What medications are used to treat bipolar disorder?

Medications for Bipolar Disorder Treatment

Mood stabilizers, antipsychotics, and anticonvulsants are the cornerstone medications for treating bipolar disorder, with lithium remaining the most effective overall treatment despite being available for over 50 years. 1, 2

First-Line Medications

Mood Stabilizers

• Lithium
  • Gold standard treatment with proven efficacy for:
    • Acute mania
    • Maintenance treatment (strongest evidence)
    • Prevention of both manic and depressive episodes
    • Suicide risk reduction (strong consensus across guidelines) 3
  • Target plasma concentration: 0.6-0.8 mmol/L for maintenance 3
  • Monitoring requirements:
    • Regular renal and thyroid function tests
    • Plasma level monitoring

Anticonvulsants

• Valproate
  • Effective for acute mania and maintenance
  • Often used in combination with lithium initially 4
• Lamotrigine
  • Particularly effective for preventing depressive episodes 1

Atypical Antipsychotics

• Olanzapine (Zyprexa)
  • FDA-approved for:
    • Schizophrenia
    • Acute manic/mixed episodes in bipolar I disorder
    • Maintenance treatment of bipolar I disorder
    • Treatment of bipolar depression (when combined with fluoxetine) 5
  • Side effect concerns:
    • Weight gain (particularly in adolescents)
    • Metabolic effects (hyperglycemia, hyperlipidemia)
    • Increased mortality in elderly patients with dementia 5
• Other effective antipsychotics:
  • Quetiapine
  • Aripiprazole
  • Asenapine
  • Lurasidone
  • Cariprazine 1

Treatment by Phase of Illness

Acute Mania

• First-line options:
  • Lithium
  • Valproate
  • Atypical antipsychotics
• For severe agitation: Antipsychotics may be preferred initially over lithium 3
• Combination therapy (lithium + antipsychotic or valproate + antipsychotic) often needed for severe cases

Acute Bipolar Depression

• First-line options:
  • Quetiapine
  • Lurasidone
  • Olanzapine + fluoxetine combination
  • Lamotrigine
• Lithium has modest evidence for acute bipolar depression 3
• Caution: Antidepressant monotherapy is NOT recommended due to risk of mood switching 1

Maintenance Treatment

• Lithium has the strongest evidence for long-term maintenance 4, 3
• Most patients who respond to combination therapy during acute episodes will require ongoing medication to prevent relapse 4
• Maintenance regimen should typically continue for 12-24 months minimum, with some patients requiring lifelong therapy 4

Special Populations

Adolescents (13-17 years)

• Lithium, olanzapine, and valproate can be effective
• Lower doses may achieve therapeutic lithium levels (0.6-0.8 mmol/L) 3
• Consider increased risk of weight gain and metabolic effects with olanzapine 5
• For comorbid ADHD: Stimulants may be added once mood is stabilized on mood stabilizers 4

Elderly Patients

• Target lower lithium levels initially
• Increased risk of side effects and drug interactions
• Avoid antipsychotics in dementia due to mortality risk 5

Important Clinical Considerations

1. Adherence challenges: More than 50% of patients are non-adherent to treatment 1

   • Single daily dosing of lithium may improve compliance compared to multiple daily doses 6

2. Monitoring requirements:

   • Lithium: Renal function, thyroid function, plasma levels
   • Antipsychotics: Weight, blood glucose, lipids

3. Relapse risk:

   • 90% of adolescents who are non-compliant with lithium relapse 4

   • Even with compliance, relapse rates remain significant (37.5% in compliant adolescents) 4

4. Physical health monitoring:

   • Essential due to increased cardiovascular mortality (1.6-2 fold) and reduced life expectancy (12-14 years) in bipolar disorder 1
   • Higher rates of metabolic syndrome (37%), obesity (21%), and diabetes (14%) 1

5. Suicide risk:

   • Annual suicide rate approximately 0.9% (vs 0.014% general population) 1
   • 15-20% of people with bipolar disorder die by suicide 1
   • Lithium significantly reduces suicide risk 3

Bipolar disorder treatment is complex and often requires combination therapy. While newer medications have expanded treatment options, lithium remains the most effective overall treatment with the strongest evidence for long-term maintenance and suicide prevention.