What is the best treatment regimen for bipolar disorder with mixed features?

From the Guidelines

The best treatment regimen for bipolar disorder with mixed features typically involves a combination of mood stabilizers, antipsychotics, and psychotherapy, with first-line medication options including lithium, valproate, or lamotrigine, often combined with an atypical antipsychotic like quetiapine, olanzapine, or aripiprazole 1.

Key Considerations

• Mood stabilizers such as lithium (600-1200 mg/day), valproate (750-1500 mg/day), or lamotrigine (100-200 mg/day) are commonly used to treat bipolar disorder with mixed features.
• Atypical antipsychotics like quetiapine (300-800 mg/day), olanzapine (5-20 mg/day), or aripiprazole (10-30 mg/day) may be particularly effective at controlling both manic and depressive symptoms simultaneously.
• Antidepressants are generally avoided as monotherapy as they may worsen mixed states or trigger rapid cycling, but may be used as adjuncts for depression as long as the patient is also taking at least one mood stabilizer 1.

Treatment Approach

• Treatment should be initiated promptly and medication doses adjusted based on symptom response and blood levels (for lithium and valproate) 1.
• Psychotherapy approaches like cognitive behavioral therapy, interpersonal therapy, and family-focused therapy should complement medication management.
• Regular monitoring of medication blood levels, metabolic parameters, and kidney/liver function is essential.

Maintenance Therapy

• Treatment is typically long-term, with maintenance therapy continuing even after symptoms resolve to prevent relapse 1.
• The regimen needed to stabilize acute mania should be maintained for 12 to 24 months, with some individuals needing lifelong therapy when the benefits of continued treatment outweigh the risks.
• Any attempts to discontinue prophylactic therapy should be done gradually, while closely monitoring the patient for relapse.

From the FDA Drug Label

1. 2 Bipolar I Disorder (Manic or Mixed Episodes) Monotherapy — Oral ZYPREXA is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder Adjunctive Therapy to Lithium or Valproate — Oral ZYPREXA is indicated for the treatment of manic or mixed episodes associated with bipolar I disorder as an adjunct to lithium or valproate.

The best treatment regimen for bipolar disorder with mixed features is monotherapy with olanzapine (PO) or adjunctive therapy with olanzapine (PO) to lithium or valproate 2.

• Monotherapy: olanzapine (PO) is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder.
• Adjunctive therapy: olanzapine (PO) is indicated for the treatment of manic or mixed episodes associated with bipolar I disorder as an adjunct to lithium or valproate. Risperidone (PO) is also an option for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder, as monotherapy or adjunctive therapy with lithium or valproate 3.

From the Research

Treatment Options for Bipolar Disorder with Mixed Features

• The treatment of mixed bipolar states is associated with more severe symptoms and outcome, and there is a need for more randomized clinical studies and post-hoc analyses on this topic 4.
• Atypical antipsychotic monotherapy has been shown to improve both manic and depressive symptoms in mixed episodes, and the combination of a mood stabilizer and an atypical antipsychotic may increase this effect 4, 5.
• Valproate and carbamazepine are effective in acute mixed episodes, but the efficacy of lithium appears questionable 4.
• The use of atypical antipsychotic-antidepressant combination for acute mixed depression does not increase the risk for mania, but its superior efficacy compared to atypical antipsychotic monotherapy is not supported by current data 4.

Efficacy of Specific Agents

• Second-generation antipsychotics (SGAs) have been shown to be efficacious in the acute treatment of bipolar disorder mood episodes with mixed features, including mania with mixed features and bipolar depression with mixed features 6, 5.
• Specific SGAs that have been studied include aripiprazole, asenapine, cariprazine, olanzapine, risperidone, and ziprasidone, with preliminary positive data for their use in treating acute mania with mixed features and depressive symptoms in depression with mixed features 5.
• Divalproex may also be efficacious for acute mania with mixed features, and has been shown to have long-term efficacy in preventing mixed features 5.

Maintenance Treatment

• Atypical antipsychotic monotherapy has been associated with a lower incidence of and a longer time to relapse of any kind in patients with mixed bipolar states 4.
• The augmentation of lithium or divalproex with atypical antipsychotics may increase prophylactic efficacy, but lithium or divalproex monotherapy have not been associated with significant prophylactic benefits following mixed mania 4.
• Further study is needed to assess the efficacy, safety, and tolerability of treatments specifically for bipolar disorder mood episodes with mixed features, including maintenance and neurostimulation therapies 6, 5.