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Biochemical Individuality

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

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

  2. 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)

  3. 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.”

  4. 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

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

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

  7. 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

  8. All psychotropic medications effect levels of neurotransmitters in the brain

  9. 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

  10. 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

  11. Neurotransmitters What causes Neurotransmitter Deficiencies? • Genes • Diet • Stress • Neurotoxins

  12. 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.

  13. 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.

  14. 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%!

  15. 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

  16. Psychosurgery

  17. 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.”

  18. 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

  19. A New Model Referenced EEG

  20. 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.

  21. 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.

  22. The rEEG Conjecture • Resting EEG is stable • Resting EEG Changes with Medications • Use Medications to normalize the EEG • Normalized EEG leads to normalized behavior

  23. 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

  24. Medical Testing includes • Blood, Urine, Saliva Assays • Microbiology • Tissue analysis • X-Ray, MRI, CT Scans, PET Scans • EKGs, EEGs, Myograms

  25. Psychiatric Testing

  26. 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

  27. How good is symptom based treatment?

  28. 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

  29. A New Model Referenced EEG

  30. 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.

  31. 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

  32. 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

  33. 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

  34. 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?

  35. 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

  36. Neurochemical Individuality Different patients within the same neuropsychiatric disorder would have different response to medications Significant EEG heterogenities within Neuropsychiatric disorders

  37. 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

  38. 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

  39. Resting EEG is stable Resting EEG Changes with Medications Use Medications to normalize EEG Normalized EEG leads to normalized behavior

  40. 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

  41. rEEG - Characteristics rEEG is a measure of abnormal brain function, NOT mental illness

  42. 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)

  43. rEEG How does it work?

  44. When appropriately medicated, abnormal brain function can be improved or normalized Patient 1:Pre and Post Treatment Z score (degree of abnormality)

  45. Using rEEG, medications are selected which affect neurophysiology in known ways Patient 2: Pre-treatment Z score (degree of abnormality)

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