Is Rexulti (brexpiprazole) effective for treating sexually inappropriate behaviors in an elderly male patient with dementia?

Rexulti (Brexpiprazole) Should NOT Be Used for Sexually Inappropriate Behaviors in Elderly Patients with Dementia

Rexulti carries an FDA black box warning for increased mortality in elderly patients with dementia-related psychosis and is explicitly not approved for this indication. 1 Using brexpiprazole for sexually inappropriate behaviors in dementia would be both off-label and contraindicated given the significant mortality risk.

Why Brexpiprazole is Contraindicated

• FDA black box warning explicitly states that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death, and brexpiprazole is not approved for treatment of patients with dementia-related psychosis. 1

• The 2019 AGS Beers Criteria strongly recommends avoiding antipsychotics in older adults with dementia due to increased mortality risk. 2

• Multiple guidelines emphasize that antipsychotics should be avoided for behavioral symptoms in dementia, with the Mayo Clinic noting that typical and atypical agents (including brexpiprazole's class) worsen cognitive function and carry FDA box warnings for risk of death when used for dementing disorders. 2

Evidence-Based First-Line Treatment Recommendations

SSRIs (particularly citalopram) and medroxyprogesterone are the most effective first-line medications for treating hypersexual behaviors in elderly male patients with dementia. 3, 4

Specific SSRI Recommendations:

• Citalopram 10-40 mg daily is well-tolerated and specifically recommended for sexually inappropriate behaviors in dementia patients. 3, 4, 5

• Start at very low doses (5-10 mg daily) in elderly patients and titrate slowly. 6

• Monitor for side effects including nausea, bradyarrhythmia, and QTc prolongation. 6

• Among SSRIs, fluoxetine should be avoided in older adults due to its long half-life and side effects. 2

Alternative First-Line Options:

• Medroxyprogesterone is recommended specifically for sexual disinhibition in men with dementia. 3, 4

• Carbamazepine can be considered when first-line treatments (SSRIs or medroxyprogesterone) are ineffective. 3, 4

Medications to Explicitly Avoid

• Thioridazine, chlorpromazine, or trazodone should not be used for behavioral symptoms including hypersexuality in dementia patients. 3, 4

• Conventional antipsychotics like haloperidol should not be used as first-line management. 3, 4

• Typical antipsychotics cause severe extrapyramidal symptoms in dementia patients, with 50% developing irreversible tardive dyskinesia after 2 years of continuous use. 6

Clinical Algorithm for Management

Step 1: Non-Pharmacological Interventions First

• Investigate and treat potential underlying causes of behavioral changes before initiating pharmacological treatment (e.g., urinary tract infection, pain, environmental triggers). 3, 4

• Implement structured routines and environmental modifications. 6

• Use redirection and other behavioral approaches with caregiver involvement. 2

Step 2: Pharmacological Treatment if Non-Pharmacological Fails

• Start citalopram 10 mg daily, titrate to 20-40 mg daily as tolerated. 3, 4, 5

• Alternative: Medroxyprogesterone for sexual disinhibition in men. 3, 4

Step 3: Evaluate Response

• Evaluate response to pharmacological interventions within 30 days; if minimal improvement is observed, consider alternative treatments. 3, 4

• If SSRIs ineffective, consider carbamazepine. 3, 4

Step 4: Long-Term Management

• Consider tapering or discontinuing pharmacological treatments after 6 months of symptom stabilization. 3, 4

Common Pitfalls to Avoid

• Never rely solely on pharmacological interventions without implementing non-pharmacological strategies. 3, 4

• Avoid medications with significant anticholinergic effects, which worsen cognitive symptoms in dementia. 3, 4

• Do not use bupropion, as it is associated with significantly lower rates of sexual adverse events and may worsen hypersexual behaviors. 4

• Failing to monitor for medication side effects, which can sometimes worsen behavioral symptoms. 3, 4

• Not considering the risk-benefit ratio of medication use, especially given limited FDA approval for psychotropics in treating neuropsychiatric symptoms in dementia. 3, 4

Evidence Quality Note

While brexpiprazole has been studied for agitation in Alzheimer's dementia 7, there are no randomized controlled trials specifically for sexually inappropriate behaviors in dementia. 8, 9 The evidence for SSRIs and medroxyprogesterone comes from case series and uncontrolled trials, but represents the best available evidence and is consistently recommended across multiple guidelines. 3, 4, 8, 9, 10