Reseach Updates in Psychiatry

Research Updates in Psychiatry


“Soft” Bipolar Does Not Affect Antidepressant Treatment Outcomes

A combination of clinical lore and some studies have led many psychiatrists to believe that it is crucial to screen depressed patients for subtle signs of “bipolarity.” These are often said to include a family history of bipolar disorder, a history of antidepressant-induced mania or hypomania, hypersomnia or hyperphagia during depression, and others. It has been suggested that patients with soft signs of bipolar disorder are relatively treatment resistant to antidepressants, and may even do worse overall if maintained on such meds. Others disagree, finding that identifying soft bipolar symptoms in depressed patients does little to help guide treatment. A recent study adds new data to inform this ongoing controversy. Researchers used data from the Sequential Treatment Alternatives to Relieve Depression (STAR*D) trials to examine whether subsyndromal bipolar symptoms predicted poor treatment response to a variety of antidepressant treatments.

A total of 4,041 patients with depression were enrolled in STAR*D, and they all completed the Psychiatric Diagnosis Screening Questionnaire (PDSQ) to assess for various types of axis I pathology including psychosis and bipolarity. Patients then received treatment in the following 14-week steps until remission occurred:

  • Step 1—citalopram (Celexa);
  • Step 2—augmentation with buspirone (BuSpar) or bupropion (Wellbutrin), or switch to sertraline (Zoloft), venlafaxine (Effexor), or bupropion (Wellbutrin); a small subset of patients received cognitive therapy rather than augmentation or switching medication;
  • Step 3—switch to nortriptyline (Pamelor) or mirtazapine (Remeron) or augmentation with lithium or thyroid hormone;
  • Step 4—switch to tranylcypromine (Parnate) or combination of venlafaxine and mirtazapine.

Broadly defined bipolarity was common, with 38% of patients reporting at least one manic or hypomanic symptom in the past six months. However, the authors found that patients with soft bipolar symptoms did no worse on antidepressants than patients with “pure” depression. In particular, neither family history of bipolar disorder nor presence of “soft” manic symptoms were associated with poorer rates of remission. However, patients who reported even a single “psychotic-like symptom” did more poorly than other patients (Perlis RH et al, Arch Gen Psychiatry 2011;68:351–360).

TCPR’s Take: The results suggest that so-called soft bipolar disorder has little, if any impact on antidepressant treatment outcomes. In fact, because the symptoms of subsyndromal bipolar disorder correlated poorly with one another, the authors suggested that their results cast doubt on the diagnostic validity of this controversial entity. While we should continue to screen for bipolar disorder in our depressed patients, if that screen proves negative, it may be a waste of time digging around for evidence of a bipolar “spectrum” disorder.

On the other hand, some members of our editorial board pointed out that the data used by these researchers has some shortcomings: it relied on self ratings to diagnose bipolarity, and was a post hoc analysis. While this doesn’t necessarily invalidate the findings, we need to be aware of the limitations of studies as we decide whether to change our practices in response.

Reseach Updates in Psychiatry

This article originally appeared in:

The Carlat Psychiatry Report
Click on the image to learn more or subscribe today!

This article was published in print 6/2011 in Volume:Issue 9:6.

The Carlat Psychiatry Report

Carlat Publishing provides clear, authoritative, engaging, independent psychiatric education to make you look forward to learning, with the goal of helping you feel smarter, more competent, and more confident in your ability to help your patients become happy. We receive no corporate funding, which allows a clear-eyed evaluation of all available treatments. Learn more and subscribe to one of their newsletters here.


APA Reference
Psychiatry Report, T. (2013). Reseach Updates in Psychiatry. Psych Central. Retrieved on July 15, 2020, from


Scientifically Reviewed
Last updated: 8 Oct 2013
Last reviewed: By John M. Grohol, Psy.D. on 8 Oct 2013
Published on All rights reserved.