QEEG-based prediction of response to antidepressant modalities Cyril Höschl www.hoschl.cz National Institute of Mental Health Prague Psychiatric Centre & Charles University, 3rdMedicalFaculty, Prague M NIH NATIONAL INSTITUTE OF MENTAL HEALTH 6th International Congress on Psychopharmacology, Antalya 17 April 2014
Onlyone-third of patientsbeingtreatedwithSSRIsfordepressionachieveremission on the first drug tried(Verqouwen AC etal. 2007; Bondolfi G etal. 2006; Trivediet al.2006 ) • 25-30% of non-responders to first-line treatment can achieve remission by switching to- or adding of a second medication(Papakostas GI etal. 2008; Ruhé HG et al.2006) Treatment of Depression All of this leads to prolonged suffering of depressed patients and to enormous expenses for society Every day in depressionrepresentshugeindividual and socialburden. • Clinical improvement generally requires 4-12 weeks • • Over 30% of patients prescribed antidepressants discontinuetreatment before 30 days of therapy( (Sheehanet al.2004) Anyinterventionshortening period of disabilitysaves a lot of suffering and expenses.
Calculated from quantitative EEG power values; integrates absolute and relative powerinformation • Associated with regional cerebral perfusion • Provides information interpretable in the context of PET and SPECT neuroimaging studies of depression Predictor: QEEG Cordance Leuchter et al, Neuroimage 1994; Cook et al, EEG Clin Neurophysiol 1998; Leuchter et al, Psychiatry Res 1999
δ (0,5-4Hz) σ (4-8 Hz) α (8-12 Hz) β (12-30Hz)
lesion hypoperfusion relativespectrum ↓absolutespectrum
www.cordance.com • Absolute power values ɑ are reattributed to each individual electrode by averaging power from all bipolar electrode pairs sharing that electrode. • (Fp2-F4)+(F8-F4)+(C4-F4)+(Fz-F4) • F4 = • 4 2.Relative power values are calculated 3.calculation of normalized absolute (ANORM (s,f)) and normalized relative (RNORM (s,f)) power values (absolute and relative power values at each electrode site (s) and for each frequency band (f ) are divided by AMAXf and RMAXf respectively). 4. Cordance calculation:
Design of our study Baseline MADRS, BDI, CGI, EEG I Onset of treatment 4weeks treatment MADRS, BDI, CGI, EEG III Medication Responders: Venlafaxine 2 Escitalopram 1 Clomipramine 1 Bupropion 1 Non-responders: Venlafaxine 5 Escitalopram 2 Mirtazapine 1 Citalopram 1 Bupropion 1 Clomipramine 1 Milnacipran 1 Response was defined as equal to or morethan 50% reduction of MADRS scores and remission asMADRS scores less than 12 points after four weeks oftreatment. Wash-out 5-7 days Notes: BDI-Beck self-rating scale for depression; CGI-clinical global impression; MADRS-Montgomery & Asberg depression rating scale; EEG-electroencephalography 1st week treatment MADRS, BDI, CGI, EEG II 5 responded (4 achievedremission ) Screening MADRS, BDI, CGI, N=17 (8M;9F) MADRS>25 Stage I criteria for resistant depression (Thase and Rush, 1997) Distribution of EEG electrodes:
Results 10/12 non-respondersshowedincrease Positivepredictive value (PPV) was0.71 Negative predictive value(NPV) was 1.0 Allrespondersshoweddecrease Bareš M, Brunovský M, Kopeček M, Novák T, Stopková P, Kožený J, Höschl C. Journal of PsychiatricResearch 2006
Results Othello Hamlet
Response was defined as equal to or morethan 50% reduction of MADRS scores after four weeks oftreatment. N=26 (8M;18F) MADRS>20 Stage I criteria for resistant depression (Thase and Rush, 1997)
Conclusions • QEEG cordance integrates absolute and relative powerinformation. • Change of QEEG average cordance from 3 frontal electrodes (Fp1, Fp2 and Fz) in theta band (4-8Hz) predicts therapeutic response to antidepressants after one week of AD administration • PPV≈0.7; NPV≈0.9; SENS 90-100%; SPEC 60-90% Predictor: QEEG Cordance Anyinterventionshortening period of disabilitysaves a lot of suffering and expenses.
Conclusions • QEEG cordancemight reflect activity changes in CG25 Predictor: QEEG Cordance + 0 -
Predictor: QEEG Cordance Conclusions • QEEG cordancemight reflect activity changes in CG25 + 0 -
Comparison between AUCs obtained for MADRS reduction and cordance change at week 1 in the prediction of treatment response AUC=0.82 AUC = 0.65 Pairwise comparison of ROC curves, z-statistic=2.55, p=0.01 Bareš et al. 2011
Comparison of predictivepowerof cordance change in rTMS and VNF Tx • AUC rTMS=0,75 (N=25) • AUC VNF=0,89 (N=25) p=0,27 NS rTMS VNF MADRS026(24-30) 25(24-30) NS MADRS2818(12-25) 18(10-24) NS Bareš et al., Clin EEG Neurosci (in press)
Psychiatric Centre Prague & Charles University, 3rd MedicalFaculty, Prague Thanks to the team of Jiří Kožený Martin Brunovský Martin Bareš Milan Kopeček Tomáš Novák Peter Šóš Vladimír Krajča Pavla Stopková