2. Functional Recovery in DepressionFunctional Recovery in Depression
Prof. Hani Hamed Dessoki, M.D.Psychiatry
Prof. Psychiatry
Chairman of Psychiatry Department
Beni Suef University
Supervisor of Psychiatry Department
El-Fayoum University
APA member

3. Disclosure
• Some promotional data provided by Lundbeck Egypt.

4. Digestive
disorder (6%) Musculoskeletal
disorders (4%)
Endocrine (4%)
Neuropsychiatric
disorders (28%)
Cancer (11%)
Cardiovascular
disease (22%)
Sense organ
impairment (10%)
Other non-communicable
diseases (7%)
Respiratory
disease
(8%)
Schizophrenia
Bipolar disorder
Dementia
Substance-use and
alcohol-use disorders
Other mental disorders
Epilepsy
Other neurological disorders
Other neuropsychiatric disorders
MDD
2%
10%
2%
2%
4%
3%
1%
2%
3%
Prince et al. Lancet 2007;370(9590):859–877
Contribution (%) by different non-communicable diseases to
disability-adjusted life-years (DALYs) worldwide in 2005
Psychiatric disorders
– underestimated and disabling conditions

6. •‫يصيب‬ ‫أصبح‬ ‫الذي‬ ‫والعصبي‬ ‫النفسي‬ ‫المرض‬450.‫الرض‬ ‫سطح‬ ‫فوق‬ ‫إنسان‬ ‫مليون‬
•‫الي‬ ‫وصل‬ ‫وحده‬ ‫الكتئاب‬ ‫وان‬140,‫انسان‬ ‫مليون‬
•‫الي‬ ‫العالم‬ ‫في‬ ‫وصلت‬ ‫فقد‬ ‫والخوف‬ ‫القلق‬ ‫حالت‬ ‫أما‬200‫خائف‬ ‫انسان‬ ‫مليون‬
..‫وقلق‬
•‫الي‬ ‫أيضا‬ ‫العالم‬ ‫في‬ ‫الدمان‬ ‫ووصل‬130..‫مدمن‬ ‫إنسان‬ ‫مليون‬
•‫و‬ ‫مليون‬ ‫وجود‬ ‫تؤكد‬ ‫فإنها‬ ‫مصر‬ ‫في‬ ‫الرقام‬ ‫أما‬200‫عذاب‬ ‫يعاني‬ ‫مصري‬ ‫إنسان‬ ‫ألف‬
.‫الكتئاب‬
‫الرهرام‬20-10-2011

7. Face the Facts
Depression is a Prevalent Disorder

8. The global burden of disease, 1990−2020
• Lower Respiratory
Infections
• Diarrheal Diseases
• Perinatal conditions
• Depression
• Heart Diseases
• Cerebrovascular D/O
• Heart Diseases
• Depression
• Traffic accidents
• Cerebrovascular D/O
• COPD
• Lower Respiratory
Infections
Lopez et al :Global burden of disease and risk factors, Oxford University
Press, New York (2006)

9. Ten leading causes of burden of disease,
world, 2004 and 2030

10. Depression IssuesDepression Issues
•Depression exists on a continuum
•Major depression is quite common
• Lifetime prevalence rates range from 5.2% to 17.1%
• Women are twice as likely to develop depression as are men
• Higher rates in young adults and among individuals in lower
socioeconomic groups.
• Depression prevalence varies across cultures
•Prevalence of depression has been increasing over the last 50
years

11. Depression
20% of those with major depression have symptoms that
persist beyond 2 years
Keller et al., (1992) & Scot & Dicky (2003), B. J. Psychiat.

12. Depression In Primary Care
• Prevalence of depression in Medically ill patients is
twice that of General populations
• Medical Disease is a risk factor itself for Depression
• Rates of Depression increases with Acuity of care from
low 9% in general population to 30% in acutely
hospitalized patients
Fava: J clin Psych Primary Care Companion 2005

13. Depression is an
Under-recognized Disorder
 Stigma
 Masked depression
 Comorbid medical illness
 Time constraints
 Inadequate medical education

14. “ICEBERG” PHENOMENON”
Depressed patients
seen by psychiatrists
Depressed patients seen in
primary care practice

15. Cost of Depression
Who pays for it?
• Patients
• Families
• Health Care Provider
• System

16. Cost of Depression
to Patients
• Unable to cope effectively
• Affects nutrition, Rx adherence, self care
• More likely to have adverse reaction to medications
• Poor physical functioning
• Increased Morbidity and mortality

17. Cost of Depression
Families
• Increased burden
• Patient being aloof from family causing more guilt and
anxiety
• Impaired relationship
• Increased risk of violence and neglect

18. Cost of Depression
Health Care Providers
• More likely to order work up
• Feelings of detachment
• May give up early
• Feelings of being a failure or not doing enough

19. System
• Increased use of resources
• Increased mortality and morbidity

20. Unmet Medical needs
GPs delayed diagnosis
Cross
diagnosis of
Bipolar
Stigma Selecting the right
treatment option
From IV to 5

21. COST
Direct
• Recurrence
• Treatment
• Hospitalization
Indirect
• Disability in work
• Poor social function
• Associated behavioral
problems
• Increase self destructive
behaviors

22. Lost productivity—
55%
Outpatient care—
6%
Suicide—17%
Inpatient care—
19%
Pharmaceuticals—
3%
Greenberg PE, et al. J Clin Psychiatry. 1993;54:405-418.
Economics of Depression —
U.S.A. Data - Total Annual Cost ~$44 Billion
U.S. data.

23. ‘Presenteeism’ is a greater problem
than absenteeism
Absenteeism
• Time spent away from the job due to illness
Presenteeism
• Impaired job performance and productivity while at work

24. Depression has huge impact on workplace
productivity
*
*
*
*
0
10
20
30
40
50
(Missed work days) (Decreased effectiveness)
Percentageofpatients
PresenteeismAbsenteeism
No depressive
symptoms (n=4,387)
Acute depressive
symptoms (n=652)
Chronic depressive
symptoms (n=501)
Druss et al. Am J Psychiatry 2001; 158: 731–734*p<0.001 vs. no depressive symptoms

25. Factors that impair work functioning
Depressive symptoms
• Fatigue and low energy
• Insomnia
• Concentration and memory
problems
• Anxiety (especially social
anxiety)
• Irritability
Medication side effects
• Daytime sedation
• Insomnia
• Headache
• Agitation/anxiety
• Nausea and GI effects
Lam et al. CANMAT Working with Depression Program, 2008

26. Is real-life functionality
the new goal of treatment?

27. Relapse is very Common
Euthymia
Symptoms
Syndrome
Remission
Response
Recovery – 6 months
Continuation
treatment
Maintenance
treatment
Relapse Recurrence

28. 2
What are the clinical milestones for
treatment of depression?
• Onset of response (≥20% improvement from baseline)
• Response (≥50% improvement from baseline)
• Different grades of remission:
Wade et al. J Psychiatr Res 2009; 43: 568–575
6 months
No residual
symptoms
No MADRS item >1
Symptom-free
remission
6 months
Corresponds to
CGI-S = 1
MADRS ≤5
Complete
remission
Defined as Reason Useful at
Remission MADRS ≤12
Prospectively
defined
8 weeks
Remission MADRS ≤10 Commonly used 8 weeks

29. 2
Response and Remission defined
Hamilton Depression Rating Scale (HAM-D): 17 Items, Total Score 0 - 52
15
7
Response
♦ ≥ 50% reduction from baseline HAM-D
score
Remission: HAM-D Score ≤ 7
Depression
(Major Depressive Disorder)
References:
1. Frank E. Conceptualization and rationale for consensus definition terms in MDD, Arch Gen Psych. 1991; 48:851-855.
HAM-D17
Scores

30. 3
Is remission the optimal outcome?
• Remission (as measured by symptom scales) is an
important target for treatment
• Residual symptoms are predictors of relapse, chronicity
and suicidality
• There are various remission criteria
• But, does remission = ‘health’ or functional recovery?
‘Health’ is a state of complete physical, mental, and social well-being
and not merely the absence of disease or infirmity.
World Health Organization
Preamble to the Constitution of the World Health Organization, 7 April 1948

31. 3
Many depressed patients are still depressed.
References:
1. Nierenberg AA, et al. J Clin Psychiatry. 1999:60(suppl 22):7-11.
2. O’Reardon JR, et al. Psychiatr Ann. 1998;28:633-640.
3. Lynch ME. J Psychiatry Neurosci. 2001;26(1):30-36.
Depressed patients continue to have needs that are not being fully addressed1
• Depressed patients present with emotional and
physical symptoms.
• Approximately 30% of depressed patients achieve
remission in clinical trials2*
• Up to 70% of patients who respond fail to remit2*
• Incomplete relief from symptoms may increase the risk
of relapse2,3
• Emotional and physical symptoms may delay
achieving remission.
*In antidepressant clinical drug trials.

32. 3
‘Feeling better’ ‘Doing better’vs
Remission does not always translate into
functional outcomes
p=ns
Percentageofpatientsachieving
remission(MADRS≤12)
ImprovementinSheehan
DisabilityScore
*
Escitalopram
20 mg/day
Duloxetine
60 mg/day
100
70
60
50
40
30
20
10
0
90
80
*p<0.05 vs. duloxetine
Escitalopram
20 mg/day
Duloxetine
60 mg/day
16
12
10
8
6
4
2
0
14
Adapted from Wade et al. Curr Med Res Opin 2007; 23: 1605–16
Remission (MADRS ≤12)
at week 24
Improvement in Sheehan
Disability Score at week 24

33. 3
What is a ‘good enough’ outcome for the
treatment of depression?
 Physician perspective:
 Signs
 Adverse events
 Patient perspective:
 Symptoms
 Adverse events
 Wellbeing
 Quality of life
 Functioning
 Economic aspects
 Society perspective:
 Functioning
 Economic aspects

34. 3
Factors identified by depressed outpatients
as very important in defining remission
In rank order:
 Presence of positive mental health
(e.g. optimism, self-confidence)
 Feeling like your usual, normal self
 Return to usual level of functioning at work, home
or school
 Feeling in emotional control
 Participating in, and enjoying, relationships with
family and friends
 Absence of symptoms of depression
Zimmerman et al. Am J Psychiatry 2006: 163 (1): 148–150

35. 3
Sick leave – the patient’s
perspective
Potential benefits
 Removal from occupational stresses and under-performing
 More time and opportunity to engage in activities conducive to
recovery
Drawbacks
 Patient inactivity, retreats to bed
 Isolation, without the usual social contacts afforded by the
workplace
 Development of a secondary anxiety pattern whereby patient
becomes more apprehensive about returning to work
 The longer the disability leave, the less likely it is that the patient
will ever return to gainful employment
Bilsker et al. Can J Psychiatry 2006; 51 (2): 76–

36. 3
Impact of depression on
sick leave duration
Naturalistic study in a working population
(Austria)
 Days on sick leave 3 months prior to and 3 months
during escitalopram treatment were compared in
2,325 patients (949 men and 1,376 women)
Winkler et al. Hum Psychopharmacol 2007; 22 (4): 245–251;
Buist-Bouwman et al. Acta Psychiatr Scand 2006; 113 (6): 492–500

37. 3
Number of sick days –
a distribution
Winkler et al. Hum Psychopharmacol 2007; 22 (4): 245–251
n=754
Days on sick leave
in 3 months during
escitalopram
treatment
Sick leave was
due to psychiatric
morbidity
Days on sick leave
in 3 months prior to
escitalopram
treatment
p<0.001
Number of sick days
1–2 3–5 6–10 11–15 16–20 21–30 >30
15
12
9
6
3
0
Patients(%)withsickdays

38. 3
How to optimize pharmacotherapy for
depressed workers
• Choose appropriate treatments
• Enhance adherence
• Monitor outcomes
• Manage non-responders
Lam et al. CANMAT Working with Depression Program, 2008

39. Influence of antidepressants on
functional outcomes

40. 4
Winkler et al. Hum Psychopharmacol 2007; 22
(4): 245–251
Effect of Cipralex® on functional
outcome – open-label results
Percent of Canadian patients on medical leave
after escitalopram treatment (n=641)
Chokka et al. Canadian J Diagnosis
May 2008: 105– 112
Sick days in Austrian patients (n=2,387)
treated with escitalopram
Numberofsickdays
Baseline 3 Months
0.0
2.0
4.0
6.0
8.0
10.0
12.0
* p<0.001
11.0
5.4*
0
2
4
6
8
10
12
14
16
Baseline Week 2 Week 6 Week 12Week 24
Percentofpatientsonmedicalleave

41. 4
Escitalopram significantly
improves daily living
Baseline Sheehan Disability Scores:
work=6.49, social=6.97, family=6.81; LOCF Wade et al. Curr Med Res Opin 2007; 23 (7): 1605–1614
Week 8 Week 24 Week 8 Week 24 Week 8 Week 24
Occupational Social Family
ChangefrombaselineinSDSscore
0
-1
-2
-3
-4
-5
* *
*
Escitalopram 20 mg/day
*p<0.05 vs duloxetine
Duloxetine 60 mg/day

42. 4
Take Home Message
• ‘Symptom free’ is a realistic remission outcome, however
success rates differ among antidepressants
• Recovery of functionality – especially work functioning –
is important to patients (and should be for clinicians)
• Remission of symptoms is not always associated with
functional improvement
• Escitalopram superiorly improves daily living and
functional outcomes compared to other SSRIs & SNRIs.