Recent Developments in the Theory

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Recent Developments in the Theory Practice of
ECT

• Iracema Leroi, MD FRCPC MRCPsych

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ECT Update Outline

• How does ECT work?
• Cognitive effects of ECT
• NICE
• Electrode placement
• Maintenance/continuation
• Special populations
• Miscellaneous

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How Does ECT Work?

• MOA is not clear
• Not dissimilar to other effective treatments in
  medicine (Captain Cooks Vit C small pox
  vaccines)
• Several proposed
• Effect on EEG/anticonvulsant effects
• Effect on neurotransmitters
• Effects on neuroendocrine system
• Neurotrophic effects/neurogenesis

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How does ECT work?(adapted from lecture by Ian
Reid)

• Neurogenesis
• Brain makes new neurons (especially in dentate
  gyrus of hippocampus), even into old age
• Brain is very plastic
• Increased neurogenesis in an enriched environment
• having a good time is good for your brain
• BUT, stress can damage neurons (decreased
  arborisation of neuronal dendrites) due to
  corticosteroid production
• Stress antidepressant restores hippocampal size
• ECS lithium can induce neurogenesis (Mahlberg
  et al)

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How does ECT work?

• Is neurogenesis related to the antidepressant
  effect?
• Neuronal conductivity of hippocampus increases
  more in ECS in rats
• Lasts 40 days same time to relapse post ECT if
  not on antidepressant

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How does ECT work?

• SPECT (Nobler et al, 2001)
• ECT responders have greater ? in prefrontal blood
  flow immediately after ECT (n10 post days
  later)
• Thus, anatomic specificity to where ECT stimulus
  is most needed is most effective
• Also seen on PET
• Some ? also in parietal cortex, anterior
  cingulate, temporal cortex (vs baseline)

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How does ECT work?

• Other
• Changes in gene expression (Fochtmann, 1998)
• Neurotrophic factors (BDNF) (Krystal Weiner,
  1999)
• Receptor modulation (Sattin)
• Anticonvulsant effect (Sackheim)

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ECT and Cognition (Sackheim Journal of ECT,
2000)

• Patients vary widely in cognitive side effects
• Most serious delirium
• ? risk if neurodegenerative disorder
• Disorientation, retrograde anterograde amnesia
• No impairment in new learning
• Most improve in cognition over course of
  treatment
• Amnesia for autobiographical or personal memories

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ECT Cognition autobiographical amnesia

• Predicted by degree of pre-ECT impairment (Sobin,
  1995)
• not generally picked up by standardised
  instruments
• Time to recover orientation post ECT is best
  predictor

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ECT and Cognition

• Risk factors for cognitive impairment
• 1. older age
• 2. pre-existing cognitive impairment
• 3. neurodegenerative disorder
• 4. bilateral ECT
• 5. medications lithium, anticholinergics
• 6. patient perceptions

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ECT and Cognition

• Ongoing validation of brief instrument sensitive
  to ECT-induced retrograde amnesia for autobiog.
• Affected by patients perception of memory
  impairment
• Often report fewer memory impairments after ECT
• Assess pre, during, post ECT
• Patient report Consider self-report pre and post
  Cognitive Failures Questionnaire (Broadbent et
  al, 1982)
• Objective measures
• Key tests orientation, anterograde retrograde
  amnesia (recall public events, famous people)
• Baseline MMSE or neuropsychological battery
• During at least 24 hours post ECT (to avoid
  postictal contamination)
• MMSE ? gt20 indicates delirium

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ECT and Cognition

• Duty to inform is key
• Give advice about memory deficits rehearse
  situation of how to overcome such a loss

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NICE and ECT

• Health Technology Appraisal No. 59 (May 2003)
• ECT only used for
• Severe depressive illness
• Prolonged or severe mania
• Catatonia
• AND IF
• Only after all other treatment options have
  failed
• Only to produce fast, short term improvement of
  severe symptoms
• Situation is life-threatening
• Risk-benefit for the individual should be made
  and documented

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NICE and ECT

• NOT FOR
• Moderate depression
• Maintenance
• Schizophrenia
• Stop as soon as recovery

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NICE and ECT

• Factors considered by NICE
• RCT evidence of efficacy
• Evidence of adverse events in trials
• Poor standard of use
• User input

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NICE and ECT

• Appeal based on several concerns
• Patient choice
• Continuation/maintenance ECT
• Mental Health Act
• Use in schizophrenia

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NICE and ECT

• What to do post-NICE
• Document carefully
• risk/benefit
• Patient choice
• Evidence against NICE guidance
• That patient informed when treatment is not
  NICE
• Patient consent

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Electrode Placement

• Affects breadth, severity and duration of
  cognitive s/e
• Bilateral ECT
• more short long-term cognitive s/e (Sackheim,
  2000)
• Increased risk transient delirium
• Autobiographical amnesia greater than UL
• BUT
• More effective for acute mania and major
  depression
• UL is as effective as BL if markedly
  suprathreshold

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Electrode Placement

• Unilateral electrode placement may replace
  bilateral as the starting point in the near
  future
• Bifrontal vs bilateral ECT
• Same efficacy but frontal may have fewer
  cognitive side effects (Bailine et al 2000)

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Maintenance/Continuation ECT

• Level 2 evidence
• No RCTs (US study ongoing)
• Case series (only some controlled)
• Case reports (several)

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Continuation/Maintenance ECT

• Datto et al 2001 (J of ECT)
• 6 month course post index course
• 1 ECT every 3 weeks (mean)
• No progressive effect on cognition

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• Relapse
• Sackheim et al (2000) reported on 84 patients
  who remitted post ECT
• Assigned to placebo, lithium or lithiumNTP
• 6 months later 84 relapse in placebo vs 60
  39

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Special Populations Elderly

• Special role in treatment of late-life depression
• Majority of ECT patients are gt65
• biologic depressions, psychotic depression,
  less Axis II
• May be intolerant of antidepressants
• Medical consequences of depressive episode may be
  greater
• Issues
• Increased risk post ECT-delirium
• May have better outcome than younger patients
• Seizure threshold may be much higher (may exceed
  max output)
• Consider more extensive pre-ECT work-up

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Special Populations Young People

• Controversial
• No child lt15 treated with ECT in UK
• Recent case of 14 year old locally refused by
  Trust on risk grounds
• Not much evidence to support use
• Guidelines by RCP suggest
• Second opinions
• Paediatric anaesthesia teams
• Consent issues
• Minimal possible dosing (very low sz threshold)
• See US Guidelines (American Academy of Child
  Adolescent Psychiatry)

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Special Populations Pregnancy

• Low risk high efficacy
• All 3 trimesters
• May be safer that psychotropics
• Risk to fetus from anaesthetic agents is less
  than risk of psychotropics
• Succinlycholine has low ratio of placental
  transfer
• Consider positioning of patient on table due to
  aorta/vena cava circulation compromise gt20 weeks
• Consider fetal monitoring before after ECT
• Premedicate with antiacid due to increased risk
  reflux
• Have resources available to deal with obstetric
  and neonatal emergencies

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Special Populations Medically unwell

• Impact on risks and efficacy of ECT
• Consider interaction of medical condition
  anaesthetic induction, electrical stimulation,
  induced seizure activity
• Risk benefit assessment
• Additional medical work-up
• Specialist assessment (cardiology, respirology)

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ECT and medically unwell

• Consider modification of technique
• pre-treat with medications
• electrode placement
• Monitoring
• pacemaker placement
• May need to do in theatre

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Role of ECT in medically unwell

• Neurologic disease (role in PD, HD, epilepsy)
• Neuroleptic malignant syndrome (current or past)
• Diabetes consider fasting period monitor
  glucose
• Hyperthyroidism risk of thyroid storm role of
  b-blockers
• Hyperkalemia (cardiotoxic) hyponatremia
  (spontaneous seizures)

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ECT in medically unwell

• Cardiovascular disease
• Risk from HR BP changes vagal output -
  pretreat
• Pacemakers are protective (use fixed mode, not
  demand)
• Can use implanted cardiac defibrillators
• May convert AF to sinus rhythms, therefore must
  anticoagulate (risk of mural thrombi)
• Ok if post cardiac transplant

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Miscellaneous

• Brief Pulse Width
• Narrower pulse width of stimulation have more
  efficient neuronal excitation at lower threshold
  density
• More efficient, less toxic, safer
• Shorter pulses are closer to chronaxie (describes
  the relationship between pulse width and
  threshold current)
• Ultrabrief pulse ECT (0.3-1.5 millisec) is
  possible
• Lower seizure thresholds, fewer side effects

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