In a patient recently hospitalized for fluid overload and shortness of breath, with diagnoses of Bipolar II disorder, Generalized Anxiety Disorder, Psychophysiologic Insomnia, Cognitive Communication Deficit, Drug‑induced Subacute Dyskinesia, Morbid Obesity, and Moderate Recurrent Major Depressive Disorder, who is currently taking sertraline, loratadine, gabapentin, lisinopril, furosemide, topical nystatin‑triamcinolone and mupirocin, buspirone, aspirin, topiramate, albuterol, oxycodone‑acetaminophen, albuterol‑budesonide, and fluticasone propionate, would starting Austedo (lurasidone) be safe, and if so what initial dose should be used and what additional medications need to be started?

Updated Provider Note: Medication Management for Bipolar II Disorder with Drug-Induced Dyskinesia

This patient requires immediate reinitiation of mood stabilization therapy with lithium or valproate as first-line treatment for Bipolar II disorder, and Austedo (deutetrabenazine) should be started at 6 mg twice daily (12 mg/day total) for the drug-induced subacute dyskinesia that was not adequately controlled by valbenazine. 1

Clinical Context

This patient presents with multiple psychiatric diagnoses following hospitalization for fluid overload/SOB where all psychiatric medications were discontinued. The primary concerns are:

• Bipolar II disorder (F31.81) - currently untreated, high risk for mood destabilization
• Drug-induced subacute dyskinesia (G24.01) - previously treated with valbenazine 60 mg without complete resolution
• Moderate recurrent major depressive disorder (F33.1) - currently on sertraline 150 mg daily
• Generalized anxiety disorder (F41.1) - currently on buspirone 5 mg BID

Critical Medication Issues

1. Sertraline Monotherapy is Contraindicated in Bipolar II Disorder

The patient is currently taking sertraline 150 mg daily without a mood stabilizer, which poses significant risk. Antidepressants should never be used as monotherapy in bipolar disorder as they may destabilize mood or precipitate manic/hypomanic episodes 2. The guidelines explicitly state that antidepressants may only be used as adjuncts when the patient is also taking at least one mood stabilizer 2.

2. Mood Stabilizer Must Be Initiated Immediately

Standard therapy for Bipolar II disorder includes lithium, valproate, and/or atypical antipsychotic agents 2. The choice should be based on:

• Evidence of efficacy
• Phase of illness (currently depressive)
• Side effect profile
• Patient's history of medication response
• Patient/family preferences

Recommended approach:

• First-line: Lithium - Gold standard with antimanic, antidepressant, and anti-suicide effects 3. However, requires close monitoring (renal function, thyroid, lithium levels). Given this patient's recent fluid overload and current furosemide use, careful monitoring is essential.

• Alternative: Valproate - Effective for acute mania and maintenance. May be preferable given cardiac/renal considerations from recent hospitalization.

• Lamotrigine - Particularly effective for bipolar depression and prevention 2, 4. Given the patient's current depressive predominance (F33.1), this is a strong consideration, though titration is slow (requires 6-8 weeks to reach therapeutic dose).

3. Austedo for Drug-Induced Dyskinesia

Yes, Austedo (deutetrabenazine) is safe to start and is specifically FDA-approved for tardive dyskinesia and chorea 1. Since valbenazine (Ingrezza) 60 mg did not completely resolve the dyskinesia:

Dosing protocol for Austedo:

• Start: 6 mg twice daily (12 mg/day total) with food 1
• Titration: Increase by 6 mg/day weekly based on reduction of dyskinesia and tolerability 1
• Maximum: 48 mg/day (or 36 mg/day if patient is a poor CYP2D6 metabolizer) 1
• Administration: Must be taken with food; tablets must be swallowed whole 1

Important consideration: The patient is currently on sertraline, which is a moderate CYP2D6 inhibitor. This may increase deutetrabenazine levels, requiring more cautious titration and potentially lower maximum doses.

Recommended Medication Plan

Immediate Actions:

1. Initiate mood stabilizer (choose one):

   • Lithium 150-300 mg daily (target level 0.6-1.0 mEq/L for acute treatment, 0.4-0.8 mEq/L for maintenance) - requires baseline labs (renal function, thyroid, ECG) and weekly monitoring initially
   • OR Valproate 250 mg BID, titrate to therapeutic level (50-125 mcg/mL)
   • OR Lamotrigine 25 mg daily, slow titration per package insert to reduce Stevens-Johnson syndrome risk

2. Start Austedo 6 mg BID with food 1

3. Continue sertraline 150 mg daily only after mood stabilizer is established (can be used as adjunct with mood stabilizer) 2

4. Continue buspirone 5 mg BID for anxiety

Medications to Continue:

• Gabapentin 300 mg TID (neuropathy)
• Lisinopril 40 mg daily (hypertension)
• Furosemide 40 mg daily (fluid management) - monitor closely with lithium if chosen
• Topiramate 50 mg BID (seizure prophylaxis) - note: has mood-stabilizing properties but insufficient evidence as monotherapy 2
• Other medical medications as prescribed

Critical Monitoring:

• If lithium chosen: Baseline and weekly lithium levels, renal function, thyroid function, ECG. Watch for lithium toxicity signs (tremor, confusion, ataxia) especially given concurrent furosemide use.

• If valproate chosen: Baseline and periodic liver function tests, CBC, ammonia levels if indicated.

• For Austedo: Monitor for depression/suicidality (black box warning for tetrabenazine class), parkinsonism, akathisia, sedation. Assess dyskinesia severity at each visit.

• Mood monitoring: Weekly initially for mood destabilization, suicidality (bipolar disorder has 0.9% annual suicide rate vs 0.014% general population) 4.

Insomnia Management

The patient has psychophysiologic insomnia (F51.04). Sleep hygiene alone is insufficient and should be combined with other therapies 5. Given the psychiatric complexity:

• First-line: Cognitive behavioral therapy for insomnia (CBT-I) 6
• Pharmacologic options if needed:
  • Trazodone 25-100 mg at bedtime 5, 7
  • Avoid benzodiazepines long-term given bipolar disorder
  • Consider ramelteon or short-acting BzRA if non-response to above 5

Common Pitfalls to Avoid

1. Do not continue antidepressant monotherapy - This is the most critical error. Sertraline without mood stabilizer risks mood destabilization.

2. Do not use typical antipsychotics for mood stabilization - While aripiprazole was previously prescribed and is FDA-approved for bipolar disorder 2, atypical antipsychotics should be considered after or alongside mood stabilizers, not as sole agents.

3. Monitor drug interactions carefully - Sertraline inhibits CYP2D6, affecting Austedo metabolism. Topiramate may interact with other medications.

4. Watch for metabolic syndrome - Patient has morbid obesity (E66.01). Many mood stabilizers and antipsychotics cause weight gain. Consider metformin prophylaxis if starting olanzapine or clozapine 8.

5. Lithium-diuretic interaction - Furosemide can increase lithium levels and risk toxicity. If lithium is chosen, more frequent monitoring is essential, and dose adjustments may be needed.

Follow-Up Schedule

• Week 1-4: Weekly visits to assess mood stability, medication tolerability, dyskinesia improvement
• Week 4-12: Every 2 weeks if stable
• After 12 weeks: Monthly maintenance visits with ongoing monitoring of mood, medication levels, metabolic parameters, and dyskinesia

The goal is mood stabilization, reduction of dyskinesia, and prevention of future mood episodes while minimizing polypharmacy and metabolic complications.