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PCMS Member Corner: When Not to Prescribe an Antidepressant

When Not to Prescribe an Antidepressant

The clinical picture of Mixed States of depression was described by German psychiatrists in the late 19th century. It took over 100 years for the American DSM to recognize and narrowly define Mixed States which it calls Mixed Features.

Contemporary research 1 over the past few decades indicates that up to 60% of all “depressive” presentations are of the mixed variety and only 20% are either pure mania or pure depression. The most clinically validated mixed features not recognized by the DSM are: absence of psychomotor slowing, mood lability or marked reactivity, psychic agitation or inner tension, irritability/anger/rage and inattention.

These patients call themselves “depressed” because they are unhappy but do not often volunteer these mixed symptoms which their close ones see clearly.

When these symptoms are present, research indicates antidepressants will either do nothing, increase the mixed symptoms, or less often produce a manic switch. Then the practitioner will usually assume treatment resistance and go on a fruitless search for the right drug rather than the right diagnosis.

In one analysis of mixed depression 2 , antidepressants caused three times more suicide attempts in persons with mixed symptoms when compared to those treated without antidepressants.

The most effective treatments validated in clinical studies indicate that low doses of valproate, lithium or carbamazepine are helpful. Additionally, dopamine blockers such as lurasidone (Latuda) is proven effective for non-bipolar mixed depression (“MDD with mixed features”), cariprazine (Vryalar) or ziprasidone (Geodon). Currently, there is no FDA approved medication for Mixed States (Features).

Neither the PHQ-9 or 2 are designed to distinguish mixed features. For clinicians, there is one validated questionnaire called The Koukopoulos Mixed Depression Rating Scale or KMDRS available on PubMed.

This Mixed Depression clinical picture needs assume diagnostic priority over other conditions like Major Depressive Disorder (MDD), anxiety disorders or ADH because if the mixed symptoms are treated well enough the same symptoms suggestive of these other disorders will abate and would not be considered comorbid. This is true for adolescents and adults.

As a wise psychiatrist from Mass General said many years ago, “Your treatment is only as good as your diagnosis”.

1. Ghaemi N. Clinical Psychopharmacology, Principals and Practice. Oxford Press 2019
2. The Koukopoulos Mixed Depression Rating Scale (KMDRS): An International Mood Network (IMN)
validation study of a new mixed mood rating scale. Journal of Affective Disorders 232 (2018) 9–16.

Written by Dr. Hunter Yost, MD
July 2023


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