What is the best approach to treat a patient with depression and tardive dyskinesia?

Treatment of Depression with Tardive Dyskinesia

For patients with depression and tardive dyskinesia, VMAT2 inhibitors such as valbenazine or deutetrabenazine are the first-line treatment for tardive dyskinesia while maintaining appropriate antidepressant therapy. 1

Understanding Tardive Dyskinesia in Depressed Patients

Tardive dyskinesia (TD) is an iatrogenic movement disorder characterized by involuntary, repetitive movements of the face, trunk, or limbs, associated with long-term use of dopamine receptor blocking agents (DRBAs), including some medications used in depression treatment 1. Key features include:

• Orofacial movements (tongue protrusion, chewing, grimacing)
• Choreic movements of extremities
• Symptoms that persist even after discontinuation of the causative medication

First-Line Treatment Approach

1. VMAT2 Inhibitors:

   • Valbenazine (Ingrezza): FDA-approved specifically for TD

     • Starting dose: 40 mg daily
     • Target dose: 80 mg once daily
     • Advantages: Convenient once-daily dosing, rapid onset (within 2 weeks) 1, 2
     • Demonstrated significant reduction in TD symptoms with response rates of 33-50% 1

   • Deutetrabenazine (Austedo): FDA-approved for TD

     • Effective doses: 24-36 mg/day
     • Requires twice-daily administration with food 1

2. Antidepressant Management:

   • Continue appropriate antidepressant therapy
   • Consider that cognitive behavioral therapy (CBT) and antidepressants have similar efficacy for depression treatment 3
   • If the patient is on an antipsychotic for depression augmentation that may have caused TD, consider:
     • Switching to antipsychotics with lower TD risk (quetiapine or clozapine) 4, 5
     • Using alternative depression augmentation strategies

Special Considerations

Dosage Adjustments

• For patients with moderate to severe hepatic impairment: Reduce VMAT2 inhibitor dose to 40 mg once daily 2
• For known CYP2D6 poor metabolizers: Use 40 mg once daily of valbenazine 2

Monitoring

• Regularly assess TD symptoms using the Abnormal Involuntary Movement Scale (AIMS)
• Monitor for potential side effects of VMAT2 inhibitors:
  • Depression and suicidal ideation (particularly in patients with Huntington's disease) 2
  • Somnolence
  • Balance issues

Alternative Approaches if VMAT2 Inhibitors Are Not Tolerated

If VMAT2 inhibitors are not tolerated or available, consider:

1. Medication adjustments:

   • Switch to antipsychotics with lower TD risk (quetiapine) if antipsychotics are necessary 6, 4
   • Consider gradual tapering of the causative agent if clinically feasible 4

2. Second-line agents:

   • Amantadine
   • Benzodiazepines (clonazepam)
   • Ginkgo biloba
   • Beta-blockers 1, 4

3. For focal TD symptoms:

   • Botulinum toxin injections can be effective for localized symptoms 4

Evidence for Efficacy in Mood Disorders

Research specifically examining TD treatment in patients with mood disorders has shown:

• Valbenazine demonstrated significant improvements in AIMS total scores at 6 weeks compared to placebo in patients with bipolar or depressive disorders 7
• Sustained improvements were observed through 48 weeks of treatment 7
• Valbenazine was generally well-tolerated without worsening psychiatric symptoms 7

Prevention Strategies

• Limit exposure to dopamine receptor blocking agents when possible
• Use minimum effective doses of antipsychotics when required
• Regular monitoring for early signs of TD using AIMS every 3-6 months
• Document baseline abnormal movements before starting antipsychotics 1
• Avoid anticholinergics (benztropine, trihexyphenidyl) as they may worsen TD symptoms 1

By implementing this treatment approach, clinicians can effectively manage both depression and tardive dyskinesia, improving quality of life and functional outcomes for patients with this challenging combination of conditions.