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AFFECTIVE DISORDERS IN INTELLECTUAL DISABILITIES DIAGNOSTIC PITTFALLS AND PHARMACOLOGICAL TREATMENT STRATEGIES

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 DISABILITIES DIAGNOSTIC PITTFALLS AND PHARMACOLOGICAL TREATMENT STRATEGIES

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  1. 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

  2. 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

  3. 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

  4. 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

  5. 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 

  6. 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 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

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

  8. FUNCTIONAL DOMAINS OF DEPRESSIVE DISORDER (n=58) 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

  9. 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 disorder Verhoeven et al., The European Journal of Psychiatry, 18:49-53, 2004

  10. 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

  11. 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

  12. DISORDERED STRESS FEEDBACK IN INTELLECTUAL DISABILITIES increased arousability  anxiousness  stereotyped behaviour  avoidant behaviour  irritability Adapted from: Einfeld & Aman, 1995

  13. FUNCTIONAL DOMAINS OF UNSTABLE 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

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

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

  24. 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

  25. CITALOPRAM IN DEPRESSIONMethods – 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

  26. CITALOPRAM IN DEPRESSIONMethods – 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

  27. CITALOPRAM IN DEPRESSIONMethods – 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

  28. RESULTS AND CONCLUSIONS CITALOPRAMVerhoeven 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

  29. 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.

  30. 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

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