Functional Outcome

Neurocognition et impacts fonctionnels
dans la dépression majeure
Serge Beaulieu, M.D., Ph.D., FRCPC
Medical Chief,
- Mood, Anxiety and Impulsivity Disorders Program,
- Bipolar Disorders Program,
- Directorate of Innovation and Knowledge Integration
Researcher,
Douglas Mental Health University Institute
Associate Professor,
Department of Psychiatry, McGill University
Disclosures (2012-14)
Speaker Bureau:
Astra Zeneca
Eli Lilly
Otsuka
Sunovion
Bristol Myers Squibb (BMS)
Lundbeck
Pfizer
Consultant/Advisory Board:
Astra Zeneca
Forest Laboratories
Merck
Pfizer
Bristol Myers Squibb (BMS)
Lundbeck
Otsuka
Sunovion
Peer-Reviewed Research
Funding:
CIHR
RSMQ
FRSQ
NARSAD
STANLEY FOUNDATION
PFIZER RESEARCH AWARD
Research Support & Contract:
Astra Zeneca
Lundbeck
Sunovion
Bristol Myers Squibb (BMS)
Otsuka
Stock holding/patents:
N/A
MDD Patients with Residual Symptoms May Experience Worse
Outcomes
Weeks to First Relapse with Any Depressive Episode
(Major, Minor, Dysthymic)
Recovery with no symptoms; 1–3 previous episodes (n=121)
Recovery with no symptoms; 3+ previous episodes (n=34)
1.0
Recovery with 1+ mild symptoms; 1–3 previous episodes (n=57)
Survival distribution function
Recovery with 1+ mild symptoms; 3+ previous episodes (n=25)
0.8
0.6
Median weeks
well
224
79
34
28
0.4
0.2
0.0
0
50
100
150
200
250
300
350
400
450
500
Survival distribution function = cumulative proportion of cases surviving to given time interval
Judd et al. J Affect Disord 1998;50:97-108.
Radaelli, D., et al. (2014). European Psychiatry:
Limbic-cortical dysregulation model of the neurocircuitry of
MDD
From Thomas & Elliot, 2009 Front Hum Neurosci., 3:30 adapted from the model
proposed by Mayberg (c.f. Seminowicz et al., 2004, NeuroImage 22
Volume du CPF sous le genou
du corps calleux (mm3)
Le TDM aurait un effet sur la structure du cortex préfrontal sous le
genou
du corps calleux
Le volume du CPF sous le genou du
corps calleux était inférieur de 48 %
300
chez les patients atteints du TDM2
250
*p < 0,0002 p/r aux sujets
témoins
200
*
150
100
50
0
Sujets témoins
(n = 21)
1. Drevets WC et al. Eur Neuropsychopharmacol. 2002;12:527-44.
2. Drevets WC et al. Nature. 1997;386:824-7.
TDM
(n = 17)
Une réponse plus rapide au traitement serait attribuable au
volume et à l’activité accrus du cortex cingulaire antérieur (CCA)
Volume de la substance grise
Corrélation entre le volume de substance grise dans le CCA et le
taux d’amélioration symptomatique (n = 17 patients atteints du
TDM)
6,0
Les patients chez
lesquels le volume du
CCA était plus élevé
se sont améliorés plus
rapidement et ont eu
moins de symptômes
résiduels
5,5
5,0
4,5
4,0
3,5
3,0
-0,14
r = - 0,80
p < 0,001
-0,12 -0,10 -0,08 -0,06 -0,04 -0,02
Taux d’amélioration symptomatique/semaine
Basé sur : Chen C et al. Biol Psychiatry. 2007; sous presse.
Reproduit avec la permission d’Elsevier.
Physiologic Overlap In Mood
and Impaired Insulin Sensitivity
↑ Proinflammatory
Cytokines
Mood
Disorders
↑ Reactive Oxygen
Species
Disruptions in:
•Insulin receptor localization (CNS)
Altered Insulin
Sensitivity
•Insulin-growth factors
•Glucocorticoid signalling
CNS: central nervous system.
McIntyre et al. Ann Clin Psychiatry 2007; 19: 257-64..
Comment mesure-t-on la cognition
en situation clinique ?
Symptoms that are commonly reported during an MDE
ECA Program1,2
INSTEL2
STAR*D2,3
Patients with symptom (%)
MDE, major depressive episode; ECA, Epidemiologic
Catchment Area; INSTEL, INterventie STudie Eerste Lijn;
STAR*D, Sequenced Treatment Alternatives to Relieve Depression
10
1. Chen LS et al. Am J Psychiatry 2000;157:573-580;
2. Conradi HJ et al. Psychol Med 2011;41:1165-1174;
3. Nierenberg AA et al. J Psychiatr Res 2007;41:214-221
Specific activity impairments mediate the effect of MDE on
work loss
More than a quarter of the impact of MDE on role functioning was mediated by cognitive impairments
Cognition: difficulty concentrating, memory, understanding, ability to think clearly
Buist-Bouwman et al 2008, Acta Psychiatry Scand., 118: 451-458 (ESEMED Study)
Tools to Assess Response & Remission
Time to
complete (mins)
Patient/
clinician rated
9-item Patient Health Questionnaire (PHQ-9)
<3
Patient
17-item Hamilton Depression Rating Scale (HDRS-17)
30
Patient or clinician
Beck Depression Inventory (BDI)
5-10
Patient
Montgomery-Asberg Depression Rating Scale (MADRS)
10-15
Patient or clinician
Quick-Inventory of Depressive Symptomatology-Self Report
(QIDS-SR)
5-10
Patient or clinician
Toronto 7-item Hamilton Depression Rating Scale (HDRS-7)
NA
Clinician
Sheehan Disability Scale (SDS)
1-2
Patient or clinician
Measure
Symptoms
Download: PHQ-9 at www.depression-primarycare.org
and HAM-D7 at www.canmat.org
McIntyre. J Clin Psych 2010;71:16-20
Comment mesure-t-on la fonctionnalité ?
Functional Outcome:
Definitions/Domains
• Focus on lives, not symptoms or episodes
• Domains
– Interpersonal (romance, friendships, family)
– Occupational (job, school, home)
– Quality of life – “Individuals’ perception of their position
in life in the context of the culture and value systems in
which they live and in relation to their goals, expectations,
standards and concerns” (WHO)
• QoL lower for MDD’s with comorbidity worsening scores1
Measurement issues/concerns/problems
– No consensus on optimal scales
IsHak, et al. 2012
Impairment in Role Function and
Depression Severity Among Bipolar
Disorder Patientsa
Is recurrent MDD that different ?
Not
Depressed
Subsyndromally
Depressed
Syndromally
Depressed
(N = 292)
(N = 291)
(N = 176)
χ2
p
Duties at work/school
31%
64%
87%
79.03
<.0001
Duties at home
38%
75%
93%
155.72
<.0001
With family
34%
59%
77%
77.42
<.0001
With friends
18%
56%
81%
168.92
<.0001
Total—all domains
32%
70%
92%
185.17
<.0001
Role Function
a
Overall χ2
Data presented as % of patients who were impaired. The total N for each sample for
each domain in this table varies according to the number of patients who completed the
item.
Abbreviation: LFQ = Life Functioning Questionnaire
Altshuler, et al.2006
Facteurs Cliniques reliés aux troubles
cognitifs et à la fonctionnalité
Clinical Factors possibly Affecting
Functional Outcome
• Syndromal outcome
– Pole specificity
– Subsyndromal outcome
•
•
•
•
Neurocognitive deficits
Comorbid disorders: personality/drug/Etoh
Substance abuse1
Chaotic environment/life events
1. Dickerson, et al. 2010
Percent Impaired in
Overall Life Functioning
Depression Severity and Impaired Life
Functioning in Depression
Not Depressed
Altshuler, et al. 2006
Subsyndromally
Depressed
Syndromally Depressed
Functional Outcomes Per Group,
Adjusted for Demographic and Baseline
Variables
Functional Outcome
Measure
Recovered
Subsyndromal
Depression
Syndromal
MDE
Life total score*
9.16
12.96
13.68
Satisfaction*
2.15
2.98
3.41
Recreation*
2.16
3.34
3.24
Work*
2.32
3.32
3.60
Relationships*
2.58
3.36
3.45
Work day missed**
1.23
3.18
5.98
Work days impaired**
3.54
10.32
11.72
Q-LES-Q*
65.03
39.62
36.58
* Differences across all 3 groups, p<.0001
** Differences between depressed & recovered, p<.001
Marangell, et al. 2009
Improvement of cognitive function by antidepressants: impacts
on general function in the treatment of depression
Ability to perform tasks and
meet psychosocial demand
NEUROCOGNITIVE
FUNCTION
CLINICAL
CHARACTERISTICS
Disease course variables
↑ number of affective episodes
↑ number of hospitalisations
↑ depressive course of illness
↓ age of onset
↑ years with illness
Baune BT et al. Psychiatry Res 2010;176:183-9
GENERAL /
DAILY FUNCTION
Function
Poor reintegration at work
Employment status
Social function
Readiness for cognitive therapies
En quoi est-ce t-il utile pour
guider le traitement ?
Enhancing Functional Outcomes:
Treatment Considerations
• Aggressive Rx of subsyndromal symptoms
– Especially for Rx of depressive symptoms
– Controversy on optimal Rx for bipolar
depression
• Psychotherapies to enhance coping skills
• Enhancing cognitions
– Cognitive remediating strategies
– ? Pharmacotherapies
• Treat comorbid disorders
Side Effect Burden
• Rarely studied as a correlate of functional
outcome
• ? More associated with QoL measures
• Differs across med classes, meds
• Distinguish between:
– Short term side effects-sedation, cognitive
impairment, weight gain vs.
– Long term health risks, such as metabolic
syndrome, Type II diabetes
Clinical Implications of
Syndrome/Function Relationship
• Circular relationship between syndrome
and function
– Syndrome affects function
– Function affects symptoms / syndrome
• Intervention at either/both levels may
reverse side
Q&A