What is the treatment for bipolar disorder?

Treatment of Bipolar Disorder

Pharmacotherapy is the primary treatment for bipolar disorder, with lithium, valproate, and atypical antipsychotics as first-line options depending on the phase of illness. 1, 2

First-Line Treatment by Phase of Illness

Acute Mania/Mixed Episodes

• Start with lithium, valproate, or an atypical antipsychotic (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) 1, 2
• For severe presentations, consider combination therapy with lithium or valproate plus an atypical antipsychotic 2
• Lithium is FDA-approved for acute mania in patients 12 years and older 1, 2
• Atypical antipsychotics have FDA approval for acute mania in adults 1, 3, 4
• Risperidone is indicated for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder as monotherapy or as adjunctive therapy with lithium or valproate 4

Maintenance Therapy

• Continue the regimen that effectively treated the acute episode for at least 12-24 months 2, 5
• Lithium shows superior evidence for prevention of both manic and depressive episodes 2, 6
• Lamotrigine is approved for maintenance therapy in adults and is particularly effective for preventing depressive episodes 1, 5
• Olanzapine is approved for maintenance therapy in adults 1, 3
• Regular monitoring of medication levels, metabolic parameters, and organ function is essential 2

Bipolar Depression

• Olanzapine-fluoxetine combination is FDA-approved for bipolar depression in adults 1, 2, 3
• Lamotrigine is effective for bipolar depression, particularly for prevention of depressive episodes 5, 7
• For milder depression, a mood stabilizer (lithium, valproate, or lamotrigine) may be used as monotherapy 2
• For more severe depression, combine a mood stabilizer with an antidepressant (bupropion, SSRI, or venlafaxine preferred) 2
• Antidepressant monotherapy is not recommended due to risk of mood destabilization 2, 5

Medication Selection Algorithm

1. First Episode of Mania/Mixed Episode:

   • Start with lithium (if no contraindications) or valproate 2, 5
   • Alternative: Atypical antipsychotic (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) 1, 2

2. Rapid Cycling Bipolar Disorder:

   • Valproate monotherapy is recommended as initial treatment 2, 8
   • Consider lithium-lamotrigine combination for prevention of both mania and depression 7

3. Bipolar Depression:

   • First-line: Olanzapine-fluoxetine combination 1, 2
   • Alternatives: Lithium, lamotrigine, or valproate 2, 5
   • For more severe depression: Add an antidepressant to a mood stabilizer 2

4. Maintenance Therapy:

   • Lithium is the gold standard with strongest evidence for long-term efficacy 2, 6, 9
   • Target lithium plasma concentration: 0.6-0.8 mmol/L 6
   • Alternatives: Valproate, lamotrigine, or atypical antipsychotics 2, 10

Monitoring Requirements

• Lithium:

  • Baseline: Renal function, thyroid function, electrolytes, pregnancy test 2, 6
  • Regular monitoring: Serum lithium levels (target 0.6-0.8 mmol/L), renal and thyroid function every 3-6 months 2, 6

• Valproate:

  • Baseline: Liver function tests, complete blood count, pregnancy test 2, 5
  • Regular monitoring: Serum drug levels, hepatic function, hematological indices every 3-6 months 2, 5

• Atypical Antipsychotics:

  • Baseline: Weight, BMI, waist circumference, blood pressure, fasting glucose, lipid profile 2, 3
  • Regular monitoring: Weight, metabolic parameters, movement disorders 2, 3

Important Clinical Considerations

• Avoid unnecessary polypharmacy while recognizing that many patients will require more than one medication for optimal control 1, 2
• Antidepressant monotherapy can trigger manic episodes or rapid cycling 1, 2, 5
• Lithium significantly reduces suicide risk (8.6-fold reduction in suicide attempt recurrence) 5, 9
• Psychoeducation and psychosocial interventions should accompany pharmacotherapy 2, 5
• Regular assessment of treatment response using standardized instruments is recommended 2

Common Pitfalls to Avoid

• Using antidepressants as monotherapy in bipolar disorder 2, 5
• Inadequate duration of maintenance therapy (should be at least 12-24 months) 2, 5
• Failure to monitor for metabolic side effects, particularly with atypical antipsychotics 2, 3
• Premature discontinuation of lithium, which can lead to a 7-fold increase in suicide attempts 5
• Overlooking comorbidities such as substance use disorders, anxiety disorders, or ADHD 2

Special Populations

• Adolescents (ages 13-17):

  • Start with lower doses (lithium 2.5-5 mg daily; target 10 mg/day) 1, 2
  • Consider increased potential for weight gain and metabolic effects with atypical antipsychotics 1, 3
  • Lithium is FDA-approved for ages 12 and older 1, 2

• Self-Harm Risk:

  • Lithium is preferred due to significant reduction in suicide risk 5
  • Regular monitoring for suicidal ideation is essential 5
  • Family involvement is crucial to help restrict access to lethal means 5