What medications are used to treat bipolar disorder?

Medications for Bipolar Disorder

First-Line Mood Stabilizers

Lithium is the gold standard medication for bipolar disorder and should be considered the single preferred first-line treatment. 1, 2, 3

• Lithium is FDA-approved for patients age 12 and older for both acute mania and maintenance therapy, with response rates of 38-62% in acute mania 1, 4
• Lithium is the only medication proven effective in preventing manic episodes, depressive episodes, and any mood episodes in non-enriched trials, demonstrating superior long-term efficacy compared to other agents 1, 2
• Lithium uniquely reduces suicide attempts 8.6-fold and completed suicides 9-fold, an effect independent of its mood-stabilizing properties 1
• Therapeutic serum levels should be maintained at 0.8-1.2 mEq/L for acute treatment and 0.6-1.0 mEq/L for maintenance 1, 4

Valproate (Valproic Acid/Depakote) is particularly effective for specific bipolar subtypes 1, 5, 6

• Valproate shows superior efficacy for mixed episodes, dysphoric mania, rapid cycling, and irritability/belligerence compared to lithium 1, 5, 6
• Valproate demonstrates higher response rates (53%) compared to lithium (38%) in children and adolescents with mania and mixed episodes 1
• Therapeutic blood levels should be 40-90 μg/mL (some sources cite 50-100 μg/mL) 1
• Valproate should be avoided in women of childbearing potential when possible due to teratogenic risk and association with polycystic ovary disease 4

Lamotrigine is approved for maintenance therapy 1

• Lamotrigine is particularly effective for preventing depressive episodes in bipolar disorder 1
• Lamotrigine significantly delays time to intervention for any mood episode compared to placebo in maintenance treatment 1
• Critical safety requirement: slow titration is mandatory to minimize risk of Stevens-Johnson syndrome and serious rash 1

First-Line Atypical Antipsychotics

The American Academy of Child and Adolescent Psychiatry recommends atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) as first-line treatments for acute mania alongside lithium and valproate. 1

• Aripiprazole (5-15 mg/day) has a favorable metabolic profile compared to other antipsychotics and is approved for acute mania in adults 1
• Quetiapine is effective for both acute mania and has evidence for bipolar depression, though it carries higher metabolic risk 1, 5
• Olanzapine (5-20 mg/day) provides rapid symptom control for acute mania and is superior to placebo, but is associated with significant weight gain and metabolic effects 1, 7, 8
• Risperidone in combination with lithium or valproate is effective in trials 1
• Lurasidone and cariprazine are newer options with evidence for efficacy 8, 5
• Asenapine is also recommended as a first-line option 8

Combination Therapy for Bipolar Depression

For bipolar depression, the American Academy of Child and Adolescent Psychiatry recommends olanzapine-fluoxetine combination as a first-line option. 1

• Antidepressant monotherapy is contraindicated in bipolar disorder due to risk of mood destabilization, mania induction, and rapid cycling 1, 6
• When antidepressants are used, they must always be combined with a mood stabilizer 1, 6
• SSRIs (particularly fluoxetine, sertraline, or escitalopram) or bupropion are preferred over tricyclic antidepressants when adding to mood stabilizers 1

Combination Strategies for Severe or Treatment-Resistant Cases

Combination therapy with a mood stabilizer (lithium or valproate) plus an atypical antipsychotic is recommended for severe presentations and treatment-resistant mania. 1, 4

• Quetiapine plus valproate is more effective than valproate alone for adolescent mania 1
• Lithium or valproate combined with atypical antipsychotics provides superior efficacy compared to monotherapy 1, 5
• Combination therapy should continue for at least 12-24 months after achieving stability 1, 4

Critical Monitoring Requirements

• Lithium: serum levels, renal function (BUN, creatinine), thyroid function (TSH), urinalysis every 3-6 months 1, 4
• Valproate: serum drug levels, liver function tests, complete blood count every 3-6 months 1, 4
• Atypical antipsychotics: BMI monthly for 3 months then quarterly; blood pressure, fasting glucose, and lipids at 3 months then yearly 1, 4

Common Pitfalls to Avoid

• Never use antidepressant monotherapy as it can trigger manic episodes or rapid cycling 1, 6
• Inadequate duration of maintenance therapy leads to relapse rates exceeding 90% in noncompliant patients versus 37.5% in compliant patients 1
• Failure to monitor for metabolic side effects of atypical antipsychotics, particularly weight gain 1, 7, 8
• Premature discontinuation of effective medications dramatically increases relapse risk, especially within 6 months following lithium discontinuation 1