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

Sarah Herremans

Addiction Therapy 2015Florida, USA

August 03-08, 2015

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

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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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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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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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




Transcranial magnetic stimulation (TMS)

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Repetitive TMS (rTMS)

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Ridding & Rothwell, 2007

DLPFC

High Frequencyvs

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)

Go NoGo

OCDSRESPONSE INHIBITION

ATTENTIONAL CONTROL

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

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

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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

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




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

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

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

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

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

Baseline – Before accelerated HF-rTMS

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dACC

Abstainers > Relapsers

=> cognitive control

Hypothesis 1 !

Effect of HF-rTMS

Abstainers:

dACC activation

Relapsers:

dACC activation

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!After HF-rTMS

=Hypothesis 2

Rate-dependent effect

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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?

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