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Referenced-EEG Redefining the Medical Management of Psychiatric Disorders James M. Greenblatt, M.D. November 17, 2007. Biochemical Individuality. “It is more important to understand what sort of patient has a disease than to know what sort of disease a patient has.” Sir William Osler

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Biochemical individuality

Referenced-EEG Redefining the Medical Management of Psychiatric DisordersJames M. Greenblatt, M.D.November 17, 2007


Biochemical individuality

Biochemical Individuality

“It is more important to understand what sort of patient has a disease than to know what sort of disease a patient has.”

Sir William Osler

(1849-1919)


Integrative medicine

Integrative Medicine

  • Integrating the best of conventional medicine and evidence based complementary therapies promotion, disease prevention and medical management.

  • “It might be too pretentious to say that such a growth at integrative medicine might restore the soul to medicine – the soul being that part of us that is the most important but the least easy to deliniate.”


An integrative approach to mental health involves

An integrative approach to mental health involves

  • The genetic and biochemical foundations that may predispose to symptoms

  • The dietary habits that present and pre-symptom history

  • The impact of the illness on social and psychological systems

  • The physical and social environment in which the symptoms occur

  • Understanding the patients experience and beliefs of his/her illness


Biochemical individuality1

Biochemical Individuality

Each individual has a unique physiological and biochemical composition based on genetics that interact with unique environmental influences


Nutrigenomics

Nutrigenomics

How dietary intake affects health by altering the expression and/or structure of an individuals genetic makeup


Biochemical individuality

Neurochemical Individuality:

Genetic Diversity Among Human Dopamine

and Serotonin Receptors and Transporters

Anibal Cravchik, MD, PhD; David Goldman, MD

ARCH GEN PSYCHIATRY VOL 57, DEC 2000

  • Human individuality arises from both genetics and the environment

  • A substantial portion of the variance in personality is genetically transmitted

  • A substantial portion of the variance in psychiatric disease risk is genetically transmitted

  • A substantial portion of the variance in metabolism and psychotropic drugs is genetically trasmitted


Biochemical individuality

All psychotropic medications

effect levels of neurotransmitters

in the brain


Neurotransmitters

Neurotransmitters

  • Most neurotransmitters are under precursor control

  • Precursors are substances obtained in whole or part from our diet

  • Precursors are most easily obtained from meats and animal products


Neurotransmitter synthesis

Neurotransmitter Synthesis

Folic Acid

Vitamin B6

Vitamin B12

Vitamin C

Vitamin D

Vitamin B3

L-Tryptophan

5-HTP

ST

L-Tyrosine

L-Dopa

DA

NE

Epi

  • Magnesium

  • Zinc

  • Iron

  • Copper


Neurotransmitters1

Neurotransmitters

What causes Neurotransmitter Deficiencies?

  • Genes

  • Diet

  • Stress

  • Neurotoxins


Digestion and health

Digestion and Health

  • Your health is a function not so much of what you eat, but what you are able to digest, assimilate and metabolize.


Treatment for obsessive compulsive disorder

Treatment for Obsessive-Compulsive Disorder

Behavior Therapy

  • Behavior therapy attempts to help patients learn to dispel the anxiety caused by obsessions or to reduce or eliminate compulsive rituals.

    Psychotropic Medications

  • Medications which enhance serotonin neurotransmission have been shown to reduce obsessive compulsive symptoms.


Medical management of ocd

Medical Management of OCD

  • SSRI’s and Anafranil utilized most

  • About 80% of patients improve with average reduction in obsessions and rituals of only 50%

  • The likelihood of complete recovery has not been shown to exceed estimates of 20%!


The art of psychopharmacology

The “Art” of Psychopharmacology

  • Heterogeneity of medication response,

  • One class of medication treats multiple disorders

  • SSRI’s:

http://www.wired.com/entertainment/theweb/news/2007/11/xkcd

  • OCD

  • Panic Disorder

  • Generalized Anxiety

  • Social Phobia

  • “No name distress”

  • PMPD

  • SAD

  • MDD

  • Bulimia


Psychosurgery

Psychosurgery


Psychosurgery1

Psychosurgery

  • 1930-1950 Prefrontal Lobotomy became “fashionable”

  • 1949 Nobel Prize for discovery of procedure, Dr. Egas Monez

  • Dr. Monez was shot and killed by one of his frontal lobotomy patients

“We don’t like to call it psychosurgery

anymore…It’s neurosurgery for severe

psychiatric illness.”


A new model

A New Model

  • Currently in Psychiatry only symptoms are available to guide therapy.

  • Currently there are few pharmacological interventions better than placebo.

  • Selecting neuroactive medications by physiological criteria may improve therapeutic outcome


A new model1

A New Model

Referenced EEG


Mental health treatment

Mental Health Treatment

  • The Problem

    • DSM directed (symptom based) therapeutic regimens often require extensive trial and error.

  • A Solution

    • Directly assess the physiology of the brain in a way that is predictive of medication responsivity.


The referenced eeg

The Referenced EEG

  • A patient’s 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 patient’s likely responsivity to particular medications.

  • This, in turn, informs the treatment strategy for the patient.


The reeg conjecture

The rEEG Conjecture

  • Resting EEG is stable

  • Resting EEG Changes with Medications

  • Use Medications to normalize the EEG

  • Normalized EEG leads to normalized behavior


Why is psychiatry different

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


Medical testing includes

Medical Testing includes

  • Blood, Urine, Saliva Assays

  • Microbiology

  • Tissue analysis

  • X-Ray, MRI, CT Scans, PET Scans

  • EKGs, EEGs, Myograms


Psychiatric testing

Psychiatric Testing


Diagnosis and treatment

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


Biochemical individuality

How good is symptom based treatment?


St john s wort vs placebo

St. John’s Wort vs Placebo

8 weeks double blind placebo controlled

31.9% responded to placebo

24.8% responded to Zoloft

23.9% responded to St. John’s Wort


A new model2

A New Model

Referenced EEG


Case history

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.


Case history1

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


Past medication trials

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


Brain wave patterns of add children

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


Is it possible

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?


Biochemical individuality

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


Neurochemical individuality

Neurochemical Individuality

Different patients within the same neuropsychiatric disorder would have different response to medications

Significant EEG heterogenities within

Neuropsychiatric disorders


39 patients with a similar eeg feature

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

  • Conclusion:DSM-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


Family history genetics

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


Biochemical individuality

Resting EEG is stable

Resting EEG Changes with Medications

Use Medications to normalize EEG

Normalized EEG leads to normalized behavior


Biochemical individuality

  • rEEG is a technology that compares the quantitative EEG of medication free patients to a large database of asymptomatic, medication free, “normal” EEGs in order to

    define an abnormality


Reeg characteristics

rEEG - Characteristics

rEEG is a measure

of abnormal brain function,

NOT mental illness


Database comparison

Database Comparison

  • Normal Subject Database:

    • 2082 QEEG’s, 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)


Biochemical individuality

rEEG

How does it work?


When appropriately medicated abnormal brain function can be improved or normalized

When appropriately medicated, abnormal brain function can be improved or normalized

Patient 1:Pre and Post Treatment

Z score

(degree of abnormality)


Using reeg medications are selected which affect neurophysiology in known ways

Using rEEG, medications are selected which affect neurophysiology in known ways

Patient 2: Pre-treatment

Z score

(degree of abnormality)


Medications that are not compatible for a neurophysiology can yield iatrogenic illness

Medicationsthat 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


Unblinded prospective study

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.

54 patients with DSM-III-R Affective Disorders (296.xx or 311.00)

46 patients with DSM-III-R Attentional Disorders (314.xx)


Unblinded prospective study cont d

Unblinded Prospective Study (Cont’d)

Results

  • Frontal Alpha Excess / Normocoherent subgroup – 87% response to antidepressants

  • Frontal Theta Excess / Normocoherent subgroup – 100% response to stimulants

  • Frontal Alpha Excess / Hypercoherent subgroup – 85% response to anticonvulsants/lithium

  • Frontal Theta Excess / Hypercoherent subgroup – 80% response to anticonvsulsants/lithium


Blinded prospective pilot study

Blinded Prospective Pilot Study

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.

Sepulveda VA: all of whom

had failed at least two prior

adequate medication trials,

with an average duration of

16 years, & at least one

prior hospitalization.

  • DSM DIRECTED

  • DSM + EEG DIRECTED


Pilot program in outpatient psychiatric practices

Pilot Program in Outpatient Psychiatric Practices

Managed Behavioral Health Organization in Atlanta (from 10 individual private practices)

  • Patients with any psychiatric diagnosis with at least two prior unsuccessful medication trials eligible for referral to program

  • 56 patients managed with EEG had adequate time pass since testing and reported results:

    • 39 (69.6%) of patients had outstanding outcomes (representing 10 different psychiatry practices)

    • 17 (30.4%) of patients were in a pending status (physicians trying other EEG indicated agents or combinations) at the time of data collection


Analysis of retrospective case series monte nido residential center

Analysis of Retrospective Case Series: Monte Nido Residential Center


Monte nido summary

Monte Nido Summary

  • 36 Anorexia

    • 29 (80%) Improved*

    • 7 (20%) No improvement

  • 36 Bulimia

    • 30 (83%) Improved*

    • 6 (17%) No improvement

  • 9 Eating Disorder, NOS

    • 8 (89%) Improved*

    • 1 (11%) No improvement

*CGI’s 2-3


Biochemical individuality

EEG Guidance of Psychopharmacologic Treatment: Multi-Site ExperienceMark 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


Eating disorder reeg cases

Eating Disorder rEEG CASES


Drug class correlations

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


Referenced eeg

Referenced-EEG

Section 2: Individual Medication Responsivity

Subgroup ratings (S, I & R) are based on comparison to other subgroups within the overall medication group. Within the subgroup individual medications ratings (1, 2, 3) are relative to other medications in the subgroup only. When there is only one medication in a subgroup only the subgroup rating appears. Specific medication combinations may be incompatible.

Anticonvulsants (Intermediate)

Antidepressants (Sensitive)

Trade Name

Generic Name

Sensitivity

Trade Name

Generic Name

Sensitivity

Benzodiazepines

I

SSRI

I

Xanax

Alprazolam

2

Prozac

Fluoxetine

3

Ativan

Lorazepam

1

Zoloft

Sertraline

3

Klonopin

Clonazepam

3

Paxil

Paroxetine

1

Tegretol

Carbamazepine

S

Luvox

Fluvoxamine

2

Depakote

Divalproex

R

Celexa

Citalopram

2

Neurontin

Gabapentin

S

TCA

S

Lithane

Lithium

R

Norpramin

Desipramine

2

Tofranil

Imipramine

1

Beta Blockers (Intermediate)

Pamelor

Nortriptyline

3

Trade Name

Generic Name

Sensitivity

Elavil

Amitriptyline

2

Lopressor

Metoprolol

I

Anafranil

Clomipramine

2

Inderal

Propranolol

I

Wellbutrin

Bupropion

S

Tenormin

Atenolol

I

Effexor

Venlafaxine

S

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.


Benefits of referenced eeg

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


What reeg is and what it isn t

What rEEG is, and What it ISN’T

  • Not a cookbook

  • Typical patient population

    • “First, Do No Harm”

  • What it predicts

    • Classes; drugs; combinations (except atypical antipsychotics)

  • What it doesn’t predict

    • Side Effects


Who s not suitable

Who’s 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


Reeg data flow

rEEG Data Flow

Digital EEG’s

Analysis

Analysis

Age NormalizedDatabase

Clinical ResponseDatabase

Medication

Recommendation


Summary

Summary

  • Psychiatric disorders are strongly familial and biological and can no longer be seen as disorders of choice!

  • The Problem

    • DSM directed (symptom based) therapeutic regimens often require extensive trial and error.

  • A Solution

    • Directly assess the physiology of the brain in a way that is predictive of medication responsivity.


Conclusion

Conclusion

  • 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.


Conclusion1

Conclusion

  • Early clinical trials show that rEEG is more than 80% effective in guiding the treatment of patients with a range of psychiatric diagnoses including, major depression, Bipolar Disorder, ADHD, Anxiety Disorder, OCD and Eating Disorders.


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