Philip Wilkinson Electricity rendered useful? Transcranial direct current stimulation for late life depression

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 ECTElectroconvulsive therapy VNSVagus nerve stimulation DBSDeep brain stimulation rTMSTranscranial magnetic stimulation tDCSTranscranial direct current stimulation

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Neurostimulatory treatments for depression Cheap ?No need for anaesthesia ? Non-invasive ?Portable ? ECT VNS DBS rTMS tDCS

Neurostimulatory treatments for depression CheapNo need for anaesthesia Non-invasivePortable ECTXXXX VNSXXXX DBSXXXX rTMSX √√ 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 McAllister- Williams

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):

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:

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 (9)

Systematic review of tDCS trials in MDD Active tDCS superior to sham on continuous outcomes at study endpoint (g = 0.37; 95% CI ) Active tDCS superior to sham on response rates (OR 1.63; 95% CI ) Active tDCS superior to sham on remission rates (OR 2.5; 95% CI ) Shiozawa P et al. Int J Neuropsychopharm (9)

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 (9)

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 25cm 2 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