What is the next best course of action for a patient with tardive dyskinesia (TD) and moderate hepatic impairment due to hepatitis C–related cirrhosis, who is currently stable on olanzapine (olanzapine) and lithium (lithium), but has distressing TD symptoms?

Treatment of Tardive Dyskinesia in a Patient with Moderate Hepatic Impairment

Start valbenazine 40 mg daily (Option C) as the definitive treatment for this patient's tardive dyskinesia, given her Child-Pugh class B cirrhosis. 1

Rationale for Valbenazine Selection

Valbenazine is specifically FDA-approved for tardive dyskinesia and has clear dosing guidance for hepatic impairment. The FDA label explicitly states: "The recommended dosage for patients with moderate or severe hepatic impairment is 40 mg once daily." 1 This patient has Child-Pugh class B (moderate) cirrhosis, making valbenazine 40 mg the appropriate choice without requiring titration.

Key Advantages in This Clinical Context

• Once-daily dosing simplifies adherence and reduces pill burden in a patient already taking multiple medications 1, 2
• Rapid onset of effect within 2 weeks addresses the urgent quality-of-life concerns affecting her work and social functioning 2
• Can be taken with or without food, providing flexibility 1
• No dose titration required in moderate hepatic impairment—start directly at 40 mg daily 1

Why Other Options Are Inappropriate

Option A: Benztropine

Benztropine is contraindicated for tardive dyskinesia. Anticholinergic agents like benztropine do not treat TD and may actually worsen symptoms. 3 The 2001 American Academy of Child and Adolescent Psychiatry guidelines explicitly state that "there is no specific treatment for TD other than discontinuing the medication" when referring to traditional approaches, and anticholinergics are not indicated. 3

Option B: Deutetrabenazine

Deutetrabenazine requires complex titration and lacks specific hepatic impairment dosing guidance comparable to valbenazine. While deutetrabenazine is effective for TD 4, it requires:

• Starting at 6 mg BID with gradual upward titration
• Multiple daily doses (BID or TID dosing)
• Must be taken with food
• More complex management in hepatic impairment

The comparative evidence shows similar AIMS score reductions (2-5 points) and response rates (33-50%) for both agents 4, but valbenazine's simpler dosing and clear hepatic guidance make it preferable here.

Option D: Tetrabenazine

Tetrabenazine is not FDA-approved for tardive dyskinesia and has significant drawbacks including:

• TID dosing requirement creating adherence challenges
• Rapid metabolism necessitating frequent intake 5
• Fluctuating response 5
• Risk of depression and parkinsonism with chronic use 5
• No established dosing for hepatic impairment in TD

Option E: Multiple Appropriate Choices

This is incorrect because only valbenazine has appropriate dosing for moderate hepatic impairment without complex titration.

Expected Clinical Outcomes

Efficacy Data

Valbenazine demonstrates substantial and sustained improvement in TD symptoms. In the KINECT 4 long-term study:

• Mean AIMS total score improvement of -10.2 to -11.0 points at 48 weeks 6
• 89-90% of participants achieved ≥50% improvement from baseline 6
• 90-96% rated as "much or very much improved" by clinicians 6
• 89-90% of patients reported feeling "much or very much improved" 6

These improvements directly address this patient's quality-of-life concerns regarding noticeable lip-smacking and tongue movements affecting her work with children and social activities. 7, 6

Safety Profile

Valbenazine is well-tolerated with minimal adverse effects. In clinical trials:

• Somnolence/sedation occurred in 10.9% (vs 4.2% placebo) 1
• Akathisia in 2.7% (vs 0.5% placebo) 1
• Only 3% discontinued due to adverse reactions 1
• No new safety concerns emerged during 48 weeks of treatment 6

Critical Monitoring Considerations

Parkinsonism Risk

Monitor closely for drug-induced parkinsonism, particularly in the first two weeks. 1 Postmarketing reports describe severe parkinson-like symptoms including:

• Falls and gait disturbances
• Tremor and drooling
• Hypokinesia

Most severe cases occurred within the first two weeks after starting or increasing the dose. 1 If clinically significant parkinson-like signs develop, reduce the dose or discontinue. 1

Psychiatric Stability

Continue current mood stabilizers (olanzapine and lithium) unchanged since the patient is psychiatrically stable and a prior taper attempt led to manic recurrence. 3 Valbenazine does not require adjustment of concurrent antipsychotics—85% of study participants continued stable antipsychotic regimens. 1

Hepatic Function

Monitor liver function tests periodically given the underlying Child-Pugh class B cirrhosis, though valbenazine does not require dose adjustment based on changing liver function once initiated at 40 mg. 1

Common Pitfalls to Avoid

Do not attempt to titrate valbenazine upward to 80 mg in this patient. The FDA label is explicit that 40 mg once daily is the recommended dose for moderate or severe hepatic impairment. 1 Increasing the dose could lead to drug accumulation and increased adverse effects.

Do not discontinue olanzapine to "treat" the TD. While the traditional approach suggested discontinuing the offending medication 3, this patient has demonstrated psychiatric instability with olanzapine reduction. The risk of manic relapse outweighs potential TD benefits from antipsychotic discontinuation, especially now that effective TD-specific treatment is available.

Do not delay treatment while attempting conservative measures. The patient has had TD for one year with progressive worsening affecting her quality of life and social functioning. Valbenazine provides rapid improvement within 2 weeks 2, addressing an urgent clinical need.

Implementation Plan

1. Initiate valbenazine 40 mg once daily (can be taken with or without food) 1
2. Assess response at 2 weeks using AIMS scoring to document baseline and early response 2
3. Monitor for parkinsonism symptoms weekly for the first month, particularly falls, gait changes, or rigidity 1
4. Continue current psychiatric medications unchanged (olanzapine 10 mg nightly, lithium 900 mg/day) 1
5. Reassess TD symptoms at 4-6 weeks with formal AIMS scoring and patient-reported outcomes 6
6. Plan long-term monitoring every 3 months once stable, as sustained improvement is expected with continued treatment 6