THE CONCEPT OF SECONDARY MANIA

IN DEMENTIA

PIERRE N. TARIOT, M.D.

UNIVERSITY OF ROCHESTER MEDICAL CENTER

DSM IV Criteria for Manic Episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).

B. 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)

DSM IV Diagnostic criteria for 293.83 Mood Disorder Due to …[Indicate the General Medical Condition]

A. 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.

Diagnosis criteria for 293.83 Mood Disorder Due to… [Indicate the General Medical Condition] (continued)

C. 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).

D. The disturbance does not occur exclusively during the course of a delirium.

E. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

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

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

INSERT TABEL HERE

Dementia in Mania

Rates up to 15% in past studies

3% incidence over 10 years (n=92)

Rothschild 1941

Bucht & Adolfsson 1983

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

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

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

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 14Tariot et al 1995

Horizon Sample

DX Mania AD Depression

N

Age

% fem

MMSE

296

74

65

21

898

81

68

12

2742

77

71

21

Folstein 1999

(with permission)

Horizon Inpatient Behaviors

Mania AD Depression

Restless 60 70 46

Disruptive 46 50 26

Affect elated 46 22 11

Noisy 29 33 12

Wandering 29 51 18

Verbal aggression 25 38 13

Active aggression 10 33 7

Destructive to property 6 12 3

Folstein 1999

(with permission)

Manic Features Often Seen in Dementia

• Irritability

• Decreased sleep

• Talkativeness

• Distractibility

• Psychomotor agitation

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

Target Symptoms Seen Total 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

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

Target Symptoms Seen Total Frequency (%)

Target Symptoms Seen Total 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

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

Target Symptoms Seen Total Frequency ( %)

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

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

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

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

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

Schematic of Efficacy Data

“Agitation” Psychosis Mania

Haloperidol

Risperidone

Olanzapine

Quetiapine (open)

Carbamazepine

Valproate

()

()

()

()pending

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

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

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