Agitation in Dementia

See Also

Pathophysiology

As Dementia progresses, behavior replaces language as the primary communication medium

Etiology
Behavior Decompensation (The 6 I's)

See Delirium
Iatrogenic
1. Anticholinergic Medications
2. Sedative-Hypnotic Medications
Infection
1. Urinary Tract Infection
2. Pneumonia
Injury
1. Occult Hip Fracture or other Fracture
2. Pain is a common exacerbating factor
  1. Consider scheduled Acetaminophen dosing (e.g. 650 mg orally three times daily)
Illness exacerbation
Impaction of feces
Inconsistency in environment or routine change
Other
1. Thirst or hunger
2. Drug or Alcohol use
3. Caffeine

Approach
General

Excluding medical causes is critical (see above)
Ask care givers which they believe is likely causative (see list below)
Cohen-Mansfield Agitation Inventory (CMAI)
1. http://www.dementia-assessment.com.au/symptoms/CMAI_Scale.pdf
2. Distinguishes between the four general categories above to help direct management
3. Can be used to monitor for treatment efficacy
Categories of behavior changes causes
1. Psychosis
  1. Presents with Delusions or Hallucinations
  2. Fear and distress from Psychosis responds to Atypical Antipsychotics (e.g. Risperidone, Quetiapine)
  3. Avoid Antipsychotics (except Quetiapine) in Lewy Body Dementia (paradoxically worsen)
  4. Avoid Antipsychotics as Chemical Restraint only
2. Mood
  1. Presents with dysphoria, screaming
  2. Consider Cornell Scale for depression assessment in Dementia
  3. Non-pharmacologic therapy is most effective
  4. Consider Bupropion or Methylphenidate to assist with withdrawn patients
  5. Consider ECT for severely withdrawn or disruptive behaviors
  6. Consider Mirtazapine for suppressed appetite
3. Physical behaviors (overstimulation response)
  1. Presents with hitting or other Violent Behaviors
  2. Always consider pain as an underlying cause of physical behaviors
  3. Consider Olanzapine (Zyprexa, Zydis) dissolvable tablet as needed for Violent Behaviors
  4. Avoid Benzodiazepines (due to paradoxical worsening)
4. Disinhibition (understimulation response)
  1. Presents with calling for help, ruminating, voiding in wrong place...
  2. Reorientation activities may help
References
1. Tung (2012) Mayo POIM Conference, Rochester

Approach
Catastrophic Reaction

Results from Task failure
1. Patient told that they're wrong
Symptoms
1. Irritability
2. Accusation
3. Tearful
4. Combative
Management: Non-Pharmacologic
1. See No-fail Environment in Dementia (Calming Measures in Dementia)

Approach
Reaction to physical Care

Occurs particularly in Frontal LobeImpairment
1. Patients Akinetic
2. Patient wants to be left alone
Management: Non-Pharmacologic
1. Limit goals (e.g. bath less often)
2. Follow strict routine at patient's best time of day
3. Use slow gentle movements in physical care
4. Approach patient from side or rear
5. Reassure ("As soon as we're done, I'll stop")

Approach
Screaming

Often no purpose
Associated with non-directed Agitation
Cause may be multifactorial
1. Pain
2. Sensory deprivation
3. Restraints
4. Depression in Dementia
Treat possible underlying causes
1. Aggression-Specific Types/Other Causes
  1. Disinhibition
  2. Agitated depression

Precautions

Antipsychotics only demonstrate benefit in anger, aggression and paranoia
1. No benefit in quality of life, care needs, or functional capacity
Atypical Antipsychotics have serious, including life-threatening side-effects
1. Atypical Antipsychotics in older patients with Dementia are associated with a two fold increased mortality
2. Adverse effects include QT Prolongation, aspiration risk and gait disturbance and increased Fall Risk
Obtain Informed Consent before starting
1. Medication risks and benefits should be reviewed with patients and their care Caregivers before starting
Avoid using newer agents without proven efficacy and longterm safety (and very expensive)
1. Example: Nuedexta (Dextromethorphan/Quinidine) - NMDA Receptor Blocker
2. (2017) Presc Lett 24(6): 33
References
1. Sultzer (2008) Am J Psychiatry 165(7): 844-54 [PubMed]
2. Gill (2007) Ann Intern Med 146(11): 775-86 [PubMed]

Management
Medications

Indications
1. Failed Behavior Modification as above (see Calming Measures in Dementia)
2. Severe and refractory Agitation
Medication preparations
1. Approach
  1. Start dosing at one third to one half of typical starting dose
  2. Titrate slowly and taper off if no effect within first 4 weeks
  3. Even if effective, attempt to taper after 4 months (often can taper without relapse)
2. Antipsychotics (all agents with similar efficacy)
  1. Atypical Antipsychotics with low Extrapyramidal Effects (but overall preferred by geriatricians)
    1. Use caution
      1. Increased risk of death on Atypical Antipsychotics
      2. Obtain baseline EKG before starting to check QT Prolongation
    2. Aripiprazole (Abilify)
      1. Consistently effective with small reductions in adverse behaviors
      2. Lower daily doses (<10 mg) are effective
      3. Increased CV and CVA risk, but unknown effect on mortality
    3. Risperidone (Risperdal) 0.5 mg orally twice daily ($78/month)
      1. Effective for Psychosis Symptoms
      2. Side effects may limit use
      3. As with Quetiapine and Olanzapine, had a 3.5% absolute increase in mortality
    4. Quetiapine (Seroquel) 25 mg orally twice daily ($85/month)
      1. Preferred of the Atypical Antipsychotics in Parkinson's Disease, Lewy Body Dementia
      2. As with Risperdal and Olanzapine, had a 3.5% absolute increase in mortality
  2. Atypical Antipsychotics that are FDA approved for Agitation in Dementia (but very expensive as of 2023)
    1. Brexpiprazole
      1. Moderately reduced Agitation and well tolerated at 12 weeks
      2. Lee (2023) JAMA Neurol 80(12): 1307-16 [PubMed]
  3. Old, cheap drugs with high Extrapyramidal Effects
    1. Haloperidol 0.5 mg orally twice daily ($5/month)
      1. Useful as initial agent in acute Agitation
      2. Switch to agent below if need to continue
      3. Avoid in Parkinson's Disease
      4. Markedly impairs mobility secondary to rigidity
  4. Agents to avoid due to low efficacy
    1. Olanzapine (Zyprexa) was associated with worse functional outcomes
      1. Sultzer (2008) Am J Psychiatry 165(7): 844-54 [PubMed]
    2. Ziprasidone (Geodon)
    3. Paliperidone (Invega)
    4. Clozapine (Clozaril)
    5. Asenapine (Saphris)
    6. Iloperidone (Fanapt)
3. Other agents with potential benefit
  1. Divalproex (Depakote)
  2. Carbamazepine (Tegretol) titrate to 300 mg/day
    1. Limited by sedation, narrow therapeutic window
  3. Trazodone (Desyrel) 50 mg PO qhs
  4. Selective Serotonin Reuptake Inhibitor
    1. Consider as a first-line agent, and taper off if no effect at 2 to 3 months
    2. Escitalopram (Lexapro) up to 10 mg orally daily
      1. Preferred over Celexa with generic status in 2012 and no known QT Prolongation
    3. Sertraline (Zoloft)
    4. Mirtazapine (Remeron)
  5. Miscellaneous Antidepressants
    1. Bupropion
  6. Newer Tricyclic Antidepressants (e.g. Pamelor)
4. Agents with only anecdotal support
  1. Beta Blockers (e.g. Propranolol)
  2. Lithium
  3. Buspirone (Buspar)
5. Agents to use with only with caution
  1. Benzodiazepines (e.g. Lorazepam (Ativan) 0.25 - 0.50 mg)
    1. Give 30 minutes prior to physical care
    2. May cause Ataxia, risk of falls, Delirium and paradoxical worsening
    3. Consider scheduled Acetaminophen instead
6. Avoid agents lacking safety and efficacy data
  1. Avoid Nuedexta (Dextromethorphan/Quinidine)
  2. Avoid Nuplazid (Pimavanserin)

References

(2022) Presc Lett 29(6): 33
Howell in Duthie (1998) Geriatrics p. 295-305
Ham (1997) Postgrad Med 101(6):57-70 [PubMed]
Reese (2016) Am Fam Physician 94(4): 276-82 [PubMed]
Stewert (1995) Am Fam Physician 52(8):2311-22 [PubMed]