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Cyril Höschl www.hoschl. cz National Institute of Mental Health Prague Psychiatric Centre & Charles University, 3 rd Medical Faculty, Prague response to antidepressant modalities 6th International Congress on Psychopharmacology, Antalya 17 April 2014 NI M NATIONAL INSTITUTE OF MENTAL HEALTH

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QEEG-based prediction of response to antidepressant modalities. Cyril Höschl. www.hoschl.cz. National Institute of Mental Health Prague Psychiatric Centre & Charles University, 3 rd Medical Faculty , Prague. M. N I H. NATIONAL INSTITUTE OF MENTAL HEALTH. - PowerPoint PPT Presentation

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Page 1: Cyril Höschl

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

Page 2: Cyril Höschl

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.

Page 3: Cyril Höschl

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

Page 4: Cyril Höschl

δ (0,5-4Hz)σ (4-8 Hz)α (8-12 Hz)β (12-30Hz)

Page 5: Cyril Höschl

lesionhypoperfusion

↓absolute spectrum

relative spectrum

Page 6: Cyril Höschl

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

Page 7: Cyril Höschl
Page 8: Cyril Höschl

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

Page 9: Cyril Höschl

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

Page 10: Cyril Höschl

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

Page 11: Cyril Höschl

Results

Depression

Response Non-response

Cordance

Positivedecrease

5 2 → PPV=0.71

Negativeincrease

0 10 → NPV=1.00

Sensitivity100%

Specificity>83%

Page 12: Cyril Höschl

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.

Page 13: Cyril Höschl
Page 14: Cyril Höschl

Results

Depression

Response Non-response

Cordance

Positivedecrease

11 5 → PPV=0.69

Negativeincrease

1 8 → NPV=0.89

Sensitivity92%

Specificity>62%

Page 15: Cyril Höschl

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

Page 16: Cyril Höschl

0

+

-

Predictor: QEEG Cordance

•QEEG cordance might reflect activity changes in CG25

Conclusions

Page 17: Cyril Höschl

0

+

-

Predictor: QEEG Cordance

•QEEG cordance might reflect activity changes in CG25

Conclusions

Page 18: Cyril Höschl

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

Page 19: Cyril Höschl

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

Page 20: Cyril Höschl

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