What medication is appropriate to order for a patient with bipolar disorder, severe without psychotic symptoms, currently on Wellbutrin (bupropion) 150 mg and Abilify (aripiprazole) 400 mg every three weeks?

Medication Management During Admission for Severe Bipolar Disorder

Primary Recommendation

Continue Abilify Maintenance 400 mg every three weeks and discontinue Wellbutrin immediately, as antidepressant monotherapy or inappropriate combination in bipolar disorder carries significant risk of mood destabilization, mania induction, and rapid cycling. 1

Critical Medication Issue: Wellbutrin (Bupropion) in Bipolar Disorder

Bupropion poses the same risks as other antidepressants in precipitating manic episodes in depressed bipolar patients, with 6 of 11 patients (55%) experiencing manic or hypomanic episodes necessitating discontinuation even when stabilized on lithium and carbamazepine or valproate. 2

Evidence Against Bupropion Continuation

• The American Academy of Child and Adolescent Psychiatry explicitly recommends against antidepressant monotherapy or inappropriate combination in bipolar disorder due to risk of mood destabilization, mania induction, and rapid cycling 1
• Antidepressant monotherapy is not recommended due to risk of mood destabilization 1
• When adding antidepressants for bipolar depression, they must always be used in combination with a mood stabilizer (lithium or valproate) to prevent mood destabilization 1

Recommended Medication Orders During Admission

Immediate Actions

• Discontinue Wellbutrin 150 mg immediately 1, 2
• Continue Abilify Maintenance 400 mg every three weeks (aripiprazole is recommended as first-line treatment for acute mania and maintenance therapy) 1, 3

Add Mood Stabilizer Foundation

Initiate lithium or valproate as the foundational mood stabilizer, as combination therapy with a mood stabilizer plus an atypical antipsychotic provides superior efficacy for both acute symptom control and relapse prevention. 1, 4

Option 1: Lithium (Preferred for Long-Term Outcomes)

• Start lithium 300 mg three times daily (900 mg/day total) for patients weighing ≥30 kg 1
• Target therapeutic level: 0.8-1.2 mEq/L for acute treatment 1
• Lithium shows superior evidence for long-term efficacy in maintenance therapy and reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties 1, 5
• Baseline labs required: complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females 1
• Ongoing monitoring: lithium levels, renal and thyroid function, urinalysis every 3-6 months 1

Option 2: Valproate (Preferred for Mixed/Dysphoric Features)

• Start valproate 125 mg twice daily, titrate to therapeutic blood level (50-100 mcg/mL) 1, 4
• Valproate is particularly effective for mixed or dysphoric mania, irritability, agitation, and aggressive behaviors 1, 4
• Baseline labs required: liver function tests, complete blood count with platelets, pregnancy test in females 1
• Ongoing monitoring: valproate levels, hepatic function, hematological indices every 3-6 months 1

Adjunctive Medications for Acute Symptom Management

For Agitation or Severe Symptoms

• Benzodiazepines (lorazepam 1-2 mg every 4-6 hours as needed) combined with aripiprazole provide superior acute control of agitation compared to either agent alone 1
• Benzodiazepines should be time-limited (days to weeks) to avoid tolerance and dependence 1
• Low-dose lorazepam (0.25-0.5 mg PRN) can be administered orally or sublingually for rapid onset, with lower doses minimizing sedation while providing anxiolytic effects 1

For Persistent Depressive Symptoms (After Mood Stabilizer Established)

• If depressive symptoms persist after 4-6 weeks on therapeutic mood stabilizer levels, consider adding lamotrigine rather than reintroducing an antidepressant 1, 5
• Lamotrigine specifically targets the depressive pole of bipolar disorder and is FDA-approved for maintenance therapy 1, 5
• Start lamotrigine at 25 mg daily for 2 weeks, then 50 mg daily for 2 weeks, then 100 mg daily for 1 week, then target 200 mg daily 5
• Critical safety requirement: Slow titration of lamotrigine is mandatory to minimize risk of Stevens-Johnson syndrome and serious rash 1, 5

Treatment Algorithm for This Admission

Week 1-2: Stabilization Phase

1. Discontinue Wellbutrin immediately 1, 2
2. Continue Abilify Maintenance 400 mg every three weeks 1, 3
3. Initiate lithium or valproate (choice based on symptom profile: lithium for classic mania, valproate for mixed/dysphoric features) 1, 4
4. Add PRN lorazepam 0.5-2 mg for agitation (maximum 2-3 times weekly for PRN use) 1
5. Order baseline labs before starting mood stabilizer 1

Week 2-4: Optimization Phase

1. Titrate mood stabilizer to therapeutic levels (lithium 0.8-1.2 mEq/L or valproate 50-100 mcg/mL) 1
2. Monitor mood symptoms weekly 1
3. Taper benzodiazepines as mood stabilizes 1
4. Assess for ongoing depressive symptoms 1

Week 4-8: Maintenance Planning

1. If depressive symptoms persist despite therapeutic mood stabilizer levels, consider adding lamotrigine 1, 5
2. Continue combination therapy (mood stabilizer + aripiprazole) for at least 12-24 months 1
3. Schedule follow-up every 1-2 weeks initially, then monthly once stable 1

Critical Pitfalls to Avoid

• Never use antidepressant monotherapy in bipolar disorder - this triggers mood destabilization, mania induction, and rapid cycling 1
• Avoid premature discontinuation of maintenance therapy - withdrawal is associated with relapse rates exceeding 90% in noncompliant patients versus 37.5% in compliant patients 1
• Do not rapid-load lamotrigine - this dramatically increases risk of Stevens-Johnson syndrome 1
• Inadequate duration of maintenance therapy leads to high relapse rates - continue for at least 12-24 months after stabilization 1

Rationale for Combination Therapy

The combination of aripiprazole with a mood stabilizer (lithium or valproate) is recommended as first-line treatment for severe bipolar disorder, offering superior efficacy compared to monotherapy for both acute symptom control and relapse prevention. 1, 4, 6

• Combination therapy with lithium or valproate plus an atypical antipsychotic is recommended for severe presentations and represents a first-line approach for treatment-resistant mania 1
• The combination of aripiprazole and mood stabilizers offers an effective and relatively well-tolerated option with lower risk of metabolic side effects compared with other combination therapies 6
• Aripiprazole has a favorable metabolic profile compared to olanzapine 1

Monitoring Requirements During Admission

For Lithium

• Check lithium level after 5 days at steady-state dosing 1
• Monitor for signs of lithium toxicity: fine tremor, nausea, diarrhea (early signs); coarse tremor, confusion, ataxia (seek immediate medical attention) 1

For Valproate

• Check valproate level after 5-7 days at stable dosing 1
• Monitor liver function tests and complete blood count at 1 month, then every 3-6 months 1

For Aripiprazole

• Monitor body mass index monthly for 3 months then quarterly 1
• Monitor blood pressure, fasting glucose, and lipids at 3 months then yearly 1

Psychosocial Interventions

• Provide psychoeducation about symptoms, course of illness, treatment options, and critical importance of medication adherence 1
• Cognitive-behavioral therapy has strong evidence for both depressive and anxiety components of bipolar disorder 1
• Family-focused therapy helps with medication supervision, early warning sign identification, and reducing access to lethal means 1