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

Disclosure

• Some promotional data provided by Lundbeck Egypt.

Digestive disorder (6%) Musculoskeletal

disorders (4%)

Endocrine (4%)

Neuropsychiatricdisorders (28%)

Cancer (11%)

Cardiovascular disease (22%)

Sense organ impairment (10%)

Other non-communicable diseases (7%)

Respiratory disease (8%)

Schizophrenia

Bipolar disorder

Dementia

Substance-use andalcohol-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

يصيب • أصبح الذي والعصبي النفسي سطح 450المرض فوق إنسان مليوناألرض.

الي • وصل وحده االكتئاب , 140وان انسان مليون

الي • العالم في وصلت فقد والخوف القلق حاالت خائف 200أما انسان مليونوقلق..

الي • أيضا العالم في اإلدمان .. 130ووصل مدمن إنسان مليون

و • مليون وجود تؤكد فإنها مصر في األرقام يعاني 200أما مصري إنسان ألف. االكتئاب عذاب

2011-10 -20االهرام

Face the Facts

Depression is a Prevalent Disorder

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)

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

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

Depression

20% of those with major depression have symptoms that

persist beyond 2 years

Keller et al., (1992) & Scot & Dicky (2003), B. J. Psychiat.Keller et al., (1992) & Scot & Dicky (2003), B. J. Psychiat.

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

Depression is an Under-recognized Disorder

Stigma

Masked depression

Comorbid medical illness

Time constraints

Inadequate medical education

“ICEBERG” PHENOMENON”

Depressed patients seen by psychiatrists

Depressed patients seen in primary care practice

Cost of DepressionWho pays for it?

• Patients• Families• Health Care Provider• System

Cost of Depressionto 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

Cost of DepressionFamilies

• Increased burden• Patient being aloof from family causing more guilt and

anxiety• Impaired relationship• Increased risk of violence and neglect

Cost of DepressionHealth Care Providers

• More likely to order work up• Feelings of detachment• May give up early• Feelings of being a failure or not doing enough

System

• Increased use of resources• Increased mortality and morbidity

Unmet Medical needs

GPs delayed diagnosis

Cross diagnosis of

Bipolar

Stigma Selecting the right treatment option

From IV to 5

COSTDirect

• Recurrence

• Treatment

• Hospitalization

Indirect

• Disability in work

• Poor social function

• Associated behavioral

problems

• Increase self destructive

behaviors

Indirect

• Disability in work

• Poor social function

• Associated behavioral

problems

• Increase self destructive

behaviors

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.

‘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

Depression has huge impact on workplace productivity

*

*

*

*

0

10

20

30

40

50

(Missed work days) (Decreased effectiveness)

Per

cen

tag

e o

f p

atie

nts

PresenteeismPresenteeism

AbsenteeismAbsenteeism

No depressivesymptoms (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

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

Is real-life functionality the new goal of treatment?

Relapse is very Common

Euthymia

Symptoms

Syndrome

Remission

Response

Recovery – 6 months

Continuation treatment

Maintenance treatment

Relapse Recurrence

28

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 monthsNo residual symptoms

No MADRS item >1Symptom-free remission

6 monthsCorresponds to CGI-S = 1

MADRS ≤5Complete remission

Defined as Reason Useful at

Remission MADRS ≤12Prospectively defined

8 weeks

Remission MADRS ≤10 Commonly used 8 weeks

29

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

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

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

‘Feeling better’ ‘Doing better’vs

Remission does not always translate into functional outcomes

p=ns

Per

cen

tag

e o

f p

atie

nts

ac

hie

vin

g

rem

issi

on

(M

AD

RS

≤12

)

Imp

rove

me

nt

in S

hee

han

D

isa

bil

ity

Sc

ore

*

Escitalopram20 mg/day

Duloxetine60 mg/day

100

70

60

50

40

30

20

10

0

90

80

*p<0.05 vs. duloxetine

Escitalopram20 mg/day

Duloxetine60 mg/day

16

12

10

8

6

4

2

0

14

Adapted from Wade et al. Curr Med Res Opin 2007; 23: 1605–1614

Remission (MADRS ≤12) at week 24

Improvement in Sheehan Disability Score at week 24

33

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

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

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): 76–83

36

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

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

Pat

ien

ts (

%)

wit

h s

ick

day

s

38

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

Influence of antidepressants on functional outcomes

40

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

Num

ber o

f sic

k da

ys

Baseline 3 Months0.0

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

Perc

ent o

f pati

ents

on

med

ical

leav

e

41

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

Ch

ang

e fr

om

bas

elin

e in

SD

S s

core

0

-1

-2

-3

-4

-5

* **

Escitalopram 20 mg/day

*p<0.05 vs duloxetine

Duloxetine 60 mg/day

42

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.