What is the best treatment for bipolar II depression?

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Last updated: June 17, 2025View editorial policy

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From the Research

The best treatment for bipolar II depression is olanzapine + fluoxetine, as it has been ranked highest for effect size and response, and has the optimal effect on response and withdrawal from treatment, according to a multiple-treatments meta-analysis 1. This treatment approach is supported by the most recent and highest quality study, which included 29 studies and 8331 participants. The study found that olanzapine + fluoxetine performed best on the primary outcome measure, and was also ranked the highest for response.

  • Other treatment options, such as olanzapine, quetiapine, lurasidone, valproate, and selective serotonin re-uptake inhibitors, are also recommended, but with a lower ranking than olanzapine + fluoxetine.
  • It is essential to note that some treatments, such as monoamine oxidase inhibitors, ziprasidone, aripiprazole, and risperidone, have limited or no therapeutic activity in bipolar depression, and should not be used.
  • Additionally, tricyclic antidepressants and lithium are worthy of consideration, but lamotrigine should not be used due to its high risk of switching and less robust efficacy.
  • Cognitive behavioral therapy (CBT) or interpersonal and social rhythm therapy (IPSRT) should accompany medication treatment, and regular sleep patterns, stress management, and avoiding alcohol and recreational drugs are important lifestyle components.
  • Treatment should be continued even during symptom-free periods to prevent relapse, with medication adjustments made under medical supervision, as supported by earlier studies 2, 3, 4, 5.

References

Research

A review of acute treatments for bipolar depression.

International clinical psychopharmacology, 2004

Research

Lamotrigine: a depression mood stabiliser.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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