דיכאון בגיל מבוגר היא תופעה נפוצה ולמרות זאת אינה זוכה לתשומת לב ראויה.

1. Cipralex
Late life depression
The good life has no age
1

2. A broad selection of slides
• The set contains slides that will be of interest to different
audiences: nurses, pharmacists, general practitioners,
geriatricians and psychiatrists
• The current order of slides represents only one example
of a presentation flow – there are many possibilities. The
set is designed to allow the user to pick and choose
depending on the audience, the theme of the
presentation as well as the local market situation
• Some slides are hidden as they may be of secondary
importance
2

3. Content
•
•
•
•
•
•
•
•
•
•
Introduction
Epidemiology
What is different about late life depression
Population ageing
Screening and diagnostic tools
Treatment
Cipralex in late life depression
Drug interactions
Health economics
Conclusion
3

4. Introduction
4

5. Introduction
Depression in older people is
• often missed
• under recognised
• untreated
5

6. Introduction
• Although many see the development depressive
symptoms as being inevitable … depression is
actually not a normal part of ageing
• Depression is a serious medical condition
• Untreated depression can delay recovery or
worsen the outcome of other medical illnesses
via increased morbidity or mortality
6

7. “It is not enough to
add years to one’s
life…one must also
add life to those
years”
7

8. Epidemiology
8

9. Prevalence of depression in late life
40
Major depression
Minor depression
35
Percentage prevalence
25–40%
30
25
15–30%
20
20%
15
15%
10
5
10%
5%
0
Community elders1,2
Primary care3,4
Nursing homes2
1. Gallo & Lebowitz. Psychiatric Services 1999; 50: 1158–1166; 2. Djernes. Acta Psychiatr Scand 2006; 113: 372–387;
3. Friedman et al. Am J Geriatr Psychiatry 2007; 15: 28–41; 4. Zung et al. J Fam Pract 1993; 37 (4): 337–344
9

10. Under treatment of late life depression
Only a minor fraction of the prevalence are identified
and treated
• WHO estimate that only app. 50 % of depressed patients is
diagnosed with a psychological illness by their treating
physician
• Recognition of depression in the late life population may be
even more difficult
• Rates for under-treatment appears to be more significant in
late life population
Wittchen et al. Int Clin Psychopharmacol 2001 16:121-135 Crystal et al J Am Geriatr Soc 51:1718–1728, 2003.
10

11. Broader goals of depression
treatment should not be forgotten
Raise disease
awareness
Reduce
stigma
Encourage
help-seeking
behaviour
11

12. What is different
about late life
depression?
12

13. Myths about depression:
more common in elderly individuals?
•
Not a real medical illness
•
Cannot be treated
•
A sign of weakness
•
Will go away by itself
•
A normal part of getting older
•
Only affects women
13

14. The extensive impact of depression
• Is a major risk factor for suicide
• Amplifies physical symptoms, increases mortality
• Often coexists with and worsens the outcome other
medical conditions
• Decreases adherence to prescribed treatments
• Impairs daily functioning
• Often requires personalized long-term care
• Is costly for the individual and society as a whole
Moussavi S et al. 2007. Lancet; 370: 851-858. Prince M et al. 2007 Lancet; 370: 859-877. DiMatteo MR et al. Arch Intern Med. 2000; 160 (14):2101-2107.
14
Ciechanowski et al. 2000 Arch Intern Med 2000 160(21):3278-3285.

15. Factors affecting prognosis and
pharmacotherapy
•
•
•
•
•
•
Altered pharmacokinetics and pharmacodynamics
End-organ physiological changes
Coexisting medical conditions
Cognitive decline
Polypharmacy
Social isolation
15

16. Specific risk factors for depression in late life
•
•
•
•
•
Bereavement
Sleep disturbances
Disability
Prior depression
Female gender
• Management of the modifiable risks and application of
relevant therapy may reduce depression symptoms
• Individuals with these characteristics should be
screened for depression
Cole & Dendukuri (Am J Psychiatry 2003; 160:1147–1156) 2003
16

17. What is the added effect of depression on the
well-being of a patient who also suffers from a
chronic medical condition?
17

18. Poorer mean health scores with comorbidity
Moussavi S et al. 2007. The Lancet; 370: 851-858.
18

19. Quality of life in older adults with and without
depressive symptoms and chronic diseases
HRQOL scales and summary scores, SF-36
100
GDS-15 ≤5 (n=795)
90
GDS-15 >6 (n=290)
80
Mean scores
70
60
50
40
30
20
10
0
Physical Physical
functioning role
Bodily
pain
General
health
Vitality
Social Emotional Mental Physical
Mental
functioning role
health component component
summary
summary
Without depressive symptoms and without chronic diseases
With depressive symptoms and without chronic diseases
Without depressive symptoms and with ≥2 chronic diseases
With depressive symptoms and with ≥2 chronic diseases
HRQOL: Health related quality of life GDS: Geriatric Depression Scale
19
Gallegos-Carrillo et al. J Psychosom Res 2009; 66: 127–135

20. Depression is often associated
with anxiety in the elderly
One or more anxiety
disorders during lifetime
50
Two or more anxiety
disorders during lifetime
45
40
Percentage
35
30
25
20
15
10
5
0
Primary care
patients with MDD
(n=36)
Psychiatric setting
outpatients with MDD
(n=40)
Psychiatric setting
inpatients with MDD
(n=40)
Lenze et al. Am J Psychiatry 2000; 157: 722–72820

21. Fatality from suicide increases with age
60
Male
Rate (per 100000)
50
40
30
Female
20
10
0
5–14
15–24
25–34
35–44
45–54
Age group (years)
55–64
65–74
75+
WHO, 200021

22. Suicide and suicidal ideation in late-life
depression
• Depression in later life is the major risk factor for suicide1
• Treatment-resistant late life depression increases the risk
for early mortality, including suicide2
• Suicidal ideation is common in elderly depressed patients
being treated in primary care3
• Care providers should monitor suicidal ideation through
the course of depression treatment3
1
Hawton et al. Int J Geriatric Psychiatry 2006; 21(6): 572–581
2 Lenze et al. Dialogues Clin Neurosci 2008; 10(4): 419–430
3 Vannoy et al. Am J Geriatr Psychiatry 2007; 15(12): 1024–1033
22

23. Population ageing
23

24. The demographic transition
The increasing proportion of elderly will impact upon the burden of diseases
Population pyramids
60+
0–59
1950
Age
80
Male
2000
2050
Female
60
40
20
10
5
0
5
Percentage
10
10
5
0
5
Percentage
10
10
5
0
5
Percentage
10
The UN estimates that the number of 80–89-year olds will increase 5-fold from 2000–2050
24

25. Populations are ageing across the world
Percent of the population aged ≥80 years
2002
2025
5.0
4.5
Percentage
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
World total
Africa
Asia
Europe
Latin
Northern
America
America
& Caribbean
Oceania
Adapted from US Census Bureau: http://www.census.gov/ipc/prod/wp02/tabA-07a.xls; http://www.census.gov/ipc/prod/wp02/tabA-07b.xls 25

26. The average age is increasing
Millions
Evolution of the population of Europe by broad age groups
475
450
425
400
375
350
325
300
275
250
225
200
175
150
125
100
75
50
25
0
0–14
15–59
60+
26
World Population Prospects: The 2006 Revision United Nations Population Division

27. Life expectancy is increasing
Past and projected female and male life expectancy at birth (US, 1900–2050)
Female
100
Male
Projection
Years of life
90
84.3
80
79.7
70
60
50
40
1900* 1910* 1920* 1930* 1940 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050
*Death registration area only. The death registration area increased from
10 states and the District of Columbia in 1900 to the entire US in 1933
27
US Department of Commerce, Bureau of the Census

28. Life expectancy – 65 does not necessarily
mean that life is coming to an end …
Number of years more to live when you have reached a given age
e.g., if you are a 65 year-old female, you can expect to live for an additional 20 years
Current age
Males
Females
At birth
75.2
80.4
55 years
24.7
28.3
65 years
17.1
20.0
75 years
10.7
12.8
85 years
6.1
7.2
28
National Vital Statistics Reports, 2007 (Volume 56; Number 9)

29. Screening and
diagnostic tools
29

30. Many clinical tools are used in
late life depression
•
Geriatric Depression Scale (GDS)
•
Cornell Scale for Depression in Dementia
•
Center for Epidemiologic Studies of Depression Scale (CES-D)
•
Patient Health Questionnaire 9
•
Geriatric Mental State Schedule (research)
•
Hamilton Depression Rating Scale (severity)
•
Montgomery-Asberg Depression Rating Scale (severity)
30

31. Screening is simple with short scales
•
•
Recognition of depression in the late life population can be facilitated
by simple and quick tools for identification and management of
individual patients
One single question may be enough for initial screening1
“Do you think you suffer from depression?”
•
•
•
Geriatric Depression Scale 15 items (GDS15) can detect and indicate
illness severity2
GDS15 is acceptable in primary care due to its shortness and high
probability of identifying depressed patients2
More thorough tools will be necessary to assess severity of specific
symptoms and to follow-up over time3
1. Aylon et al. Int J Geriatr Psychiatry 2009 (e-pub ahead of print) 2. Mitchell et al. J Affect Disord 2009 (e-pub ahead of print)
31
3. Almeida et al. Int J Geriat Psychiatry 14, 858-865 (1999)

32. Geriatric Depression Scale 15 items
Choose the best answer for how you have felt over the past week
1. Are you basically satisfied with your life?
Yes
No
2. Have you dropped many of your activities and interests?
Yes
No
4. Do you often get bored?

Yes 
Yes 
5. Are you in good spirits most of the time?
Yes
No
6. Are you afraid that something bad is going to happen to you?
Yes
7. Do you feel happy most of the time?
Yes
8. Do you often feel helpless?
Yes
9. Do you prefer to stay at home, rather than going out and doing new things?
Yes

3. Do you feel that your life is empty?
No
No


No
No


No
No
10. Do you feel you have more problems with memory than most?

Yes 
11. Do you think it is wonderful to be alive now?
Yes
No
12. Do you feel pretty worthless the way you are now?
Yes
13. Do you feel full of energy?
Yes
14. Do you feel that your situation is hopeless?
Yes
15. Do you think that most people are better off than you are?
Total score
• Although differing
sensitivities and
specificities have been
obtained across studies,
for clinical purposes a
score >5 points is
suggestive of depression
and should warrant a
follow-up interview
• Scores >10 are almost
always depression
No

• Answers ticked indicate
depression, and each
score one point

No
No

Yes 
No
No
15

Sheikh & Yesavage (p165–173)
In: Clinical gerontology: a guide to
assessment and intervention.
(Ed. Brink TL). 1986 Haworth, New York
Mitchell et al. J Affect Disord 2009
(e-pub ahead of print)
32

33. Treatment
33

34. Treatment phases
Phase 1: Getting started
At the start of treatment not all
patients feel a change and side
effects are more likely
Phase 2: To the top
Most patients begin feel more
optimistic and have more
energy. Functionality tends to
improve
Phase 3: Keep going
Persistence with treatment is
important to achieving
remission. Premature
discontinuation, despite feeling
better can “undo” the progress
already made
Phase 4: Back to the good life
Better disease awareness and
optimized thought patterns can
help to prevent reoccurrence
34

35. What key factors influence our
selection of antidepressants
for the late life population ?
35

36. Key factors influencing selection
• Overall efficacy
• Safety and tolerability
• Potential to interact
• Control of co-morbid anxiety
• Healthcare costs
36

37. Antidepressant DDD/1000 population/day
Antidepressant usage increases with age
120
2003
2004
100
2005
2006
80
60
40
20
0
0–4
5–14
15–24
25–34
35–44
45–54
55–64
65–74
75–84
≥85
Age (years)
Smith & Tett. Drugs Aging 2009; 26 (2): 113–12237

38. An inappropriate imbalance?
100
SSRIs
TCAs
80
SNRIs
70
Percentage
90
Other
60
50
40
30
20
10
0
≥65
35–44
Age groups (years)
SSRIs = Fluvoxamine, fluoxetine, escitalopram, paroxetine, citalopram and sertraline
TCAs = Dothiepin and amitriptyline; SNRIs = Venlafaxine; Other = Mirtazapine
Smith & Tett. Drugs Aging 2009; 26 (2): 113–12238

39. Cipralex
in late life depression
39

40. Escitalopram prevents relapse in
older patients with major
depressive disorder
Gorwood et al.
Am J Geriatr Psychiatry 2007; 15: 581–593
40

41. Objectives and key findings
Objectives
•
To assess the efficacy and tolerability of escitalopram in the
prevention of relapse of major depressive disorder (MDD) in older
patients who had responded to acute treatment with escitalopram
Key findings
•
•
Escitalopram was effective in preventing relapse of MDD – elderly
patients who achieved remission after 12 weeks of open-label
treatment with escitalopram were four times more likely to remain in
remission over a 6-month period, if taking escitalopram than if taking
placebo
Escitalopram was well tolerated as continuation treatment
Gorwood et al. Am J Geriatr Psychiatry 2007; 15: 581–593
41

42. Study design
Period I
Acute treatment
(12-week, open label)
Period II
Continuation treatment
(24 weeks, double-blind)
n=152
Escitalopram fixed dose (10 or 20 mg)
Escitalopram 10 or 20 mg
TAPER
Relapse
MADRS 22 or lack of efficacy
Flexible dose for the first 6-week
MADRS 22
n=405
TAPER
Placebo
n=153
Relapse
MADRS 22 or lack of efficacy
Run in
W-1 W0
Remitters only
MADRS 12
W12 W13
W36 W37
Gorwood et al. Am J Geriatr Psychiatry 2007; 15: 581–593
42

43. Study overview
Patients
• Outpatients, ≥65 years, with moderate or severe MDD
(MADRS total score ≥22; MMSE total score ≥24)
Endpoints
• Primary
•
The time to relapse (MADRS ≥22, or lack of efficacy as judged by
investigator)
from the start of the double-blind period
Demographics
Open-label
Double-blind period
Escitalopram
Escitalopram
Placebo
Patients, n
405
152
153
Age, years, mean
73
73
72
313 (77)
119 (78)
121 (79)
Gender, women, n (%)
MADRS=Montgomery-Åsberg Depression Rating Scale; MMSE=Mini-Mental State Examination
CGI-I=Clinical Global Impression – Improvement; CGI-S=Clinical Global Impression – Severity
Gorwood et al.
Am J Geriatr Psychiatry 2007; 15: 581–593
43

44. Kaplan-Meier analysis of relapse over
24 weeks
Escitalopram
Kaplan-Meier estimate
1.0
Placebo
0.9
p<0.001 vs placebo (log-rank test)
Hazard ratio for time to relapse: 4.44
Number needed to treat: 5
0.8
0.7
0.6
12
16
20
24
28
32
36
40
Treatm ent w eek
•
•
Open-label period: 79.5% of patients achieved remission after 12 weeks of
escitalopram treatment
Double-blind period: 88.2% of escitalopram-treated patients remained in
remission after 24 weeks, compared with 59.5% of placebo-treated patients
Gorwood et al. Am J Geriatr Psychiatry 2007; 15: 581–593
44

45. Secondary outcome measures
Response rates (≥50% reduction in MADRS score; CGI-I ≤2)
100
***
***
***
Response rate (%)
90
***
***
MADRS escitalopram (n=152)
80
MADRS placebo (n=153)
70
CGI-I escitalopram (n=152)
60
CGI-I placebo (n=153)
50
12
•
•
•
13
14
16
20
24
Study week
28
32
36
Response rates were statistically significantly greater with escitalopram than placebo from Week 20
to study end
MADRS total score was stable over long-term treatment; placebo group saw slight deterioration
Statistically significant differences in all secondary measures in favour of escitalopram vs placebo
Intent-to-treat population; Last observation carried forward;
***p<0.001 for both MADRS and CGI-I response definitions
Gorwood et al. Am J Geriatr Psychiatry 2007; 15: 581–593
45

46. Tolerability
Open-label period
•
•
•
72 patients withdrew from study (18%)
46 patients withdrew as a result of AEs – including nausea (n=14),
anxiety (n=7), depression (n=5)
Majority of AEs were mild to moderate
Double-blind period
•
•
•
Excluding patients who withdrew due to relapse, the overall
withdrawal rate for both treatment groups was comparable
– escitalopram, n=10, 6.6%; placebo, n=13, 8.5%
Incidence of AEs similar in both groups (40.1% escitalopram;
41.2% placebo); the majority of AEs were mild to moderate
Withdrawal due to AEs – escitalopram 1.3%; placebo 3.9%
Gorwood et al. Am J Geriatr Psychiatry 2007; 15: 581–593 46

47. Tolerability improves over time
Open-label escitalopram (n=405)
60
Taper escitalopram (n=152)
Percentage of patients
50
Taper placebo (n=153) *
40
Week 2 to completion
escitalopram (n=130)
30
Week 2 to completion placebo
(n=91)
20
10
0
≥ 1 AE
Nausea
Taper = 2-week dose adjustment period following randomisation to
double-blind treatment
*Patients tapering from escitalopram to placebo
Headache
Dizziness
Diarrhoea
Gorwood et al. Am J Geriatr Psychiatry 2007; 15: 581–593
47

48. Conclusion
•
Escitalopram was four times as effective as placebo in preventing
relapse over 6 months in older patients with MDD who had achieved
remission during 12-weeks of open-label treatment with escitalopram
•
Good tolerability in a vulnerable population (the study did not exclude
patients who were 75 years and over, had late-onset depression or
recurrent depressive episodes)
•
The study is a good representation of treatment of patients in the
„real-life‟ setting
Escitalopram is significantly superior to placebo
in preventing relapse of MDD in older patients, and is
well tolerated in acute and continuation treatment
Gorwood et al. Am J Geriatr Psychiatry 2007; 15: 581–593
48

49. Escitalopram in the long-term
treatment of Major Depressive
Disorder in elderly patients
Kasper et al.
Neuropsychobiology 2006; 54: 152–159
49

50. Objectives and key findings
Objectives
•
•
Assess the safety and tolerability of escitalopram (10 or 20 mg/day)
in the long-term treatment of elderly outpatients from MDD
Evaluation of the long-term response of elderly outpatients with MDD
to open-label treatment with escitalopram
Key findings
•
•
Escitalopram has a favourable tolerability profile in elderly
populations with MDD
Escitalopram produced continued improvement in depressive
symptom scores and remission/response rates
Kasper et al. Neuropsychobiology 2006; 54: 152–159
50

51. Study overview
Design
• Outpatients with MDD, ≥65 years (MADRS ≥22 and ≤40; MMSE ≥22)
• 52-week open-label extension study in which patients were treated with
escitalopram 10 or 20 mg/day, following an 8-week double-blind lead-in study
Assessments – extension study
• Adverse events, clinical laboratory tests and physical examination
• Changes in MADRS and CGI-S scores
• Response rates (≥50% reduction in lead-in study baseline MADRS score)
• Remission rates (MADRS ≤12)
Demographics – extension study
Patients, n
Age, years, mean (SD)
Gender, women, %
MMSE=Mini-Mental State Examination;
MADRS=Montgomery-Åsberg Depression Rating Scale
225
74 (6)
82%
Kasper et al. Neuropsychobiology 2006; 54: 152–159
51

52. Tolerability – extension study
Completers, n (%)
171 (76.0)
Discontinuation, n (%)
54 (24.0)
Due to:
AEs
20 (8.9)
Lack of efficacy
4 (1.8)
Non-compliance with study product
1 (0.4)
Protocol violation
4 (1.8)
Withdrawal of consent
15 (6.7)
Lost to follow-up
5 (2.2)
Administrative/other reasons
5 (2.2)
Kasper et al. Neuropsychobiology 2006; 54: 152–159
52

53. Tolerability – extension study
AEs reported in ≥5% of patients
Patients, n (%)
Patients with AEs
175 (77.8)
Accidental injury
29 (12.9)
Rhinitis
19 (8.4)
Weight increase
19 (8.4)
Arthralgia
18 (8.0)
Coughing
18 (8.0)
Diarrhoea
16 (7.1)
Headache
16 (7.1)
Nausea
16 (7.1)
Bronchitis
15 (6.7)
Hypertension
15 (6.7)
Back pain
13 (5.8)
Dyspepsia
13 (5.8)
Insomnia
13 (5.8)
Weight decrease
12 (5.3)
Kasper et al. Neuropsychobiology 2006; 54: 152–159
53

54. Efficacy assessments during extension study –
MADRS and CGI-S scores
Mean MADRS total score
16
MADRS scores, mean (LOCF):
Start extension study: 13.4
End extension study: 8.5
14
12
10
LOCF
8
6
4
2
0
0
4
8
12
16
20
24
28
32
36
40
44
48
52
Treatment week of extension study (OC)
CGI-S scores
• Start extension study: 2.6; End extension study: 1.6 (OC)
• This decrease confirms the clinical relevance of the efficacy results
LOCF=Last observation carried forward
Kasper et al. Neuropsychobiology 2006; 54: 152–159
54

55. Response and remission – extension study
Response
• Start of extension study: 57% of patients were responders
• End of extension study: 77% of patients were responders (LOCF)
Remission
• Start of extension study: 48% of patients were remitters
• End of extension study: 72% of patients were remitters (LOCF)
Importance of long-term treatment emphasised
• Of the 116 non-remitters at extension study entry, 50% achieved
remission by last assessment
• Of the 97 non-responders at extension study entry, 46% achieved
remission by last assessment
Response = ≥50% reduction in lead-in study baseline MADRS score
Remission = MADRS ≤12
Kasper et al. Neuropsychobiology 2006; 54: 152–159
55

56. Patients in remission – extension study
Percentage of patients in remission
80
70
60
50
40
30
20
10
0
0
1
2
4
8
12
16
20
24
28
32
36
40
44
48
52
Visit week
Intent-to treat population; LOCF; Remission = MADRS ≤12
Kasper et al. Neuropsychobiology 2006; 54: 152–159
56

57. Conclusion
•
78% of patients reported AEs
•
•
•
•
The majority of AEs were considered unrelated to study drug
No new types of AEs were reported in extension study
The majority of AEs were mild to moderate in intensity
Continued exposure to escitalopram provided continued benefit
•
•
Mean MADRS and CGI-S scores, as well as response and remission
rates, were better at the end of the extension period
Results support the concept that even after remission is attained,
further exposure is needed to consolidate remission and allow it to
become sustained
A favourable tolerability profile, coupled with evidence of sustained
efficacy, demonstrate that escitalopram is a valid choice for the
long-term treatment of elderly patients suffering from MDD
Kasper et al. Neuropsychobiology 2006; 54: 152–159
57

58. An open-label trial in 2,050 elderly
outpatients with depression treated
with escitalopram in a naturalistic
setting in Germany
Möller et al.
Poster presented at the 26th CINP congress
Munich, Germany, 2008
58

59. Objectives and key findings
Objectives
•
To investigate the efficacy and tolerability of escitalopram in the
treatment of outpatient depression in patients aged 65 and over in a
more clinically relevant, naturalistic setting
Key findings
•
•
Length of symptoms and duration of illness are key factors
influencing treatment response and remission, which have
implications for treatment regimens
This study confirmed the efficacy and tolerability of escitalopram
treatment in elderly patients in a clinically relevant, naturalistic setting
Möller et al. Poster presented at CINP, 2008
59

60. Study overview
Design
•
8-week, naturalistic, open-label, multicentre, German trial of outpatients with depression receiving
escitalopram treatment*
•
Subgroup analysis of patients >65 years of age
Assessments
•
Short version of the MADRS scale (svMADRS) – used to assess depression severity1
•
CGI-I and CGI-S – used to assess degree of improvement
•
Response rates (≥50% decrease of svMADRS total score from baseline)
•
Remission rates (svMADRS total score ≤12)
•
Group comparisons of old (66–75 years) and old–old (>75 years) patients were conducted
Demographics
66–75 years
>75 years
Total
1,295
755
2,050
Age, years, mean (SD)
70.1 (2.8)
80.9 (4.2)
74.1 (6.2)
Gender, women, n (%)
926 (71.6)
601 (79.7)
1,527 (74.6)
Patients, n**
*Previously published: Möller et al. Pharmacopsychiatry 2007; 40: 53–57
**2,280 patients were enrolled, and 2,050 patents completed 8 weeks of treatment and were
included in the analysis; MADRS=Montgomery-Åsberg Depression Rating Scale;
CGI-I=Clinical Global Impression – Improvement; CGI-S=Clinical Global Impression – Severity
1. Möller et al Nervenarzt 2007; 78:685–690
Möller et al. Poster presented at CINP, 2008
60

61. •
Decreasing svMADRS total
score [mean (SD)]:
•
•
•
•
Baseline: 31.9 (7.9)
Week 8: 14.2 (8.5)
Statistically significant
(p<0.001) baseline adjusted
improvement in svMADRS for
patients 66–75 years (18.3)
The improvement was lower
for patients >75 years (16.8)
Adjusted mean change in svMADRS
Change in svMADRS score from baseline to
Week 8
0
66–75 years (n=1,295)
>75 years (n=755)
-5
-10
-15
-20
0
2
4
6
8
Treatment week
Möller et al. Poster presented at CINP, 2008
61

62. Response and remission
Response
• 63.9% of patients were responders
•
•
Positive factors significantly affecting response:
•
•
•
•
Significantly more patients responded in the 66–75 years group
vs the >75 years group (67.5%, n=874 versus 57.7%, n=436; p<0.001)
Having a current episode ≤1 month
Duration of illness ≤1 year
Having a diagnosis of depressive episode or recurrent depressive disorder
Negative factors significantly affecting response:
•
•
•
•
Being male
Being older than 75 years
Having a diagnosis of bipolar disorder or persistent affective disorder
Using psychotropics
Remission
• 48.6% of elderly patients achieved remission at Week 8
• Factors affecting remission were comparable to those affecting response,
with baseline severity as an additional factor influencing remission
Response = ≥50% decrease of svMADRS total score from baseline
Remission = svMADRS total score ≤12
Möller et al. Poster presented at CINP, 2008
62

63. CGI-S
•
Decreasing CGI-S values [mean (SD)]:
•
•
•
Baseline: 3.75 (0.76)
Week 8: 2.27 (1.04)
Statistically significantly greater
(p<0.001) baseline-adjusted mean
decrease for patients 66–75 years (1.54)
than for patients aged >75 years (1.40)
CGI-I
•
80.3% of patients had symptoms that
were much or very much improved
(CGI-I ≤2)
•
Response rate based on CGI-I scores
was statistically significantly greater
(p=0.011) for patients aged 66–75 years
(82.0%) than for patients aged >75 years
(77.4%)
Adjusted mean change in CGI-S
Change from baseline to Week 8 on CGI-S
and CGI-I
0
-0.2
66–75 years (n=1,295)
>75 years (n=755)
-0.4
-0.6
-0.8
-1.0
-1.2
-1.4
-1.6
-1.8
-2.0
0
2
4
6
8
Treatment week
Möller et al. Poster presented at CINP, 2008
63

64. Tolerability
•
•
The majority (>90%) of patients and physicians rated tolerability as
good or very good
No statistical differences in tolerability assessment between patients
66–75 years and patients >75 years
AEs possibly or probably related to treatment
66–75 years
>75 years
Patients with ≥1 related AE
57 (4.4%)
41 (5.4%)
Gastrointestinal disorders
28 (2.2%)
20 (2.6%)
General and administration site disorders
6 (0.5%)
3 (0.4%)
Nervous system disorders
16 (1.2%)
14 (1.9%)
Psychiatric disorders
14 (1.1%)
10 (1.3%)
Skin and subcutaneous tissue disorders
3 (0.2%)
4 (0.5%)
Möller et al. Poster presented at CINP, 2008
64

65. Conclusions
•
•
•
•
Escitalopram treatment was shown to be efficacious and well
tolerated in this trial
Patients aged 66–75 years achieved slightly better results than
patients >75 years
Duration of illness and length of current symptoms were significant
factors affecting treatment response, suggesting that treatment
should be initiated soon after diagnosis
Baseline severity of illness was a highly significant factor in achieving
remission, reflecting the need for a longer treatment period for
severely depressed patients
The study population reflected patients seen in real-life clinical
practice, and confirmed the efficacy and tolerability of
escitalopram seen in controlled clinical trials
Möller et al. Poster presented at CINP, 2008
65

66. Escitalopram for comorbid depression
and anxiety in elderly patients:
a 12-week, open-label, flexible-dose,
pilot trial
Mohamed et al.
Am J Geriatr Pharmacother 2006; 4: 201–209
66

67. Objectives and key findings
Objectives
•
To assess the efficacy and tolerability of short-term (12 weeks)
administration of escitalopram 10–20 mg/day for moderate to marked
comorbid depression and anxiety in elderly patients
Key findings
•
•
Elderly patients with comorbid anxiety and depression treated with
escitalopram (10–20 mg/day) demonstrated statistically significant
improvements in both MADRS and HAM-A scores from baseline
Significant changes from baseline were also noted in four of eight
subscale scores in the SF-36 survey
MADRS=Montgomery-Åsberg Depression Rating Scale; HAM-A=Hamilton Rating
Scale for Anxiety; SF-36=36-item Short-Form health survey
Mohamed et al. Am J Geriatr Pharmacother 2006; 4: 201–209
67

68. Study overview
Design
• 12 week, open-label, flexible dose, pilot trial
• Outpatients, ≥65 years, with moderate to marked comorbid major depressive
disorder (MDD; MADRS >22) and generalised anxiety disorder
(GAD; HAM-A ≥18)
• Treatment with escitalopram (up to 20 mg/day depending on clinical
judgement)
Endpoints
• Primary – changes from baseline in MADRS and HAM-A scores
• Secondary – change from baseline in SF-36 subscale scores
Demographics
Patients, n
Age, years, mean (SD)
Sex, women, n (%)
20
73.0 (4.8)
6 (30)
Mohamed et al. Am J Geriatr Pharmacother 2006; 4: 201–209
68

69. Changes from baseline in MADRS and HAM-A
scores after 12 weeks of escitalopram
(10–20 mg/day) treatment
20
Mean (SD) change in score
*
15
*
10
5
0
MADRS
n=20; LOCF (last observation carried forward); *p<0.001 vs baseline;
Baseline MADRS score, mean (SD)=29.8 (5.2);
Baseline HAM-A score, mean (SD)=23.8 (5.6)
HAM-A
Mohamed et al. Am J Geriatr Pharmacother 2006; 4: 201–209
69

70. Response rates in MADRS and HAM-A scores after
12 weeks of escitalopram (10–20 mg/day) treatment
Percentage of patients responding
70
60
50
40
30
20
10
0
MADRS
n=20; LOCF; Response = ≥50% improvement from baseline to endpoint
HAM-A
Mohamed et al. Am J Geriatr Pharmacother 2006; 4: 201–209
70

71. Quality of life and social functioning before and after
12 weeks of escitalopram treatment
Physical
functioning
*
Mental
health
*
Social
functioning
Role
functioning –
physical
Baseline
*
Energy/
fatigue
Week 12
Pain
Role
functioning –
emotional
General
health
*
0
20
40
60
Mean (SD) SF-36 score
n=18; LOCF; *p<0.01 vs baseline based on paired-samples t test
80
0
20
40
60
80
Mean (SD) SF-36 score
Mohamed et al. Am J Geriatr Pharmacother 2006; 4: 201–209
71

72. Tolerability
Completers, n (%)
17 (85)
Discontinuation, n (%)
3 (15)
Discontinuation due to AEs, n (%)
2 (10)
Discontinuation due to lack of efficacy, n (%)
1 (5)
•
Two patients withdrew due to adverse events (AEs)
•
•
•
Dizziness (n=1, 5%) and somnolence (n=1, 5%)
There were no other AEs reported
There were no clinically significant changes in laboratory values at
endpoint
Mohamed et al. Am J Geriatr Pharmacother 2006; 4: 201–209
72

73. Conclusions
•
Elderly patients with comorbid moderate to marked depression and
anxiety treated with escitalopram (10 or 20 mg/day) for 12 weeks
showed:
•
Statistically significant improvement from baseline in MADRS scores
•
Statistically significant improvement from baseline in HAM-A scores
•
Numerical improvement in four of eight subscales, and statistically
significant improvement in four of eight subscales from the SF-36
survey
Escitalopram was associated with significant
improvements in the symptoms of
depression and anxiety
Mohamed et al. Am J Geriatr Pharmacother 2006; 4: 201–209
73

74. Antidepressive therapy with
escitalopram improves mood, cognitive
symptoms, and identity memory for
angry faces in elderly depressed
patients
Savaskan et al.
Int J Neuropsychopharmacol 2008; 11: 381–388
74

75. Objectives and key findings
Objectives
•
To assess the effects of treatment with escitalopram on affective and
cognitive symptoms, and on memory for facial identity in elderly
depressed patients compared with healthy age-matched controls
Key findings
•
•
Escitalopram treatment had significant benefits for mood, cognitive
performance, and memory for negative facial stimuli in elderly
depressed patients
Escitalopram is effective in decreasing negative bias of depressed
patients and may help improve patients‟ dysfunctional social
interactions
Savaskan et al. Int J Neuropsychopharmacol 2008; 11: 381–388
75

76. Study overview
Design
•
4-week, single centre, open-label trial
•
Elderly depressed in-patients (ICD-10; >65 years old) vs healthy, age-matched controls
•
Treated with escitalopram (up to 20 mg/day depending on clinical judgement)
Assessments
•
GDS – used to assess affect (scores >6 indicate depressive disorder)
•
MMSE – used to assess cognitive functioning (scores <26 indicate cognitive
disturbances)
•
Emotional facial recognition test – used to investigate memory for facial identity
(happy and angry male faces)
Demographics
Depressed patients
Control group
18*
22
Age, years, mean (SEM)
76.2 (1.8)
76.9 (1.8)
Gender, women, n (%)
14 (77.8)
16 (72.7)
Patients, n
*22 patients were enrolled, but 4 withdrew before Week 4 and were excluded from the analysis
GDS=Geriatric Depression Scale; MMSE=Mini-Mental State Examination
Savaskan et al.
Int J Neuropsychopharmacol 2008; 11: 381–388
76

77. GDS and MMSE score from baseline to Week
4 of treatment
Baseline
Week 4
p-value
GDS,
Mean (SEM)
9.4 (0.4)
4.7 (0.6)
<0.0001
MMSE,
Mean (SEM)
26.8 (0.5)
27.9 (0.4)
=0.023
Savaskan et al. Int J Neuropsychopharmacol 2008; 11: 381–388
77

78. Identity recognition memory performance
Prior to escitalopram treatment
•
Depressive patients have lower
identity recognition memory
performance than healthy agematched controls (p=0.038)
This difference is mainly due to
memory performance on faces
with happy expressions (p=0.018)
• The control group had a
better recognition of
identities with happy faces
(p=0.046)
• This was not the case for
depressed patients
Depressed
d’ (identity recognition)
•
Control
p=0.046
1.5
p=0.018
1.0
0.5
Happy faces
Angry faces
Savaskan et al. Int J Neuropsychopharmacol 2008; 11: 381–388
78

79. Identity recognition memory performance
Depressed patients after escitalopram treatment
• No improvement in identity recognition memory for happy
faces
• Improvement in identity recognition memory for angry
faces
•
•
Before treatment the mean d‟ was 0.46 ( 0.13)
After treatment mean d‟ was 0.62 ( 0.1, p=0.05)
• Individual improvement in GDS or MMSE scores did not
significantly correlate with changes in identity recognition
performance
Savaskan et al. Int J Neuropsychopharmacol 2008; 11: 381–388
79

80. Conclusions
•
•
•
Antidepressant therapy with escitalopram improved mood and overall
cognitive performance
Elderly depressed patients have not only affective and overall
cognitive symptoms, but also deficits in facial identity recognition
memory
Antidepressant therapy with escitalopram improved the memory for
negative facial stimuli (angry faces), but not memory for positive
stimuli (happy faces)
Escitalopram seems to be effective in decreasing the negative
bias of depression, and may improve patients’
maladaptive social interactions
Savaskan et al. Int J Neuropsychopharmacol 2008; 11: 381–388
81

81. Drug interactions
82

82. Metabolism of antidepressants –
an important consideration in late life
Second generation
antidepressant
Enzymes involved in biotransformation
Isozymes inhibited
Bupropion
CYP2B6
CYP2D6 (moderate)
Citalopram
CYP2C19, CYP2D6, and CYP3A4
CYP2D6 (weak)
Duloxetine
CYP2D6 and CYP1A2
CYP2D6 (moderate)
Escitalopram
CYP2C19, CYP2D6, and CYP3A4
CYP2D6 (weak)
Fluoxetine
CYP2D6, CYP2C9, CYP2C19, and CYP3A4
CYP2D6 (strong), CYP2C9 (moderate), CYP2C19
(weak to moderate), CYP3A4 (weak to moderate),
CYP1A2 (weak)
Fluvoxamine
CYP1A2 and CYP2D6
CYP1A2 (strong), CYP2C19 (strong), CYP2C9
(moderate), CYP3A4 (moderate), CYP2D6 (weak)
Mirtazapine
CYP2D6, CYP1A2, and CYP3A4
None known
Nefazodone
CYP3A4
CYP3A4 (strong), CYP2D6 (weak)
Paroxetine
CYP2D6 and CYP3A4
CYP2D6 (strong), CYP1A2 (weak),
CYP2C9 (weak), CYP2C19 (weak), CYP3A4 (weak)
Reboxetine
CYP3A4
CYP2D6 (weak)
Sertraline
CYP2C9, CYP2C19, CYP2D6, and CYP3A4
CYP2D6 (weak to moderate), CYP1A2 (weak),
CYP2C9 (weak), CYP2C19 (weak), CYP3A4 (weak)
Venlafaxine
CYP2D6 and CYP3A4
CYP2D6 (weak)
83
Spina et al. Clin Therapeutics 2008; 30 (7): 1206–1227

83. Health economics
84

84. Depression alone is costly
Global drug costs by therapy area1
Depression treatment: cost distribution2
100%
Cholesterol and triglyceride
regulators
90%
Antiulcerants
80%
70%
Antidepressants and mood
stabilisers
60%
Direct Costs (%)
Antipsychotics
All other Antineoplastics
Anti-epileptics
Oral anti-diabetics
Erythropoietins
50%
40%
30%
20%
10%
Calcium antagonists
0%
5
10
15
20
25
30
35
A
B
C
D
E
F
G
STUDY
World sales ($US dollars)
12 month period to Q2 2008
Drugs
Hospital admissions
Consultations
Other
1. IMS Knowledgelink 2. Berto P et al. 2000. The Journal of Mental Health Policy and Economics. 3: 3-10.
85

85. Escitalopram vs citalopram
– healthcare costs in the late life population
Comparison of 6-month healthcare costs per patient by sensitivity analysis
Escitalopram
25,000
p<0.001
Citalopram
19,899
20,000
Cost ($)
p<0.001
18,945
15,000
11,604
9,855
10,000
5,000
p=0.049
1,756 1,547
0
Total
drug cost
Total medical
cost
Total
healthcare
costs
Wu et al. Curr Med Res Opin 2008; 24 (9): 2587–2595
86

86. Conclusion
87

87. Conclusions
• Safety and tolerability, efficacy, potential to interact and
healthcare costs are key criteria for selecting an
antidepressant in this population
• Dispelling myths and raising disease awareness is of
particular importance
• Accurate screening and diagnosis is crucial for optimal
management of depressive patients
• Escitalopram is effective and well tolerated in the late life
depressed patients – both in acute and continuation
treatment
88

88. Final thought
In 1890, Vincent van Gogh
painted this picture.
Seen by some as
symbolizing the despair
and hopelessness felt in
depression.
Van Gogh himself suffered
from depression and
committed suicide later
that same year.
89