Referenced EEG

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Referenced EEG

• Redefining the Medical Management of Eating
  Disorders

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The Referenced EEG

• A patients pretreatment QEEG data is obtained
  and statistically compared with similar QEEG data
  from patients with known medication responsivity.
• The result is a prediction of the patients
  likely responsivity to particular medications.
• This, in turn, informs the treatment strategy for
  the patient.

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The rEEG Conjecture

• Resting EEG is stable
• (abundant literature references support this)
• Resting EEG Changes with Medications
• (Abundant literature references support this)
• Use Medications to normalize the EEG
• (rEEG technology)
• Normalized EEG leads to normalized behavior
• (CNSR clinical results)

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Why is Psychiatry Different?

• Medical treatment for mental disorders differs
  from treatment of all other medical specialties.
• Psychiatrists typically do not use objective
  measurements to guide treatment of mental or
  addictive illness

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Medical Testing includes

• Blood, Urine, Saliva Assays
• Microbiology
• Tissue analysis
• X-Ray, MRI, CT Scans, PET Scans
• EKGs, EEGs, Myograms

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Psychiatric Testing
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Diagnosis and Treatment
General Medical Treatment Symptoms Measure
Physiology Anti-physiology treatment Measure
physiology and symptoms
Psychiatric Treatment Symptoms Anti-Symptom
treatment given Measure symptoms
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• How good is symptom based treatment?

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The Art of Psychopharmacology

• Heterogeneity of medication response,
• One class of medication treats multiple disorders
• SSRIs

• PMPD
• SAD
• MDD
• Bulimia

• Panic Disorder
• Generalized Anxiety
• Social Phobia
• No name distress

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Response to Psychopharmacologic Treatment

• 50 improvement of the primary symptoms of
  depression is the standard measure of treatment
  response
• 20-40 do not show substantial clinical
  improvement
• 50 who show improvement have residual symptoms
  that impact functioning

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St. Johns Wort vs Placebo

• 8 weeks double blind placebo controlled
• 31.9 responded to placebo
• 24.8 responded to Zoloft
• 23.9 responded to St. Johns Wort

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A New Model

• Currently in Psychiatry only symptoms are
  available to guide therapy.
• Currently there are no pharmacological
  interventions better than placebo for AN.
• Selecting neuroactive medications by
  physiological criteria may improve therapeutic
  outcome

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A New Model

• Referenced EEG

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Case History

• History
• 44 year old employed female
• Depressed since childhood.
• Anxiety, anergia, weight gain, irritability,
  negativity, hopelessness, low self-esteem, poor
  concentration like walking through Jell-O
• Active treatment for 14 years with internist,
  endocrinologist, psychiatrist
• Unsatisfactory response to fluoxetine (Prozac),
  sertraline (Zoloft), bupropion (Wellbutrin),
  paroxetine (Paxil), doxepin (Serzone),
  venlafaxine (Effexor) and fluvoxamine (Luvox)
• rEEG Medication Prediction
• Anticonvulsant and Stimulant in combination
• Physician selected Lamictal and Ritalin
• Response
• Improved concentration, increased tolerance
• Significant decrease in negativity and anxiety
• Experienced modest weight loss over several weeks
• Feelings of hopelessness and low self-esteem have
  diminished markedly
• After seven antidepressant trials, rEEG
  identified non-intuitive medication sensitivities.

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Case History

• 23 y/o female
• ED beginning age 16
• Restrictive eating, purging, depression, passive
  SI
• 3 month treatment at Laurel Hill Inn, 11/04 -
  2/05
• Shephard Pratt, 4/05 7/05
• WBC Alcott unit approx 2 wks 11/05
• WBC Thoreau unit approx 2 wks 12/05
• WBC Residential Program 12/05-2/06
• rEEG completed 12/28/05

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Past Medication Trials

• Medication
• Trazadone, Abilify, Ativan, Lamictal, Zoloft,
  Effexor, Prozac, Ambien, Naltrexone
• rEEG data
• Trileptal/Cymbalta
• Current status
• Engaged in Outpatient Treatment
• Recommending rEEG to friends

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Brain wave patterns of ADD children

• Theta waves are associated with daydreaming and
  inattentiveness
• Beta waves are associated with concentration and
  focus
• Brain Wave patterns of ADD children show an
  abundance of theta, and diminished beta

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Is it possible ...

• Is there a relationship between
  neurophysiological findings and medication
  response?
• Can this relationship be used to predict
  response?
• Can these predictions be used to inform treatment
  design?

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Yes!

• Major depression with excess alpha responds to
  antidepressants
• ADHD with excess slow waves respond to stimulants
• OCD with excess Theta are non responders to
  anti-depressants
• Low voltage EEGs are poor responders to
  anti-depressants and anti-psychotics

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• Significant EEG heterogenities within
  Neuropsychiatric disorders
• Different patients within the same
  neuropsychiatric disorder would have
  different response to medications

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39 Patients with a similar EEG feature

• 39 Patients with 17 different DSM-based diagnoses
  (x axis)
• All have the same rEEG defined abnormality
• All responded well to the same specific agent
• ConclusionDSM-diagnosis does not correlate well
  with drug responsivity. rEEG does correlate well.

293.83 296.2 296.22 296.23 296.3 296.32 296.33 296
.7 299.8 300.01 300.4 301.13 309.89 311 312.3 312.
39 314
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Family History/Genetics

• Inherited EEG patterns have been documented
• Clinicians use family history of medication
  response as guides for selecting a psychotropic
  medication
• EEG abnormalities maybe a marker for familiar
  medication responses
• Two Generation rEEG study

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The rEEG Conjecture

• Resting EEG is stable
• (abundant literature references support this)
• Resting EEG Changes with Medications
• (Abundant literature references support this)
• Use Medications to normalize the EEG
• (rEEG technology)
• Normalized EEG leads to normalized behavior
• (CNSR clinical results)

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rEEG - Characteristics

rEEG is a measure of abnormal brain function,
NOT mental illness
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Database Comparison
Normal Subject Database 2082 QEEGs, Subjects
6-90 Original Pharmacotherapy Outcome Database

• 1600 patients followed for at least 26 wks
• 84 medications tracked for effectiveness over
  more then 6000 treatment episodes
• 8467 patient follow-up assessments
• Outcome assessment using clinical Global
  Improvement scale (CGI)

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rEEG

• How does it work?

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When appropriately medicated, abnormal brain
function can be improved or normalized
Patient 1 Pre and Post Treatment
Z score (degree of abnormality)
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Using rEEG, medications are selected which affect
neurophysiology in known ways
Patient 2 Pre-treatment
Z score (degree of abnormality)
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Medications that are not compatible for a
neurophysiology can yield iatrogenic illness
Patient 2 Pre and Post treatment
Z score (degree of abnormality)
Frequently occurs with symptom/behavioral-based
treatment selection
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UNBLINDED PROSPECTIVE STUDY

• Neurometric Subgroups in Attentional and
  Affective Disorders and their Association with
  Pharmacotherapeutic Outcome
• Stephen C. Suffin and W. Hamlin Emory, Clinical
  Electroencephalography, Vol. 26, No. 2, 1995.
• Hypothesis
• Quantitative electrophysiologic measures
  correlate better with pharmacotherapeutic
  response than diagnosis

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UNBLINDED PROSPECTIVE STUDY

• Design
• 54 patients with DSM Affective Disorders
• 46 patients with Attentional Disorders
• Affective Disorders Treatment Protocol
• Heterocyclic antidepressant or SSRI treatment
• If CGI lt 2 or 3 after 6 weeks then anticonvulsant
  or lithium treatment
• If no improvement 3 weeks post therapeutic levels
  then methylphenidate challenge.
• Attentional Disorders Treatment Protocol
• Methylphenidate not exceeding 1 mg/kg of body
  weight
• If CGI lt 2 or 3 post 4 weeks then stimulant
  discontinued and antidepressant medication
  initiated
• If no improvement post 6 weeks antidepressant
  augmented with anticonvulsant or lithium

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rEEG First study 1995

• QUESTION
• Is rEEG a better indicator for determining drug
  therapy than the symptom-based diagnosis itself?
• 100 patients 54 depressive, 46 ADD
• ANSWER Yes
• Patient response was predicted by rEEG 80 of the
  cases
• Journal of Clinical Electroencephalography in
  1995

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BLINDED PROSPECTIVE STUDY 1997-1999

• A QEEG METHOD FOR PREDICTING PHARMACOTHERAPEUTIC
  OUTCOME IN REFRACTORY MAJOR DEPRESSIVE DISORDER
  Suffin SC, Emory WH, Gutierrez N, Karan S, Arora
  GS, Johnstone J, Kling A, in revision for
  submission.
• Hypothesis
• Is treatment guided by EEG/QEEG measures
  superior to standard psychiatric treatment of
  refractory major depression?

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BLINDED PROSPECTIVE PILOT STUDY (contd)

• Design
• Randomized, controlled, multiply-blinded study of
  major depressive patients at the Sepulveda VA all
  of whom had failed at least two prior, adequate
  medication trials
• DSM DIRECTED group (N6) 4 males and 2 females,
  avg. age 45, age range 39-54
• DSM EEG DIRECTED group (N7) 5 males and 2
  females, avg. age 41, age range 31-64

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Second Study 1997-1999

• QUESTION
• Can rEEG indicate appropriate medications for the
  most difficult depressive patients?
• ANSWER Yes
• Patients averaged 16 years unresponsive to
  treatment with at least one hospitalization each.
• All patients but one of rEEG led group
  significantly improved, only one patient of the
  control group did.

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BLINDED PROSPECTIVE PILOT STUDY (contd)
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Pilot Market Introduction 2000-2002

• QUESTION
• Can rEEG guide one of the largest MBHOs
  psychiatrists to successful treatment for their
  most challenging cases?
• ANSWER Yes
• 70 of these most difficult patients
  significantly improved
• All patients had two or more unsuccessful
  medication trials

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Monte Nido Residential Center Outcomes Anorexia
36 Anorexic patients complied for gt8
weeks Median follow up 10 months
Improved 29 of 36 (80) ?CGIs 2-3 Not Improved 7 of 36 (20) ?CGIs 0-1
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Monte Nido Residential Center Outcomes Bulimia
36 Bulimic patients complied for gt8 weeks Median
followup 8 months
Improved 30 of 36 (80) ?CGIs 2-3 Not Improved 6 of 36 (17) ?CGIs 0-1
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Monte Nido Residential Center Outcomes Eating
Disorder, NOS
9 ED, NOS patients complied for gt8 weeks Median
followup 10 months
Improved 8 of 9 (83) ?CGIs 2-3 Not Improved 1 of 9 (11) ?CGIs 0-1
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Monte Nido Residential Center

• Six Medication Classes identified from the
  rEEG database
• Antidepressants
• Anticonvulsants
• Lithium
• Stimulants
• Beta Blockers
• Benzo diazepines

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Monte Nido Treatment Center

• 84 Eating Disorder Patients Treated by rEEG
  Protocols After 8 weeks
• 80 (29/36) Anorexia Nervosa patients responded
• 83 (30/36) Bulimia Nervosa patients
• 89 (8/9) EDNOS

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EEG Guidance of Psychopharmacologic Treatment
Multi-Site Experience Mark J. Schiller, M.D.,
W. Hamlin Emory, M.D., Jay Shaffer, M.D., James
T. Hamilton, M.D., Daniel A. Hoffman, M.D.,
Albert Davis, M.D., Stephen S. Suffin, M.D. APA
May 2005 Scientific Poster - 500 patients
Size Results
ADD Depression Trial 100 gt80
VA Blinded Study 13 85
CIGNA-Atlanta Pilot 56 70
Dr. Davis Case Series 15 100
Monte Nido Case Series 150 80
Dr. Hamilton Case Series 34 78
Dr. Hoffman Case Series 74 76
Rancho LAbri Case Series 58 93
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Eating Disorder rEEG CASES
16 y/o AN (RT) - Lamictal, Adderall
21 y/o AN (BD) - Trileptal, Zoloft, Wellbutrin
22 y/o ED NOS - Topamax, Parnate
25 y/o ED NOS/AL DUP - Lamictal, Wellbutrin
16 y/o AN - Neurontin, Parnate
43 y/o ED NOS/Depress - Neurontin, Wellbutrin
22 y/o AN (RT) - Lamictal, Effexor
29 y/o Bulimia/OCD/Depress - Trileptal, Wellbutrin
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Drug Class Correlations

• Sensitive
• Greater than 80 of the neurophysiological
  similar patients exhibit a change in CGI of two
  or more
• Minimum of 45 days post treatment
• Resistant
• Less than 35 of patients with similar
  neurophysiology had a CGI change of two or more
• Intermediate
• Between 35-85 of patients with similar
  neurophysiology had a CGI change of two or more

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Referenced-EEG
 
Key to symbols S sensitive, patients with
similar neurophysiology were most often very
responsive to medications with this
designation. R resistant, patients with similar
neurophysiology were least often very responsive
to medications with this designation. I
intermediate, patients with similar
neurophysiology were neither consistently
sensitive or consistently resistant to medication
with this designation ND No data in the
database to support recommendations 1,2,3
relative rankings amongst agents in a subgroup
where 1 is highest and 3 is lowest.
 
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Benefits of Referenced EEG

• rEEG can indicate and support non-intuitive
  recommendations
• - Prescribing stimulants for anorexics
• rEEG helps physician organize complex cases
• rEEG helps physician avoid unnecessary and costly
  therapies

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Whos not suitable

• Under 6 or over 90 years old
• Intramuscular depo-neuroleptic therapy within the
  preceding twelve months
• History of craniotomy (with or without metal
  prostheses) or cerebral vascular accident
• Spikes on the conventional EEG
• Current diagnosis of seizure disorder or dementia
  
• Mental retardation
• Current use of marijuana cocaine, hallucinogens
  or other drugs of abuse or alcohol in the last
  three days
• Significant abnormality of the CBC, chemistry or
  thyroid function tests including TSH until
  corrected

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rEEG Data Flow
Medication Recommendation
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Summary

• The Problem
• DSM directed (symptom based) therapeutic regimens
  often require extensive trial and error.
• In Eating Disorders medications are often
  ineffective.
• A Solution
• Directly assess the physiology of the brain in a
  way that is predictive of medication
  responsivity.
• Multi site Research Study starting for Treatment
  Refractory Depression

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Conclusion

• Psychiatric disorders are strongly familial and
  biological and can no longer be seen as disorders
  of choice!
• We can directly assess the physiology of the
  brain in a way that is predictive of medication
  responsivity.
• Using that information allows us to medicate more
  effectively and with much less trial and error.

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Thank You
Thank You