AFFECTIVE DISORDERS IN
INTELLECTUAL DISABILITIES
DIAGNOSTIC PITTFALLS AND PHARMACOLOGICAL
TREATMENT STRATEGIES
Mental Health in Intellectual Disabilities
(formerly MHMR), Antwerp, May 31th 2007
Prof.Dr. Willem M.A. Verhoeven
Vincent van Gogh Institute for Psychiatry, NL-Venray
Prevalence of affective spectrum disorders
Lund, 1985
(Bipolar)Affective
1.7
Anxiety
2.0
OCD
-
4.0
25.4
-
6.0
7.2
2.5
11
25
9
6.6
3.8
0.7
Acta Psychiatr Scand
Corbett, 1979
In: Psychiatric Illness
and Mental Handicap
Cooper & Bailey, 2001
Ir J Psychol Med
Holden & Gitlesen, 2004
J Intellect Disabil Res
Cooper et al., 2007
Br J Psychiatry
DIMENSIONAL DIAGNOSTIC PROCEDURES AND
FUNCTIONAL PHARMACOTHERAPY OF AFFECTIVE
DISORDERS IN INTELLECTUAL DISABILITIES
•
•
•
•
•
diagnostic procedures
manifestations of depression
unstable mood disorder
behavioural phenotypes and depression
pharmacotherapeutic strategies
DIAGNOSTIC INSTRUMENTS
•
•
•
•
ICD-10 Guide for Mental Retardation
DSM-IV
ICD-10
Diagnostic Criteria for psychiatric disorders
for use with adults with Learning
Disabilities/Mental Retardation (DC-LD)
• Clinical Diagnosis
DIAGNOSTIC PROCEDURES
REFERENCE COMPLAINT

VIDEO REGISTRATION + CONSENSUS MEETING

SPECIFICATION OF SYMPTOMATOLOGY

QUESTIONS:
genetic etiology
neurological examination
epilepsy
somatic examination
course
hereditary factors
plasma concentrations psychotropics and anticonvulsants
delirious state
environmental variables
results previous interventions
attenuation of treatment effects
tar dive behavioural effects of psychotropics and anticonvulsants

NEUROPSYCHIATRIC EXAMINATION

DIFFERENTIAL DIAGNOSIS
DIAGNOSTIC HYPOTHESIS

TREATMENT ADVISE

BEHAVIOURS, SIGNS AND SYMPTOMS OF DEPRESSION
Diagnosis
Level of intellectual disability (number of subjects)
Severe/profound (n=15)
Mild/moderate (n=7)
Depressed affect
Sleep disturbance (insomnia = 13; hypersomnia = 1)
Appetite disturbance (decrease = 12; increase = 1)
Loss of interest
Social isolation
Self-injurious behaviour
Psychomotor agitation
Aggression
Irritability
Lack of emotional response
Screaming
Stereotypical behaviour
Psychomotor retardation
Weight loss
Anxiety
Constipation
Loss of energy
Unreasonable self-reproach
Delusion (mood congruent)
Diurnal variation of mood
15
14
13
12
11
10
10
9
7
6
6
6
5
6
5
5
5
x
x
x
From: Tsiouris, JIDR, 2001
6
5
3
0
0
5
6
2
2
4
0
0
3
0
6
0
2
3
2
2
SYMPTOMS OF DEPRESSION IN
INTELLECTUAL DISABILITIES
MORE THAN 50%
irritability
depressed affect
tearfulness
loss of interest
sleep disturbance
psychomotor agitation
self-injurious behaviour
loss of energy
constipation
anxiety
aggression
social isolation
antisocial behaviour
decreased concentration
anhedonia
increased speech
decreased appetite
withdrawn behaviour
LESS THAN 50%
somatic complaints
lack of emotional response
diurnal variation
psychomotor retardation
loss of appetite
weight loss
suicidal ideation
obsessive-compulsive behaviour
euphoria
labile mood
screaming
stereotyped behaviour
vomiting
incontinence
guilt feelings
change in sexual activities
hallucinations
delusions
Adapted from Charlot et al. 1993; Meins, 1995; Marston et al., 1997
FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER (n=58)
Domains
Affect
Depressed affect
Labile mood
Dysphoria
Tearfullness
Anxieties
Motivation
Loss of energy
Loss of interest
Anhedonia
Withdrwan behaviour
Motor
Psychomotor retardation
Psychomotor agitation
Stereotyped behaviour
Irritability
Screaming
Aggression
Impulsivity
Self-injurious behaviour
Vital
Loss of appetite
Sleep disturbances
Diurnal variation
Verhoeven et al., 2004
mild/moderate (n=47)
n
%
severe/profound (n=11)
n
%
36
22
20
22
28
77
47
43
47
60
4
8
4
6
7
36
73
36
55
64
31
27
7
27
66
57
15
57
3
2
0
6
27
18
0
55
6
26
17
28
22
26
10
18
13
55
36
60
47
55
21
38
2
9
9
10
6
7
3
8
18
82
82
91
55
64
27
73
18
20
8
38
43
17
5
5
0
45
45
0
SYMPTOMS (PRESENCE ≥50%) OF AFFECTIVE SPECTRUM
DISORDERS* IN INTELLECTUAL DISABILITIES (n=285)
psychomotor agitation
stereotypies
aggression
self-injuries
anxieties
irritability
depressed mood
mood swings
dysphoria
loss of energy
loss of interest
withdrawn behaviour
difficult to handle
depression
(n=58)
+
+
+
+
+
+
+
+
+
*depression, anxiety disorder, bipolar disorder and unstable mood disorder
Verhoeven et al., The European Journal of Psychiatry, 18:49-53, 2004
affective spectrum
(n=136)
+
+
+
+
+
+
+
+
+
UNSTABLE MOOD DISORDER
Sollier (1901)
"on voit des changements brusques d’humeur que rien ne paraît motiver,
des actes bizarres et des mouvements capricieux"
Duncan (1936)
considerable degree of emotional instability that could not be considered
as typical for bipolar affective disorder
Verhoeven & Tuinier (1997):
high prevalence of atypical bipolar and mood disorders with features like
inactivity, lability and irritability  unstable mood disorder, characterized
by an episodic pattern of disturbed mood, anxiety and behaviour
UNSTABLE MOOD DISORDER
IN INTELLECTUAL DISABILITIES
affective instability
episodic motor inhibition or disinhibition
irritability
rapid mood changes
unprovoked crying
sleep disturbances
Adapted from: Matson et al., 1991; Einfeld & Aman, 1995; Meins, 1994
DISORDERED STRESS FEEDBACK
IN INTELLECTUAL DISABILITIES
increased arousability
anxiousness
stereotyped behaviour
avoidant behaviour
irritability
Adapted from: Einfeld & Aman, 1995
FUNCTIONAL DOMAINS OF
UNSTABLE MOOD DISORDER (n=64)
Domains
mood
rapide mood swings
mood swings
episodic dysphoria
anxiety
anxieties
irritability
motor
disorganized behaviour
hyperactivity
stereotypies
self-injuries
impulsivity
aggression
Verhoeven et al., 2001, 2004
Presence
Percentage
22
41
37
34
64
56
35
35
55
55
17
39
36
25
25
35
27
61
56
39
39
55
UNSTABLE MOOD DISORDER (n=28)
METHODS - 1
subjects:
- 18 male, 10 female
- mean age: 37.3 year
- mild to severe intellectual disabilities
etiology:
- unknown: 18
- perinatal complications: 6
- encephalitis postvaccinalis: 1
- specific syndromes: 6
diagnosis:
- rapid or episodic fluctuations in behaviour
- prominent mood deviations mostly with motor signs like self-injuries
and aggression
Verhoeven & Tuinier, JARID, 14:147-154, 2001
UNSTABLE MOOD DISORDER (n=28)
METHODS - 2
previous psychiatric diagnoses:
- mood disorder: 12
- (atypical) autism: 4
- psychotic disorder: 3
- panic disorder: 1
current medication:
- anticonvulsants for epilepsy: 3
- anticonvulsants for behaviour control: 2
- antipsychotics: 20
- antidepressants: 6
- anxiolytics: 8
Verhoeven & Tuinier, 2001
UNSTABLE MOOD DISORDER (n=28)
METHODS - 3
treatment:
- valproic acid, starting at a daily dose of 300 mg
- dosage adjustment over 6 weeks according to
plasma concentration or clinical effect
- concomitant medication unchanged 3 months prior and
during the first 12 weeks of treatment
Verhoeven & Tuinier, 2001
CYCLOTHYMIA AND UNSTABLE
MOOD DISORDER
cyclothymia:
- persistent instability of mood, involving numerous periods
of mild depression and mild elation
- mood swings not related to life events
unstable mood disorder:
- long-lasting episodic disturbances in the mood,
anxiety and motor domains
main difference:
- presence of elation in cyclothymia
CONCLUSIONS UNSTABLE
MOOD DISORDER
* often described as (atypical) bipolar disorder without, however, familial
load
* the here advocated unstable mood disorder resembles the description of the
ICD-10 diagnosis cyclothymia but lacks episodes of elation
* treatment effects of valproic acid at a mean daily dose level and mean plasma
concentration of 1343 mg and 63 mg/l respectively
* clinically relevant and sustained improvement both in terms of behaviour
stability and symptom reduction in 68% of the subjects
RAPID CYCLING BIPOLAR
AFFECTIVE DISORDER
characteristics
- symptomatology characterized by observable behaviours rather than
by reports of subjective mood states
- mostly family history with affective disorder
- first episode affective disorder at or before age of 17
- gender differences not present
- not associated with particular organic pathology
treatment
- mood stabilizers, preferably sodium valproate
From: JIDR, 43, 349-359, 1999
EXAMPLES OF BEHAVIOURAL PHENOTYPES
ASSOCIATED WITH AFFECTIVE DISORDERS
VELO-CARDIO-FACIAL-SYNDROME (chromosome 22)
- affective spectrum disorders
KLINEFELTER SYNDROME (47XXY)
- bipolar affective disorders
PRADER-WILLI SYNDROME (chromosome 15)
- bipolar (affective) disorders
WOLFRAM SYNDROME CARRIERS (chromosome 4)
- affective disorders
- suicidal ideation
FRAGILE-X SYNDROME CARRIERS (X-chromosome)
- affective/anxiety disorders
DOWN SYNDROME (trisomy-21)
- affective disorders
EXAMPLES OF BEHAVIOURAL PHENOTYPES
ASSOCIATED WITH AFFECTIVE DISORDERS
DOWN SYNDROME (trisomy-21)
atypical depression:
social withdrawal
reduced energy
irritability
psychomotor retardation
regression of self-care
hypochondriasis
aggression
sleep disturbances
reduced speech
auditory hallucinations
From: Myers & Pueschel, 1995
PATIENTS WITH DOWN SYNDROME REFERRED
FOR DEPRESSION (n=20)
domains
motor
disorganized behaviour
obsessive-compulsive rituals
stereotypies
psychomotor-agitation
psychomotor retardation
impulsivity
aggression
self-injuries
temper tantrums
difficult to handle
psychotic features
confusion
visual hallucinations
auditory hallucinations
delusional ideas
paranoid ideation
Verhoeven & Tuinier, 2002
presence
percentage
3
6
8
7
5
7
9
9
5
5
15
30
40
35
25
35
45
45
25
25
3
2
3
1
2
15
10
15
5
10
PATIENTS WITH DOWN SYNDROME REFERRED
FOR DEPRESSION (n=20)
psychiatric diagnoses
major depression
unstable mood disorder
self- injurious behaviour
hypothyroidism
obsessive compulsive disorder
anxiety disorder
Gilles de la Tourette
no disorder
Verhoeven & Tuinier, 2002
8
5
1
2
1
1
1
1
FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER IN PATIENTS
TREATED WITH CITALOPRAM (N=20)
Verhoeven et al. European Psychiatry, 16:104-108, 2001
domains
Affect
Depressed affect
Labile mood
Dysphoria
Tearfulness
Anxieties
Motivation
Loss of energy
Loss of interest
Anhedonia
Withdrawn behavior
Motor
Psychomotor retardation
Psychomotor agitation
Stereotyped behaviour
Irritability
Screaming
Aggression
Impulsivity
Self-injurious behaviour
Vital
Loss of appetite
Sleep disturbances
Diurnal variations
presence
percentage
7
4
7
3
9
35
20
35
15
45
7
3
1
9
35
15
5
45
2
7
7
9
1
7
6
6
10
35
35
45
5
35
30
30
1
3
1
5
15
5
CITALOPRAM IN DEPRESSION
Methods – 1
Verhoeven et al. European Psychiatry, 16:104-108, 2001
Subjects:
Etiology:
10 male, 10 female
mild to severe ID
mean age: 36,9 years
unknown: 11
perinatal complications: 4
(meningo)-encephalitis: 2
rhesus antagonism: 1
specific syndromes: 2
CITALOPRAM IN DEPRESSION
Methods – 2
Previous (psychiatric) diagnoses:
-mood disorder: 4
-(atypical) autism: 2
-pychotic disorder: 1
-history of epilepsy: 4
-congenital cataract: 2
-Current medication:
-anticonvulsants: 12
-antipsychotics: 11
-anxiolytics: 3
CITALOPRAM IN DEPRESSION
Methods – 3
Treatment:
-citalopram, starting at 20mg daily and kept
stable during first 6 weeks
-dose adjustment according to clinical
response up to 60mg daily maximally
-follow-up period 6 (n=11) to 12 (n=9) months
-measurement of plasmaconcentrations of
anticonvulsants, citalopram and desmethylcitalopram
RESULTS AND CONCLUSIONS
CITALOPRAM
Verhoeven et al. European Psychiatry, 16:104-108, 2001
Results:
-Daily dose range: 20-60mg; mean: 33mg
-Plasmaconcentrations: 30-105 respectively 19-75µgr/l
-Side effects: seizure: n=1; delirious state: n=1
-Marked improvement in 12 out of 20 patients
-No relapse during long term treatment over >12 months
-No pharmacokinetic drug-drug interactions
Conclusion:
-Well tolerated, safe and effective
-Optimal dose: 20-30mg daily
RESULTS OF TREATMENT WITH SSRI’S
IN INTELLECTUAL DISABILITIES
-Studies:
case reports only
-Compounds:
fluoxetine (19), sertraline (7), paroxetine (5),
citalopram(1), fluvoxamine (1)
depressive and obsessive-compulsive disorders,
maladaptive behaviours
results questionable because of publication bias;
sometimes deterio ration of behaviour;
anxiety as target symptom virtually absent
over 15 years tenfold increase of prescription of SSRI’s
-Indications:
-Conclusions:
-Note:
Verhoeven & Tuinier, 2005 In: Trends in Serotonin Uptake Inhibitor Research
Nova Science Publishers, Inc, New York.
CONCLUSIONS
* increased vulnerability for stress-related disorders in ID
* categorical diagnostic systems, particularly DSM-IV, are not
appropriate in ID
* dimensional diagnostic approach is necessary for delineation of
atypical manifestations of affective disorders, unstable mood
disorder and psychopathological phenotypes
* symptom profile and course of disease (rapid cycling!) determine
choice of pharmacological strategy; antidepressant and/or mood
stabilizer
• compounds of first choice: antidepressants: citalopram,
nortriptyline; mood stabilizers: valproic acid, lithium