What medications can be taken with Lexapro (escitalopram) for agitation?

Medications for Agitation When Taking Lexapro (Escitalopram)

For patients taking Lexapro (escitalopram) who experience agitation, atypical antipsychotics such as quetiapine or olanzapine are the preferred adjunctive medications due to their efficacy and relatively favorable side effect profiles. 1

First-Line Options

Atypical (Second-Generation) Antipsychotics

• Quetiapine: Start with 25 mg orally once or twice daily; less likely to cause extrapyramidal symptoms (EPS) than other antipsychotics; may cause orthostatic hypotension and dizziness 1
• Olanzapine: Start with 2.5-5 mg orally or subcutaneously daily (usually at bedtime); may cause drowsiness and orthostatic hypotension; caution when combining with benzodiazepines due to risk of oversedation 1
• Risperidone: Start with 0.5 mg orally (can give up to twice daily); increased risk of EPS at doses >6 mg/24 hours; may cause insomnia, agitation, anxiety, drowsiness 1
• Aripiprazole: Start with 5 mg orally or IM daily; less likely to cause EPS; may cause headache, agitation, anxiety, insomnia 1

Second-Line Options

Benzodiazepines

• Use with caution as they can potentially worsen agitation in approximately 10% of patients (paradoxical agitation) 1
• Lorazepam: 0.5-1 mg orally, sublingually, or parenterally every 1-4 hours as needed; lower doses in elderly or frail patients 1, 2
• Midazolam: For severe agitation not responding to other treatments; 0.5-2.5 mg subcutaneously or IV hourly as needed 1
• Avoid regular use as they can lead to tolerance, addiction, depression, and cognitive impairment 1

First-Generation Antipsychotics (Use with caution)

• Haloperidol: Start with 0.5-1 mg orally or subcutaneously; may cause EPS; do not use in patients with Parkinson's disease or Lewy body dementia 1
• Methotrimeprazine (Levomepromazine): 5-12.5 mg orally or subcutaneously; sedating with anticholinergic effects 1

Mood Stabilizers (For longer-term management)

• Divalproex sodium: Start with 125 mg twice daily; generally better tolerated than other mood stabilizers; monitor liver enzymes, platelets, PT/PTT 1
• Trazodone: Start with 25 mg daily; maximum 200-400 mg daily in divided doses; use with caution in patients with premature ventricular contractions 1

Important Considerations and Precautions

Serotonin Syndrome Risk

• Combining Lexapro with other serotonergic medications can increase the risk of serotonin syndrome 3
• Signs of serotonin syndrome: Mental status changes (agitation, hallucinations), autonomic instability (tachycardia, hyperthermia), neuromuscular symptoms (tremor, rigidity) 3
• Avoid combining Lexapro with MAOIs, as this can cause life-threatening serotonin syndrome 3

Drug Interactions

• Escitalopram may interact with drugs that prolong QT interval 1, 3
• Use caution when combining with medications metabolized by CYP2D6 enzymes 1
• Benzodiazepines combined with high-dose olanzapine can lead to oversedation, respiratory depression, and even fatalities 1

Special Populations

• Elderly patients: Use lower starting doses of all medications 1
• Patients with renal/hepatic impairment: Reduce doses and monitor closely 1
• Patients with respiratory conditions: Use benzodiazepines with extreme caution 1

Monitoring

• Assess for emergence of suicidal thoughts, especially during initial treatment or dose changes of Lexapro 3
• Monitor for worsening agitation, as antipsychotics and benzodiazepines can sometimes increase agitation 1
• For patients on antipsychotics, monitor for EPS, orthostatic hypotension, and sedation 1

Common Pitfalls to Avoid

• Avoid haloperidol monotherapy for agitation as it has a relatively weak effect when given alone and can cause side effects such as early dyskinesia and seizures 4
• Avoid abrupt discontinuation of Lexapro as this can lead to withdrawal symptoms including agitation, irritability, anxiety, and sensory disturbances 3
• Avoid combining multiple serotonergic agents without careful monitoring 3
• Do not use benzodiazepines as first-line for chronic agitation due to risks of tolerance, dependence, and cognitive impairment 1