As we have become more sophisticated in our ability to diagnose psychiatric disorders, a large hurdle remains: the ability to differentiate between a primary bipolar I disorder (BDI) major depressive episode versus a unipolar major depressive episode in a newly presenting patient that meets clear diagnostic criteria for a DSM-5 major depressive episode. Significantly, as has been the case with previous editions of the psychiatric Diagnostic and Statistical Manual of Mental Disorders, the DSM-5 criteria for a major depressive episode is identical for both a unipolar depression and a bipolar depression.
Misdiagnosis and resulting issues
From an epidemiological perspective, 17% of individuals in the US will have at least one unipolar major depressive episode in their life, in contrast to 1% that will be diagnosed with BDI and up to 4% that will be diagnosed with bipolar II disorder (BDII). (In both bipolar I and II disorders, depression is a more common mood state than mania/hypomania.) A complicating epidemiological reality is that 50% of patients that ultimately are diagnosed as having BDI initially present with a major depressive episode (rather than mania or hypomania), and many will have recurrent depressive episodes with no periods of mania or hypomania for up to 5 years after their first depressive episode. This often leads to the wrong diagnosis, and consequently a less optimal treatment.
For example, according to a commonly referenced publication,1 69% of 600 patients diagnosed with bipolar disorder were initially misdiagnosed, and the most common misdiagnosis was unipolar depression. Even more alarming, it took 10 or more years for one third of these initially misdiagnosed patients to be accurately diagnosed with bipolar disorder.
Similar rates of misdiagnosis were found in a study of children (mean age=10.3 years) with prepubertal major depressive disorder who were participants in a clinical trial of nortriptyline for childhood depression.2 At approximately 10 year follow-up (mean age=20.7), 33.3% had subsequently been diagnosed with BDI and 48.6% with “Bipolar I disorder or bipolar II disorder or hypomania.” The authors concluded, “High rates of switching to mania are an important consideration for treatment of prepubertal major depressive disorder because of concerns that antidepressants may worsen childhood mania.”
This presents a treatment challenge, as the treatment varies considerably depending on the primary diagnosis. In addition, treating an individual with BDI with antidepressant medications can contribute to a poorer long-term outcome. Increased mood instability, shorter periods of time between mood episodes, less significant psychosocial stressors inducing a mood episode, and poorer response to treatment can result when BDI diagnosis is missed.
If an individual with bipolar depression is treated with an antidepressant medication, especially in the absence of a co-prescribed mood stabilizer (eg, lithium or divalproex), there is a risk for destabilizing the patient’s mood into a manic state, a manic state with mixed features, or a depressive state with mixed features, all of which can result in considerable morbidity and possibly mortality. Additionally, chronic antidepressant treatment in a patient with bipolar disorder can accelerate mood instability.
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.
