ECT and other physical
treatments
Prof Declan McLoughlin
Dept of Psychiatry & TCIN
Trinity College Dublin
St Patrick’s University Hospital
STAR*D Programme
Remission
28%
Treatment
Citalopram
Bupropion/ Venlafaxine/ Sertraline
or +bupropion/ buspirone
18-30%
Mirtazapine/ nortriptyline
or +lithium/T3
12-25%
MAOI or Mirtazepine+Venlafaxine
7-14%
Therapeutic brain stimulation
• Electroconvulsive therapy (ECT)
• Transcranial magnetic stimulation (TMS)
• Vagus nerve stimulation (VNS)
• Deep brain stimulation (DBS)
Dunne & McLoughlin (2008) Psychiatry;
McLoughlin (2008) Psychol Med
1. What is ECT?
2. Who gets ECT?
3. How is it given?
4. How does it work?
5. What are the side-effects?
1. What is ECT?
1938, Rome: Ugo Cerletti and Bini
39 yo manic male: placed electrodes on temples,
unmodified alternating current at 220V x 1s
 administration of an electrical charge is not sufficient
and subconvulsive stimuli are ineffective
 to be therapeutic a grand mal seizure is required
 by 1940 ECT was found to be effective in depression
 by the mid 1940s ECT was being used for a broad
spectrum of mental illness, irrespective of symptoms
 1950s antidepressant medications became available
Diagnosis
2. Who gets ECT?
Indications
Outcomes
INTERPRETATION
ECT is an effective short-term
treatment for depression, and is
probably more effective than
drug therapy.
Bilateral ECT is moderately more
effective than unilateral ECT, and
high dose ECT is more effective
than low dose.
ECT remains an important
treatment option for the
management of severe depression
NICE Guidance 2009
Evidence-base to use ECT for:
1. severe depressive illness
2. previous good response
3. catatonia
4. prolonged or severe manic episode
5. maintenance for depression
3. How is ECT given?
–
–
–
–
–
Electrode positions
Laterality
Waveform
Pulse width
Stimulus intensity
Bitemporal
Right unilateral
Bifrontal
ISRCTN23577151
OBJECTIVE: to perform a pragmatic, randomised,
non-inferiority trial comparing standard bitemporal
ECT (1.5 x ST) and high-dose unilateral ECT (6 x
ST) in severe depression in routine practice
Semkovska et al (2016) Am J Psychiatry
Primary outcome: HDRS-24
Mean HDRS
estimated to be 1.2
points higher in the
Bitemporal group;
95% CI, -1.510 to
3.995,
i.e. within the
non-inferiority
threshold.
1. Mood outcomes
Standardised mean change in Hamilton Depression
Rating Scale from baseline to end of treatment
Kolshus, Jelovac, McLoughlin (2017) Psychol Med
2. Recovery of orientation
Forest plot of mean time (in minutes) to
achieve reorientation after ECT
treatments.
4. Retrograde autobiographical amnesia
Forest plot of retrograde amnesia (as
% of baseline) for autobiographical
memory (CAMI-SF) at end of
treatment.
Ultrabrief pulse ECT
• Shortening pulse widths
• Ultrabrief : <0.5ms
• Increasingly used
– 26% of Dutch clinics
in 2009
• Efficacy unknown
4. How does ECT work?
Effects of Stimulus Intensity
and Electrode Placement on
the Efficacy and Cognitive
Effects of Electroconvulsive
Therapy
Conclusions
Increasing the electrical dosage
increases the efficacy of right
unilateral electroconvulsive
therapy, although not to the level of
bilateral therapy.
High electrical dosage is
associated with a more rapid
response, and unilateral treatment
is associated with less severe
cognitive side effects after
treatment.
Sackeim HA et al, NEJM 1993
ECT: neurobiology of depression
Altar et al (2009) Neuropsychopharmacology
Biochemical pathways implicated
in response to ECT
5. What are the side-effects of ECT?
Side-effects
• ? Brain damage: no evidence of this to date
• Transient confusion post ECT
• Cognitive impairment, esp memory but usually short-lived; however,
retrograde amnesia is increasingly being recognised (?12-30%)
• Headache, nausea, muscle aches, fatigue
Complications
• (Panic)
• (Fracture of long bones, vertebrae; injury to dentition and mouth)
• Cardiovascular changes: parasympathetic surge ( HR, asystole;
consider muscarinic anticholinergic eg glycopyrrolate) followed by
a sympathetic response (optimise tx of risk factors)
• Death 1:10,000 – 100,000 treatments
ES: small, 0.2-0.5; medium, 0.5-0.8; large, 0.8-1.3; very large, >1.3
Cognitive effects of ECT in
depression: a meta-analysis
• Cognitive impairments caused by
ECT, as measured by standardised
tests, are limited to the first 3 days
after end of treatment.
• Unable to include retrograde
memory
Sub-acute effects (0-3 days)
• Afterwards, most cognitive
functions improve beyond
baseline.
• Differences in ECT techniques,
parameters or patient characteristics
contributed mainly to short-term
effects
Semkovska & McLoughlin (2010),
Biological Psychiatry
Long-term effects (>15 days)
vs
Attitudes to ECT
“Good” ECT
vs
“Bad” ECT
Note: Attitudes to ECT change over time
Attitudes to ECT
Dir. Clint Eastwood (2008);
“A True Story”, set in 1928
Therapeutic brain stimulation
• Electroconvulsive therapy (ECT)
• Transcranial magnetic stimulation (TMS)
• Vagus nerve stimulation (VNS)
• Deep brain stimulation (DBS)
Transcranial magnetic stimulation
Therapeutic brain stimulation
• Electroconvulsive therapy (ECT)
•Transcranial magnetic stimulation (TMS)
• Vagus nerve stimulation (VNS)
• Deep brain stimulation (DBS)
Vagus nerve stimulation (VNS)
• peripheral stimulation of afferent sensory fibres (80%) of
the left cervical vagus nerve
• diffuse effects upon many brain regions via the nucleus
tractus solitarius
autonomic feedback loop
reticular formation
ascending projections to the forebrain
• used for refractory partial-onset
seizures (1988), mood changes noted
• intermittent but continuous stimulation
with a bipolar pulse generator
• antidepressant mechanism unknown
hyperpolarisation
reduces neuronal excitability
alters limbic/cingulate blood flow
↑ NA and 5HT
Vagus nerve stimulation (VNS)
S/E related to surgery and/or stimulation
• coughing, hoarseness
• vocal cord paralysis
• pain, infection
• asystole on initial stimulation
Vagus nerve stimulation (VNS)
• Open studies: ~40% responders after 10-12 weeks (Rush et
al, 2000; Schlaepfer et al, 2008)
• One RCT (n=235): response 15.2% for active vs 10% for
sham after 10 weeks (p=0.25; Rush et al, 2005)
• Success of blinding not reported
• Voice alteration: real = 68%, sham = 38%
• Increase cough: real = 29%, sham = 9%
• 1 year open follow-up (n=202): response, 27.2% (remitters,
15.8%); after 2 years, ¾ still responders (Rush et al, 2005;
Sackeim et al, 2007)
• Approved by FDA but not by Medicare/Medicaid
Therapeutic brain stimulation
• Electroconvulsive therapy (ECT)
• Transcranial magnetic stimulation (TMS)
• Vagus nerve stimulation (VNS)
• Deep brain stimulation (DBS)
Deep brain stimulation (DBS)
•direct continuous focal stimulation
•reversible and adjustable alternative to ablative
psychosurgery; used for PD, essential tremor,
dystonia
•use DBS to inhibit
activity
•high frequency
stimuli: blocks
depolarisation
Deep brain stimulation (DBS)
Stimulating the brain,
healing the mind
CONCLUSIONS
• ECT is a very effective treatment
• Further scope for reducing s/e of ECT (e.g. pulse width,
electrode placement)
• Understanding molecular mechanisms of action of ECT will
be informative about neurobiology of depression
• DBS, VNS
experimental
and
TMS
are
currently
best
considered