Electricity
rendered
useful?
Transcranial
direct current
stimulation
for late life
depression
Philip Wilkinson
Head Wrightson iron works
Richard Lovett
1756
Electricity
rendered useful
Aims
Overview of tDCS in context of range of
neurostimulatory therapies
Discussion of proposed use of tDCS in clinical
setting
Discussion of clinical governance and ethical
implications
Neurostimulatory treatments
for depression
ECT
Electroconvulsive therapy
VNS
Vagus nerve stimulation
DBS
Deep brain stimulation
rTMS
Transcranial magnetic stimulation
tDCS
Transcranial direct current
stimulation
NeuroStarTMSTherapy - YouTube
Black Dog videos
Neurostimulatory treatments
for depression
Cheap ?
ECT
VNS
DBS
rTMS
tDCS
No need for Non-invasive ?
anaesthesia ?
Portable ?
Neurostimulatory treatments
for depression
Cheap
No need for
anaesthesia
Non-invasive
Portable
ECT
X
X
X
X
VNS
X
X
X
X
DBS
X
X
X
X
rTMS
X
√
√
X
tDCS
√
√
√
√
tDCS applications
Stroke
Parkinson’s disease
Migraine
Cognitive enhancement
Depression
"Depression is the most
important psychiatric
disorder in old age.
With at least 20-30%
not responding to
standard treatments,
the management of
such patients is a
science and a craft..."
Dr Hamish McAllisterWilliams
Late life depression
Late-life depression is associated with more
severe impairment in verbal learning and
memory and motor speed than depression in
earlier adult life and this is not due to ageing
alone
Thomas AJ et al. Psychol Med. 2009;39(05):725-33.
Late life depression
White matter abnormalities in frontosubcortical
and limbic networks play a key role even in the
absence of changes in resting functional
connectivity and grey matter
Sexton CE et al. Archives Gen Psychiatry.2012;69(7):680-9
SSRI resistance associated with white matter
abnormalities in anterior cingulate, dorsolateral
prefrontal cortex, etc.
Alexopoulos G. et al. Am J Psychiatry. 2008;165:238-44
White matter activation
TMS and ECT appear to increase prefrontal
fractional anisotropy
Computer modelling of DLPFC tDCS suggests
currents in distant limbic structures are
comparable to stimulation current
Sadleir R. et al. Neuroimage. 2010;51:1310-8.
Cognitive effects of tDCS
Improvement in declarative and working
memories after one session in healthy
volunteers
Oliveira et al. Neurosci Lett. 2013;537(0):60-4
tDCS – possible mechanisms of action
in depression
Increased neuronal excitability
Correction of right-left imbalance in DLPFC
Long-term neuroplastic effects via NMDA
Improved integrity of white matter tracts
GABAergic (enhanced learning after CVA)
Systematic review of tDCS trials in MDD
7 RCTs
259 participants
Mean age 44 years
Mean no. of previous antidepressant trials: 2.16
Shiozawa P et al. Int J Neuropsychopharm 2014 17(9) 1443-52
Systematic review of tDCS trials in MDD
Active tDCS superior to sham on continuous
outcomes at study endpoint (g = 0.37; 95% CI 0.04-0.7)
Active tDCS superior to sham on response rates
(OR 1.63; 95% CI 1.26-2.12)
Active tDCS superior to sham on remission rates
(OR 2.5; 95% CI 1.26-2.49 )
Shiozawa P et al. Int J Neuropsychopharm 2014 17(9) 1443-52
Systematic review of tDCS trials in MDD
On meta-regression, no influence of baseline
severity, treatment resistance, treatment
parameters.
Shiozawa P et al. Int J Neuropsychopharm 2014 17(9) 1443-52
tDCS side-effects
tingling (71%)
itching (30%)
headache (12%)
burning under the electrodes
difficulties in concentrating
acute mood changes
Brunoni AR et al. Int J Neuropsychopharm, 2011
Aims of project
To make available to patients with poor
prognosis depression an additional intervention
Assess acceptability and feasibility of the tDCS in
a clinical setting
Use experience of intervention in design of
future clinical trial ? home use device
Exclusion criteria
Requiring urgent ECT
Treatment with anticonvulsant or memantine
Cranial metallic implant
Cardiac pacemaker
Exclusion criteria
Dementia
Bipolar disorder
Unable to consent
tDCS parameters
30 minutes 2mA with 25cm2 electrodes and
bifrontal montage (F3/F4)
Daily stimulations five days per week, up to four
weeks.
Weekly taper stimulations, up to four weeks.
Pre and post-treatment
MÅDRS
MOCA
Working memory (n-back test)
CGI
n-back
Clinical monitoring
Standard nursing and medical review
Weekly MÅDRS
Weekly YMRS
Weekly AEQ
Innovative treatment or research?
‘This is a field marked by uncertainty and hype.
Decisions taken by professionals and patients to use
novel neurotechnologies must be based on the best
available evidence of their benefits and risks.
Achieving this demands responsible communication
that is open about the limits of our current
understanding of efficacy and risk, while
maintaining trust in these technologies.
It must also be underpinned by collaborative
approaches to capitalise more effectively on
existing evidence.’
Novel neurotechnologies: intervening in the brain
‘Three virtues in particular should guide
actors across a wide range of settings and
applications of novel neurotechnologies.
These virtues are inventiveness, humility
and responsibility.’
Novel neurotechnologies: intervening in the brain
philip.wilkinson@psych.ox.ac.uk