What should my mom do about persistent slurred speech that started after adding Latuda (lurasidone) and Buspirone to her Topiramate regimen and continued after switching to Divalproex (valproate)?

Management of Medication-Induced Slurred Speech

Your mother should immediately see her doctor for evaluation of medication-induced dysphonia (slurred speech), as this could indicate a serious adverse reaction to her medication regimen, particularly hyperammonemic encephalopathy from the combination of topiramate and divalproex. 1, 2, 3

Likely Cause of Symptoms

The slurred speech your mother is experiencing is likely due to one of these medication-related issues:

1. Medication toxicity from topiramate: Topiramate alone can cause speech disturbances, confusion, and ataxia 4

2. Hyperammonemic encephalopathy: The combination of topiramate and divalproex (valproate) is particularly concerning as it can cause:

   • Elevated ammonia levels in the blood
   • Neurological symptoms including slurred speech
   • Mental status changes
   • This reaction can occur even with normal liver function 2, 3

3. Drug interaction effects: Multiple CNS-active medications (topiramate, divalproex, buspirone) can have additive effects on speech and cognition

Immediate Steps

1. Contact her doctor immediately - Do not wait for her next scheduled appointment

   • This is a potentially serious adverse reaction requiring prompt evaluation
   • Slurred speech that persists after medication changes is a red flag 1

2. Request blood ammonia level testing - This is critical to rule out hyperammonemic encephalopathy 2

   • This condition can occur with the topiramate-divalproex combination
   • It can develop even in patients who previously tolerated either medication alone

3. Do not abruptly stop medications - Wait for medical guidance on medication adjustments

Diagnostic Approach

Her doctor should perform:

1. Laryngoscopy - Clinical practice guidelines recommend visualization of the larynx when dysphonia (voice disturbance) fails to resolve within 4 weeks 1

2. Laboratory testing:

   • Ammonia levels (critical)
   • Liver function tests
   • Medication levels (particularly valproate)
   • Electrolytes and kidney function 2

Treatment Options

Based on clinical guidelines, treatment will likely involve:

1. Medication adjustment:

   • Discontinuation of divalproex is likely necessary if hyperammonemia is present 2
   • Dose reduction or discontinuation of topiramate may be required 2, 3
   • Alternative medications may be considered based on her underlying conditions

2. Voice therapy:

   • If dysphonia persists after medication adjustment, referral to speech-language pathology is recommended 1
   • Techniques to reduce excessive muscle tension in speech muscles
   • Exercises to normalize articulation 1

Important Considerations

1. Medication combinations to avoid:

   • The FDA specifically warns about the combination of topiramate and valproate (divalproex) due to risk of hyperammonemia with or without encephalopathy 2
   • This reaction can occur even in patients who previously tolerated either drug alone

2. Watch for other neurological symptoms:

   • Confusion or altered mental status
   • Lethargy
   • Vomiting
   • Ataxia (unsteady gait)
   • These would indicate worsening encephalopathy and require emergency evaluation 2

3. Alternative medication options:

   • If your mother is taking these medications for migraine prevention, alternatives like beta-blockers (propranolol, metoprolol), candesartan, or amitriptyline could be considered 1
   • If for mood stabilization, alternatives would depend on her specific diagnosis

Follow-up

After medication adjustment:

1. Regular monitoring of speech function
2. Repeat ammonia levels if they were elevated
3. Assessment of underlying condition control with new medication regimen

This situation requires prompt medical attention as medication-induced dysphonia can significantly impact quality of life and may indicate a serious adverse reaction that could progress if not addressed.