What are the recommended medications for treating bipolar disorder?

Recommended Medications for Bipolar Disorder

Lithium, valproate, and atypical antipsychotics are the primary pharmacological treatments for bipolar disorder, with specific medication selection based on the phase of illness and symptom presentation. 1

First-Line Treatments for Bipolar Disorder

Acute Mania Treatment

• Lithium is FDA-approved for acute mania and maintenance therapy (down to age 12) and remains a cornerstone treatment with strong evidence for preventing manic episodes 1
• Valproate is FDA-approved for acute mania in adults and is particularly effective for mixed or dysphoric subtypes of mania 1
• Atypical antipsychotics approved for acute mania include aripiprazole, olanzapine, risperidone, quetiapine, and ziprasidone 1, 2
• Haloperidol is recommended for bipolar mania, with second-generation antipsychotics as alternatives when availability and cost allow 1
• For severe or treatment-resistant mania, combination therapy with lithium or valproate plus an atypical antipsychotic is recommended 1

Bipolar Depression Treatment

• The combination of olanzapine and fluoxetine is FDA-approved for bipolar depression in adults 1, 2
• Quetiapine monotherapy is effective for acute depressive episodes associated with bipolar disorder 3, 4
• Lamotrigine has demonstrated efficacy for bipolar depression, particularly in bipolar II disorder 1, 5
• Antidepressants should always be used in combination with a mood stabilizer (lithium or valproate) to prevent triggering manic episodes 1
• SSRIs (particularly fluoxetine) are preferred over tricyclic antidepressants when an antidepressant is needed 1

Maintenance Treatment

• Lithium or valproate should be used for maintenance treatment of bipolar disorder, continuing for at least 2 years after the last episode 1, 6
• Lamotrigine and olanzapine are FDA-approved for maintenance therapy in adults 1, 7
• Quetiapine is indicated for maintenance treatment of bipolar I disorder as an adjunct to lithium or divalproex 3, 6
• Aripiprazole, ziprasidone, and risperidone long-acting injection are effective in preventing mania but not depression during maintenance treatment 6

Treatment Algorithm Based on Symptom Presentation

For Manic Episodes:

1. Start with lithium or valproate monotherapy (valproate preferred for mixed/dysphoric mania) 1, 8
2. If inadequate response, combine lithium and valproate 8
3. If still inadequate, add an atypical antipsychotic (olanzapine, risperidone, quetiapine, aripiprazole) 1, 4
4. For severe agitation, consider short-term benzodiazepines (caution in younger patients due to potential disinhibition) 1

For Depressive Episodes:

1. For mild depression: Lithium, lamotrigine, or valproate monotherapy 1, 5
2. For moderate-severe depression: Combine lithium or valproate with an SSRI or bupropion 1, 8
3. Consider olanzapine-fluoxetine combination for treatment-resistant bipolar depression 2
4. Taper antidepressants 2-6 months after remission to reduce risk of cycling 8

For Maintenance/Prevention:

1. Continue the effective acute treatment regimen 1
2. Lithium has stronger evidence for preventing mania than depression 6, 5
3. Lamotrigine has stronger evidence for preventing depression than mania 6
4. Olanzapine and quetiapine have bimodal efficacy in preventing both mania and depression 6, 7

Special Considerations

• For rapid cycling: Divalproex monotherapy is recommended as initial treatment 8
• For psychotic features: Add an atypical antipsychotic (olanzapine or risperidone preferred over conventional antipsychotics) 8, 4
• Clozapine should be reserved for treatment-refractory cases due to its side-effect profile 1
• Combination therapy is often necessary for optimal management, as manic symptoms may respond best to one agent and depressive symptoms to another 5
• Careful monitoring for metabolic side effects is essential with atypical antipsychotics, particularly weight gain, hyperglycemia, and dyslipidemia 2
• Antidepressants may destabilize mood or trigger manic episodes if used without mood stabilizers 1

Monitoring and Adjustments

• Regular monitoring of medication blood levels is required for lithium therapy 1
• Weight monitoring is essential with atypical antipsychotics, particularly olanzapine 2, 7
• Medication selection should consider side effect profiles, with atypical antipsychotics having lower risk of extrapyramidal symptoms but higher risk of metabolic effects 2
• Psychoeducation should be routinely offered alongside pharmacotherapy 1