Sarah Herremans Addiction Therapy 2015 Florida, USA August 03-08, 2015
The predictive value of alcohol- related cues for relapse after accelerated HF-rTMS treatment in alcohol addiction Herremans Sarah
titel Overview Neuromodulation techniques and addiction HF-rTMS and alcohol addiction Alcohol relapse and accelerated HF-rTMS
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
Transcranial direct current stimulation 5
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 both active stimulation conditions Boggio et al., 2009: 27 subjects, randomized, double blind, placebo-controlled Stimulation of the DLPFC, during 5 consecutive days (anodal left/cathodal right) => Increasingly craving (cue-exposure) over time
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
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
Deep Brain Stimulation 9
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
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
Vagal Nerve Stimulation 12
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
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
Electroconvulsive therapie 15
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
titel Overview Neuromodulation techniques and addiction HF-rTMS and alcohol addiction Alcohol relapse and accelerated HF-rTMS
Transcranial magnetic stimulation (TMS) titel
Repetitive TMS (rTMS) titel Ridding & Rothwell, 2007 DLPFC High Frequency vs Low Frequency
Previous research (2012,2013) 1 HF-rTMS session at Right DLPFC Craving Cognition Response Inhibition Attentional Control Randomized placebo controlled cross-over Detoxified alcohol-dependent patients
Go-NoGo task (Zimmerman & Fimm, 1992) GoNoGo OCDS RESPONSE INHIBITION ATTENTIONAL CONTROL
Study Design 50 pts29 pts Active HF-rTMS Placebo HF-rTMS Go-NoGo task OCDS 1 WEEK OCDS until three days after the stimulation
Results No effect on craving (until three days after the stimulation) No effect on response inhition Increase in attentional control => distractibility
Mutiple HF-rTMS sessions titel alcohol craving No difference in anti-craving efficacy in both groups 20 detoxified alcohol- dependent patients Mishra et al, daily sessions left DLPFC 10 daily sessions right DLPFC Mishra et al, 2010: 14% relapsed in the active stimulation 33% in the placebo stimulation Höppner et al, 2011
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
Predictors of relapse Craving Stress Severity of alcohol dependence Cognitive dysfunction, especially impaired response inhibition Changes/Adaptations at the neurobiological level titel
Neurobiological predictors of relapse titel ACCACCC vmPFC precuneus Nucleus accumbens Seo et al., 2013De Raedt et al., 2010
titel Overview Neuromodulation techniques and addiction HF-rTMS and alcohol addiction Alcohol relapse and accelerated HF-rTMS
Goal 1 Can we predict alcohol relapse after accelerated HF-rTMS treatment based on baseline brain activation during a cue-exposure? titel
Hypothesis 1 titel Hyperactivation during the alcohol-related stimuli => ABSTAINERS
Goal 2 How does 15 ACCELERATED HF-rTMS sessions influence the relapse neurocircuitry in detoxified alcohol-dependent patients? titel
Hypothesis 2 titel HF-rTMS only affects the relapse neurocircuit in ABSTAINERS
Study design titel accelerated sessions over 1 week Four weeks after the last fMRI: “have you already consumed an alcoholic beverage?” Right DLPFC 20 Hz 1560p/session
29 recently detoxified (benzodiazepines) alcohol-dependent patients were included over one year 10 patients were lost to follow-up 19 patients: 13 relapsers, 6 abstainers titel
titel Relapsers (13 patients) Abstainers (6 patients) Significance Gender (M/F)7/64/2P>0.99 Age (years)M=43.6; SD=7.3M=47.7; SD=13.6P=0.40 BZD free days before stimulation M=13.0; SD=6.0M=12.0; SD=4.1P=0.72 Heavy Drinking Days during the last month M=17.7; SD=10.6M=20.0; SD=10.0P=0.68 Duration of alcohol addiction M=14.5; SD=9.9M=9.8; SD=9.6P=0.35
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
Neurobiological level titel
ANOVA – ROI analysis: Interaction cluster titel P<0.001 AlphaSim corrected
Baseline – Before accelerated HF-rTMS titel dACC Abstainers > Relapsers => cognitive control Hypothesis 1 !
Effect of HF-rTMS Abstainers: dACC activation Relapsers: dACC activation titel ! After HF-rTMS = Hypothesis 2
Rate-dependent effect titel Contrast: alcohol > neutral Rate-dependent effect
How can we interpret? In detoxified hospitalized patients During exposure to alcohol stimuli 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 without a clinical effect? short duration of action? dosage? titel
Limitations No placebo stimulation No control group that received treatment as usual was assessed 4 weeks after discharge Only info about alcohol lapses titel
Future research Patients with low dACC activity larger number of placebo-controlled HF-rTMS interventions Optimize HF-rTMS parameters titel
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
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
Addiction Therapy 2016 Website: addictiontherapy.conferenceseries.com Meet the eminent gathering once again at Addiction Therapy 2016 Miami, USA October 06-08, 2016