sarah herremans addiction therapy 2015 florida, usa august 03-08, 2015
TRANSCRIPT
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Sarah Herremans
Addiction Therapy 2015Florida, USA
August 03-08, 2015
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The predictive value of alcohol-related cues for relapse after accelerated HF-rTMS treatment in alcohol addiction
Herremans Sarah
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Overview
Neuromodulation techniques and addiction
HF-rTMS and alcohol addiction
Alcohol relapse and accelerated HF-rTMS
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Neuromodulation techniques
Non-invasive techniquestranscranial direct current stimulation (tDCS)transcranial magnetic stimulation (TMS)
Invasive techniquesdeep brain stimulation (DBS)vagal nerve stimulation (VNS)electroconvulsive therapy (ECT)
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Transcranial direct current stimulation
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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-controlledStimulation of the DLPFC, during 5 consecutive days (anodal
left/cathodal right)=> Increasingly craving (cue-exposure) over time
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tDCS and substance dependence
Alcohol:Boggio et al., 2009: 13 subjects, stimulation of DLPFC, randomized placebo-controlledEach 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 -randomizedplacebo - an anodal left/cathodal right - an anodal right/cathodal left=> craving only for anodal right/cathodal left stimulation
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Neuromodulation techniques
Non-invasive techniquestranscranial direct current stimulation (tDCS)transcranial magnetic stimulation (TMS)
Invasive techniquesdeep brain stimulation (DBS)vagal nerve stimulation (VNS)electroconvulsive therapy (ECT)
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Deep Brain Stimulation
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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 disorderVoges, 2013 : 5 treatment-resistant alcohol-dependent pts
=> decrease in relapse rate or abstinenceKuhn, 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
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Neuromodulation techniques
Non-invasive techniquestranscranial direct current stimulation (tDCS)transcranial magnetic stimulation (TMS)
Invasive techniquesdeep brain stimulation (DBS)vagal nerve stimulation (VNS)electroconvulsive therapy (ECT)
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Vagal Nerve Stimulation
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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
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Neuromodulation techniques
Non-invasive techniquestranscranial direct current stimulation (tDCS)transcranial magnetic stimulation (TMS)
Invasive techniquesdeep brain stimulation (DBS)vagal nerve stimulation (VNS)electroconvulsive therapy (ECT)
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Electroconvulsive therapie
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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
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Overview
Neuromodulation techniques and addiction
HF-rTMS and alcohol addiction
Alcohol relapse and accelerated HF-rTMS
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Transcranial magnetic stimulation (TMS)
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Repetitive TMS (rTMS)
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Ridding & Rothwell, 2007
DLPFC
High Frequencyvs
Low Frequency
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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
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Go-NoGo task (Zimmerman & Fimm, 1992)
Go NoGo
OCDSRESPONSE INHIBITION
ATTENTIONAL CONTROL
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Study Design
50 pts 29 pts
Active HF-rTMS
Active HF-rTMSPlacebo HF-rTMS
Placebo HF-rTMS
Go-NoGo taskOCDS
1 WEEK
1 WEEK
OCDS until three days after the stimulation
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Results
No effect on craving (until three days after the stimulation)
No effect on response inhition
Increase in attentional control
=> distractibility
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Mutiple HF-rTMS sessions
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alcohol craving
No difference in anti-craving efficacy in both groups
20 detoxified alcohol-dependent patients
Mishra et al, 2015
10 daily sessionsleft DLPFC
10 daily sessionsright DLPFC
Mishra et al, 2010:14% relapsed in the active stimulation33% in the placebo stimulation
Höppner et al, 2011
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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,…
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Predictors of relapse
Craving
Stress
Severity of alcohol dependence
Cognitive dysfunction, especially impaired response inhibition
Changes/Adaptations at the neurobiological level
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Neurobiological predictors of relapse
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ACC
vmPFC
precuneus
Nucleus accumbens
Seo et al., 2013De Raedt et al., 2010
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Overview
Neuromodulation techniques and addiction
HF-rTMS and alcohol addiction
Alcohol relapse and accelerated HF-rTMS
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Goal 1
Can we predict alcohol relapse after accelerated HF-rTMS treatment
based on baseline brain activation during a cue-exposure?
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Hypothesis 1
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Hyperactivation during the alcohol-related stimuli=> ABSTAINERS
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Goal 2
How does 15 ACCELERATED HF-rTMS sessions influence the relapse neurocircuitry
in detoxified alcohol-dependent patients?
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Hypothesis 2
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HF-rTMS only affects the relapse neurocircuit in ABSTAINERS
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Study design
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15 accelerated sessions over 1 week
Four weeks after the last fMRI:“have you already consumed an alcoholic beverage?”
Right DLPFC20 Hz1560p/session
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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
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Relapsers (13 patients)
Abstainers (6 patients)
Significance
Gender (M/F) 7/6 4/2 P>0.99
Age (years) M=43.6; SD=7.3 M=47.7; SD=13.6
P=0.40
BZD free days before stimulation
M=13.0; SD=6.0 M=12.0; SD=4.1 P=0.72
Heavy Drinking Days during the last month
M=17.7; SD=10.6
M=20.0; SD=10.0
P=0.68
Duration of alcohol addiction
M=14.5; SD=9.9 M=9.8; SD=9.6 P=0.35
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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)
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Neurobiological level
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ANOVA – ROI analysis: Interaction cluster
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P<0.001AlphaSim corrected
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Baseline – Before accelerated HF-rTMS
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dACC
Abstainers > Relapsers
=> cognitive control
Hypothesis 1 !
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Effect of HF-rTMS
Abstainers:
dACC activation
Relapsers:
dACC activation
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!After HF-rTMS
=Hypothesis 2
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Rate-dependent effect
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Contrast: alcohol > neutral
Rate-dependent effect
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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?
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Limitations
No placebo stimulation
No control group that received treatment as usual was assessed 4 weeks after discharge
Only info about alcohol lapses
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Future research
Patients with low dACC activitylarger number of placebo-controlled HF-rTMS interventions
Optimize HF-rTMS parameters
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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)
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Thank you for your attention!
Collaborators:
Chris Baeken, MD, PHDFrieda Matthys, MD, PHDPeter Van Schuerbeek, MScRudi De Raedt, PhD,Johan De Mey, MD, PhDDaniele Marinazzo, PhD
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Addiction Therapy 2016 Website:
addictiontherapy.conferenceseries.com
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Addiction Therapy 2016Miami, USA
October 06-08, 2016