BOCA RATON, FLA. – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

DSM-5 Proposes Broader Criteria for Mixed Depression