Elder Care Interprofessional Provider Sheets

Psychosis in Dementia - Pharmacotherapy

Nina Vadiei, PharmD and Jeannie Lee, PharmD, College of Pharmacy, University of Arizona

April 2018

TIPS FOR DEALING WITH PSYCHOTIC SYMPTOMS AND AGITATION IN OLDER ADULTS WITH DEMENTIA

Try non-pharmacologic methods first (establishing daily routines, identifying the source of agitation, etc.)

  • When pharmacologic treatment is warranted, be keenly aware of the risk-benefit ratio.
  • Periodically reassess the ongoing need for medications used for disruptive behaviors.
  • Work with behavioral health providers, pharmacists, and social workers on a comprehensive treatment plan that includes behavioral intervention, pharmacotherapy, and working with care-givers.

Psychotic symptoms occur at some point in as many as 23% of older adults. Most of these individuals have secondary psychosis (i.e., the psychotic symptoms are associated with an underlying medical, psychiatric, or neurological disorder). Examples of underlying causes include dementia and other neurocognitive disorders, delirium, mood disorders, and medical illness. Sometimes, psychosis is due to medications or nutritional supplements.

Most commonly, however, psychosis in older adults is associated with dementia. Psychosis in these instances is less often characterized by clear-cut psychotic symptoms such as delusional ideation or hallucinosis but rather, inferred from grossly disorganized behaviors. This Elder Care will focus primarily on treatment of dementia-associated psychosis. Treatment poses a challenge because there are no medications that reverse the course of dementia.

Management Goals

Psychotic symptoms in demented patients typically come to clinicians' attention because of disruptive behaviors. The goal of treatment is to contain such behaviors, especially when they pose a risk to the patient or others. The first line of treatment is non-pharmacologic. This includes minimizing sensory deficits; addressing possible contributing factors such as pain and constipation; creating a structured, predictable environment; and, importantly, modifying or discontinuing any concurrent medications that might cause or aggravate psychosis, such as certain drugs prescribed for Parkinson's disease. Ultimately, however, pharmacologic approaches are often needed. These rely, to date, primarily on antipsychotics, and these drugs can have serious side effects (Table 1).

Table 1. Adverse Effects of Antipsychotics
Organ System Adverse Effects
Cardiovascular
ECG changes, orthostatic hypotension, edema, hypertension, syncope, tachycardia
Central Nervous System
Extrapyramidal symptoms (e.g., akathisia, Parkinsonian movements), anxiety, dizziness, fatigue, headache, insomnia, sedation
Gastrointestinal
Abdominal pain, constipation, increased appetite, nausea
Genitourinary
Cystitis, incontinence, sexual dysfunction
Metabolic Weight gain, dyslipidemia, type-2 diabetes
Neuromuscular Dyskinesia, myalgia, tremor
Respiratory Congestion, cough, pneumonia, rhinitis

All antipsychotics now carry a black-box warning of a 1-2% increased risk of sudden death when given to older adults with dementia. The increased risk of death is primarily due to cerebrovascular events. Thus, before prescribing an antipsychotic, clinicians should assess whether the potential benefit of treatment (e.g., preventing injury to the patient or others) outweighs the risk. Medications should not be prescribed simply to control behavior for the convenience of caretakers or staff.

It is also important to distinguish the type of dementia. Patients with Lewy body dementia are at increased risk of serious side-effects from antipsychotic treatment. Patients with vascular dementia may have more risk of adverse cardiovascular effects, particularly when taking antipsychotics that have an intermediate-to-high metabolic risk (Table 2).

Table 2. Metabolic Risk Categories of Second-Generation Antipsychotic Medications
Category
Examples
High
Clozapine, Olanzapine
Intermediate
Quetiapine, Risperidone
Low
Aripiprazole, Ziprasidone, Lurasidone

Pharmacotherapy

The first-line, evidence-based psychopharmacologic treatment of disruptive behaviors in dementia should include acetylcholinesterase inhibitors (ACEIs - donepezil, rivastigmine, and galantamine) and memantine. ACEIs (especially donepezil) and memantine have been shown to reduce behavioral symptoms in dementia. Since they have a more favorable safety profile than antipsychotics, they should be tried first.

If ACEIs and memantine fail, second-generation antipsychotics that have shown efficacy in treating disruptive behaviors in dementia are the next choice. Selection of the agent should be based on side-effect profiles (Table 3), as well as the patient's comorbidities. Dosing should start low and be titrated slowly since older adults are more sensitive to side-effects. Target doses are typically lower than those used for younger patients with primary psychotic disorders (Table 4).

Antidepressants, especially SSRIs such as citalopram and sertraline, can reduce behavioral disturbances associated with dementia if there are no psychotic symptoms. They are safer than antipsychotics, but the lag time until improvement is longer. The benefits of other mood stabilizers and other psychotropic agents are currently unclear.

Table 3. Antipsychotic Pharmacologic Differences 
Medication
Problems in Older Adults
Aripiprazole (Abilify) Less α , H1, M1 activity, but more akathisia
Olanzapine (Zyprexa) High H1 (↑ sedation and metabolic side-effects) and M1 activity (anticholinergic)
Quetiapine (Seroquel) High H1 and α activity (↑ risk of orthostatic hypotension)
Risperidone (Risperdal) High α activity (↑ risk of postural hypotension), high D2 activity (↑ risk of extrapyramidal symptoms)

α =alpha; H1=histaminergic; M1=muscarinic; D2=dopaminergic

 

Table 4. Common Medications for Dementia and Psychosis: Initial Geriatric Dose, Target Dose, Geriatric Considerations 
Medications FDA-Approved for Dementia Initial Dose Target Dose Geriatric Considerations
Donepezil (Aricept) 5 mg  10 mg GI side-effects are most common (nausea, vomiting, diarrhea) and are dose-dependent. May cause weight loss, increased fatigue, or insomnia. 
Galantamine (Razdyne) 8 mg 16-24 mg GI side-effects, decreased appetite, weight loss, dizziness, headache. Take with meals and assure adequate fluid intake. Dose adjustments required in renal and hepatic impairment. 
Memantine (Namenda) 5 mg 10 mg BID Common side-effects are dizziness, headache, fatigue, constipation. Minimum of 1 week recommended before increasing dose. NTE 5 mg BID in severe renal impairment. 
Rivastigmine (Exelon) 4.6 mg  9.5-13.3 mg Dose-dependent GI side-effects are most common (nausea, vomiting, diarrhea).  Monitor closely for toxicity in low weight (< 50 kg) patients. Titrate every 4 weeks. 
Antipsychotic Medications 
Aripiprazole (Abilify) 2.5 mg 2.5-12.5 mg Increased risk of akathisia which can mimic agitation, leading to further dose increases. Long half-life (72 hours), steady state not achieved for up to 2 weeks. Monitor A1c and lipids. 
Olanzapine (Zyprexa) 2.5 mg 2.5-10 mg High risk of weight gain; metabolic side-effects are dose-dependent. Monitor A1c and lipids. Dosing can be daily or split into BID-TID. Takes 6 hours to peak (oral); effects for agitation are not immediate. 
Quetiapine (Seroquel) 12.5 mg 12.5-200 mg Monitor for orthostatic hypotension and use gradual dose increases; educate patient on how to minimize risk of falls. Dosing can be daily or split into BID-TID. Monitor A1c and lipids. 
Risperidone (Risperdal) 0.25 mg 0.25-1.5 mg Monitor for orthostatic hypotension and use gradual dose increases; educate patient on how to minimize risk of falls. Dosing can be daily or split BID. Monitor A1c and lipids. 
Antidepressant Medications
Citalopram (Celexa) 10-20 mg 20-60 mg May cause hyponatremia. GI distress may limit adherence; may cause weight gain or loss; decreased sexual function possible. Risk of QT prolongation with dose >20mg/day.
Sertraline (Zoloft) 25 mg 50-200 mg Less adverse effects compared to other agents; most common side-effects are GI distress, fatigue, insomnia, tremor, and sexual dysfunction.

A1c=hemoglobin A1c; GI=gastrointestinal; NTE=not to exceed

References and Resources

  • Colijn MA, Nitta BH, Grossberg GT. Psychosis in Later Life: A Review and Update. Harv Rev Psychiatry. 2015;23(5):354-67.
  • Correll CU. From receptor pharmacology to improved outcomes: individualizing the selection, dosing, and switching of antipsychotics. Eur Psychiatry. 2010;25(Suppl 2):S12-21.
  • Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008;13(1):27-35.
  • Reinhardt MM, Cohen CI. Late-Life Psychosis: Diagnosis and Treatment. Curr Psychiatry Rep. 2015;17:1.