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(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 2.5Ir J Psychol Med

Holden & Gitlesen, 2004 11 25 9

J Intellect Disabil Res

Cooper et al., 2007 6.6 3.8 0.7Br 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 examinationepilepsy

somatic examinationcourse

hereditary factorsplasma concentrations psychotropics and anticonvulsants

delirious stateenvironmental variables

results previous interventionsattenuation of treatment effects

tar dive behavioural effects of psychotropics and anticonvulsants

NEUROPSYCHIATRIC EXAMINATION

DIFFERENTIAL DIAGNOSISDIAGNOSTIC HYPOTHESIS

TREATMENT ADVISE

BEHAVIOURS, SIGNS AND SYMPTOMS OF DEPRESSION Level of intellectual disability (number of subjects)

 Diagnosis Severe/profound (n=15) Mild/moderate (n=7) Depressed affect 15 6Sleep disturbance (insomnia = 13; hypersomnia = 1) 14 5Appetite disturbance (decrease = 12; increase = 1) 13 3Loss of interest 12 0Social isolation 11 0Self-injurious behaviour 10 5Psychomotor agitation 10 6Aggression 9 2Irritability 7 2Lack of emotional response 6 4Screaming 6 0Stereotypical behaviour 6 0Psychomotor retardation 5 3Weight loss 6 0Anxiety 5 6Constipation 5 0Loss of energy 5 2Unreasonable self-reproach x 3Delusion (mood congruent) x 2Diurnal variation of mood x 2

From: Tsiouris, JIDR, 2001

SYMPTOMS OF DEPRESSION IN INTELLECTUAL DISABILITIES

 MORE THAN 50% LESS THAN 50%irritability somatic complaintsdepressed affect lack of emotional responsetearfulness diurnal variationloss of interest psychomotor retardationsleep disturbance loss of appetitepsychomotor agitation weight lossself-injurious behaviour suicidal ideationloss of energy obsessive-compulsive behaviourconstipation euphoriaanxiety labile moodaggression screamingsocial isolation stereotyped behaviourantisocial behaviour vomitingdecreased concentration incontinenceanhedonia guilt feelingsincreased speech change in sexual activitiesdecreased appetite hallucinationswithdrawn behaviour delusions Adapted from Charlot et al. 1993; Meins, 1995; Marston et al., 1997

FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER (n=58) Domains mild/moderate (n=47) severe/profound (n=11)

n % n %AffectDepressed affect 36 77 4 36Labile mood 22 47 8 73Dysphoria 20 43 4 36Tearfullness 22 47 6 55Anxieties 28 60 7 64MotivationLoss of energy 31 66 3 27Loss of interest 27 57 2 18Anhedonia 7 15 0 0Withdrwan behaviour 27 57 6 55MotorPsychomotor retardation 6 13 2 18Psychomotor agitation 26 55 9 82Stereotyped behaviour 17 36 9 82Irritability 28 60 10 91Screaming 22 47 6 55Aggression 26 55 7 64Impulsivity 10 21 3 27Self-injurious behaviour 18 38 8 73VitalLoss of appetite 18 38 5 45Sleep disturbances 20 43 5 45Diurnal variation 8 17 0 0

Verhoeven et al., 2004

SYMPTOMS (PRESENCE ≥50%) OF AFFECTIVE SPECTRUM DISORDERS* IN 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 disorderVerhoeven et al., The European Journal of Psychiatry, 18:49-53, 2004

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 Presence Percentage

moodrapide mood swings 22 34mood swings 41 64episodic dysphoria 37 56

anxietyanxieties 35 55irritability 35 55

motordisorganized behaviour 17 27hyperactivity 39 61stereotypies 36 56self-injuries 25 39impulsivity 25 39aggression 35 55

 Verhoeven et al., 2001, 2004

•

UNSTABLE MOOD DISORDER (n=28) METHODS - 1

subjects:- 18 male, 10 female- mean age: 37.3 year- mild to severe intellectual disabilitiesetiology:- unknown: 18- perinatal complications: 6- encephalitis postvaccinalis: 1- specific syndromes: 6diagnosis:- 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 withdrawalreduced energyirritabilitypsychomotor retardationregression of self-carehypochondriasisaggressionsleep disturbancesreduced speechauditory hallucinations

 From: Myers & Pueschel, 1995

PATIENTS WITH DOWN SYNDROME REFERRED FOR DEPRESSION (n=20)

domains presence percentage motordisorganized behaviour 3 15obsessive-compulsive rituals 6 30stereotypies 8 40psychomotor-agitation 7 35psychomotor retardation 5 25impulsivity 7 35aggression 9 45self-injuries 9 45temper tantrums 5 25difficult to handle 5 25psychotic featuresconfusion 3 15visual hallucinations 2 10auditory hallucinations 3 15delusional ideas 1 5paranoid ideation 2 10 Verhoeven & Tuinier, 2002

PATIENTS WITH DOWN SYNDROME REFERRED FOR DEPRESSION (n=20)

psychiatric diagnoses major depression 8unstable mood disorder 5self- injurious behaviour 1hypothyroidism 2obsessive compulsive disorder 1anxiety disorder 1Gilles de la Tourette 1no 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 percentageAffectDepressed affect 7 35Labile mood 4 20Dysphoria 7 35Tearfulness 3 15Anxieties 9 45MotivationLoss of energy 7 35Loss of interest 3 15Anhedonia 1 5Withdrawn behavior 9 45MotorPsychomotor retardation 2 10Psychomotor agitation 7 35Stereotyped behaviour 7 35Irritability 9 45Screaming 1 5Aggression 7 35Impulsivity 6 30Self-injurious behaviour 6 30VitalLoss of appetite 1 5Sleep disturbances 3 15Diurnal variations 1 5

CITALOPRAM IN DEPRESSION Methods – 1

Verhoeven 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

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 desmethyl- citalopram

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)

-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 * 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