EEG and QEEG as Predictors of Medication Response Thomas F. Collura, Ph.D., QEEG-D, BCN-A July 11, 2012 BCIA-Sponsored Webinar copyright 2012 T. F. Collura Overview • Factors Influencing EEG • EEG Considerations re: medication for: – ADD/ADHD – Depression – Migraines • General Recommendations copyright 2012 T. F. Collura Factors Influencing EEG copyright 2012 T. F. Collura Concentration/Relaxation Cycle copyright 2012 T. F. Collura Phenotypes • • • • • • • • • • • Diffuse Slow Focal Abnormalities, not epileptiform Mixed Fast & Slow Frontal Lobe Disturbances – excess slow Frontal Asymmetries Excess Temporal Lobe Alpha Spindling Excessive Beta Generally Low Magnitudes Persistent Alpha “Epileptiform” (requires visual inspection of EEG waveforms) Faster Alpha Variants, not Low Voltage (requires live z-score for peak frequency) • + Diffuse Alpha deficit copyright 2012 T. F. Collura Common EEG Deviations • Depression – Asymmetric frontal alpha – Also beta excess or deficit variants • OCD – Excess orbitofrontal, temporofrontal alpha • ADHD – Frontal slowing, frontal theta, excess central alpha – Also low-voltage variants copyright 2012 T. F. Collura Drugs and EEG copyright 2012 T. F. Collura EEG changes due to medications • Opioids / Cannabis / PCP / Antidepressants – Increase slow wave activity • Barbiturates – Rhythmic 18 to 26 Hz activity • Neuroleptics / Tranquilizers – Increase coherence, decrease beta • Anxiolytics – Decrease alpha, increase beta • SSRI’s – Increase fronto-central beta copyright 2012 T. F. Collura Atypical Antipsychotics • Dopamine and Serotonin agonist • Side effects: constipation, extrapyramidal, sedation, tremor, restlessness • Anecdotal reports of seizures, convulsions • Arora and Arndorfer (2007) reported twitching, spells with Aripiprazole (Abilify) • EEG revealed “generalized epilepsy,” “seizure activity” in 13 YO male • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2 880927/ copyright 2012 T. F. Collura General Principles • • • • • Record, classify EEG and/or QEEG Identify particular markers or traits Associate with likely mechanisms Consider effects of drugs on EEG Assess likelihood of positive outcome for – Medication – Neurofeedback – Other Therapies copyright 2012 T. F. Collura ADD/ADHD • • • • • At least 5 subtypes identified Distinct EEG signatures Prognostic for EEG Biofeedback Prognostic for Stimulant Effectiveness May point to alternative medications copyright 2012 T. F. Collura Depression • Two basic forms: – Left/Right Frontal Asymmetry • Davidson, Rosenfeld, Baehr – Localized or General Beta Excess/Deficit • Hirshberg / Brown / Tufts / Harvard copyright 2012 T. F. Collura Anxiety • Various EEG manifestations – Excess beta – Excess alpha – Alpha deficit copyright 2012 T. F. Collura General EEG-Based Pharmacotherapy • Phenotype-Based – Arns et al. ADD/ADHD subtyping • QEEG-Based – DeBattista, Hoffman, CNS Response copyright 2012 T. F. Collura Migraines • Walker (2011) compared EEG with • Medication Effectiveness • EEG Biofeedback Effectiveness copyright 2012 T. F. Collura Bolwig et al. (2007) copyright 2012 T. F. Collura Arns et al. (2012) copyright 2012 T. F. Collura Arns et al. (2012) • ADHD patients with excess frontal theta EEG power and excess frontal alpha EEG power are more likely to respond to stimulant medication • Low-voltage EEG occurs more often in ADHD than in controls • These three subgroups reflect “lower and more instable vigilance regulation” • Contrast to “vigilance auto-stabilization (Hegerl, Sander) which are less responsive to stimulants copyright 2012 T. F. Collura Arns et al. (2012) • Another subgroup: excess beta or beta spindling (Arns, Chabot, Serfonetin, Clarke) • Lack of improvement on impulsivity and inattention in response to stimulants. • Slowed individual Alpha Peak Frequency (iAPF) also do not respond to stimulant medication. • Non-specific trait; also non-responsive to antidepressants and rTMS copyright 2012 T. F. Collura Arns et al. (2012) copyright 2012 T. F. Collura Arns et al. (2012) copyright 2012 T. F. Collura Arns et al. (2012) copyright 2012 T. F. Collura DeBattista et al. (2010) copyright 2012 T. F. Collura DeBattista et al. (2010) copyright 2012 T. F. Collura DeBattista et al. (2010) copyright 2012 T. F. Collura DeBattista et al. (2010) copyright 2012 T. F. Collura DeBattista et al. (2010) copyright 2012 T. F. Collura Iosifescu (2011) copyright 2012 T. F. Collura Pizzagalli (2001) copyright 2012 T. F. Collura Walker (2011) copyright 2012 T. F. Collura Walker (2011) copyright 2012 T. F. Collura Walker (2011) copyright 2012 T. F. Collura Walker (2011) copyright 2012 T. F. Collura Summary • ADD/ADHD – Subtyping, differential response to stimulants – Slow-wave variants respond to stimulants • Depression – Frontal Asymmetry type responds to antidepressants – Avoid SSRI’s when excess or spindling beta present • Migraines – Medication of limited long-term value – EEG can be used to select NF copyright 2012 T. F. Collura References • Arns, M., Gunkelman, J., Breteler, M., & Spronk, D. (2008) EEG phenotypes predict treatment outcome to stimulants in children with ADHD. Journal of Integrative Neuroscience, 7(3), 421-38. • Arns, M. Gunkelman, J., Olbrich, S., Sander, C., & Hegerl, U. (2011) EEG vigilance and phenotypes in neuropsychiatry: implications for intervention. In R. Coben and J. Evans (Eds.). Neurofeedback and Neuromodulation Techniques and Applications. Amsterdam: Elsevier. • Arns, M., Drinkenburg, W., & Kenemans, J.L. (2012) The effects of qeeg-informed neurofeedback in ADHD: an openlabel pilot study. Appl Psychophysiol Biof. March 2012. published online. copyright 2012 T. F. Collura References • Lansbergen, M., Arns, M., van Dongen-Boomsma, M., Sprink, D., & Buitelaar, J.K. (2011) The increase in Theta/Beta ratio on resting state EEG in boys with attention-deficit/hyperactivity disorder is mediated by slow Alpha peak frequency. Progress in NeuroPsychopharmacology & Biological Psychiatry, 35, 4752. • Sander, C., Arns, M., Olbrich, S., & Hegerl, U. (2010). EEG-Vigilance and response to stimulants in pediatric patients with attention deficit/hyperactivity disorder. Clinical Neurophysiology, 121, 1511-1518. copyright 2012 T. F. Collura References • Bares, M., Brunovsky, M., Kopecek, M., Novak, T., Stopkova, P., Kozeny, J., et al. (2007). Changes in QEEG prefrontal cordance as a predictor of response to antidepressants in patients with treatment resistant depressive disorder: A pilot study. Journal of Psychiatric Research, 41(3-4), 391-325. • Bares, M., Brunovsky, M., Kopecek, M., Novak, T., Stopkova, P., Kozeny, J., et al. (2008). Early reduction in prefrontal Theta QEEG cordance value predicts response to venlafaxine treatment in patients with resistant depressive disorder. European Psychiatry, 23(5), 350-355. • Benedetti, F., Colombo, C., Pirovano, A., Marino, E., & Smeraldi, E. (2009). The catechol-o-methyltransferase val(108/158)met polymorphism affects antidepressant response to paroxetine in a naturalistic setting. Psychopharmacology, 203(1), 155-60. copyright 2012 T. F. Collura References • Bruder, G.E., Sedoruk, J.P., Stewart, J.W., McGrath, P.J., Quitkin, F.M., & Tenke, C.E. (2008). Electroencephalographic Alpha measures predict therapeutic response to a selective serotonin reuptake inhibitor antidepressant: Pre- and post-treatment findings. Biological Psychiatry, 63(12), 1171-7. • Bruder, G.E., Steward, J.W., Tenke, C.E., McGrath, P.J., Leite, P., Bhattacharya, N., et al. (2001). Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant. Biological Psychiatry, 49(5), 416-25. copyright 2012 T. F. Collura References • Chabot, R.J., di Michele, F., Prichep, L., & John, E.R. (2001). The clinical role of computerized EEG in the evaluation and treatment of learning and attention disorders in children and adolescents. The Journal of Neuropsychiatry and Clinical Neurosciences, 13(2), 171-86. • Chabot, R.J. & Serfontein, G. (1996). Quantitative electroencephalographic profiles of children with attention deficit disorder. Biological Psychiatry, 40(10), 951-63. copyright 2012 T. F. Collura References • Clarke, A.R., Barry, R.J., McCarthy, R., & Selikowitz, M., (2001a). Age and sex effects in the EEG: Differences in two subtypes of attention-deficit/hyperactivity disorder. Clinical Neurophysiology, 112(5), 815-26. • Clarke, A.R., Barry, R.J., McCarthy, R., & Selikowitz, M., (2001b). EEG-defined subtypes of children with attentiondeficit/hyperactivity disorder. Clinical Neurophysiology, 112(11), 2098-2105. • Clarke, A.R., Barry, R.J., McCarthy, R., Selikowitz, M., Brown, C.R., & Croft, R.J. (2003) Effects of stimulant medication on the EEG of children with attention-deficit/hyperactivity disorder predominantly inattentive type. International Journal of Psychophysiology, 47(2), 129-37. copyright 2012 T. F. Collura References • Cook, I.A., Leuchter, A.F., Morgan, M., Witte, E., Stubbeman, W.F., Abrams, M., et al. (2002). Early changes in prefrontal activity characterize clinical responders to antidepressants. Neuropsychopharmacology, 27(1), 120-31. • DeBattista, C., Kinrys, G., Hoffman, D., Goldstein, C., Zajecka, J., Kocsis, J., et al. (2010) The use of referenced-EEG (rEEG) in assisting medication selection for the treatment of depression. Journal of Psychiatric Research, 45(1), 64-75. copyright 2012 T. F. Collura References • Iosifescu, D.V. (2008). Prediction of response to antidepressants: Is quantitative EEG (QEEG) an alternative? CNS Neuroscience & Theraputics, 14(4), 263-265. • Iosifescu, D.V. (2011) Electroencephalography-derived biomarkers of antidepressant response. Harvard Review of Psychiatry, 19(3), 144-54. • Iosifescu, D.V., Greenwald, S., Devlin, P., Mischoulon, D., Denninger, J.W., Alpert, J.E., et al. (2009). Frontal EEG predictors of treatment outcome in major depressive disorder. European Neuropsychopharmacology, 19(11), 772-7. copyright 2012 T. F. Collura References • Johnstone, J. & Lunt, J. (2011) Use of quantitative EEG to predict therapeutic outcome in neuropsychiatric disorders. In In R. Coben and J. Evans (Eds.). Neurofeedback and Neuromodulation Techniques and Applications. Amsterdam: Elsevier. • Korb, A.S., Hunter, A.M., Cook, I.A., & Leuchter, A.F. (2009). Rostral anterior cingulate cortex Theta current density and response to antidepressants and placebo in major depression. Clinical Neurophysiology, 120: 1313-9. • Leuchter, A.F., Cook, I.A., Marangell, L.B., Gilmer, W.S., Burgoyne, K.S., Howland, R.H., et al. (2009). Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in major depressive disorder: Results of the BRITE-MD study. Psychiatry Research, 169(2), 124-31. copyright 2012 T. F. Collura References • Pizzagalli, D., Pascual-Marqui, R.D., Nitchke, J.B., Oakes, T.R., Larson, C.L., Abercrombin, H.C. et al. (2001) Anterior cingulate activity as a predictor of degree of treatment response in major depression: Evidence from brain electrical tomography analysis. The American Journal of Psychiatry, 158(3), 405-15. • Pizzagalli et al. (2001) Anterior cingulate activity as s predictor of treatment resonse in major depression: evidence from brain electrical tomography. Am J. Psychiatry 158(3) 405-415. copyright 2012 T. F. Collura