colleen loo - nact

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: ECT-CARE@unsw.edu.au

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