AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES DIAGNOSTIC PITTFALLS AND PHARMACOLOGICAL TREATMENT STRATEGIES

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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

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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

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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

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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

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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

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BEHAVIOURS, 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

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SYMPTOMS 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

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FUNCTIONAL 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

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SYMPTOMS (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

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UNSTABLE 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

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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

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DISORDERED STRESS FEEDBACK IN INTELLECTUAL
DISABILITIES

• increased arousability 
• anxiousness 
• stereotyped behaviour 
• avoidant behaviour 
• irritability
• Adapted from Einfeld Aman, 1995

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FUNCTIONAL 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

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UNSTABLE 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

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UNSTABLE 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

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UNSTABLE 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

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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

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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

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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

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EXAMPLES 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

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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

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PATIENTS 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
•  

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PATIENTS 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

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FUNCTIONAL 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

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CITALOPRAM 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

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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

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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 (n11) to 12 (n9) months
• -measurement of plasmaconcentrations of
  anticonvulsants, citalopram and desmethyl-
  citalopram

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RESULTS 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

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RESULTS 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.

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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