What is the treatment for bipolar depression?

From the Guidelines

Bipolar depression should be treated with a combination of mood stabilizers and antidepressants, with lithium or valproate as the primary mood stabilizer, and selective serotonin reuptake inhibitors (SSRI) as the preferred antidepressant, always used in combination with a mood stabilizer to prevent triggering mania. When managing bipolar depression, it is crucial to consider the risk of triggering manic episodes, which makes the medication strategy more complex compared to unipolar depression 1. The treatment approach should prioritize mood stabilizers, with lithium (600-1200 mg/day) or valproate being commonly used options 1. Antidepressants, such as selective serotonin reuptake inhibitors (SSRI), may be considered for moderate or severe depressive episodes, but should always be used in combination with a mood stabilizer 1. Psychotherapy, including cognitive behavioral therapy and interpersonal therapy, is also an essential component of treatment, and lifestyle modifications such as regular sleep patterns, stress management, and avoiding alcohol and recreational drugs are important for stability. Regular appointments with a healthcare provider are necessary to monitor medication effectiveness and side effects, with blood tests needed for certain medications like lithium 1. In cases where suicidal thoughts occur, immediate professional help should be sought through emergency services or crisis hotlines. Key considerations in the treatment of bipolar depression include the prevention of new mood episodes and the management of comorbid conditions, which may require the use of adjunctive therapies 1. Overall, the goal of treatment is to improve symptoms, prevent relapse, and enhance quality of life, while minimizing the risk of triggering manic episodes 1.

From the FDA Drug Label

As ZYPREXA and Fluoxetine in Combination for the: Treatment of depressive episodes associated with bipolar I disorder. Efficacy was established with Symbyax (olanzapine and fluoxetine in combination); refer to the product label for Symbyax.

Bipolar Depression Treatment: Olanzapine, in combination with fluoxetine, is indicated for the treatment of depressive episodes associated with bipolar I disorder.

• The dosage for this condition is:
  • Adults: 5 mg of oral olanzapine and 20 mg of fluoxetine once daily
  • Children and adolescents: 2.5 mg of oral olanzapine and 20 mg of fluoxetine once daily
• Important Note: Olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder or treatment-resistant depression 2.

In bipolar depression studies (up to 8 weeks), the most commonly observed treatment emergent adverse reactions associated with the use of quetiapine (incidence of 5% or greater) and observed at a rate on quetiapine at least twice that of placebo were somnolence (57%) dry mouth (44%), dizziness (18%), constipation (10%), and lethargy (5%)

Quetiapine for Bipolar Depression: Quetiapine is used in the treatment of bipolar depression.

• Common adverse reactions include somnolence, dry mouth, dizziness, constipation, and lethargy.
• The dosage of quetiapine for bipolar depression is 300 or 600 mg/day 3.

From the Research

Treatment Options for Bipolar Depression

• Various treatment options are available for bipolar depression, including pharmacotherapy and psychosocial interventions 4.
• Medications such as lithium, valproate, and carbamazepine are efficacious in treating acute mania, while quetiapine and the olanzapine-fluoxetine combination are efficacious for treating bipolar depression 4.
• Antidepressants should only be used in combination with an antimanic agent to avoid inducing switching to mania/hypomania/mixed states/rapid cycling 4.

Efficacy of Specific Medications

• Olanzapine + fluoxetine and olanzapine have been ranked highest for effect size in treating bipolar depression 5.
• Quetiapine and ziprasidone have been shown to have a lower risk of switch to mania 5.
• Bupropion has been suggested as a first-line antidepressant in the treatment of severe bipolar depression, with a probable lower risk of inducing switches to hypomania or mania 6.

Recommendations for Treatment

• Mood stabilizers, such as lithium, are recommended as the first-line treatment for bipolar depression 7.
• Addition of a second mood stabilizer or a cyclic antidepressant may be an appropriate next step 7.
• Lithium may be effective in treating acute mania and preventing both manic and depressive episodes, and may be a better treatment choice in patients with a positive family history for bipolar disorder, mania-depression-interval pattern, and high risk for suicide 8.
• Valproate may be more effective as an antimanic rather than prophylactic agent, and may be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities 8.