The Effects of Misdiagnosing Depression With Mixed Features as Unipolar Depression

During a session at the 2017 Neuroscience Education Institute Congress in Colorado Springs, Colorado, Roger S. McIntyre, MD, FRCPC, professor, Departments of Psychiatry and Pharmacology, University of Toronto; Head of the Mood Disorders Psychopharmacology Unit, University Health Network, discussed the contributing factors and effects of misdiagnosing or inappropriately treating patients with antidepressants.

“We know that major depressive disorder and bipolar disorders are common conditions,” said McIntyre. “And we know still, in 2017, that the majority of people who have major depressive disorder or bipolar disorder either are not diagnosed accurately and/or are not diagnosed in a timely fashion.”

McIntyre first explained that many patients with unipolar depression that show a “little bit of mania” are more likely to have an eventual diagnostic conversion to bipolar disorder.

He then discussed how the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), the standard classification of mental disorders used by mental health professionals in the United States, is a contributing factor to the difficulty of diagnosing depression with mixed features (DMX).

“Although irritability, distractibility, and psychomotor agitation are among the most common symptoms of DMX, they are excluded from DSM-5 mixed features criteria due to the overlap of these symptoms with other disorders and between mania and depression,” said McIntyre.

When utilizing research-based diagnostic criteria, 4 times as many cases were identified.

Using DSM-5 with criteria, all patients identified as DMX will have DMX, however, only 5.1% of individuals who have DMX will be identified, and about 95% are at risk of receiving inappropriate treatment. Following criteria by psychiatrist Franco Benazzi, MD, PhD, approximately 10% of patients who are identified as having DMX will not actually have DMX, but less than 50% are at risk of receiving inappropriate treatment.

There is a question of which will be more detrimental, McIntire said; misdiagnosing someone who is “pure unipolar” as DMX or treating unidentified DMX with antidepressants?

The consequences of misdiagnosis/inappropriate treatment include: years (often a decade or more) of unnecessary suffering; treatment resistance; reduced likelihood of responding to eventual appropriate mood stabilizer treatment; treatment-emergent activation syndrome; and suicidality.

There are several tools that can be used to assess DMX, said McIntyre.

• Bipolar Depression Rating Scale: A clinician-administered assessment of current symptoms.
• Mini International Neuropsychiatric Interview: Patient self-report assessing current symptoms.
• Clinically Useful Depression Outcome Scale with DSM-5 Mixed: Patient self-report assessing current (hypo)manic symptoms.
• Hypomania Checklist: Patient self-report that screens for lifetime (hypo)manic symptoms.

“The inappropriate overprescribing of antidepressants may contribute to drug-induced (hypo)manic episodes, treatment resistance, suicidality, and overall poor quality of life for many patients suffering from depression,” concluded McIntyre. “You will not know if a depressed person has (hypo)manic symptoms or a positive family history of bipolar disorder unless you ask every patient, every time.”