How should treatment be tailored for the DSM-5 mixed features specifier?

The mixed features specifier for manic and depressive episodes introduced in DSM-5 reflects the spectrum of mood disorders along a continuum from pure mania to pure depression. Evidence on how best to treat patients with bipolar disorder and the mixed features specifier is missing, said Professor Lakshmi Yatham of The University of British Columbia at the ISBD 2020 Virtual conference, but preliminary guidance will be published by the end of 2020.

The DSM-5’s mixed features specifier reflects the spectrum of mood disorders. It is diagnosed when a patient has at least three non-overlapping symptoms that differ from their normal behavior of either mania/hypomania or major depressive disorder (MDD) and present nearly every day,1 explained Professor Yatham.

An opportunity to tailor treatment to the patient’s behaviors

For patients with mania/hypomania, such symptoms include:

  • dysphoria or depressed mood
  • anhedonia
  • psychomotor retardation
  • fatigue or loss of energy
  • feelings of worthlessness or guilt
  • death or suicidal ideation

For patients with MDD, the symptoms might be:

  • expansive or elevated mood
  • grandiose ideas
  • pressured speech
  • flight of ideas
  • increased activity or energy
  • excessive involvement in enjoyable activities
  • decreased need for sleep

How should treatment be tailored for patients with the mixed features specifier?

Nearly one-third of patients with mood disorders have the mixed features specifier2

The mixed features specifier provides an opportunity to tailor treatment to the patient’s behaviors. However, the Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder2 do not provide guidance on how to do this.

Nearly one-third of patients with mood disorders meet the criteria for the mixed features specifier3 but evidence on how best to manage them is missing, representing a huge gap, said Professor Yatham.

CANMAT in collaboration with the ISBD has therefore assembled a group of experts to develop treatment recommendations for people with bipolar disorder with mixed features.

An urgent need for much more evidence to inform treatment

Post-hoc analyses using proxy criteria of efficacy, safety and tolerability and risk of treatment-emergent switch have been carried out on the limited evidence that is available. Most of this evidence reports improvements in the primary mood episode and not in the mixed features or even overall improvement.

In the absence of primary data, this very limited review has led to some preliminary guidance, which will be published by the end of 2020, concluded Professor Yatham.

To read more on the mixed features specifier and its implications for treatment see here and here.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, Fifth edition. Arlington. VA: APA; 2013.

2. Yatham LN, et al. Bipolar Disord 2018;20:97–170.

3. Vázquez GH, et al. J Affect Disord 2018;225:756–60.

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