# Presentation: 011883

## THE CONCEPT OF SECONDARY MANIA

** ****IN DEMENTIA**
**PIERRE N. TARIOT, M.D.**
**UNIVERSITY OF ROCHESTER MEDICAL CENTER**

## 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)

## 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.

## 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.

## 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		     14

- Tariot 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