by Dr. Adam Klapperich, DO

Over 1/3 of unipolar depression patients are eventually re-diagnosed with bipolar disorder. The primary care clinic is often the first line of medical treatment of mood disorders such as depression, as well as anxiety disorders. The first line medication intervention for major depression and anxiety disorders for both children and adults are SSRIs. However, as we all know, these medications, along with SNRIs and TCAs, are known to have the risk of “activation” in some individuals. Though this phenomenon is not sufficient to diagnose bipolar I or II, it is an important “red flag” for ongoing risk of conversion. However, there are other more subtle clues in a person’s personal and family history that can be predictive of future conversion to bipolar disorder. This brief article will address these clues, and Depression with Mixed Features (DMX).

Family history of bipolar disorder (type I or II) is the single most important predictive factor of future bipolar diagnosis, and should be asked when seeing a patient initially for depression treatment. Lifetime risk of bipolar diagnosis is 5-10% in a first degree relative, and 40-70% in monozygotic twins. Other clues include early age of onset of first depressive episode, rapid onset of depressive episodes, postpartum depression, greater severity of depressive episodes and number of hospitalizations, increased number of depressive episodes, poor response to antidepressants, antidepressant induced hypomania or mania, depression with psychotic features, and mixed features. The underlined portion indicates (in my opinion) important factors to consider in a primary care setting, and should influence your decision to adjust treatment or refer to psychiatry.

Depression with mixed features, according to DSM-V criteria, indicates full criteria met for a major depressive episode, with at least three manic/hypomanic symptoms present concurrently nearly every day during the episode. Symptoms include elevated/expansive mood, inflated self-esteem or grandiosity, more talkative, flight of ideas or racing thoughts, increase in energy or goal directed activity, increased risky activities, and decreased need for sleep (not insomnia).

Due to overlap of irritability, distractibility, and psychomotor agitation (non-euphoric (hypo)manic symptoms) with other disorders (anxiety/ADHD/borderline personality), these symptoms are excluded from the DSM diagnostic criteria for depression with mixed features. Some argue that these are in fact the defining features of DMX, and several research criteria include these. DMX is a “significant risk factor for the development of bipolar I or bipolar II” according to the DSM-V. Patients with DMX are less likely to respond to treatment as usual, perhaps because their eventual diagnosis will not be unipolar depression.

According to Balazs et al, presence of mixed features increases risk of suicidality by 4x in both unipolar and bipolar depression. This may underlie the connection between antidepressant use and suicidality.

The message I feel you should incorporate into your primary care practice are simply asking the questions consistently for patients you are seeing for depression “Any manic or hypomanic symptoms?” and “Any family history of bipolar disorder?” Some psychiatrists argue that a person with the slightest hint of hypomania or family history of bipolar disorder should not be treated with antidepressant as a monotherapy. This outlook may be somewhat drastic in a complicated patient population with comorbid trauma history, substance use, and emerging personality characteristics. At the least, any person on antidepressant therapy should be monitored for emergence of hypomania.

Sources:

1. Balázs J et al. The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention. J Affect Disord. 2006 Apr;91(2-3):133-8. Epub 2006 Feb 3.
2. Dudek D et al. J Affective Disord 2013; 144(1-2): 112-5
3. Fiedorowicz et al. Subthreshold Hypomanic Symptoms in Progression From Unipolar Major Depression to Bipolar Disorder. Am J Psychiatry. 2011 Jan; 168(1): 40-48.
4. McIntyre RS. Somewhere Over the Rainbow: Recommendations for the Diagnosis and Treatment of Depressive Mixed States. 2017 Neuroscience Education Institute Congress presentation.