 rue Saint Jacques, 44093 Nantes cedex 1, France; Phone: +33 2 40 84 61 16; Fax: +33 2 40 84 61 18; E-mail: marie.bronnec@ 123456chu-nantes.fr
                Article
                10.1556/2006.7.2018.14
                6035030
                29463098
                12c469eb-d427-4ded-ad21-36d1a4d64353
                © 2018 The Author(s)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

                History
                : 07 July 2017
                : 27 November 2017
                : 21 January 2018
                : 25 January 2018
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 54, Pages: 11
                Funding
                Funding sources: The STIMJEU study was funded by a grant from the University Hospital of Nantes (Internal call for tenders, 2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                FULL-LENGTH REPORT

                Medicine,Psychology,Social & Behavioral Sciences,Clinical Psychology & Psychiatry
                pathological gambling,treatment,non-invasive brain neurostimulation,sham,craving,rTMS

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