colleen loo - nact
TRANSCRIPT
Colleen Loo
Professor, Psychiatry, University of New South Wales
Director, ECT, Wesley Hospital, Sydney
Professorial Fellow, Black Dog Institute
SYDNEY, AUSTRALIA.
Development of ECT in last ~ 25 years
1990: One form ECT: RUL or Bitemporal (BT)
‘Brief” pulse
Set dose for all patients
Sackeim 1993: suprathreshold dosing essential for RUL
(i.e. individualised dosing – need to measure seizure
threshold for each patient)
2000: RUL, 3 x seizure threshold, brief pulse (1.0 ms)
Bitemporal, 1.5 x seizure threshold, brief pulse (1.0 ms)
SyNC Sydney Neurostimulation Centre
Development of ECT in last ~25 years
2000: RUL, 3 x seizure threshold, brief pulse (1.0 ms)
Bitemporal, 1.5 x seizure threshold, brief pulse (1.0 ms)
Sackeim 2000: suprathreshold dosing RUL @ 6 x threshold
McCall 2000: confirm importance of individual threshold
titration and dose setting
2008: RUL, 5-6 x seizure threshold, brief pulse (1.0 ms)
Bitemporal, 1.5 x seizure threshold, brief pulse (1.0 ms)
SyNC Sydney Neurostimulation Centre
Development of ECT in last ~ 25 years
2008: RUL, 5-6 x seizure threshold, brief pulse (1.0 ms)
Bitemporal, 1.5 x seizure threshold, brief pulse (1.0 ms)
Sackeim 2008: Ultrabrief RUL ECT
Kellner 2010: Bifrontal ECT
2017: RUL, 5-6 x seizure threshold, brief pulse (1.0 ms)
Bitemporal, 1.5 x seizure threshold, brief pulse (1.0 ms)
Ultrabrief RUL ECT
Bifrontal ECT
Further developments of pulse parameters, etc
SyNC Sydney Neurostimulation Centre
Electrode Placements
Bifrontotemporal Unilateral Bifrontal
How do BT, BF and RUL ECT differ in brain effects?
Lee et al, 2012
Bitemporal
Bifrontal
RUL
Effect of ECT Stimulus on Heart Rate
Start Stimulus End StimulusBaseline
Measurement
Expected Beats = 9
Observed beats = 2
Expected Beats = 11
Observed beats = 9
Asystole ≥ 5s
Incidence:
RUL 49% (39/80)
RUL-UB 24% (43/180)
BF 2.5% (2/79)
BT 11.6% (14/121)
Adjusted Odds ratios:
RUL 1.0ms vs 0.3 ms OR =45
RUL vs BF OR = 207
BT vs BF OR = 24
RUL vs BT OR = 9
Stewart et al, 2011
Stimulation
Level
MillicoulombsParameter Settings
Pulse
Width (ms)
Frequency
(Hz)
Duration
(sec)
Current
(amp)
1 32 1 40 0.5 0.8
2 48 1 40 0.75 0.8
3 80 1 40 1.25 0.8
4 128 1 40 2 0.8
5 192 1 60 2 0.8
6 288 1 60 3 0.8
7 432 1 60 4.5 0.8
8 576 1 60 6 0.8
9 864 1 90 6 0.8
10 1152 1 120 6 0.8
ECT dose chart
Ultrabrief Pulse ECTStandard
Pulsewidth
Amplitude
Duration
1 cycle.
Frequency = No. cycles/second
Ultrabrief Pulse ECTStandard
Pulsewidth
Amplitude
Duration
1 cycle.
Frequency = No. cycles/second
Ultrabrief
Pulsewidth
Comparisons of Brief &
Ultrabrief RUL ECT
Studies: N
Sackeim 2008 RCT 45
Loo 2008/2012 Effectiveness 185
Mayur 2013 RCT 35
Spaans 2013 RCT 116
Galletly 2014 Naturalistic 214
Loo 2014 RCT 95
(in press)
Tor et al, 2015. Meta:analysis :
Ultrabrief vs Brief RUL ECT - Effiacy
(in press)
(in press)
Tor et al, 2015. Meta:analysis :
Ultrabrief vs Brief RUL ECT - Cognition
(in press)
Tor et al, 2015. Meta:analysis :
Ultrabrief vs Brief RUL ECT - Cognition
Ultrabrief Pulse RUL ECT
Tor et a, 2015
Slight decrease in efficacy : SMD = 0.25
Average 9.6 vs 8.7 ECT treatments
Response 55% vs 58%
Remission 34% vs 45%
Substantive decrease in
neuropsychological side effects :
SMDs = 0.36-0.56
Model Construction ProcessMethodology
Image Segmentation
Mesh Generation Model Simulation
CT/MRI Images
SyNC Sydney Neurostimulation Centre
Brief vs Ultrabrief Pulse Width
See Bai, Loo & Dokos, 2012
Pulse width
Bitemporal Bifrontal Right
Unilateral
0.3 ms
0.5 ms
1.0 ms
Pulse width
Bitemporal Bifrontal Right
Unilateral
0.3 ms Low Efficacy ?
DRST ?
Low Efficacy ?
DRST ?
Efficacy ✓
≥ 6 x ST
0.5 ms Efficacy
(clinical
evidence)
≥ 1.5 x ST ?
Efficacy ?
DRST?
Efficacy
(clinical
evidence)
≥ 3 - 6 x ST?
1.0 ms “Gold
Standard”
≥ 1.5 x ST
Efficacy ✓
≥ 1.5 x ST
Efficacy ✓
≥ 3-6 x ST
SyNC Sydney Neurostimulation Centre
Australian Community ECT Study
Health related Quality of Life outcomes (Q –
LES – Q- SF)
3 hospitals : Wesley Sydney (Loo), QE
Adelaide (Waite), Perth Clinic (De Felice)
488 depressed patients – 355 QOL data
Low QOL scores before ECT – mean 32
(community norm = 58)
Overall 54% increase in QOL – mean score
end ECT = 45Galvez….Loo, 2016
Pulse
width
Bitemporal Bifrontal Right
Unilateral
0.3 ms
31 242 20
0.5 ms
4 73 8
1.0 ms
2 32 76
Total =488
Pulse
width
Bitemporal Bifrontal Right
Unilateral
0.3 ms
31 242 20
0.5 ms
4 73 8
1.0 ms
2 32 76
Less QOL improvement
≈ less efficacy
Significant
differences
compared to
RUL 1.0 ms
Ultrabrief
RUL
@ 6 x ST
Brief RUL
(0.5 ms)
@ 5 x ST
Brief Bifrontal
(0.5 ms)
@ 1.5–2.5 x ST
Brief Bifrontal
(1.0 ms)
@ 1.5 x ST
Higher
Efficacy
Ultrabrief
RUL
@ 6 x ST
Brief RUL
(0.5 ms)
@ 5 x ST
Brief Bifrontal
(0.5 ms)
@ 1.5–2.5 x ST
Brief Bifrontal
(1.0 ms)
@ 1.5 x ST
Brief RUL
(1.0 ms)
@ ~ 5x ST
Brief
Bitemporal
(0.5 ms)
@ 1.5-2.5 x ST
Higher
Efficacy
Ultrabrief
RUL
@ 6 x ST
Brief RUL
(0.5 ms)
@ 5 x ST
Brief Bifrontal
(0.5 ms)
@ 1.5–2.5 x ST
Brief Bifrontal
(1.0 ms)
@ 1.5 x ST
Brief RUL
(1.0 ms)
@ ~ 5x ST
Brief
Bitemporal
(0.5 ms)
@ 1.5-2.5 x ST
Brief
Bitemporal
(1.0 ms)
@ 1.5 x ST
Higher
Efficacy
Ultrabrief
RUL
@ 6 x ST
Brief RUL
(0.5 ms)
@ 5 x ST
Brief Bifrontal
(0.5 ms)
@ 1.5–2.5 x ST
Brief Bifrontal
(1.0 ms)
@ 1.5 x ST
Brief RUL
(1.0 ms)
@ ~ 5x ST
Brief
Bitemporal
(0.5 ms)
@ 1.5-2.5 x ST
Brief
Bitemporal
(1.0 ms)
@ 1.5 x ST
Brief
Bitemporal
(1.0 ms)
@ 2.5 x ST Higher
Efficacy
Clinical Decisions in ECT Prescribing
Less Efficacy More Efficacy
Less Side Effects More Side Effects
RUL, bifrontal Bitemporal
Lower dose Higher dose
Shorter pulsewidth Longer pulsewidth
SyNC Sydney Neurostimulation Centre
Finessing ECT : Monitoring Cognition
Antero-
grade
memory
Pre ECT
Verbal
Fluency
Retro-
grade
memory
Antero-
grade
memory
Post ECT
Verbal
Fluency
Retro-
grade
memory
Brief ECT
Cognitive
Screen
(3 min)
Brief ECT
Cognitive
Screen
(3 min)
Pre ECT 1 week
Orie
nta
tion a
fter
EC
T
Orienta
tion a
fter
EC
T
1 week 2 week
Martin et al, 2013; 2015
faculty of sciencefaculty of science30
Martin et
al, 2013
Finessing ECT :Monitoring Cognition
Form available in Martin et al, J ECT, in press (validation study)
SyNC Sydney Neurostimulation Centre
Anaesthesia & Concurrent Medications
Thiopentone or Propofol ?
Remifentanil
Ketamine
Lithium
Benzodiazpines
Anticonvulsants
SyNC Sydney Neurostimulation Centre
ECT & Ketamine
• Ketamine: powerful antidepressant effects• Rationale of adding to ECT
- boost efficacy - reduce cognitive SEs ? (Loo & MacPherson, J ECT 2007)
• Sole anaesthetic or adjunctive agent (eg 0.5 mg/kg)• Increases BP• Psychotomimetic effects – less in context ECT ? • Risks of repeated treatments – ulcerative cystitis, abnormal
LFT. • Systematic review & critical commentary – Galvez & Loo,
World J Biol Psychiatry, 2016
Li et al, 2017: Meta-analysis - Efficacy
Li et al, 2017: Meta-analysis - Efficacy
Li et al, 2017: Meta-analysis – Adverse Effects
Ie need to monitor safety of repeated use of ketamine.
Anaesthesia and ECT
ECT stimulusAnaestheticinjection
Strategy - Adjuvant (assist in sedation)eg Remifentanil• Short acting opioid• Cost• Nausea• Not in itself seizure
enhancing
Anaesthesia and ECT
ECT stimulusAnaestheticinjection
Strategy – Delay ECT Stimulus
• BIS (Bispectral Index) helpful in judging timing ?
BIS
Sco
re
Anaesthesia & ECT: Galvez et al, 2016
ECT stimulusAnaestheticinjection
Time (s)
Veronica Galvez
84 patients
771 ECT treatments
RUL ECT
Propofol
Outcome = EEG quality
SyNC Sydney Neurostimulation Centre
Analysis
Mixed Effects Analyses
Time
interval • Patient ID
• Anaesthetic Dose
• ECT dose (millicoulombs)
• ECT number (within course)
• Days since last ECT
• Age
• Medications :
• Antidepressant Y/N
• Antipsychotic Y/N
• Benzodiazepine Y/N
• Lithium Y/N
• Anticonvulsant Y/N
EEG
Quality:• T slow
• Amplitude
• Regularity
• Stereotypy
• Postictal
suppression
EEG Duration
SyNC Sydney Neurostimulation Centre
Results
Mixed Effects Analyses
Time
interval • Anaesthetic Dose
• ECT dose (millicoulombs)
• ECT number (within course)
• Days since last ECT
• Age
• Medications :
• Antidepressant Y/N
• Antipsychotic Y/N
• Benzodiazepine Y/N
• Lithium Y/N
• Anticonvulsant Y/N
EEG
Quality:• T slow
• Amplitude
• Regularity
• Stereotypy
• Postictal
suppression
EEG Duration
TP FP
D’Elia 1973
N=20
Single session, crossover
Loo et al, J ECT, 2014TP vs FP (several sessions, alternating)
Reorientation time 28 mins vs 50 mins
Temporoparietal Frontoparietal
% current
delivered to brain
(blue):
BF
BT
TP
FP
AP
Loo, Bai, Lovell, Dokos, Brain Stimulation Conference Poster 2015
Finessing ECT: The Future ?
ACC Hippocampus
RUL
SyNC Sydney Neurostimulation Centre
Electrode shape,
size & placement
(eg Bitemporal,
RUL, BF
Other…)
Stimulus parameters
(eg pulse width, pulse
frequency, pulse
amplitude)
Mode of stimulation –
electrical current (ECT)
magnetic stimulus (MST)
Topographical
distribution of
current in brain
Finessing Convulsive Brain Stimulation
Lee et al, 2012Clinical Effects.
SyNC Sydney Neurostimulation Centre
What is “ECT” ?
Increasing Efficacy →
Weaker forms
“ECT”Non convulsive
electrotherapy*
(under GA)
“NET”
MST
General Anaesthetic
required
TMS
(tDCS & other future
Novel Brain Stimulation Treatments)
ECT
-0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8
Global Cognition**
Anterograde (HVLT & MCG)
Anterograde Memory
Learning
Executive Function
Executive (letters only)
Speed & Concentration
Retrograde Memory*
Pre to Post Change (z-score)
Val/Val Met/Val Met/Met
Figure 1. Change in cognitive performance from pre- to post-ECT by COMT Val158Met genotype*only significant in unadjusted (p=0.020) but not adjusted (p=0.111) model**significant in unadjusted (p=0.037) and adjusted (p=0.023) modelsNote z=0 is mean group change from baseline, not no change. –ve z score indicates less change from pre to post ECT than group mean, ie less decline in cog function than group mean
Genetics & Cognitive Risk with ECT
Bai, Loo, Dokos 2011
SyNC Sydney Neurostimulation Centre
C. A. R. E. The Clinical Alliance and Research in ECT Project
➢Clinical Framework for Data Collection
➢Patient characteristics
➢ECT treatment approach,
➢Symptom ratings
➢Cognitive assessments
➢UNSW team developed forms and corresponding database
➢ ~30 hospitals involved
➢National/International
➢To be developed into Clinical Registry for ECT, TMS, tDCS, ketamine etc
SyNC Sydney Neurostimulation Centre
C. A. R. E. 2015The Clinical Alliance and Research in ECT Project
➢Aims
1. Assist/ Improve Clinical Services
– eg CORE measures meet NSW Minimum Standards ECT
2. Facilitate auditing / benchmarking – QA/QI
– At country/ state/ hospital / clinician level
3. Allow future research analysis of data collected in “real life” settings
– Answer Qs not ethically feasible in RCTs.
– E.g. does lithium increase ECT-related confusion and cognitive impairment ?
– Large datasets
– “Real life” – generalisable
Email: [email protected]
ECT & tDCS Courses in Sydney
International Society for ECT and Neurostimulation
(ISEN): 6 May 2018. New York.
23-25 Nov, 2017
TMS & tDCS Courses
TMS Masterclass
23-25 Nov, 2017
Wesley ECT Course
20-21 Oct, 2017