The DSM change
A novel change in DSM-5 is the elimination of the DSM-IV-TR diagnosis of Bipolar I Disorder, Mixed Episode (the current episode meeting criteria simultaneously for a major depressive episode and a manic episode for at least one week). This was replaced by a new specifier for both bipolar disorder and unipolar depression called mixed features. The mixed features specifier is listed if the primary mood state co-exists with three symptoms usually associated with the opposite mood state. Evidence is accumulating that major depression with mixed features may represent a population of depressed patients at increased risk of a switch to hypomania or mania during antidepressant therapy and possibly a more severe course of illness.
The antidepressant question
Since the publication of the 2007 New England Journal of Medicine Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study3 comparing treatment of depressed patients with bipolar disorder on a mood stabilizer demonstrated no statistical difference between adding a placebo versus an antidepressant to the patient’s primary mood stabilizer, a healthy dialogue has transpired as to whether or not there is a role for antidepressants in the treatment of bipolar depression. Although clinicians continue to argue this point, the growing consensus is that antidepressant medications should be avoided in the treatment of BDI. Established bipolar depression expert S. Nassir Ghaemi, MD, went so far as to say, “Before you can figure out what to do, you need to know what not to do… Stop using antidepressants. That’s half the story.”4
Additionally, none of the US FDA-approved antidepressants for the treatment of a unipolar depressive episode (approximately 29 in total) are FDA approved to treat bipolar depression. (Note of clarity: some will argue that fluoxetine is approved for bipolar depression in its formulation/combination with olanzapine. However, this argument is not valid, as fluoxetine is not approved as a monotherapy.) The first medications to be FDA- approved for treating bipolar depression was the olanzapine-fluoxetine combination in 2003. The only other medications currently FDA approved to treat bipolar depression are quetiapine (approved in 2006) and lurasidone (approved in 2013). There have been many failed double-blind/placebo-controlled trials of other agents over the years, further highlighting the difficulty of treating bipolar depression.
Tools to get to the right diagnosis
When a new patient presents for treatment of a major depressive episode, it is prudent for the clinician to spend time in the clinical interview obtaining history that may aid in the differentiation of a bipolar depression from a unipolar depression. Differentiating BDI depression from unipolar depression can be straightforward if the patient (or their family/advocate/guardian) is an accurate historian or if they can provide comprehensive past treatment records of mood episodes. If the patient has a past episode of mania or mania with mixed features, the diagnosis of BDI can be made and antidepressant medications should be avoided. Unfortunately, getting a comprehensive and accurate psychiatric history can be difficult for many reasons. In addition, it is common for patients to not view episodes of hypomania as problematic (in fact, patients may experience hypomania as a productive and enjoyable mood state). This may result in lack of reporting.
Although laborious, a detailed initial psychiatric evaluation is needed and should include: a family history (especially in first degree relatives), details of any prior mood episodes, past treatments that may have unmasked symptoms suggestive of mania or hypomania, symptoms that may have preceded substance use disorders, effects of any past treatment with antidepressants (ie, for previously treated depression, anxiety disorders, premenstrual dysphoric disorder, obsessive compulsive disorder, posttraumatic stress disorder, or other disorders). Similarly, obtaining additional history from a partner, family member or friend can assist in a more informed clinical assessment as to what the primary psychiatric disorder may be.
Dr Miller is Medical Director of Brain Health and Staff Psychiatrist at Seacoast Mental Health Center in Exeter, NH. Dr Miller notes he serves as a speaker/consultant for Sunovion and Otsuka/Lundbeck, and on the speaker’s bureau for Allergan and Teva. He is also on an advisory board for Alkermes and Janssen Virtual Feedback Committee, and has consulted for Align2Action.
1. Hirschfeld R, Lewis L, Vornik L. Perceptions and Impact of Bipolar Disorder: How Far Have We Really Come? Results of the National Depressive and Manic-Depressive Association 2000 Survey of Individuals With Bipolar Disorder. J Clin Psychiatry. 2003;64:161-174.
2. Geller B, Zimmerman B, Williams M, et al. Bipolar Disorder at Prospective Follow-Up of Adults Who Had Prepubertal Major Depressive Disorder. Am J Psychiatry. 2001;158:125-127.
3. Sachs G, Nierenberg A, Calabrese J, et al. Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression. N Engl J Med. 2007;356:1711-1722
4. Ghaemi SN. Antidepressants in Bipolar Depression: An Update. Presented at the 29th Annual U.S. Psychiatric & Mental Health Congress; October 23, 2016; San Antonio, TX.
5. Hirschfeld R, Williams J, Spitzer R, et al. Development and Validation of Screening Instrument for Bipolar Spectrum Disorder: The Mood Disorder Questionnaire. Am J Psychiatry. 2000;157:1873-1875.
6. Musliner KL, Østergaard SD. Patterns and predictors of conversion to bipolar disorder in 91,587 individuals diagnosed with unipolar depression. Acta Psychiatr Scand. 2018; 137:422-432.