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Addiction Therapy 2015 Florida, USA August 03-08, 2015

Explore the use of neuromodulation techniques like HF-rTMS in alcohol addiction treatment and the predictive value of alcohol-related cues for relapse after therapy. Discover the effectiveness of non-invasive (tDCS, TMS) and invasive (DBS, VNS, ECT) techniques.

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Addiction Therapy 2015 Florida, USA August 03-08, 2015

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  1. Addiction Therapy 2015Florida, USAAugust 03-08, 2015 Sarah Herremans

  2. The predictive value of alcohol-related cues for relapse after accelerated HF-rTMS treatment in alcohol addiction Herremans Sarah

  3. Overview • Neuromodulation techniques and addiction • HF-rTMS and alcohol addiction • Alcohol relapse and accelerated HF-rTMS titel

  4. Neuromodulation techniques • Non-invasive techniques transcranial direct current stimulation (tDCS) transcranial magnetic stimulation (TMS) • Invasive techniques deep brain stimulation (DBS) vagal nerve stimulation (VNS) electroconvulsive therapy (ECT) titel

  5. Transcranial direct currentstimulation

  6. tDCS and substance dependence • Nicotine: Fregni et al., 2008: 24 subjects, stimulation of DLPFC (dorsolateral prefrontal cortex) Each subject: 1 placebo, 1 anodal left/cathodal right and 1anodal right/cathodal left stimulation =>  craving (cue-exposure) in bothactivestimulationconditions Boggio et al., 2009: 27 subjects, randomized, double blind, placebo-controlled Stimulation of the DLPFC, during 5 consecutivedays (anodalleft/cathodal right) => Increasingly  craving (cue-exposure) over time

  7. tDCS and substance dependence • Alcohol: Boggio et al., 2009: 13 subjects, stimulation of DLPFC, randomized placebo-controlled Each subject: 1 placebo, 1 anodal left/cathodal right & 1 anodal right/cathodal left stimulation   craving (cue-exposure) in both ACTIVE stimulation conditions • Cannabis: Boggio et al., 2010: 25 cannabis users – 3 groups -randomized placebo - an anodal left/cathodal right - an anodal right/cathodal left =>  craving only for anodal right/cathodal left stimulation

  8. Neuromodulation techniques • Non-invasive techniques transcranial direct current stimulation (tDCS) transcranial magnetic stimulation (TMS) • Invasive techniques deep brain stimulation (DBS) vagal nerve stimulation (VNS) electroconvulsive therapy (ECT) titel

  9. Deep Brain Stimulation

  10. DBS and substance dependence • DBS in substance dependence as a comorbid disorder => case reports (Kuhn, 2007, 2009; Mantione, 2010) • DBS in substance dependence as primary disorder Voges, 2013 : 5 treatment-resistant alcohol-dependent pts => decrease in relapse rate or abstinence Kuhn, 2011: 2 TR heroïne dependent patients => decrease in relapse rate Stimulation place: nucleus accumbens In animals: nucleus accumbens, insula, medial forebrain bundle, subthalamic nucleus, lateral habenula

  11. Neuromodulation techniques • Non-invasive techniques transcranial direct current stimulation (tDCS) transcranial magnetic stimulation (TMS) • Invasive techniques deep brain stimulation (DBS) vagal nerve stimulation (VNS) electroconvulsive therapy (ECT) titel

  12. VagalNerveStimulation

  13. VNS and substance dependence • No human case studies • Liu et al., 2011: study with heroine dependent rats: inhibition of heroine reinstatement after heroine priming and after exposure to heroin cues

  14. Neuromodulation techniques • Non-invasive techniques transcranial direct current stimulation (tDCS) transcranial magnetic stimulation (TMS) • Invasive techniques deep brain stimulation (DBS) vagal nerve stimulation (VNS) electroconvulsive therapy (ECT) titel

  15. Electroconvulsive therapie

  16. ECT and substance dependence • Outdated!!! • 1966: Roper et al.: effective in 4 of 6 cases, most of them were morphine-dependent • After that nothing was published …Reason??? Possibly because APA did not specify addiction as an indication in ECT guidelines

  17. Overview • Neuromodulation techniques and addiction • HF-rTMS and alcohol addiction • Alcohol relapse and accelerated HF-rTMS titel

  18. Transcranial magnetic stimulation (TMS) titel

  19. Repetitive TMS (rTMS) High Frequency vs Low Frequency DLPFC Ridding & Rothwell, 2007 titel

  20. Previous research (2012,2013) 1 HF-rTMSsession at Right DLPFC CravingCognition Response Inhibition Attentional Control Detoxified alcohol-dependent patients Randomized placebo controlled cross-over

  21. Go-NoGotask(Zimmerman & Fimm, 1992) ATTENTIONAL CONTROL RESPONSE INHIBITION OCDS Go NoGo

  22. Study Design 1 WEEK Active HF-rTMS Placebo HF-rTMS Go-NoGo task OCDS 50 pts 29 pts Placebo HF-rTMS Active HF-rTMS 1 WEEK OCDS until three days after the stimulation

  23. Results • No effect on craving (until three days after the stimulation) • No effect on response inhition • Increase in attentional control => distractibility

  24. Mutiple HF-rTMS sessions Mishra et al, 2015 Höppner et al, 2011 10 daily sessions left DLPFC alcohol craving No difference in anti-craving efficacy in both groups 20 detoxified alcohol-dependent patients 10 daily sessions right DLPFC Mishra et al, 2010: 14% relapsed in the active stimulation 33% in the placebo stimulation titel

  25. Relapse • Often (80 -> 92% in one year ) • Definition: binary (yes or no drink) different outcomes • Pharmacological/psychotherapy not always beneficial • only 30% in actual treatment; reasons for this treatment gap: - problem is not acknowledged - the desire to not involve outside help/ that the treatment is not effective - the belief that the problem will pass by itself - stigma - financial problems,… titel

  26. Predictors of relapse • Craving • Stress • Severity of alcohol dependence • Cognitive dysfunction, especially impaired response inhibition • Changes/Adaptations at the neurobiological level titel

  27. Neurobiological predictors of relapse Nucleus accumbens precuneus A CC vmPFC De Raedt et al., 2010 Seo et al., 2013 titel

  28. Overview • Neuromodulation techniques and addiction • HF-rTMS and alcohol addiction • Alcohol relapse and accelerated HF-rTMS titel

  29. Goal 1 Can we predict alcohol relapse afteraccelerated HF-rTMS treatment based on baselinebrainactivationduring a cue-exposure? titel

  30. Hypothesis 1 Hyperactivation during the alcohol-related stimuli => ABSTAINERS titel

  31. Goal 2 How does 15ACCELERATED HF-rTMS sessionsinfluencethe relapse neurocircuitry in detoxified alcohol-dependentpatients? titel

  32. Hypothesis 2 HF-rTMS only affects the relapse neurocircuit in ABSTAINERS titel

  33. Study design Right DLPFC 20 Hz 1560p/session 15 accelerated sessions over 1 week Four weeks after the last fMRI: “have you already consumed an alcoholic beverage?” titel

  34. 29recently detoxified (benzodiazepines) alcohol-dependent patients were included over one year • 10 patients were lost to follow-up • 19 patients: 13 relapsers, 6 abstainers titel

  35. titel

  36. Relapse rate • 68% High! • Compared to Mishra et al, 2010 much higher! • Not easy to compare since we used accelerated protocol • Accelerated protocol less efficient? • Mean duration of alcohol addiction of our patients +/- 5 years longer • Comparable to studies assessing naltrexone, acamprosate (Laaksonen et al., 2008) titel

  37. Neurobiological level titel

  38. ANOVA – ROI analysis: Interaction cluster P<0.001 AlphaSim corrected titel

  39. Baseline – Before accelerated HF-rTMS dACC Abstainers > Relapsers => cognitive control Hypothesis 1 ! titel

  40. Effect of HF-rTMS • Abstainers: dACC activation • Relapsers: dACC activation ! After HF-rTMS = Hypothesis 2 titel

  41. Rate-dependent effect Contrast: alcohol > neutral Rate-dependent effect titel

  42. How can we interpret? • In detoxified hospitalized patients • During exposure to alcoholstimuli • Is HF-rTMS relevant in patients with high baseline dACC activation (abstainers)? • Patients with a low baseline dACC activation (relapsers) have a larger proportional increase of dACC activation, but withouta clinical effect? short duration of action? dosage? titel

  43. Limitations • No placebo stimulation • No control group that received treatment as usual was assessed 4 weeks after discharge • Only info about alcohol lapses titel

  44. Future research • Patients with lowdACC activity larger number of placebo-controlled HF-rTMS interventions • Optimize HF-rTMS parameters titel

  45. Take away message • 15 accelerated HF-rTMS sessions in detoxified alcohol-dependent patients: • High relapse rate (68%) • Abstaining patients: more cognitive control (dACC) • Accelerated HF-rTMS has a rate-dependent effect on dACC activation • Only a limited effect at the clinical level (HF-rTMS effect probably short-lived) titel

  46. Thank you for your attention! Collaborators: Chris Baeken, MD, PHD Frieda Matthys, MD, PHD Peter Van Schuerbeek, MSc Rudi De Raedt, PhD, Johan De Mey, MD, PhD Daniele Marinazzo, PhD titel

  47. Meet the eminent gathering once again atAddiction Therapy 2016Miami, USAOctober 06-08, 2016 Addiction Therapy 2016 Website: addictiontherapy.conferenceseries.com

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