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THE CONCEPT OF SECONDARY MANIA IN DEMENTIA PIERRE N. TARIOT, M.D. UNIVERSITY OF ROCHESTER MEDICAL CENTER

THE CONCEPT OF SECONDARY MANIA IN DEMENTIA PIERRE N. TARIOT, M.D. UNIVERSITY OF ROCHESTER MEDICAL CENTER. DSM IV Criteria for Manic Episode.

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THE CONCEPT OF SECONDARY MANIA IN DEMENTIA PIERRE N. TARIOT, M.D. UNIVERSITY OF ROCHESTER MEDICAL CENTER

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  1. THE CONCEPT OF SECONDARY MANIA IN DEMENTIA PIERRE N. TARIOT, M.D. UNIVERSITY OF ROCHESTER MEDICAL CENTER

  2. DSM IV Criteria for Manic Episode • A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary). • During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree. • 1. inflated self-esteem or grandiosity • 2. decreased need for sleep (e.g., feels rested after only 3 hours of sleep) • 3. more talkative than usual or pressure to keep talking • 4. flight of ideas or subjective experience that thoughts are racing • 5. distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli) • 6. increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation • 7. excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

  3. DSM IV Diagnostic criteria for 293.83 Mood Disorder Due to …[Indicate the General Medical Condition] • A prominent and persistent disturbance in mood predominates in the clinical picture and is characterized by either (or both) of the following: • 1. depressed mood or markedly diminished interest or pleasure in all, or almost all, activities • 2. elevated, expansive, or irritable mood • B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct physiological consequence of a general medical condition.

  4. Diagnosis criteria for 293.83 Mood Disorder Due to… [Indicate the General Medical Condition] (continued) • The disturbance is not better accounted for by another mental disorder (e.g., Adjustment Disorder with Depressed Mood in response to the stress of having a general medical condition). • The disturbance does not occur exclusively during the course of a delirium. • The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

  5. Bipolar Disorder (with mania) vs Secondary Mania Age of onset young (25) older (>55) Prior psychiatric hx common uncommon Family psychiatric hx common uncommon Presence of neurologic disease uncommon common Li response good poor Snowdon 1991 Stone 1992 VanGerpen et al 1999

  6. Association with Cerebral Organic Disorders • 25 – 43% of all cases of mania in later life • Heterogeneous group including stroke, head trauma, masses, dementia • Insult to key areas associated with mania: • right hemisphere lesions • basotemporal connections to limbic system

  7. INSERT TABEL HERE

  8. Dementia in Mania Rates up to 15% in past studies 3% incidence over 10 years (n=92) Rothschild 1941 Bucht & Adolfsson 1983

  9. Mania in Dementia Chart review of patients with AD (n=134): 2% prevalence Prevalence in sample of patients with AD (n=110): 3.8% n=250 psychiatric inpatients with dementia 5.2% met DSM IV criteria for bipolar disorder 17.6% had “features” of bipolar disorder These are generally similar to US population rates Burns 1992 Lyketsos et al 1995 Holm et al 1999 Regier et al 1988

  10. Ratings of Signs and Symptoms Often Scale-Dependent e.g., Behave-AD (n = 33 outpatients) Behavior% Affected Agitation 48 Day-night disturbance 42 Motor restlessness 36 Violence 30 Verbal outbursts 24 Tearful 24 Mood fluctuations 3 Reisberg et al 1987

  11. Dementia Signs & Symptoms Scale (n=56 outpatients) Behavior% Affected Overactivity 64 Disruptive 50 Aggression (verbal) 40 Insomnia 39 Out of bed at night 27 Wandering 24 Physical aggression 14 Loreck et al 1994

  12. BRSD (n=303 outpatients) Behavior% Affected Verbal repetitiveness 76 Purposeless behavior 73 Agitation 68 Irritable 65 Sad 58 Restlessness 52 Uncooperative 48 Altered sleep 48 Crying 41 Verbal aggression 27 Sudden changes in emotion 25 Physical aggression 14 Tariot et al 1995

  13. Horizon Sample Folstein 1999 (with permission)

  14. Horizon Inpatient Behaviors Folstein 1999 (with permission)

  15. Manic Features Often Seen in Dementia • Irritability • Decreased sleep • Talkativeness • Distractibility • Psychomotor agitation

  16. Major Manic Features Lacking in Dementia • Elevated, expansive mood • -but affective instability common • Inflated self-esteem • -but note “grandiosity?” • Flight of ideas • Excessive involvement in pleasurable activities

  17. Target Symptoms SeenTotal Frequency (%) Hiding objects 7.8 Hoarding objects 8.6 Threatening gestures 9.5 Repetitive motor behaviors 9.5 Spitting 10.3 Complaining 10.3 Vocalizing 12.1 Wandering (in & out of other rooms) 12.1 Pushing 13.8 Robing and disrobing 13.8 Delusional 15.5 Sleep/wake cycle disturbance 17.2 Target Symptoms Seen Total Frequency (%) Crying 19.8 Irritable 19.8 Grabbing 24.1 Trying to get to another place 24.1 Requests for attention 36.2 Pacing (within a room) 40.5 Screaming/yelling 40.5 Repeats words or sentences 40.5 Verbally aggressive 50.9 Restless 50.9 Assaultive (hits or attempts to hit) 51.7 Uncooperativeness or resistant 59.5

  18. Target Symptoms SeenTotal Frequency (%) Withdrawal 0.9 Tearing 0.9 Picking 0.9 Mimicking (verbal or physical) 0.9 Urinating in inappropriate places 1.7 Physically aggressive toward objects 1.7 Affective lability 1.7 Mannerisms 1.7 Biting 2.6 Eating substances 2.6 Hallucinating 2.6 Sad 2.6 Target Symptoms SeenTotal Frequency ( %) Physically aggressive toward self 3.4 Verbal sexual advances 4.3 Scratching 5.2 Physical sexual advances 5.2 Anxious 5.2 Handling things 6.0 Logorrhea 6.0 Self-deprecating statements 6.0 Paranoia 6.9 Kicking 7.8 Cursing 7.3 Throwing things 7.8

  19. Treatment Notes from the Field Porsteinsson 1999 23% (126/540) LTC residents on an anticonvulsant 10.2% for behavioral indication McFarland 1999 1% Oregon LTC residents on valproate 50% of these had behavior problems on MDS Holm 1999 250 acute psych inpatients w/ dementia 41% on anticonvulsants at discharge

  20. Carbamazepine in Dementia • Uncontrolled Studies  N = 26  All positive • Controlled Studies  1 negative (flawed), n = 19  2 positive (n = 75)  Consistent benefit >50%  Lability, aggression  Usual dose 300 mg/d  Concerns about SE’s, drug-drug interactions Tariot et al 1998, 1999

  21. Valproate in Dementia • Uncontrolled studies  N = 141  All positive (2/3 rated as improved) • Controlled studies  N = 56 subjects with “agitation”  40% markedly improved  N = 172 subjects with manic features  Data under review Porsteinsson et al, under review Tariot et al, under review

  22. Symptoms Showing Change in Rochester Anticonvulsant Studies Crying Restless Verbally aggressive Delusional Screaming/yelling Assaultive (hits or attempts to hit) Wandering (in & out of other rooms) Tariot et al, unpublished

  23. Symptoms Not Showing Change in Rochester Anticonvulsant Studies Trying to get to another place Grabbing Requests for attention Pacing (within a room) Irritable Pushing Robing and disrobing Tariot et al, unpublished

  24. Schematic of Efficacy Data

  25. Simplistic Summary of Efficacy Data Rates of global improvement generally more similar than different across trials with different agents: 65+/-% drug 30 – 50+/-% placebo Unproven whether target symptoms matter

  26. Mania in Dementia - Conclusions Is there a distinct etiopathology ? Unknown Are clinical features of mania in dementia well-defined? Yes for rare manic syndrome No for manic features Do these features identify a homogenous patient group? Yes for manic syndrome No for manic features Are there appropriate instruments to assess these clinical features? No Are antimanic drugs specifically effective for these clinical features? Unknown

  27. Mania in Dementia - Conclusions Full–fledged manic syndrome rare “Manic features” overlap with manic syndrome and “agitation” Lack of evidence to achieve consensus re syndromal significance of manic features despite overlap with manic syndrome

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