Bipolar Depression Updated Guidelines: Psychopharmacology Algorithm Project

The Psychopharmacology Algorithm Project at the Harvard South Shore Program published algorithms for bipolar depression in 1999 and 2010.

They just released their updated guidelines on 25 October 2019. We have summarized them in the following table:

(a) For the urgent treatment of bipolar depression: Electroconvulsive therapy (ECT) is still the first‐line option.

(b) For acute bipolar depression: lamotrigine, lurasidone, lithium, quetiapine, and cariprazine.

  • either as single or in combination (if monotherapy fails)

  • medication choice is determined by side effects vulnerability and patient preference.

(c) If the above medications fail:

  • antidepressants (bupropion and SSRI) or

  • valproate (very small evidence‐base)

(d) In bipolar II depression, the support for antidepressants is a little stronger

(e) depression with mixed features and rapid cycling would usually lead to further postponement of antidepressants.

(f) Medication not considered beyond this point: Olanzapine+fluoxetine

  • due to metabolic side effects.


  • Giakoumatos CI, Osser D. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Update on Unipolar Nonpsychotic Depression. Harv Rev Psychiatry. 2019 Jan/Feb;27(1):33-52. PubMed PMID: 30614886. (Pubmed)


Read the following chapters discussing the other guidelines for the treatment of bipolar depression:

(1) CANMAT and ISBD (2018 guidelines): Acute Management of Bipolar I Depression.

  • First-line
  • Second line
  • Third line
  • Not recommended

(2) Florida Best Practice Guidelines (2017- 2018): Bipolar Depression.

  • Level 1
  • Level 2A
  • Level 2B
  • Level 3
  • Level 4

(3) British Association for Psychopharmacology (2016)

  • Patient NOT on long term treatment.
  • Patient ON long term treatment.
  • Note on antidepressants.

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  1. what about symbax? doesn’t it fall in 2nd line for acute depression in BD?

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