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eCase: Accurate Diagnosis Leads to Appropriate Treatment Selection in Patients With Bipolar Depression
  • CME
  • CE

Leslie Citrome, MD, MPH
Program Director
Released: September 30, 2022


Bipolar disorder is a relatively common mental illness with a prevalence rate in the United States of approximately 1% for bipolar type I and 1% for bipolar type II.1-3 The 2 types are principally distinguished by the presence of a history of mania for bipolar I disorder and the requirement of a depressive episode for bipolar II disorder (Figure 1. Bipolar I Disorder vs Bipolar II Disorder). However, in both types of bipolar disorder, depressive episodes generally predominate. For bipolar type I, the ratio of number of major depressive episodes (MDEs) to manic/hypomanic episodes is 3:1 and 70% of time ill is due to depression.4,5 For bipolar type II, the ratio of MDEs to hypomanic episodes is 39:1 and 81% of time ill is due to depression.5,6

Figure 1. Bipolar I Disorder vs Bipolar II Disorder


The major obstacle to the accurate identification of bipolar depression is that on cross-sectional examination, symptoms are the same for both major depressive disorder (MDD) (unipolar depression) and bipolar depression. Of note, patients with bipolar disorder often do not have any insight into their symptoms of mania or hypomania and often fail to report them as such,7,8 leading the healthcare professional to mistakenly assume that the patient has unipolar depression. This has significant consequences in terms of treatments offered and exposes patients with bipolar depression to unhelpful or potential harmful interventions such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and other medications that have been approved for the treatment of MDD but have never been approved for the treatment of bipolar disorder.9-11

It has been estimated that as many as 1 in 5 primary care patients who have clinically significant depressive symptoms and are receiving antidepressant treatment actually have bipolar I or bipolar II disorder.12 The use of ineffective or harmful treatments in bipolar depression may explain the poor outcomes often encountered in this population, including a higher risk of suicide compared with unipolar depression.13,14 Screening instruments are available that can potentially assist the healthcare professional in identifying bipolar disorder in depressed patients, including the Mood Disorder Questionnaire (MDQ)15 (Figure 2. Mood Disorder Questionnaire) and the newly developed Rapid Mood Screener (Figure 3. Rapid Mood Screener).16

Figure 2. Mood Disorder Questionnaire


Figure 3. Rapid Mood Screener


The DSM-5 introduced the mixed features specifier for MDEs associated with either MDD or bipolar disorder, as well as for manic or hypomanic episodes associated with bipolar disorder.17 This concept can be especially helpful when evaluating a person with MDE and there is uncertainty regarding a past history of mania or hypomania, but there is co-occurrence of manic-like symptoms together with the symptoms of MDE. This may direct the healthcare professional to consider treatments used for bipolar depression rather than for MDD.18

To date, the FDA has approved 5 medications to treat acute bipolar depression, far fewer than the number of options approved for the treatment of mania or for maintenance/prevention of relapse.19 The first to be approved was olanzapine/fluoxetine combination (2003), followed by quetiapine in 2006 (extended-release version in 2008). Of note, olanzapine/fluoxetine was evaluated in patients with bipolar I disorder with or without psychotic symptoms, whereas quetiapine was assessed in patients with bipolar I and bipolar II disorder. The 3 newer agents approved by the FDA for acute bipolar depression are lurasidone (2013; bipolar I), cariprazine (2019; bipolar I), and lumateperone (2021; bipolar I and II). All agents differ from another in terms of tolerability, with the most common adverse events being weight gain/metabolic effects, sedation/somnolence, and drug-induced movement disorders, although the newer agents appear to be better tolerated than their predecessors.19,20

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