an introduction to vns therapy in depression...an introduction to vns therapy in depression...
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TRDFullPPT17E2
An introduction to VNS THERAPY in depression
TRDFullPPT17E2
TRDFullPPT17E2
The Reality of Difficult to Treat Depression
High healthcare burden (1)
Increased suicide risk (3)
High health care utilisation (4)
Resistant depression accounts for 40% of annual depression treatment costs (2)
Current antidepressant therapies have limited effectiveness for patients with true resistant depression (3)
High Healthcare
burden
Current Therapy Limited
2
TRDFullPPT17E2
Relapse during psychopharmaceutical
therapy (1)
57%
Relapse after remission with ECT
within 6 months (2)
65%
Challenges of Difficult to Treat Depression
3
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Treatment of Difficult to Treat Depression
Reduce relapse and recurrence
Restore psychosocial function
Reduce risk of suicide
Optimise safety and side-effects
Optimise compliance
Improve Quality of Life(2)
Aim for long-term disease management
4
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What is VNS Therapy?
5
TRDFullPPT17E2 Antidepressant Mechanisms of VNS Summary
Short- and medium-term antidepressant effects of VNS
Long-term antidepressant effects of VNS
Attenuates interhemispheric imbalance associated with depression (right side inhibition & left side activation) (3)
Emerging antidepressant effects of VNS
Increases availability of serotonin and noradrenalin (1,2)
May reduce inflammation contributing to depression (4)
6
TRDFullPPT17E2 D-23 VNS Registry – US (2006 – 2015)
History and Study Design
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Objective Follow clinical course and outcome for TRD patients treated with and without adjunctive VNS Therapy (requirement of FDA for approval)
Observational study of unipolar or bipolar depression.
500 VNS + TAU ‘v’ 300 TAU
Treated at same medical centres
Patient Choice
5 Years
D-21
Subjects permitted to choose between VNS and TAU at screening
Pts from completed D-21 dose finding study could enter TRD registry
All received VNS and entered the VNS Group
TRDFullPPT17E2 D-23 VNS Registry - US Patient Demographics – Safety Population
*** ***
***
Characteristic VNS Therapy + TAU D23 + D21 TAU
Patient Number 494 301
Female % 70.9 70.1
% Caucasian 96.8 91.0
Mean Age at BL (yrs) (SD) 48.9 (10.1) 49.9 (11.1)
Mean Age at onset of Depression (SD) 20.9 (11.8) 21.1 (11.4)
Mean Age at dx of Depression (SD) 28.9 (10.8) 29.5 (11.9)
# MDE’s (mean, SD) 14.9 (24.1) 12.0 (23.9)
# Failed treatments (mean, SD)1 8.2 (3.30) 7.3 (2.92)
#Suicide attempts (mean, SD) 1.8 (4.0) 1.2 (2.4)
Prior ECT (%) 57% 40%
Psychiatric hospitalisations within 5 years prior to enrollment 3.0 (4.6) 1.9 (4.7)
Baseline MADRS Score 33.1 (7.0) 29.4 (6.9)
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TRDFullPPT17E2 D-23 VNS Registry - US Patient Demographics
Diagnosis VNS Therapy + TAU D23 + D21 TAU
Recurrent MDD (moderate) 12.8% 22.9%
Recurretn MDD (severe) 45.5% 31.6%
Single MDD (moderate) 3.2% 10.0%
Single MDD (Severe) 11.3% 12.0%
Bipolar I Depressed (Moderate) 5.1% 7.0%
Bipolar I Depressed (Severe) 12.6% 4.0%
Bipolar II Depressed 9.5% 12.6%
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TRDFullPPT17E2 C
um
ula
tive
Per
cen
t R
esp
onse
Cumulative First-Time Responders by Visit Month by Treatment Group: MADRS – VNS + TAU vs TAU (ITT Population)
0
10
20
30
40
50
3 mo 6 mo 9 mo 12 mo 18 mo 24 mo 30 mo 36 mo 42 mo 48 mo 54 mo 60 mo
20.3 22.3
8
31.8 34.4 16
38.8 42.8 20.7
45.2 50.4 25
49.4 53.3 27.2
53.9 56.8 29
56.9 59.5 31.9
61.4 63.6 33.3
61.7 64.4 35.1
63.2 66.2 37.3
63.8 67.2 38.7
63.8 67.8 40.9
Follow-up Visit Month
VNS D23 VNS D23+D21
TAU
Database lock as of 5 May, 2015
Cyberonics Inc.
Protocol: D23/TRD Registry
VNS + TAU
TAU
D-23 VNS Registry - US MADRS Response
Cumulative Response Rate at 5 years
Primary Endpoint – First Time Response Rate based on MADRS
67.6% for VNS Therapy vs. 40.9% for TAU (P<0.001)
60
70
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Cumulative First-Time Remitters by Visit Month by Treatment Group: MADRS – VNS + TAU vs TAU (ITT Population)
0
10
20
30
40
50
3 mo 6 mo 9 mo 12 mo 18 mo 24 mo 30 mo 36 mo 42 mo 48 mo 54 mo 60 mo
7.3 8
2.5
14.3 15.8 6.5
18.2 20.7 9.4
22.1 26
12.7
25.1 28
14.5
28.7 30.5 16.3
31.7 33.6 18.1
34.4 36.7 19.9
36.5 38.7 21.3
37.7 40.9 22
38.9 41.9 22.7
40.7 43.3 25.6
VNS D23 VNS D23+D21
TAU
Database lock as of 5 May, 2015
Cyberonics Inc.
Protocol: D23/TRD Registry
VNS + TAU
TAU
D-23 VNS Registry - US MADRS Remission
Cumulative Remission Rate at 5 years
43.3% for VNS Therapy D-23 + D-21 vs. 25.7% for TAU (P<0.001)
Secondary Endpoint – First Time Remission Rate based on MADRS (≤9)
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Cu
mu
lati
ve P
erce
nt
Rem
issi
on
Follow-up Visit Month
TRDFullPPT17E2 C
um
ula
tive
Per
cen
t R
esp
ond
ers
Cumulative First-Time Response by Visit Month by Treatment Group: MADRS – VNS D-23 + D-21 vs. TAU (ITT Population) based on whether
subjects had responded or not to ECT
0
10
20
30
50
70
3 mo 6 mo 9 mo 12 mo 18 mo 24 mo 30 mo 36 mo 42 mo 48 mo 54 mo 60 mo
15.4 4.5 23.8 15.6
24.6 13.6 35.4 23.9
27.7 18.1 43.1 31.2
35.4 24.9 49.7 37.6
35.4 29.4 51.9 42.2
40 29.4 55.8 46.8
43.1 29.4 59.7 50.5
47.7 29.4 66.3 55.1
49.2 31.7 68
59.7
49.2 34
69.1 59.7
53.8 34
70.2 59.7
56.9 34
71.3 59.7
Follow-up Visit Month
TAU ECT Resp TAU ECT No resp
VNS ECT Resp VNS ECT No Resp
VNS ECT Resp
VNS ECT No Resp
TAU ECT No Resp
D-23 VNS Registry - US MADRS – Response by History of Prior Response to ECT
Cumulative Response Rate Based on ECT Response (yes/no)
Exploratory Analysis – Response based on MADRS
VNS (ECT resp) (n=129) 71.3%
TAU (ECT resp) (n=37) 56.9%
VNS (ECT nonresp) (n=65) 59.7%
TAU (ECT nonresp) (n=15) 34.0%
TAU ECT Resp
40
60
13
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VNS for Depression in England – Current Spread of Centres
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Conclusions
VNS Therapy® is an effective treatment for Difficult to Treat Depression
There is a significant cumulative and sustained effect of treat-ment over time
VNS Therapy has a favorable safety profile
Risk of suicide is decreased by adding VNS Therapy
15
There is evidence of improved QOL and restored psychosocial functioning
Compliance is guaranteed
With limited treatment options and the morbidity/mortality associated with the disease, VNS Therapy® is needed in a psychiatrists’ therapeutic armamentarium to treat and manage these difficult to treat patients
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