Evidence-Based Reviews

Controversies in bipolar disorder: Trust evidence or experience?

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Confused by conflicting studies and opinions? 2 clinicians offer their perspective on how to manage real-life patients.



Today’s buzzword in health care is evidence-based medicine. Most clinicians would agree that evidence from clinical research should guide decisions about treating bipolar disorder. In theory, randomized controlled trials should tell us how to manage bipolar patients and achieve therapeutic success. page 40.)

We rarely have encountered a patient with postpartum depression or psychosis who does not have a history of (often undiagnosed and untreated) recurrent mood episodes. For most of these patients, a mood stabilizer may be a better choice than an antidepressant.

The role of thyroid hormones

Adding a thyroid hormone—usually liothyronine—to an antidepressant has been demonstrated to accelerate, page 47.)

Atypical depression and the bipolar spectrum

Depressive episodes are considered either “typical” (a category that includes melancholic depression—in DSM-IV-TR, major depression with melancholic features) or “atypical” (in DSM-IV-TR, major depression with atypical features). Atypical features were originally associated with response to monoamine oxidase inhibitor antidepressants, whereas non atypical depression was thought more likely to respond to tricyclic antidepressants.34 The depression of bipolar disorder is usually atypical ( Box 4 ), especially in patients with softer variants of the illness.35

We believe that depressed patients with atypical symptoms aggregate into groups according to the presence, severity, and character of interdepressive manic or hypomanic episodes. Some patients experience recurrent depressive episodes with intervening euthymia (recurrent major depression), whereas others experience depressive episodes punctuated by brief subthreshold hypomanic episodes. Patients in these groups occasionally tolerate or even benefit from cautiously managed antidepressant monotherapy. Patients with atypical depressive episodes alternating with frank hypomanic, manic, mixed, or manic-psychotic episodes usually require a mood stabilizer and may benefit from cotreatment with an atypical antipsychotic.

Akiskol and Benazzi35 suggest that atypical depression may be a subtype of the bipolar spectrum. Our experience suggests that the bipolar spectrum is a continuum of degrees of risk for mood instability in persons with recurrent atypical depression.

Box 4

Atypical depression: Who sees ‘leaden paralysis’?

DSM-IV-TR defines atypical depression as depression characterized by mood reactivity and at least 2 of these 4 features:

  • hypersomnia
  • increased appetite or weight gain
  • leaden paralysis
  • sensitivity to interpersonal rejection.

The term ‘hypersomnia’ is misleading. Many of these patients do not sleep excessively because work or school attendance prevents oversleeping. Instead, they experience an increased sleep requirement manifested by difficulty getting up in the morning and increased daytime sleepiness.

Increased appetite and weight gain (hyperphagia) often are present, but almost as often our patients report no change in appetite or weight or even anorexia and weight loss.

We rarely see a condition one would term ‘leaden paralysis.’ We also find that ‘sensitivity to interpersonal rejection’ is too narrow a construct. Our patients with atypical depression experience increased sensitivity to every stressor in their lives—work, school, family, and social stressors—not just interpersonal rejection.

Related resources

  • Lieber AL. Bipolar spectrum disorder: an overview of the soft bipolar spectrum. www.psycom.net/depression.central.lieber.html.
  • Phelps J. Why am I still depressed? Recognizing and managing the ups and downs of bipolar II and soft bipolar disorder. www.psycheducation.org.
  • Maier T. Evidence-based psychiatry: understanding the limitations of a method. J Eval Clin Pract. 2006;12(3):325.

Drug brand names

  • Liothyronine • Cytomel
  • Sertraline • Zoloft


The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

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