Electroconvulsive Therapy and other - PowerPoint Presentation

Slide1

Electroconvulsive Therapy and other Neurostimulation Techniques

Dr. Patrick ClarkeSlide2

Major DepressionAustralian figures:

1 in 4 females1 in 6 males1 in 7 General Practice presentations (MJA 2008)

4

th

most frequent managed condition in General Practice in 2004-2005Slide3

Major DepressionBy 2020 predicted to be 2

nd main cause of disability worldwide (WHO, 1998).Over 50% of patients are severely depressed (Kendler et al, JAMA June 2003)

STAR*D study demonstrates that clinical benefit declines with increased previous treatment failure. Relapse rate increases with each level. Slide4

Major DepressionFailure to achieve initial remission leads to worse long term outcomes (Judd et al, J Affect Disord 1998)

With repeated episodes there is less need for a precipitating stressor (Kendler et al, AJPsych 2000).Slide5

Major DepressionFew proven effective and tolerated treatments in pharmacoresistent patients

Significant unmet needReduced compliance with increased treatment resistanceSlide6

Stages of TRD – STAR*D

Stage I – Failure of 1 AD

Stage II – Failure of 2 classes of AD.

Stage III – Failure of 2 classes of AD plus TCA. (Remission with next intervention 13%)

Stage IV – Failure of 2 classes of AD plus TCA, plus MAOI. (Remission with next intervention 14%)

Stage V – Above plus failure of BL ECT. (Remission with next intervention 13%).Slide7

Suicide1987: 2,240 people died by suicide in Australia

Since 1990, more male deaths in Australia have been attributed to suicide than to non-intentional motor traffic fatalities.

Overall rate is stable at 11 per 100,00 population per yearSlide8

Electroconvulsive Therapy

History

Hippocrates saw that insane patients showed reduced symptoms after suffering from convulsions brought on by malaria

Physician used an electric eel to cure headaches of the Roman emperor Claudius in AD 47

In the 1800s there were reports of insanity being cured with electric shock

Chemically induced seizures used as treatment for schizophrenia in 1934 by Hungarian physician, Laszlo

Meduna

First human treatment in 1938, by

Cerletti

and

Bini

.

Performed unmodified until 1950’s to 1960’s.Slide9

ECT Historical

Early machines provided the current in sine wave distribution. Energy inefficient and correlates with increased cognitive ADR.

Replaced by machines providing the current in a series of pulses. Initially these were fixed dose (high), e.g.

Kabtronics

. Nevertheless, charge could vary according to pulse width, frequency, and current.

Sackeim

1990 introduced dose titration.Slide10

Electroconvulsive Therapy in Adelaide 2010-2011

6393

ECT treatments were

given:

59

%

in public hospitals

41

% in private hospitals.

People from their 20s to their 80s receive ECT, with

the majority

in their 60s and 70s.

ECT

treatments:

69% inpatient/acute

20% maintenance

11% outpatientSlide11

ECT Mechanism of action

Mechanism of action remains unclear. Seizure is necessary, and for RUL ECT therapeutic dose is several times seizure threshold (

Sackeim

1990). Seizure threshold varies 80 fold within the general population, and is influenced by age, gender, etc. Seizure results in changes in Serotonin receptors (5HT2). More recent theories focus upon how the brain physiology is recruited to bring the seizure to a halt.Slide12

PhysiologyDuring ECT an electrical stimulus is delivered through the scalp and skull to the brain, which depolarises a sufficient number of neurones to cause a generalised seizure.

With BL ECT, the seizure is believed to occur by direct activation of diencephalic nuclei. With RUL ECT, underlying cortical structures are activated first with a secondary activity arising in large pyramidal cell fields and related dendritic fields.Slide13

EEGPost stimulus there is a recruiting phase.

During the tonic and early clonic phase there is high voltage polyspike activity which decreases in frequency.The clonic motor response is followed by high amplitude slow waves.

This is replaced by post-ictal suppression.

The ictal EEG lasts longer than the motor activity.Slide14

Recruitment

Tonic phase of seizure

The following four slides show a typical two lead EEG during an ECT treatment

Robert OstroffSlide15

Clonic phase of seizure

Robert OstroffSlide16

End of Motor Seizure

Robert OstroffSlide17

Postictal Suppression

Robert OstroffSlide18

IndicationsMajor Depression

PsychoticAgitatedRetarded

Treatment Resistant

With significant riskSlide19

Bipolar Affective DisorderDepressive Episode

Manic EpisodeSlide20

SchizophreniaAcuteWith Affective symptoms

CatatonicChronic, unresponsive to other treatment.Slide21

Puerperal DisordersPost Natal DepressionPuerperal PsychosisSlide22

OtherNeuroleptic Malignant SyndromeParkinson’s Disease

Status EpilepticusSlide23

ContraindicationsThere are few true contraindications, provided that the patient is deemed fit for General Anaesthetic.

Raised Intracranial Pressure. Slide24

Work UpHistory of ECT, medical, G.A., allergies.

Physical examination (Fundoscopy).CBE, MBA20, TFT’s.

ECG.

CXR.

CT Head.

Consent (inform patient and family).

Fasting.Slide25

Side Effects and RisksRisk of G.A. (Mortality 1/64,000).

Headache.Muscle Ache.Cognitive: Delerium, STM, Autobiographical Memory Loss. There is no evidence of structural brain damage.Slide26

Dental: use a bite block.Enzyme deficiency.Burns.

Mania.Prolonged seizure.Slide27

EfficacyIn Psychotic and Melancholic Major Depression, without comorbidity, remission rates over 80%, often over 90% achieved.

Most efficacious treatment available for endogenous depression.High relapse rate i.e. 43% in 6 months, 46% in 12 months, if no maintenance treatment provided. Slide28

Special CircumstancesCardiovascular

Bradycardia occurs due to vagal stimulation. Catecholamine release associated with the seizure corrects this. May require Atropine.Cardiac Pacemakers and Defibrillators.

HT.

MI. Greatest risk in the first 10 daysSlide29

EndocrineAddison’s Disease: ECT causes a transient adrenocortical stimulation, and increased corticosteroids may be required prior to ECT.

Diabetes: exclude hypoglycaemia prior to ECTThyroid: Treat hyperthyroidism as ECT can induce thyroid storm.Phaeochromocytoma. Slide30

MetabolicDehydration: risk of DVT.Hyperkalaemia: increased risk of cardiac arrhythmias.

Hyponatraemia: Occurs with SIADH, seen occasionally with antidepressants and antipsychotics. Lowers seizure threshold.Slide31

NeurologicalDementia: increased risk of cognitive ADR. May need to space treatments.

Epilepsy: Anticonvulsants raise seizure threshold.Raised intracranial pressure and intracranial masses: small, slow growing masses unlikely to cause problems.

MS: Generally tolerate ECT well.

Parkinson’s Disease: ECT increases the permeability of the BBB, and therefore concomitant LDopa can increase to toxic levels.

CVA: Wait 1 month or more.Slide32

GORIncreased risk of aspiration, therefore, consider Ranitidine, or cuffed endotrachael tube.Slide33

OphthalmicECT causes a brief increase in intraocular pressure, problematic in open-angle glaucoma.Slide34

PregnancyNot contraindicated.Fetal monitoring is not routine.Slide35

ElderlyECT efficacious in elderly.Have higher seizure threshold.

May require longer courses.EEG may be less impressive.Slide36

Respiratory DisordersSleep Apnoea: CPAP Machine available in Recovery.Slide37

Skull DefectAvoid area of the defect.Avoid area of metal plates.Slide38

Urine retentionCatheterise.Slide39

Concomitant MedicationAntidepressants: MAOI may be associated with hyper-reflexia, seizures, and hypertension or hypotension.

Anticonvulsants: increase seizure and should be avoided. If prescribed for epilepsy, continue.Antipsychotics: Clozapine can result in increased confusion with ECT.

Lithium: Delerium, associated with increased permeability of BBB. Slide40

AnaestheticsMonitoring: Pulse Oximetry and ECG.

Induction: Propofol. Shorter seizure than Thiopentone. Methohexitone not available.Muscle Relaxant: Suxamethonium.

Cuff Technique. Slide41

Electrode PlacementSlide42

Electrical StimulusSlide43

Seizure ThresholdSlide44

Seizure DurationSlide45

Dose TitrationSlide46

Continuation ECTSlide47

Maintenance ECTSlide48

Standard ECT

Variations in Electrical Dose and Electrode Placement

Less Efficacy More Efficacy

Less Side Effects More Side Effects

Unilateral ECT Bilateral ECT

Low Dose High DoseSlide49

Ultrabrief ECT

A relatively recent advance in ECT has been the development of ultrabrief

ECT. This uses a pulse width of 0.3 ms, compared with 1.0 ms used in standard pulse ECT.

This results in the use of a far smaller stimulus dose in order to induce a seizure, and consequently a reduction in cognitive side effects, comparable to placebo (

Sienaert

2010,

Loo

2008,

Sackheim

2008).

Ultrabrief

ECT has been associated with a slightly longer course of ECT (30 to 50% longer), and the need to switch to standard pulse ECT in 20 to 50% of patients who show inadequate response.Slide50

Pulse and sine wave comparison. Energy = area under curveSlide51

Stimulus Parameters

Standard Pulsewidth

Amplitude

Duration

1 cycle.

Frequency = No. cycles/second

Ultrabrief Pulsewidth

0.5-2ms

0.2-0.4 msSlide52

ECT Study

Ultrabrief ECT was introduced to 2 private psychiatric hospitals in Adelaide, The Adelaide Clinic and

Fullarton

Private Hospital, in August 2010.

Data was gathered between August 2010 and April 2012 on patients receiving an acute course of

ultrabrief

ECT or standard pulse ECT. The treating Psychiatrist, together with the patient, decided whether patients would receive

ultrabrief

or standard pulse ECT. Slide53

ECT was administered using a

Thymatron Series IV ECT machine.

The right unilateral electrode placement was used for all

ultrabrief

patients and was also most commonly used for patients receiving standard pulse width ECT.

UB ECT was given at 5 to 6 times the seizure threshold, with a 0.3 ms pulse width, and standard pulse ECT was given at 3 to 5 times seizure threshold, with a 1.0 ms pulse width.Slide54

Rating Scales included Montgomery-Asberg Rating Scale (MADRS), Mini-Mental State Examination (MMSE), and Zung Self-Rated Depression Scale (Zung).

Data was gathered by trained nursing staff prior to treatment commencing, weekly during treatment, and after completion of the course.Slide55

ResultsTotal of 252 patients. 190 commenced UB ECT, and 35 (18.4%) changed to standard ECT during their course. 62 commenced standard ECT, and 3 (4.8%) changed to UB during their course.

Loo 2008, reported that 41 of 74 (55.4%) patients switched from UB ECT.Slide56

Total Patients Receiving ECTSlide57

Number of ECT

The Mean number of treatments for UB ECT was 10.1, versus 8.0 for Standard Pulse.

This compares with the findings of

Loo

2008 of 10.3 for UB ECT, and 7.6 for Standard Pulse.

The longer course translates into an average 27% longer LOS for patients receiving UB

cf

patients receiving SPW.

Patients who switch have the longest LOS, reflecting their relatively treatment resistant status. Slide58

Number of treatments

Number of Treatments

Mean

Standard Deviation

Minimum

Maximum

Ultrabrief

10.1

4.0

1

25

Standard

Pulse

8.0

3.1

1

18

UB change to Standard

8.6

3.4

3

19

Patients receiving a full course of ultra-brief ECT had significantly more treatments than patients receiving a full course of standard pulse width ECT

(t(212)=3.76, p<0.001).

Slide59

Length of Stay (days)

Length of Stay

Mean

Standard Deviation

Minimum

Maximum

UB

23.4

13.4

1

56

Standard Pulse

18.4

10.4

1

76

UB

change to Standard

28.9

6.8

14

46

Patients receiving a full course of ultra-brief ECT had a significantly longer stay in hospital than patients receiving a full course of standard pulse width

(t(204)=2.55, p<0.01).

Overall, patients receiving UB ECT had a longer stay in hospital and received more treatments than patients receiving Standard Pulse Width ECT.Slide60

Change in Assessment Scores

MADRS and Zung decreased over time. The mean improvement in MADRS for UB was 49% and for SW, 54%. This difference was not significant, meaning both treatments were equally effective.

Patients had similar baseline illness severity to begin with (in fact UB patients were slightly more unwell to start with, but this was not statistically significant).

For the MADRS, this improvement equates to a categorical reduction in severity of depression from severe to mild.

Similarly, on the

Zung

there was equivalent improvement in scores (of a more modest amount ,as expected with self rated scales) and in categorical terms there was a reduction from depressed to the normal range. Slide61

MADRS before and after treatment

MADRS

UB Mean

Standard Pulse Mean

Mean difference between UB and Standard Pulse

P value

Pre-treatment

33.9

(SD 8.6)

30.9

(SD 14)

3.1

Post-treatment

17.2

(SD 9.1)

14.1

(SD 8.6)

3.1

Mean reduction in MADRS over course

16.4

(SD 11.8)

17.0

(SD 15.3)

0.6

0.8Slide62

Zung before and after treatment

Zung

UB Mean (SD)

Standard Pulse Mean (SD)

Pre-treatment

59.1 (8.3)

53.7 (20.1)

Post-treatment

46.0 (12.4)

43.4 (9.9)

Change

in Zung after Treatment

-12.8 (13.7)

-10.2 (22.2)Slide63

Change in Cognitive Function Scores

UB patients commenced with high MMSE scores (28.4) and these had not significantly changed by the end of the course (28.91).

SPW patients actually had lower MMSE scores at baseline (25.49) which had improved to the same post-treatment scores as UB at the end of the course (28.11).

It is hard to explain why the SPW patients had lower MMSE scores at baseline - it did not reflect depression severity, as UB Patients were, on average, slightly more unwell according to MADRS scores.

It is encouraging that patients either maintained or improved cognitive function for both types of ECT.

However, this probably reflects the lack of sensitivity of the MMSE in detecting change in memory, and probably the main conclusion is that MMSE is not a good cognitive assessment tool in ECT.Slide64

MMSE before and after treatment

MMSE

UB Mean (SD)

Standard Pulse Mean

Mean difference between UB and

Standard

Sig.

Pre-treatment

28.4 (3.0)

25.5 (9.0)

2.91

0.03*

Post-treatment

28.9 (2.1)

28.11 (3.8)

0.81

0.17

Change

in MMSE after Treatment

0.4 (3.0)

2.61 (9.9)

2.21

0.13

*There was a significant difference in pre-ECT scores between the SPW and UB ECT groups.Slide65

Assessment ScoresSlide66

Response

110 of 213 patients satisfied criteria for Response to an acute course of ECT, defined as at least 50% improvement on MADRS (Loo

, 2007).

26 (54.2%) received Standard Pulse ECT, and 84 (50.9%) received UB ECT. There was not a significant difference in terms of type of ECT and likelihood of Response.

Loo

2008, reported 11 of 22 (50%) for Standard Pulse, and 32 of 74 (43.2%) for UB ECT.Slide67

Remission

Remission was defined as MADRS<10.

Using this criteria, 16 (34%) patients receiving Standard Pulse achieved remission, as did 29 (22%) receiving UB ECT.

Patients who changed ECT type were excluded from this analysis.

Pearson’s Chi-Square indicates that type of ECT is not associated with the likelihood of remission (p=0.10).

In comparison

Loo

2008, reported remission rates of 36% for Standard Pulse, and 27% for UB ECT. Our study showed a non significant trend in

favour

of higher remission with SW ECT, although the slightly lower baseline depression scores in the SW group may account for at least some of this.Slide68

Remission

Remission

Non Remission

Total

Standard Pulse

Number

16

31

47

% within type of ECT

34%

66%

UB

ECT

Number

29

103

132

% within type of ECT

22%

78%

Total

45

134

179Slide69

ECT Service Level Data for TACTotal Number of ECT

2008 - 1162 2009 - 14042011 - 1728

Increase of 23.1% from 2009 to 2011.Slide70

Conclusion

Patients who received UB ECT received 20% more treatments and had a 27% greater length of stay.

Both the UB ECT and Standard Pulse groups showed a good response to ECT, and there were no significant differences between the groups in terms of symptom response.

There was not a significant difference between the groups in terms of Remission rate.

UB ECT was well accepted by psychiatrists referring to the Ramsay Health S.A. ECT Services, with rapid take up of the treatment option and an overall increase in treatment with ECT.Slide71

Lessons Learnt

The Folstein MMSE is unsuitable to monitor cognitive side effects of ECT.

UB ECT is as effective as SPW ECT for patients with severe levels of depression, and if one is patient and prepared to treat for the longer course, UB ECT will lead to similar levels of remission and improvement.

The cost of the longer LOS may be offset by greater patient acceptance (and therefore willingness to go to ECT earlier) and fewer cognitive side effects (and possibly return to work sooner after discharge)Slide72

TMS-APA Toronto 2006Slide73

TMS Introduction

TMS was first described by Pascual-Leone in 1996.

It relies on direct stimulation of the brain using a magnetic pulse to generate brief electrical currents that stimulate nerve cells in the regions of the brain involved in mood regulation and depression (

Padberg

et al, 2009).

TMS uses repeated pulses over 15 to 30 minutes to stimulate the cortex.Slide74

TMS – proposed mechanism of action

Imaging studies in depression: left dorsolateral prefrontal cortex underactive c.f. right DLPFC

High frequency rTMS (10 Hz) activates the cortex

Low frequency rTMS (1 Hz) inhibits the cortex

Therefore: high frequency over the left DLPFC and/or low frequency over the right DLPFC restores L-R symmetry and exerts an antidepressant effect Slide75

TMS Mechanism of ActionImproves Porsolt Forced Swim Test

Increases brain monoamine turnoverIncreases Dopamine in Hippocampus

Increases flow to the Cingulate Gyrus

Normalises HTP AxisSlide76

TMS Advantages

Non-invasive

No General

Anaesthetic

No seizure

No cognitive ADR

Increased control over site and intensity of stimulation (DLPFC)

No weight gain, sedation, or sexual ADR.

Treatment can be administered by nursing staff

It works completely differently to medication, and so some medication

resistent

patients respond to it (1/3 achieve a significant response)Slide77

TMS EfficacyA recent meta analysis involving 1164 patients demonstrated that high frequency TMS to the left DLPFC is effective in the treatment of MDD, compared to sham TMS, with an effect size comparable to antidepressant medications (Schutter 2009).

TMS has been approved by the TGA in Australia, and by the FDA in the USA.Slide78

Efficacy of rTMS

Over 30 published DB-RCT of

rTMS

vs

sham control

Most favoured

rTMS

over sham

Effect sizes were good to modest – 0.35 to 0.89

Open study response rates are around 50%

Slotema

’

s

meta-analysis

2010

(

Slotema

&

Blom

et al, J

Clin

Psychiatry July 2010

)

34 studies, N=1382

Effect size 0.55 (CI 0.42 - 0.66), p<0.001Slide79

Neurostar

TMS Trial

HAM-D and MADRS response rates at 4 and 6 weeks, and remission rates at 6 weeks (but not at 2 weeks) showed significant benefit of

rTMS

over sham.

Resulted in TMS being licensed by FDA as a therapy for depression in USA.

Biggest efficacy trial with TMS.

Multi-centre, Randomized, Double Blind, Sham-Controlled trail with over 300 patients .Slide80

TMSSlide81

TMSSlide82

Ramsay TMS Service

Set up Dec 12th 2007

First patients began treatment in Aug 2008

2 clinical directors responsible for administration and clinical assessments including mapping i.e. locate the motor cortex and then the DLPFC is located 6 cm forward. Determine the threshold for intensity and treatment is built up to 110% of threshold. A template is prepared for each patient so that nursing staff giving the treatment can position the coil correctlySlide83

Ramsay TMS ServiceSlide84

TMS Treatment - very relaxing!Slide85

Initial StudyA randomised trial comparing rTMS given 3 days per week versus 5 days per week for the treatment of Major Depression.Slide86

Participants

Variable

SPACED GROUP

3 day/week

(n=45) M(SD)

DAILY GROUP

5 day/week

(n=39) M (SD)

Difference between groups

p value

Age

51.2 (13.47)

47.2 (12.79)

0.17 NS

Gender

Females

29

26

1.00 NS

Males

16

13

1.00 NS

Years unwell

23.6 (14.43)

18.5 (11.98)

0.08 NS

Previous history of ECT

24 (53.3%)

27 (69.2%)

0.21 NS

Trialled five or more antidepressants

33 (73.3%)

32 (82.1%)

0.31 NS

Baseline HAM-D score

24.2 (6.34)

24.5 (5.61)

0.83 NS

Baseline HAM-A score

21.5 (7.71)

21.9 (7.81)

0.81 NS

Baseline MADRS score

30.8 (7.40)

30.3 (7.86)

0.80 NS

Baseline Zung score

57.7 (6.57)

57.3 (6.27)

0.76 NSSlide87

Overall Response Rates

Full Response- 41.7% (n=35)

Partial Response- 27.4% (n=23)Slide88

Overall Remission Rate

Remission- 31% (n=26)Slide89

Comparison of Spaced and Daily TreatmentSlide90

Conclusions

Number of treatments is the important factor, rather than the period of time over which treatment had been administered

We did not find evidence that spacing treatments, at least to 3 days/ week, was associated with reduced efficacy

Therefore, worth giving TMS 3 days/week instead of 5 days/week in a clinical service to increase capacitySlide91

Transcranial Direct Current Stimulation

Relatively weak constant current flow through the cerebral cortex via scalp electrodes

I

ntroduced in 1960s for treatment of depression.

R

ecent studies have shown clinical improvement similar to antidepressant medication

Also used to enhance cognition and

learning

Available in Sydney – research trialsSlide92
Slide93

You should see the other bloke!Slide94

Further Clinical and Research Opportunities

A working group has been developed in S.A. to explore the possibility of developing a Deep Brain Stimulation (DBS) service in S.A. for psychiatric indications. 2 services exist already for the management of intractable movement disorders (at RAH and FMC). It is also performed in the private sector (Wakefield Hospital).

Management of treatment resistant OCD is being considered.Slide95

Deep Brain Stimulation

In Deep Brain Stimulation (DBS), electrical

stimulation directly changes brain activity in

a controlled manner and

its effects are

reversible

Parkinsons

Disease,

Tourettes

OCD targets:

nucleus accumbens

subthalmic

nucleus

Depression targets:

subcallosal

cingulate area

nucleus accumbens

ventral striatum.Slide96

Efficacy in depressionSlide97

Further Clinical and Research Opportunities

The RANZCP has just ratified the development of an ECT and

Neurostimulation

Special Interest Group (ENSIG), which met for the first time at Congress in Hobart in May 2012. 4 South Australians have been elected to the ENSIG Committee, and Dr. Clarke elected Chair.

In 2011, an Australian Chapter of International Society for ECT and

Neurostimulation

(ISEN) was

recognised

, with Prof Colleen

Loo

as Chair.Slide98

Thank You