What is the recommended medication guidance for selecting and sequencing pharmacotherapies, including mood stabilizers and antipsychotics, for the treatment of bipolar disorder?

From the Guidelines

Medication guidance for bipolar disorder typically follows a stepwise approach, starting with mood stabilizers as first-line treatments, such as lithium, valproate, and lamotrigine, due to their proven efficacy in preventing both manic and depressive episodes and reducing suicide risk, as supported by studies 1. The selection of medications and the order in which to trial them for the treatment of bipolar disorder should be based on the patient's specific symptoms, predominant polarity, previous treatment response, side effect profile, and comorbidities.

• Mood stabilizers, such as lithium and valproate, are often considered first-line options due to their efficacy in treating acute mania and preventing relapse, as noted in studies 1.
• Second-generation antipsychotics, such as quetiapine, olanzapine, risperidone, and aripiprazole, are also first-line options, especially for acute mania, as supported by studies 1.
• If monotherapy is insufficient, combination therapy is typically tried next, such as lithium plus an antipsychotic or valproate plus an antipsychotic, as suggested by studies 1.
• For treatment-resistant cases, additional options include carbamazepine, oxcarbazepine, or adding antidepressants, though these must be used cautiously due to the risk of triggering mania, as noted in studies 1. Regular monitoring of medication levels, side effects, and overall mood stability is essential for optimal management of bipolar disorder, as emphasized in studies 1. Key considerations in medication selection include:
• The patient's specific symptoms and predominant polarity
• Previous treatment response and side effect profile
• Comorbidities, such as ADHD or substance abuse
• The potential for medication interactions and side effects
• The need for ongoing maintenance therapy to prevent relapse, as supported by studies 1.

From the Research

Medication Guidance for Bipolar Treatment

The selection of medications for the treatment of bipolar disorder involves considering various factors, including the type of episode (depressive or manic), the patient's medical history, and potential side effects.

• The first-line treatment options for bipolar depression include:
  • Olanzapine + fluoxetine combination 2
  • Quetiapine (immediate or extended release) 2, 3
  • Lurasidone (monotherapy or adjunctive to lithium or valproate) 2, 3
• For maintenance treatment, the recommended options are:
  • Lithium 4, 5, 6
  • Lamotrigine 4, 6
  • Valproate 4, 6
  • Quetiapine 4, 6
  • Aripiprazole 4, 6
• Antidepressants are not recommended as monotherapy for bipolar depression, but may be used in combination with mood stabilizers or antipsychotics 4, 2, 3
• The order of trialing medications may vary depending on the patient's specific needs and circumstances, but generally, the treatment should start with a mood stabilizer or an antipsychotic, followed by the addition of an antidepressant if necessary 4, 2, 3

Considerations for Medication Selection

When selecting medications for bipolar treatment, it is essential to consider the potential side effects and the likelihood of the patient being helped or harmed.

• The number needed to treat (NNT) and the number needed to harm (NNH) can be used to quantify the efficacy and tolerability of different medications 3
• The likelihood to be helped or harmed (LHH) metric can illustrate the tradeoffs inherent in selecting medications 3
• Individualizing treatment decisions requires consideration of the different potential adverse events that are more likely to occur with each medication 3