The most recent study, a landmark trial of rEEG in patients with depression treatment failure, was completed in September 2009 and has been published in the Journal of of Psychiatric Research.
DeBattista C, et al., The use of referenced-EEG in assisting medication selection for the treatment of depression, Journal of Psychiatric Research (2010), doi:10.1016/j.jpsychires.2010.05.009. In Press.
This was a randomized single-blind, controlled, 12-week study of rEEG-guided therapy compared to the optimal treatments from the NIH STAR*D trial. Forty (40) subjects in the rEEG group received statistically greater proportions of CGI-Improvement scores of 2 or 1 compared to STAR*D (49 subjects) (72.5% vs 53.06%, p<0.0001). Both primary endpoints and nearly all secondary endpoints were statistically greater for rEEG than STAR*D.
Eleven previous studies evaluated rEEG-guided therapy in 405 treatment-refractory patients. Of these eleven studies, two were controlled and published, one of which was controlled with random assignment. The remaining eight studies were non-controlled where the patients acted as their own control. The following was concluded:
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Positive treatment responses (CGI-Improvement scores of 2 or 1) in 82% of patients.
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Robust and highly consistent with effectiveness rates exceeding 69% across numerous psychiatrists practicing in diverse settings.
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Non-intuitive medication and medication combinations were often involved.
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Sustainable treatment gains with all effectiveness ratings conducted 3 to 24 months following treatment initiation, compared to STAR*D’s 64.6% and 71.1% relapse rates within several months following an initial step 3 or step 4 remission.
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Enhanced treatment compliance and decreased dropout rates. In the five studies that reported such rates, 85% (153 of 180) of rEEG patients were medication compliant and remained in treatment versus STAR*D’s 44.8% and 60.1% dropout rates during steps 3 and 4 despite receiving exemplary free acute and continuing care.
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Evidenced real-world clinical efficacy with all studies done in naturalistic practice settings.
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RESEARCH DETAIL (Click to expand and collapse)
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STUDY |
STUDY N |
rEEG N |
FINDINGS |
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| Randomized Controlled Trials |
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DeBattista C, et al., The use of referenced-EEG in assisting medication selection for the treatment of depression, Journal of Psychiatric Research (2010), doi:10.1016/j.jpsychires.2010.05.009. In Press.28 |
89 evaluable out of 114 |
40 |
89 depressed patients who had failed one or more antidepressant medication trials. Patients were randomly assigned between the STAR*D modified algorithm medication and rEEG® guided treatment. All patients had baseline rEEG® and were blind to treatment assignment. Key findings were:
- rEEG® resulted in significant (p<.0001) improvements in both primary outcome measures—decreasing patients’ depressive symptoms (QIDS-SR) and increasing their quality of life (Q-LES-Q-SF)—compared to those treated using STAR*D’s modified algorithm.
- On both primary outcomes measures, the mean level of separation between rEEG® and the STAR*D control group was significant after only two weeks of treatment and the level of separation increased in each subsequent assessment through to the 12 week endpoint.
- rEEG® resulted in significant superiority in remission and response rates as measured by the QIDS-SR16. 65% versus 38.8% response; 35% versus 26.5% remission
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Suffin & Emory. Published in Clinical
EEG and Neuroscience, 1995 2 |
103 Attentional and Affective Participants (3 Drop Outs) |
62 |
Attentional and affective disordered patients were administered a pretreatment QEEG. The treating psychiatrist was not guided by the QEEG findings but instead followed a structured protocol for patients in each DSM group with up to three medication steps.
Of the 100 subjects’ QEEGs revealed significant electro-physiologic heterogeneity within both the attention deficit and affective patients (p<0.01). In 62 patients, clear correlations were found between QEEG findings and responsiveness to selected drugs independent of diagnosis. At six months following treatment initiation: 22 of 25 (88%) with excess frontal alpha had moderate or marked improvement to antidepressants; 7 of 7 (100%) with excess frontal theta responded to stimulants; 22 of 25 (88%) with excess frontal alpha and hypercoherence responded to lithium or anticonvulsants; and 4 of 5 (80%) with excess frontal theta and hypercoherence responded to anticonvulsants. The overall predictive efficacy for these 62 patients was 89% (55 of 62). |
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Suffin et al. Published in Journal of American Physicians and Surgeons, 2007 21 |
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Treatment-resistant MDD patients who had been non-responsive to at least two prior medication trials of adequate dosage and duration. Patients were randomly assigned between psychiatrists’ best treatment and rEEG® guided treatment. All patients had baseline rEEG®. Patients and 17-item HDRS raters were blind to treatment assignment.
Despite the small N, the difference in pre/post HDRS scores was highly significant (p<0.009) at a mean follow-up of 25 weeks. Control group’s pre/ post mean HDRS scores were 24 and 18 respectively vs. 23 and 9 for the rEEG group. 1 of 6 (16.7%) control group patients had a 50% or greater reduction on the HDRS vs. 4 of 6*** (66.7%) rEEG® patients. 6 of 7 of the rEEG® group (85.7%) were rated on the CGI-I as either much or very much improved. The control group’s 6 rEEG® reports, which were kept sealed during the study, accurately predicted the outcomes of all 6 patients: the 1 success and 5 failures. *** 1 rEEG® patient did not have a follow-up HRDS and therefore was excluded despite having a “much improved” CGI-I rating. |
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| Case Series |
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Schiller , Emory, & Suffin. Presented at NIMH’s 44th NCDEU, 2004 13 |
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104 eating disorder patients 83% of whom had failed in prior medication trials (mean=4). 81 patients accepted rEEG® and were medication compliant; 13 accepted rEEG® and then refused medication. 10 refused rEEG® and continued current medications.
At median 9-month follow-up, 67 out of the 81 rEEG® compliant patients (75.3%) were rated as much or very much improved. Anorexic: 25 of 36 (69%); Bulimic: 28 of 36 (78%); and Eating Disorder NOS: 8 of 9 (89%). The 13 who refused rEEG® recommended medication had at most only minimal improvement. None of the 10 who continued their current medications scored as having “very much” improvement. |
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Greenblatt et al. Presented at APA, 2008 14 |
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rEEG predicted potential efficacy for medications from the following classes: anticonvulsants, antidepressants and stimulants. Following rEEG medication recommendations, hospitalization days decreased dramatically. At baseline, HDRS scores averaged 39.8±5.7, indicating all patients suffered from moderate to severe depression symptoms. By week 8, scores decreased to an average of 13.2±6.9; and by 6 months, scores decreased to 8.5±5.2. Paired sample t-tests indicated that these changes were significant at 8 weeks (p<.001; t=12.627; df=12) and at 6 months follow-up (p<.001; t=15.687; df=12). At baseline, average CGS score was 5.54±.66. This score represents a rated illness severity between ‘Severely ill’ and ‘Markedly ill.’ By week 8, CGS scores had decreased to an average of 2.85±1.14, representing an illness severity of ‘Mildly ill’’; CGS scores further decreased to 2.23±.83 at 6 months representing a CGS score between “Mildly ill” and “Borderline Mentally ill”. These changes were significant at 8-weeks (p<.001; t=11.355; df=12) and at 6 months (p<.001; t=18.917; df=12). CGI scores improved to an average of 1.77±.72 at 8 weeks reflecting a “much improved” change in symptoms. At 6 months average final CGI was 1.23 ±.44, representing a CGI category between ‘much improved’ (score of 2) and ‘very much improved’ (score of 1). |
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Schiller et al. Presented at APA, 2005 25 |
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68 treatment-refractory MBHO patients from 10 different psychiatric practices followed for at least three months. 12 patients were non-compliant and dropped out.
39 of the 56 rEEG® treatment compliant patients (69.6%) were rated as much or very much improved while 17 were using other rEEG® indicated agents after not receiving an initial adequate response. |
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Schiller et al. Presented at APA, 2005 25 |
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28 dually diagnosed treatment-refractory patients in an addiction practice.
22 of 28 (78.6%) were rated as much or very much improved. |
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Schiller et al. Presented at APA, 2005 25 |
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82 treatment-refractory patients treated in two psychiatric practices.
64 of 82 (78%) were rated as much or very much improved. |
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Shaffer, Milner, & Schiller. Presented at APA, 2005 26 |
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58 dually diagnosed patients in a residential substance abuse treatment program 48 of whom (83%) were rated “markedly ill” and 10 (17%) were rated “mild to moderately ill.” Patients were assessed >6 weeks after starting rEEG® guided treatment. 35 of the markedly ill patients (73%) were rated as “very much improved” while 7 (15%) were rated as “much improved” following rEEG® guided treatment. 9 (90%) from the “mild to moderately ill group were rated as “very much improved” and 1 was rated as “much improved.” Overall, 52 of the 58 patients (90%) were rated as much improved or very much improved. Treating physicians rated rEEG® guidance “essential” in 56 of 58 (97%) cases. |
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Schiller. Presented at CPDD, 2008 27 |
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19 dually diagnosed patients in a residential substance abuse treatment program 17 of whom (89%) were rated “markedly ill” and 2 (11%) were rated “mild to moderately ill.” Patients were assessed >6 weeks after starting rEEG® guided treatment.
15 of the 17 markedly ill patients (88%) were rated as much or very much improved following rEEG® guided treatment. 2 of 2 (100%) from the “mild to moderately ill” group were rated as much or very much improved. Overall, 17 of the 19 patients (89%) were rated as much improved or very much improved. |
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Hoffman. Published in Journal of Neurotherapy, 2006 20 |
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4 rEEG® case studies with 6 months to 1 year follow-up.
The 1st case with prior diagnoses of bipolar and MDD-recurrent had an exceptional response to oxcarbazepine and nortriptyline, which was maintained at 1-year follow-up. The other 3 case studies dramatically improved during the medication wash-out required for their rEEG® and elected to remain off medication with their positive responses being maintained for 6 month to 1 year. |
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Suffin et al. Published in Journal of American Physicians and Surgeons, 2007 21 |
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Treatment-resistant MDD patients who had been non-responsive to at least two prior medication trials of adequate dosage and duration. Patients were randomly assigned between psychiatrists’ best treatment and rEEG® guided treatment. All patients had baseline rEEG®. Patients and 17-item HDRS raters were blind to treatment assignment.
Despite the small N, the difference in pre/post HDRS scores was highly significant (p<0.009) at a mean follow-up of 25 weeks. Control group’s pre/ post mean HDRS scores were 24 and 18 respectively vs. 23 and 9 for the rEEG group. 1 of 6 (16.7%) control group patients had a 50% or greater reduction on the HDRS vs. 4 of 6*** (66.7%) rEEG® patients. 6 of 7 of the rEEG® group (85.7%) were rated on the CGI-I as either much or very much improved. The control group’s 6 rEEG® reports, which were kept sealed during the study, accurately predicted the outcomes of all 6 patients: the 1 success and 5 failures. *** 1 rEEG® patient did not have a follow-up HRDS and therefore was excluded despite having a “much improved” CGI-I rating. |
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RESEARCH REFERENCES (Click to expand and collapse)
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Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry.2006;163:1905–1917.
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Suffin SC, Emory WH. Neurometric subgroups in attentional and affective disorders and their association with pharmacotherapeutic outcome. Clin EEG & Neuro.1995;26:76-83.
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Itil TM, Marasa J, Bigelow A, Saletu B. Prediction of neuroleptic effects of CI-686 based on quantitative pharmaco-electroencephalography: drug profiles and dose response curves based on computerized cerebral bio-potentials. Current Therapeutic Research.1973;16:80-95.
-
Itil TM, Shapiro DM, Herrmann WM, Schulz W, Morgan V. HZI systems for EEG parametrization and classification of psychotropic drugs. Pharmakopsychiat.1979;12:4-19.
-
Saletu B, Anderer P, Kinsperger K, Grunberger J. Topographic brain mapping of EEG in neuropsychopharmacology. Part II. Clinical applications (pharmaco EEG imaging). Meth and Find Exptl Clin Pharmacol.1987;9(6):385-408.
-
Small JG, Milstein V, Kellams JJ, et al. EEG topography in psychiatric diagnosis and drug treatment. Ann Clin Psychiat.1989;1:7-17.
-
Struve FA. Lithium-specific pathological electroencephalographic changes: a successful replication of earlier investigative results. Clin EEG.1987;18(2):46-53.
-
Herrmann WM, Fichta K, Itil TM, Kubricki S. Pharmakopsychiat. 1979;12:20-34.
-
Satterfield JH, Cantwell DP, Saul RE, Lesser LI, Podosin RL. Response to Stimulant drug treatment in hyperactive children: prediction from EEG and neurological findings. J of Autism and Childhood Schizophrenia.1973;3(1):36-48.
-
Prichep LS, Mas F, Hollander E, et al. Quantitative electroencephalographic subtyping of obsessive compulsive disorder. Psychiat Res: Neuroimaging.1993;Apr;50(1):25-32.
-
Ohashi Y. The baseline EEG traits and the induced EEG changes by antidepressant medication in patients with major depression. Seishin Shinkeigaku Zasshi.1994;96(6):444-460.
-
Guy, W. (ed.). ECDEU assessment for psychopharmacology, revised edition. NIMH Publication: Rockville, MD.1976.
-
Schiller MJ, Emory WH, Suffin SC. rEEG®- in the treatment of eating disorders. Presented at NIMH’s 44th NCDEU Conference, 2004.
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Greenblatt J, Sussman C, Jameson M, Kasumova G. Referenced-EEG® guided medication predictions in treatment-refractory eating disorder patients. Presented at APA, 2008.
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Mitchel JE, deZwaan M, Roerig JL. Drug therapy for patients with eating disorders. Current Drug Targets – CNS & Neurological Disorders.2003;2:17-29.
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Godart NT, Perdereau F, Rein Z, Berthoz S, et al. Comorbidity studies of eating disorder and mood disorders. Critical review of the literature. J Affect Disord.2007;97:37-49.
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Jordan J, Joyce PR, Carter FA, et al. Specific and nonspecific comorbidity in anorexia nervosa. International J of Eating Disord.2008;41(1):47–56.
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Jacobs DG, Baldessarini RJ, Conwell Y, et al. Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry.2003;160(supplement):1-60.
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McKenzie JM, Joyce PR. Hospitalization for anorexia nervosa. Int J Eat Disord 1992;11:235-241.
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Hoffman, D. “First, do no harm:” a basic tenet in jeopardy? J Neurotherapy 2006;10(4):53-61.
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Suffin SC, Emory WH, Gutierrez G, et al. A QEEG database method for predicting pharmacotherapeutic outcome in refractory major depressive disorders. J of Am Physicians and Surgeons.2007;12(4):104-108.
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Benson K, Hartz AJ. A comparison of of observational studies and randomized controlled trials. N Eng J of Med.2000;342(25):1878-1886.
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Britton A, McPherson K, KcKee M, et al. Choosing between randomized and non- randomized studies: a systematic review. Health Tech Assess.1998;2(13):1-124.
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DePaulo JR. Bipolar disorder treatment: an evidence-based reality check. Am J Psychiatry 2006;163(2):175-176.
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Schiller MJ, Emory WH, Shaffer J, et al. EEG guidance of psychopharmacologic treatment: multi-site experience. Presented at APA ,2005.
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Shaffer JH, Milner JE, Schiller MJ. rEEG® guided pharmacotherapy for severely ill dually- diagnosed patients. Presented at APA, 2005.
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Schiller MJ. Referenced-EEG® guided pharmacotherapy of dually-diagnosed patients. Presented at College on Problems in Drug Dependence annual meeting, 2008.
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DeBattista C, et al., The use of referenced-EEG in assisting medication selection for the treatment of depression, Journal of Psychiatric Research (2010), doi:10.1016/j.jpsychires.2010.05.009. In Press.
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