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Cyril Höschl www.hoschl.cz
National Institute of Mental HealthPrague Psychiatric Centre
& Charles University, 3rd Medical Faculty, Prague
QEEG-based prediction of response to antidepressant
modalities
6th International Congress on Psychopharmacology, Antalya 17 April 2014
NI HM
NATIONAL INSTITUTE OF MENTAL HEALTH
Treatment of Depression•Only one-third of patients being treated with SSRIs for depression achieve remission on the first drug tried (Verqouwen AC et al. 2007; Bondolfi G et al. 2006; Trivedi et 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 et al. 2008; Ruhé HG et al.2006)
•Clinical improvement generally requires 4-12 weeks
• Over 30% of patients prescribed antidepressants discontinue treatment before 30 days of therapy (
(Sheehan et al.2004)
All of this leads to prolonged suffering of depressed patients and to enormous expenses for society
All of this leads to prolonged suffering of depressed patients and to enormous expenses for society
Every day in depression represents huge individual and social burden.
Every day in depression represents huge individual and social burden.Any intervention
shortening period of disability saves a lot of suffering and expenses.
Any intervention shortening period of disability saves a lot of suffering and expenses.
Predictor: QEEG Cordance
•Calculated from quantitative EEG power values; integrates absolute and relative power information
•Associated with regional cerebral perfusion
•Provides information interpretable in the context of PET and SPECT neuroimaging studies of depression
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)
lesionhypoperfusion
↓absolute spectrum
relative spectrum
1. 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
4. Cordance calculation:
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).
www.cordance.com
Design of our studyBaseline MADRS, BDI, CGI, EEG IOnset of treatment
Screening MADRS, BDI, CGI,
Wash-out 5-7 days
1st week treatment MADRS, BDI, CGI, EEG II
4 weeks treatment MADRS, BDI, CGI, EEG III
Notes: BDI-Beck self-rating scale for depression; CGI-clinical global impression; MADRS-Montgomery & Asberg depression rating scale; EEG-electroencephalography
Distribution of EEG electrodes:
N=17 (8M;9F)MADRS>25Stage I criteriafor resistant depression (Thase and Rush, 1997)
Response was defined as equal to or more than 50% reduction of MADRS scores and remission as MADRS scores less than 12 points after four weeks of treatment.
Response was defined as equal to or more than 50% reduction of MADRS scores and remission as MADRS scores less than 12 points after four weeks of treatment.
5 responded (4 achieved remission )
5 responded (4 achieved remission )
MedicationResponders:Venlafaxine 2Escitalopram 1Clomipramine 1Bupropion 1
Non-responders:Venlafaxine 5Escitalopram 2Mirtazapine 1Citalopram 1Bupropion 1Clomipramine 1Milnacipran 1
Bareš M, Brunovský M, Kopeček M, Novák T, Stopková P, Kožený J, Höschl C. Journal of Psychiatric Research 2006
Results
Positive predictive value (PPV) was 0.71 Negative predictive value (NPV) was 1.0
All responders showed decrease
10/12 non-responders showed increase
Results
Condition
Positive Negative
Test outcome
Positive True positiveFalse positive(Type I error;
p- value)
→ Positive predictive value
Negative False Negative(Type II error)
True Negative→ Negative
predictive value
↓sensitivity
↓specificityHamlet
Othello
Results
Depression
Response Non-response
Cordance
Positivedecrease
5 2 → PPV=0.71
Negativeincrease
0 10 → NPV=1.00
Sensitivity100%
Specificity>83%
N=26 (8M;18F)MADRS>20Stage I criteriafor resistant depression (Thase and Rush, 1997)
Response was defined as equal to or more than 50% reduction of MADRS scores after four weeks of treatment.
Results
Depression
Response Non-response
Cordance
Positivedecrease
11 5 → PPV=0.69
Negativeincrease
1 8 → NPV=0.89
Sensitivity92%
Specificity>62%
Predictor: QEEG Cordance
•QEEG cordance integrates absolute and relative power information.
•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%
Any intervention shortening period of disability saves a lot of suffering and expenses.
Any intervention shortening period of disability saves a lot of suffering and expenses.
Conclusions
0
+
-
Predictor: QEEG Cordance
•QEEG cordance might reflect activity changes in CG25
Conclusions
0
+
-
Predictor: QEEG Cordance
•QEEG cordance might reflect activity changes in CG25
Conclusions
Comparison between AUCs obtained for MADRS reduction and cordance change at week 1
in the prediction of treatment response
0 10 20 30 40 50 60 70 80 90 100
0
10
20
30
40
50
60
70
80
90
100
100-Specificity
Sen
sitiv
ity
%w1 MADRSCO2-CO1
AUC=0.82
AUC = 0.65
Pairwise comparison of ROC curves, z-statistic=2.55, p=0.01
Bareš et al. 2011
Comparison of predictive power of cordance change in rTMS and VNF Tx
• AUC rTMS=0,75 (N=25)• AUC VNF=0,89 (N=25)
p=0,27MADRS0 26(24-30) 25(24-30) NSMADRS28 18(12-25) 18(10-24) NS
rTMS VNF
Bareš et al., Clin EEG Neurosci (in press)
NS
Martin Brunovský
Psychiatric Centre Prague & Charles University, 3rd Medical Faculty, Prague
Milan KopečekMartin Bareš
Jiří Kožený
Pavla Stopková
Tomáš Novák
Thanks to the team of
Peter ŠóšVladimír Krajča