Evidence-Based Reviews

Unipolar vs bipolar depression: A clinician’s perspective

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As we observed in our previous article,1 thyroid laboratory monitoring and supplementation are critical components of managing mood disorders (Box 138-41).

Box 1

The role of thyroid hormones

Conventional laboratory reference ranges often indicate that thyroid-stimulating hormone (TSH) levels as high as 4.0, 4.5, or 5.0 mU/L are normal. A recent meta- analysis determined that treatment of subclinical hypothyroidism (elevated TSH with normal free thyroxine) does not benefit patients’ quality of life.38 Patients with mood disorders, however, often fail to respond to mood stabilizers and other psychiatric medications unless their TSH is <3.0 or even <2.5 mU/L.39,40 We typically augment with liothyronine because, unlike levothyroxine, it works quickly, does not require deiodination to be activated, and, contrary to some reports, its elimination and biologic half-life are sufficient for single daily dosing.41

Moving towards better diagnoses

The emergence of a criteria-based psychiatric system in 1980 with the publication of DSM-III, and its subsequent revisions and updates, constituted a major advance in psychiatric diagnosis. As we learn more about the pathophysiology, genetics, and epigenetics of psychiatric symptoms and syndromes, future diagnostic systems will improve problems of validity that have yet to be resolved. While we believe that, for the most part, DSM-5 was an advance over the previous diagnostic iteration, we have 2 issues with DSM-5 in terms of the diagnosis of bipolar disorder (Box 210,12,13,18,19,42).

Box 2

Bipolar disorder in DSM-5: 2 issues

Based on our clinical experience treating thousands of patients over 25 years, we have 2 issues with DSM-5 regarding bipolar disorder:

1. The DSM-5 criteria for hypomania fail to reflect the features of clinical presentations commonly seen in our practice. The majority of patients with authentic bipolar syndromes do not have hypomanias that last for at least 4 days or reach the level of severity required for a DSM-5 diagnosis of hypomania. This results in misdiagnosis of patients with bipolar depression as suffering from unipolar depression, which leads to inappropriate treatment with antidepressant monotherapy.

2. Bipolar disorder frequently makes its first appearance in childhood and adolescence,10,18,19 and increasing numbers of young patients have been receiving this diagnosis.42 In our opinion, this increase reflects clinicians’ improved diagnostic skills. Perhaps alarmed by the increase in young people receiving a diagnosis of bipolar disorder, the authors of DSM-5 created a new diagnosis for children: disruptive mood dysregulation disorder. This diagnostic addition is based on the finding that children with these mood symptoms may not subsequently exhibit classic DSM-5 manic or hypomanic episodes. But the lack of such episodes does not preclude a diagnosis of bipolar disorder, because many adults with unequivocal bipolar spectrum disorders have subthreshold hypomanias and thus fail to exhibit classic manic or hypomanic episodes.12,13

A rose by any other name would smell as sweet. Children who exhibit symptoms of disruptive mood dysregulation disorder— chronic irritability and protracted temper outbursts—usually suffer from depression and mood instability. In our opinion, it is irrational and confusing to clinicians to separate out with a new diagnosis an arbitrarily defined group of children who exhibit substantially the same symptoms as those who receive a diagnosis of bipolar disorder.

Patients with a chief complaint of depression are often given a diagnosis of “major depression, rule out bipolar disorder.” We believe that this formula should be turned on its head. In our opinion, based on our clinical experience, we think that most patients who present to a clinician’s office or psychiatric hospital with depression have bipolar depression, not unipolar depression. We hope that our experience and observations derived from treating thousands of patients over more than 25 years may be helpful to clinicians who sometimes struggle to bring relief to their patients with mood disorders.


Return to work

Mrs. W is now doing well. She is taking a lower dosage of duloxetine, 60 mg/d, in combination with the mood stabilizer lamotrigine, 200 mg/d. She returns to work full-time as a paralegal and no longer is experiencing depressive episodes.

Bottom Line

Patients with bipolar depression are often misdiagnosed with unipolar depression and treated inappropriately with antidepressant monotherapy, which often results in mood destabilization. Based on our clinical experience, a careful assessment of select criteria, including age of onset, rapidity of onset, comorbidities, diurnal mood variations, and more, can be useful for distinguishing between unipolar and bipolar depression.

Related Resources

  • Nasrallah HA. Misdiagnosing bipolar depression as major depressive disorder. Current Psychiatry. 2013;12(10):20-21,A.
  • Ghaemi SN. Bipolar spectrum: a review of the concept and a vision for the future. Psychiatry Investig. 2013;10(3):218-224.

Drug Brand Names

Aripiprazole • Abilify
Brexpiprazole • Rexulti
Bupropion • Wellbutrin
Carbamazepine • Tegretol, Equetro
Cariprazine • Vraylar
Divalproex • Depakote
Duloxetine • Cymbalta
Esketamine • Spravato
Fluoxetine • Prozac
Lamotrigine • Lamictal
Levothyroxine • Synthroid, Levoxyl
Liothyronine • Cytomel
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Oxcarbazepine • Oxtellar XR, Trileptal
Paroxetine • Paxil
Sertraline • Zoloft

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