Title: AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES DIAGNOSTIC PITTFALLS AND PHARMACOLOGICAL TREATMENT STRATEGIES
1AFFECTIVE DISORDERS IN INTELLECTUAL
DISABILITIESDIAGNOSTIC 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
2Prevalence of affective spectrum disorders
- (Bipolar)Affective Anxiety OCD
- Lund, 1985 1.7 2.0 -
- Acta Psychiatr Scand
- Corbett, 1979 4.0 25.4 -
- In Psychiatric Illness
- and Mental Handicap
- Cooper Bailey, 2001 6.0 7.2 2.5
- Ir J Psychol Med
- Holden Gitlesen, 2004 11 25 9
- J Intellect Disabil Res
- Cooper et al., 2007 6.6 3.8 0.7
- Br J Psychiatry
3DIMENSIONAL 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
4DIAGNOSTIC 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
5DIAGNOSTIC 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
6BEHAVIOURS, SIGNS AND SYMPTOMS OF DEPRESSION
- Level of intellectual disability (number of
subjects) - Diagnosis Severe/profound (n15) Mild/moderate
(n7) -
- Depressed affect 15 6
- Sleep disturbance (insomnia 13 hypersomnia
1) 14 5 - Appetite disturbance (decrease 12 increase
1) 13 3 - Loss of interest 12 0
- Social isolation 11 0
- Self-injurious behaviour 10 5
- Psychomotor agitation 10 6
- Aggression 9 2
- Irritability 7 2
- Lack of emotional response 6 4
- Screaming 6 0
- Stereotypical behaviour 6 0
- Psychomotor retardation 5 3
- Weight loss 6 0
- Anxiety 5 6
- Constipation 5 0
7SYMPTOMS OF DEPRESSION IN INTELLECTUAL
DISABILITIES
- MORE THAN 50 LESS THAN 50
- irritability somatic complaints
- depressed affect lack of emotional response
- tearfulness diurnal variation
- loss of interest psychomotor retardation
- sleep disturbance loss of appetite
- psychomotor agitation weight loss
- self-injurious behaviour suicidal ideation
- loss of energy obsessive-compulsive behaviour
- constipation euphoria
- anxiety labile mood
- aggression screaming
- social isolation stereotyped behaviour
- antisocial behaviour vomiting
- decreased concentration incontinence
- anhedonia guilt feelings
- increased speech change in sexual activities
- decreased appetite hallucinations
- withdrawn behaviour delusions
8FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER (n58)
- Domains mild/moderate (n47) severe/profound
(n11) - n n
- Affect
- Depressed affect 36 77 4 36
- Labile mood 22 47 8 73
- Dysphoria 20 43 4 36
- Tearfullness 22 47 6 55
- Anxieties 28 60 7 64
- Motivation
- Loss of energy 31 66 3 27
- Loss of interest 27 57 2 18
- Anhedonia 7 15 0 0
- Withdrwan behaviour 27 57 6 55
- Motor
- Psychomotor retardation 6 13 2 18
- Psychomotor agitation 26 55 9 82
- Stereotyped behaviour 17 36 9 82
- Irritability 28 60 10 91
- Screaming 22 47 6 55
9SYMPTOMS (PRESENCE 50) OF AFFECTIVE SPECTRUM
DISORDERS IN INTELLECTUAL DISABILITIES (n285)
- depression affective spectrum
- (n58) (n136)
- 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, anxiety disorder, bipolar disorder
and unstable mood disorder - Verhoeven et al., The European Journal of
Psychiatry, 1849-53, 2004
10UNSTABLE MOOD DISORDER
- Sollier (1901)
- "on voit des changements brusques dhumeur 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
11UNSTABLE 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
12DISORDERED STRESS FEEDBACK IN INTELLECTUAL
DISABILITIES
- increased arousability
- anxiousness
- stereotyped behaviour
- avoidant behaviour
- irritability
-
- Adapted from Einfeld Aman, 1995
13FUNCTIONAL DOMAINS OF UNSTABLE MOOD DISORDER
(n64)
- Domains Presence Percentage
- mood
- rapide mood swings 22 34
- mood swings 41 64
- episodic dysphoria 37 56
- anxiety
- anxieties 35 55
- irritability 35 55
- motor
- disorganized behaviour 17 27
- hyperactivity 39 61
- stereotypies 36 56
- self-injuries 25 39
- impulsivity 25 39
- aggression 35 55
-
- Verhoeven et al., 2001, 2004
14UNSTABLE MOOD DISORDER (n28)
- 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, 14147-154, 2001
15UNSTABLE MOOD DISORDER (n28)
- 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
16UNSTABLE MOOD DISORDER (n28)
- 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
17CYCLOTHYMIA 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
18CONCLUSIONS 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
19RAPID 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
20EXAMPLES OF BEHAVIOURAL PHENOTYPESASSOCIATED
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
21EXAMPLES 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
22PATIENTS WITH DOWN SYNDROME REFERRED FOR
DEPRESSION (n20)
- domains presence percentage
- motor
- disorganized behaviour 3 15
- obsessive-compulsive rituals 6 30
- stereotypies 8 40
- psychomotor-agitation 7 35
- psychomotor retardation 5 25
- impulsivity 7 35
- aggression 9 45
- self-injuries 9 45
- temper tantrums 5 25
- difficult to handle 5 25
- psychotic features
- confusion 3 15
- visual hallucinations 2 10
- auditory hallucinations 3 15
- delusional ideas 1 5
- paranoid ideation 2 10
-
23PATIENTS WITH DOWN SYNDROME REFERRED FOR
DEPRESSION (n20)
- psychiatric diagnoses
-
- major depression 8
- unstable mood disorder 5
- self- injurious behaviour 1
- hypothyroidism 2
- obsessive compulsive disorder 1
- anxiety disorder 1
- Gilles de la Tourette 1
- no disorder 1
-
- Verhoeven Tuinier, 2002
24FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER IN
PATIENTS TREATED WITH CITALOPRAM (N20)Verhoeven
et al. European Psychiatry, 16104-108, 2001
- domains presence percentage
- Affect
- Depressed affect 7 35
- Labile mood 4 20
- Dysphoria 7 35
- Tearfulness 3 15
- Anxieties 9 45
- Motivation
- Loss of energy 7 35
- Loss of interest 3 15
- Anhedonia 1 5
- Withdrawn behavior 9 45
- Motor
- Psychomotor retardation 2 10
- Psychomotor agitation 7 35
- Stereotyped behaviour 7 35
- Irritability 9 45
- Screaming 1 5
- Aggression 7 35
25CITALOPRAM IN DEPRESSION Methods 1 Verhoeven
et al. European Psychiatry, 16104-108, 2001
- Subjects 10 male, 10 female
- mild to severe ID
- mean age 36,9 years
- Etiology unknown 11
- perinatal complications 4
- (meningo)-encephalitis 2
- rhesus antagonism 1
- specific syndromes 2
26CITALOPRAM 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
27CITALOPRAM 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 (n11) to 12 (n9) months
- -measurement of plasmaconcentrations of
anticonvulsants, citalopram and desmethyl-
citalopram -
28RESULTS AND CONCLUSIONS CITALOPRAM Verhoeven et
al. European Psychiatry, 16104-108, 2001
- Results
- -Daily dose range 20-60mg mean 33mg
- -Plasmaconcentrations 30-105 respectively
19-75µgr/l - -Side effects seizure n1 delirious state n1
- -Marked improvement in 12 out of 20 patients
- -No relapse during long term treatment over gt12
months - -No pharmacokinetic drug-drug interactions
- Conclusion
- -Well tolerated, safe and effective
- -Optimal dose 20-30mg daily
29RESULTS OF TREATMENT WITH SSRIS IN INTELLECTUAL
DISABILITIES
- -Studies case reports only
- -Compounds fluoxetine (19), sertraline (7),
paroxetine (5), - citalopram(1), fluvoxamine (1)
- -Indications depressive and obsessive-compulsive
disorders, maladaptive behaviours - -Conclusions results questionable because of
publication bias - sometimes deterio ration of behaviour
- anxiety as target symptom virtually absent
- -Note over 15 years tenfold increase of
prescription of SSRIs - Verhoeven Tuinier, 2005 In Trends in
Serotonin Uptake Inhibitor Research - Nova Science Publishers, Inc, New York.
30CONCLUSIONS
- 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