Transcript Developing a research programme on women and eating disorders

Brain-Directed Therapies as
Adjuncts to Treatment of
Eating Disorders
Ulrike Schmidt, MD PhD FRCPsych FAED
Professor of Eating Disorders
King’s College London
[email protected]
Productivity impacts of ED: Estimated as $15.1 billion in 2012, similar to anxiety &
depression.
Includes:
(a) Lost lifetime earnings for young people who die.
(b) Productivity impacts of living
with ED:
e.g. lower employment participation and
November
2012
greater absenteeism & presenteeism.
Anorexia Nervosa (AN) in Adults
• One of the most difficult psychiatric
disorders to treat or study (Halmi et al.,
2005; Fairburn et al., 2013)
– Especially those with severe and enduring AN
• Talking therapies are the treatment of
choice, but only moderately effective
• New approaches to treatment are needed.
Citation Classics (> 400 Citations) and Top
Cited Papers in Major Depression & AN
Depression
Anorexia Nervosa
Total number of papers
240,000
12,004
Percentage of papers that are
citation classics
243 (0.1%)
34 (0.3%)
In AN, because there were few citation classics, the top 100 most cited
papers were also examined.
•Papers addressing psychosocial mechanisms were the most common
category.
•Very few were on Neurobiology or Treatment.
Lipsman & Lozano (2011); Lipsman et al (2013)
Neurobiology/Neurocircuitry in AN
‘Top-down’ vs ‘bottom-up’
dysregulation
Lozano & Lipsman, 2013
European Eating Disorders Review
Special Edition: Brain-Directed Treatments
e.g.
Non-invasive Brain Stimulation
Deep Brain Stimulation
Growing Public Interest in
Brain-Directed Treatments
Repetitive Transcranial Magnetic Stimulation
(rTMS)
• Employs an electromagnetic field
generated by a figure -eight coil to
suppress (low-frequency) or
enhance (high frequency) cortical
neuronal activity in a localised area
of the brain
• Many different stimulation
protocols
• Clinical Applications: e.g.
Depression (2nd line FDA approved
treatment), Addictions, Psychosis
For review see: McClelland, Bozhilova, Campbell & Schmidt, 2013; Medina
& Tunez, 2013
Repetitive Transcranial
Magnetic Stimulation (rTMS)
Potential Mechanisms of Action:
•Altered cortical excitability
•Changes in regional cerebral blood
flow
•Effects on neuroendocrine &
neurotransmitter systems
•Increased neural plasticity
Growing interest in biomarkers
and predictors of rTMS
e.g. Medina & Tunez, 2013;
Fidalgo et al.,2013; Downar et al., 2013
Our Proof of Concept Studies:
rTMS in Food Craving and BN
• One session of real high-frequency rTMS applied to the left DLPF
cortex vs sham treatment in the context of a Food Challenge Task in:
– Women with high food craving
– People with bulimic disorders
• Results:
– Reduction in craving
– Reduction in binges over the following 24 hours
– Reduction in salivary cortisol
Uher et al., 2005; Van den Eynde, et al., 2010; Claudino et al., 2011
One-off High-Frequency DLPFC rTMS in AN:
A Pilot Study (n=10)
VAS 10
9
8
7
6
5
4
3
2
1
0
**
**
*
Pre
Post
Anxiety
Urge to
Restrict
Feeling
Full
Feeling Fat
Van den Eynde et al.(2013) European Psychiatry
Pilot Study of Therapeutic rTMS in TreatmentResistant AN: Participants
Age
Illness
Duration
Subtype
Concurrent
Treatment
Treatment History
Medications
Fluoxetine,
Olanzapine,
Diazepam
23
12 years
R
Inpatient
Inpatient (12yrs),
ECT
51
35 years
BP
-
Outpatient
Fluoxetine
32
5 years
BP
-
Outpatient
-
41
30 years
R
-
Inpatient
-
30
19 years
BP
-
Inpatient
(>6 years)
Fluoxetine
McClelland et al., 2013b, EEDR; McClelland et al., in preparation
Within Session Measures:
Urge to Restrict Food (Average)
10
Pre (average)
Post (average)
9
Visual Analogue Scale
8
7
6
5
4
3
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20
Sessions
McClelland et al., 2013b, EEDR; McClelland et al., in preparation
Within Session Measures: Urge to Restrict
Example of a Responder and a Non-Responder
Patient 1: VAS-responder
Patient 2: VAS-nonresponder
9
9
8
7
Patient 1 pre
Patient 1 post
6
5
4
Visual Analogue Scale
10
Visual Analogue Scale
10
8
7
Patient 2 pre
6
Patient 2 post
5
4
3
3
2
2
1
1
0
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Sessions
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Sessions
McClelland et al., 2013b, EEDR; McClelland et al., in preparation
Eating Disorder Examination Questionnaire
6
Pre (5)
Post (5)
1mnth FU (4)
6mnth FU (2)
5
4
3
2
1
0
Restraint
Eating
Shape
Weight
Total
McClelland et al, 2013b; McClelland et al., in preparation
Depression, Anxiety & Stress Scale
Pre (5)
18
Post (5)
1mnth FU (4)
6mnth FU (2)
16
14
12
10
8
6
4
2
0
Depression
Anxiety
McClelland et al., 2013b, EEDR; McClelland et al., in preparation
Stress
Body Mass Index
Pre
20
Mid
Post
1mnth FU
6mnth FU
18
16
14
12
10
8
6
4
2
0
Patient 1
Patient 2
Patient 3
Patient 4
McClelland et al., 2013b, EEDR; McClelland et al., in preparation
Patient 5
Feedback from Patients
Affect & Cognition
Most patients want
to have more rTMS
sessions
Eating Behaviours
“Better equipped to cope with things”
“Helps reinforce
positive feelings”
“Calmer, more positive”
“Binge/purge behaviours are less
rewarding”
McClelland et al., 2013b, EEDR; McClelland et al., in preparation
Feedback from Carers
Affect & Cognition
Better able to cope
with non-routine
activities, more
flexible & accepting
of change
Clearer thinking…
Eating Behaviours
She noticed improvements in mood, but
less so with eating so a felt a sense of
disappointment
Some periods of
normal eating
Improved & more consistent mood,
much ‘brighter’, more relaxed & positive,
energised outlook on life, more
confident…
McClelland et al., 2013b, EEDR; McClelland et al., in preparation
Transcranial Direct Current Stimulation
(tDCS)
• Delivery of a weak electrical current between
two surface electrodes; anodal and cathodal
tDCS cause excitatory & inhibitory effects
respectively on underlying cortical neurons
• Clinical Applications: e.g. Depression,
Addictions, Alzheimer’s & Parkinson’s
Disease
• In MDD: tDCS superior to sham (medium
effect size)
For review see Shiozawa et al., 2014, Int J Neuropsychopharmacology
Effects of Prefrontal Cortex tDCS on
Food Craving and Temporal Discounting in
Women with Frequent Food Craving
Participants: 17 women with frequent food cravings
Aims: (a) Assess effects of tDCS on food craving; (b)
Assess whether tDCS effects on food craving are
moderated by Temporal Discounting (Assessed on a
Monetary Task; Rubia et al., 2009)
Design: Randomised sham-controlled within subjects
cross-over design
Method: 1 session of bilateral tDCS applied to the
DLPFC (anode right/cathode left)
Participants were exposed to real food and to a film of
people eating. Food craving and Temporal Discounting
(TD) were assessed before and after real and sham
tDCS
Mean Percentage Change in Food Challenge Task
(FCT) Scores
Kekic et al. (2014) Appetite, in press.
Mean Pre- and Post-tDCS Global FCT Scores for Participants
with High and Low Temporal Discounting
• No difference in TD in real vs sham tDCS
• Those with Low TD (i.e. more reflective choice behaviour) were more responsive to anti-craving effects
of real tDCS than those with high TD (i.e. more impulsive choice behaviour)
Kekic et al. (2014) Appetite, in press.
Effects of non-invasive neurostimulation
on craving (Jansen et al., 2013)
DBS: Yearly Growth in the Number of
Publications from 1980 to 2011
Figure 1
Lozano & Lipsman, Neuron 77, 406-24
Positioning of DBS Electrodes in the
Sub-Callosal Cortex
Lipsman et al. (2013) The Lancet
Changes in BMI of Each Patient
Lipsman et al. (2013) The Lancet
Yale-Brown-Cornell Eating Disorders Scale
Lipsman et al., (2013) The Lancet
Summary
• Neural models of eating disorders support investigations into
therapeutic potential of neuromodulation (NIBS; DBS)
• Existing research has demonstrated effects on ED symptoms
following rTMS, tDCS & DBS in clinical and analogue populations.
• Neuromodulation treatments may be useful as adjuncts to
psychotherapy in those patients with severe and enduring AN.
– Many questions remain regarding patient selection, efficacy and mechanisms
of action (mediators, moderators, predictors)
• We need RCTs – but these are difficult to do (Brunoni & Fregni,
2011)
• We need studies of neural predictors and correlates of these
treatments
Ongoing Work
• Sham-controlled RCT assessing effects of 1
session neuronavigated rTMS on ED symptoms
and choice behaviour in patients with AN (n=60)
• Neural (structural MRI, fMRI, DTI) predictors
and correlates of therapeutic rTMS in AN
• Effects of tDCS on eating disorder symptoms
and choice behaviour in AN and BN
Acknowledgements:
The ED-NIBS team: J Mcclelland, M Kekic,
S Bartholdi & I Campbell
Collaborators: A David, K Rubia & S Nestler