What is the recommended treatment for bipolar disorder?

Treatment of Bipolar Disorder

Lithium, valproate, or atypical antipsychotics are the recommended first-line treatments for bipolar disorder, with treatment selection based on the specific phase of illness and patient characteristics. 1

First-Line Treatment by Phase

Acute Mania/Mixed Episodes

• Lithium, valproate, or atypical antipsychotics (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) are recommended first-line treatments 1
• For severe presentations, combination therapy with lithium or valproate plus an atypical antipsychotic is recommended 1
• Risperidone is FDA-approved for acute manic or mixed episodes associated with Bipolar I Disorder as monotherapy or adjunctive therapy with lithium or valproate 2
• Olanzapine is FDA-approved for acute treatment of manic or mixed episodes associated with bipolar I disorder, both as monotherapy and as adjunct to valproate or lithium 3

Maintenance Therapy

• The regimen that effectively treated the acute episode should be continued for at least 12-24 months 1, 4
• Some individuals will need lifelong treatment when benefits outweigh risks 4
• Lithium shows superior evidence for prevention of both manic and depressive episodes 1, 5
• Valproate is also effective for maintenance therapy 1
• Withdrawal of maintenance lithium therapy significantly increases risk of relapse, especially within 6 months following discontinuation 4
• Over 90% of adolescents who were noncompliant with lithium treatment relapsed, compared to 37.5% of those who were compliant 4

Bipolar Depression

• Olanzapine-fluoxetine combination is recommended as a first-line option 1
• Antidepressant monotherapy is not recommended due to risk of mood destabilization 1
• Lamotrigine is particularly effective for preventing depressive episodes 1
• For milder depression, a mood stabilizer (especially lithium) may be used as monotherapy 6
• For more severe depression, combining a standard antidepressant with lithium or valproate is recommended 6

Medication Selection Considerations

Lithium

• Lithium is FDA-approved for both acute mania and maintenance therapy in patients age 12 and older 1
• Response rates for lithium are around 38-62% in acute mania 1
• Lithium has the most robust evidence for long-term efficacy and suicide prevention 1, 7
• Baseline laboratory assessment should include complete blood cell counts, thyroid function tests, urinalysis, blood urea nitrogen, creatinine, and serum calcium levels 4
• Once a stable lithium dose is obtained, lithium levels, renal and thyroid function should be monitored every 3-6 months 4
• Target lithium plasma concentration for maintenance is 0.6-0.8mmol/L 7

Valproate

• Valproate shows higher response rates (53%) compared to lithium (38%) in children and adolescents with mania and mixed episodes 1
• Baseline liver function tests, complete blood cell counts, and pregnancy tests are recommended before starting valproate 4
• Serum drug levels, hepatic and hematological indices should be monitored every 3-6 months 4
• A 6-8 week trial using adequate doses is recommended before adding or substituting other mood stabilizers 4

Atypical Antipsychotics

• Atypical antipsychotics may provide more rapid symptom control than mood stabilizers alone 1
• Quetiapine plus valproate is more effective than valproate alone for adolescent mania 1
• Risperidone in combination with either lithium or valproate is effective in open-label trials 1
• Regular monitoring for metabolic side effects is essential, particularly weight gain 1

Special Populations

Adolescents

• Lithium is the only FDA-approved agent for bipolar disorder in youths age 12 and older 1
• Olanzapine is FDA-approved for adolescents (ages 13-17) with schizophrenia and bipolar I disorder 3
• Risperidone is indicated for children and adolescents (ages 10 to 17) with bipolar mania 2
• The increased potential for weight gain and dyslipidemia with atypical antipsychotics may lead clinicians to consider other drugs first in adolescents 3
• Start with lower doses in adolescents (e.g., olanzapine 2.5-5 mg once daily) 3

Comorbid Conditions

ADHD

• Treatment with low-dose mixed amphetamine salts is safe and effective for comorbid ADHD once mood symptoms are stabilized with mood stabilizers 4
• Prioritize mood stabilization before reintroducing stimulants 1

Anxiety

• For anxiety symptoms in bipolar disorder, low-dose benzodiazepines can be used cautiously as needed 1
• Cognitive behavioral therapy (CBT) should be considered as an adjunctive non-pharmacological approach for anxiety management 1

Common Pitfalls to Avoid

• Antidepressant monotherapy can trigger manic episodes or rapid cycling 1, 8
• Inadequate duration of maintenance therapy leads to high relapse rates 1, 4
• Failure to monitor for metabolic side effects of medications, particularly atypical antipsychotics 1
• Overlooking comorbidities such as substance use disorders, anxiety disorders, or ADHD that may complicate treatment 1
• Premature discontinuation of effective medications 4
• Unnecessary polypharmacy while recognizing that many patients will require more than one medication for optimal control 1

Psychosocial Interventions

• Psychoeducation and psychosocial interventions should accompany pharmacotherapy to improve outcomes 1
• Patients and families must be thoroughly educated about early signs and symptoms of mood episodes to enable prompt intervention if relapse occurs 4
• Cognitive-behavioral therapy has strong evidence for both anxiety and depression components of bipolar disorder 1