What are the implications of stopping Lexapro (escitalopram) and adding Depakote (valproate) in an elderly female patient with dementia, hypertension, heart disease, hyperlipidemia, and possible mood disorders, who is currently on multiple medications including two selective serotonin reuptake inhibitors (SSRIs)?

Stopping Lexapro and Adding Depakote in an Elderly Patient with Dementia

Direct Recommendation

This medication switch is not recommended and represents a potentially dangerous prescribing decision that contradicts established geriatric guidelines. The patient is already on two SSRIs (which itself is inappropriate), and replacing one SSRI with Depakote (valproate) in an elderly dementia patient lacks evidence-based support and introduces significant risks without clear benefit 1, 2.

Critical Problems with This Proposed Change

The Current Dual SSRI Regimen is Already Inappropriate

• The patient is currently on both Lexapro (escitalopram) and another SSRI, which is not evidence-based and increases serotonin syndrome risk 3.
• Before considering adding any new medication, the first priority should be addressing this polypharmacy issue by consolidating to a single SSRI if antidepressant therapy is indicated 1.

Depakote is High-Risk in Elderly Dementia Patients

Depakote carries a black box warning specifically relevant to this patient population:

• In elderly patients with dementia, valproate causes significantly higher rates of somnolence compared to placebo, with associated risks of dehydration, reduced nutritional intake, and weight loss 2.
• The FDA label specifically warns that "in elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events" 2.
• Dose reductions or discontinuation should be considered in patients with decreased food or fluid intake and excessive somnolence 2.

Lack of Indication for Mood Stabilizers in This Context

Depakote is recommended for specific psychiatric conditions, not as a general substitute for SSRIs:

• In dementia with agitation, the 2002 American Family Physician guidelines list Depakote as a "mood-stabilizing (antiagitation) drug" for control of severe agitated, repetitive, and combative behaviors—but only as an alternative to antipsychotics, not as replacement for antidepressants 1.
• The recommended use is for "control of problematic delusions, hallucinations, severe psychomotor agitation, and combativeness" 1.
• There is no guideline support for using Depakote to treat depression or anxiety in elderly patients with dementia 1.

The Safer Approach: Deprescribing Rather Than Switching

The 2021 Mayo Clinic guidelines on polypharmacy management emphasize deprescribing in elderly patients:

• Reducing polypharmacy through purposeful deprescribing has been shown to reduce medication-associated emergencies and hospitalizations 1.
• The first step should be medication reconciliation and identifying drug therapy problems, including duplicate therapy (the two SSRIs) 1.
• In elderly patients with multiple comorbidities, the 2012 AGS guidelines recommend that "adding medications for multiple conditions may produce less drug benefit and additional harms, burdens, and side effects" 1.

Recommended Alternative Approach

Step 1: Address the Dual SSRI Problem First

• Discontinue one of the two SSRIs (likely the one added most recently or the one with more drug interactions) 1.
• Taper gradually over 2-4 weeks to avoid discontinuation syndrome 4, 3.
• The American Academy of Child and Adolescent Psychiatry recommends gradual discontinuation to avoid withdrawal symptoms such as anxiety, irritability, and mood changes 4.

Step 2: Optimize the Remaining SSRI

• If continuing escitalopram, it is preferred in elderly patients due to minimal CYP450 interactions 5.
• Sertraline is also a reasonable choice with favorable safety profile in older adults 5.
• Monitor for efficacy at 4 and 8 weeks using standardized instruments 5.

Step 3: Consider Non-Pharmacological Interventions

• Cognitive behavioral therapy has the highest level of evidence for anxiety disorders in all age groups 5.
• Address environmental factors, communication, and reversible causes of behavioral symptoms 5.

Step 4: Only Add Depakote if Specific Indications Exist

Depakote should only be considered if:

• The patient has severe psychomotor agitation, combativeness, or repetitive behaviors unresponsive to other interventions 1.
• Antipsychotics have been tried and failed or are contraindicated 1.
• The patient has bipolar disorder with mania (not mentioned in this case) 1, 6.

If Depakote is ultimately deemed necessary:

• Start at 125 mg twice daily 1.
• Titrate to therapeutic blood level (40-90 mcg/mL) 1.
• Monitor liver enzymes, platelets, PT/PTT as indicated 1.
• Monitor closely for somnolence, dehydration, and nutritional intake given the specific risks in elderly dementia patients 2.

Critical Monitoring if This Change Proceeds Despite Recommendations

If the prescriber proceeds with this switch against guideline recommendations:

• Monitor fluid and nutritional intake daily for the first 2 weeks 2.
• Assess for excessive somnolence and consider dose reduction or discontinuation if present 2.
• Check baseline and periodic liver function tests 1.
• Monitor platelet counts, especially if doses approach therapeutic levels 2.
• Assess for drug-drug interactions with the patient's cardiovascular medications 1.

Common Pitfalls to Avoid

• Do not abruptly discontinue escitalopram—taper over at least 2-4 weeks to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability) 4, 3.
• Do not assume Depakote is "safer" than continuing an SSRI—it carries significant risks in elderly dementia patients that may outweigh any theoretical benefit 2.
• Do not add medications without first addressing existing polypharmacy—the dual SSRI regimen should be simplified before considering additional agents 1.
• Do not use Depakote for depression or anxiety—it is not indicated for these conditions in elderly patients 1.