What are the best medications for treating Bipolar II (Bipolar Disorder Type II) mixed episodes?

Best Medications for Bipolar II Mixed Episodes

For Bipolar II mixed episodes, a combination of a mood stabilizer (preferably lamotrigine) with an atypical antipsychotic (preferably aripiprazole) is the most effective treatment approach. 1

First-Line Treatment Options

Mood Stabilizers

• Lamotrigine: Preferred mood stabilizer for Bipolar II due to its:

  • Efficacy specifically for bipolar II depression 1
  • Metabolically neutral profile 1
  • Effectiveness in preventing depressive recurrences 2

• Valproate: Strong evidence for efficacy in mixed states 3, 4

  • Requires baseline and periodic monitoring of:
    • Liver function tests
    • Complete blood counts
    • Pregnancy tests in females of childbearing potential 1
  • Monitor serum drug levels, hepatic function, and hematological indices every 3-6 months 1
  • Be aware of risks including gastrointestinal disorders, neuropsychological disorders, rare severe hepatitis/pancreatitis, and potential polycystic ovary disease in females 1

• Lithium: Less evidence for mixed states specifically 3

  • Can be effective as part of combination therapy 3
  • Supported by several older controlled studies for long-term prevention 2
  • Cardiovascular monitoring needed (can cause bradycardia, T-wave changes, AV-block) 1

Atypical Antipsychotics

• Aripiprazole: Preferred due to:

  • Efficacy for mixed features 4
  • Lower risk of weight gain and metabolic effects 1

• Other effective options with evidence in mixed states:

  • Olanzapine 3, 4
  • Quetiapine 5
  • Risperidone 4
  • Ziprasidone 4
  • Asenapine 4
  • Cariprazine 4

Treatment Algorithm

1. Initial Assessment:

   • Confirm Bipolar II diagnosis with history of hypomania and depression
   • Assess severity of mixed features
   • Evaluate metabolic and cardiovascular risk factors

2. First-line approach:

   • Start with lamotrigine + aripiprazole combination
   • Alternative: valproate + atypical antipsychotic for more severe presentations

3. Monotherapy options (for milder presentations):

   • Lamotrigine for predominantly depressive symptoms
   • Valproate for more balanced mixed presentations
   • Quetiapine has demonstrated efficacy in controlled trials 5

4. Treatment-resistant cases:

   • Consider lithium augmentation
   • Try alternative atypical antipsychotic
   • Consider combinations of mood stabilizers

Monitoring and Safety

• For atypical antipsychotics, obtain baseline:

  • Body mass index
  • Waist circumference
  • Blood pressure
  • Fasting glucose
  • Lipid panel 1

• Follow-up monitoring:

  • Monthly BMI for first 3 months, then quarterly
  • Blood pressure, glucose, and lipids after 3 months and then yearly 1

Common Pitfalls to Avoid

1. Antidepressant monotherapy: May worsen mixed features and trigger rapid cycling 1, 2

   • If antidepressants are necessary, bupropion has lower switch risk than sertraline 1
   • Always combine antidepressants with mood stabilizers

2. Inadequate duration of treatment: Most patients require ongoing medication to prevent relapse 1

   • Maintenance treatment should continue for at least 2 years after the last episode 1

3. Abrupt discontinuation: Can lead to withdrawal symptoms and rapid relapse 1

   • Use gradual tapering when discontinuation is necessary
   • Close monitoring for mood destabilization during tapering

4. Underdiagnosis of Bipolar II: Often misdiagnosed as unipolar depression 2

   • Carefully assess for history of hypomania, particularly focusing on increased goal-directed activity rather than just mood changes 2

5. Stimulant use before mood stabilization: Can precipitate or worsen manic episodes 1

   • Low-dose mixed amphetamine salts can be considered only after mood is stabilized 1

Remember that psychoeducational therapy, family-focused therapy, interpersonal and social rhythm therapy, and cognitive-behavioral therapy are important adjuncts to medication management 1.