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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.

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AFFECTIVE 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


Prevalence of affective spectrum disorders

Prevalence 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


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
DIAGNOSTIC INSTRUMENTS PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

  • 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
DIAGNOSTIC PROCEDURES PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

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
BEHAVIOURS, SIGNS AND SYMPTOMS OF DEPRESSION PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

Level of intellectual disability (number of subjects)

Diagnosis Severe/profound (n=15) Mild/moderate (n=7)

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

Loss of energy 5 2

Unreasonable self-reproach x 3

Delusion (mood congruent) x 2

Diurnal variation of mood x 2

From: Tsiouris, JIDR, 2001


Symptoms of depression in intellectual disabilities
SYMPTOMS OF DEPRESSION IN INTELLECTUAL DISABILITIES PHARMACOTHERAPY OF AFFECTIVE DISORDERS 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

Adapted from Charlot et al. 1993; Meins, 1995; Marston et al., 1997


Functional domains of depressive disorder n 58
FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER (n=58) PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

Domainsmild/moderate (n=47) severe/profound (n=11)

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

Aggression 26 55 7 64

Impulsivity 10 21 3 27

Self-injurious behaviour 18 38 8 73

Vital

Loss of appetite 18 38 5 45

Sleep disturbances 20 43 5 45

Diurnal variation 8 17 0 0

Verhoeven et al., 2004


Symptoms presence 50 of affective spectrum disorders i n intellectual disabilities n 285
SYMPTOMS (PRESENCE ≥50%) OF AFFECTIVE SPECTRUM DISORDERS* PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIESIN INTELLECTUAL DISABILITIES (n=285)

depression affective spectrum

(n=58) (n=136)

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, 18:49-53, 2004


Unstable mood disorder
UNSTABLE MOOD PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIESDISORDER

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
UNSTABLE MOOD DISORDER PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIESIN 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
DISORDERED STRESS FEEDBACK PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIESIN INTELLECTUAL DISABILITIES

increased arousability 

anxiousness 

stereotyped behaviour 

avoidant behaviour 

irritability

Adapted from: Einfeld & Aman, 1995


Functional domains of unstable mood disorder n 64
FUNCTIONAL DOMAINS OF PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIESUNSTABLE MOOD DISORDER (n=64)

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


Unstable mood disorder n 28
UNSTABLE MOOD DISORDER (n=28) PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

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 281
UNSTABLE MOOD DISORDER (n=28) PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

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 282
UNSTABLE MOOD DISORDER (n=28) PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

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 PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIESAND 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
CONCLUSIONS UNSTABLE MOOD DISORDER PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

* 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
RAPID CYCLING BIPOLAR AFFECTIVE DISORDER PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

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
EXAMPLES OF BEHAVIOURAL PHENOTYPES PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIESASSOCIATED 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 a ssociated with affective disorders
EXAMPLES OF BEHAVIOURAL PHENOTYPES PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES 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
PATIENTS WITH DOWN SYNDROME REFERRED FOR DEPRESSION (n=20) PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

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

Verhoeven & Tuinier, 2002


Patients with down syndrome referred for depression n 201
PATIENTS WITH DOWN SYNDROME REFERRED FOR DEPRESSION (n=20) PHARMACOTHERAPY OF AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES

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


FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER IN PATIENTS TREATED WITH CITALOPRAM (N=20)Verhoeven et al. European Psychiatry, 16:104-108, 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

Impulsivity 6 30

Self-injurious behaviour 6 30

Vital

Loss of appetite 1 5

Sleep disturbances 3 15

Diurnal variations 1 5


Citalopram in depression methods 1 verhoeven et al european psychiatry 16 104 108 2001

CITALOPRAM IN DEPRESSION TREATED WITH CITALOPRAM (N=20)Methods – 1Verhoeven et al. European Psychiatry, 16:104-108, 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


Citalopram in depression methods 2

CITALOPRAM IN DEPRESSION TREATED WITH CITALOPRAM (N=20)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

CITALOPRAM IN DEPRESSION TREATED WITH CITALOPRAM (N=20)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 desmethyl- citalopram


Results and conclusions citalopram verhoeven et al european psychiatry 16 104 108 2001

RESULTS AND CONCLUSIONS CITALOPRAM TREATED WITH CITALOPRAM (N=20)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

RESULTS OF TREATMENT WITH SSRI’S TREATED WITH CITALOPRAM (N=20)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 SSRI’s

Verhoeven & Tuinier, 2005 In: Trends in Serotonin Uptake Inhibitor Research

Nova Science Publishers, Inc, New York.


Conclusions
CONCLUSIONS TREATED WITH CITALOPRAM (N=20)

* 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


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