Bipolar Disorder: Got Antidepressants?

Psychiatric TimesVol 32 No 9
Volume 32
Issue 9

Unspecified bipolar disorder? Comorbid borderline personality disorder? Or, in the case presented here, is it time to break out the mixed specifier from DSM-5?

In a scenario common to psychiatrists, patient M presents to the clinic, requesting treatment for “mood swings.”

The clinician’s first reaction may be to take a breath and exhale slowly-and perhaps reach up to massage his or her neck before considering the differentials. Unspecified bipolar disorder? Comorbid borderline personality disorder (BPD)? Is it time to break out the mixed specifier from DSM-5?


A 32-year-old man with thin cut marks on his arms, M describes irritability and changes in mood that last hours or days, reduced sleep, impaired appetite, and distractibility. He is easily provoked, has been having racing thoughts and increased activity. He describes his mood as “depressed” and complains that his work and interpersonal relationships are impaired. He admits to multiple past suicide attempts.


After gathering collateral and nailing down a diagnosis, the next question is management. Given M’s depressive symptoms, is an antidepressant suitable?

Bipolar disorder mixed state

Diagnostic criteria for bipolar disorder mixed state in DSM-5 were discussed at APA 2015 by Roger McIntyre, MD. They are defined as:

• Full mania or

• Hypomania plus 3 depressive symptoms or

• A full depression plus 3 mania symptoms

The latter criterion applies to patient M. If a major depression is present, one cannot count irritability, insomnia, distractibility, or indecisiveness toward mania. The specifier was previously applied to bipolar I but is now also applied to bipolar II and unipolar depression in DSM-5.

Manic symptoms that characterize mixed manic episodes typically include greater mood lability and irritability. Affective instability may be defined as rapid oscillations of intense affect, with difficulty regulating these oscillations or their behavioral consequences.1 Nevertheless, it is a common presenting complaint, as was the case with patient M.

Bipolar disorder mood instability tends to last days, rather than minutes or hours as in BPD. Linked to episodic high-energy states rather than interpersonal sensitivity and self-injury, the mood instability is defined more by euphoria than the anger seen in BPD. However, when applied to bipolar disorder, the positive predictive value (PPV) for mood instability is a mere 0.14.2 In other words, when included in a clinical diagnosis, it is accurate only 14% of the time. On the other hand, mood elevation has a PPV of 0.81; reduced need for sleep, 0.62; racing thoughts, 0.64; and increased goal-directed activity, 0.71.2

Treatment considerations

One particularly divisive topic has been the use of antidepressants in bipolar disorder. Should a patient who has bipolar disorder with depressive features be treated with an antidepressant? This question was discussed at length by S. Nassir Ghaemi, MD, in his talk at APA 2015. In clinical practice, 55% of physicians were not concerned that their choice of treatment would lead to a manic episode; 5% thought there was no further risk of treatment-emergent mood disorder when giving antidepressants to patients with bipolar I disorder; and 54% would prescribe antidepressants as a monotherapy for depressed patients with risk factors for bipolar I disorder.3 As discussed by Dr Ghaemi, however, antidepressants are often ineffective for bipolar depressive symptoms.

Dr Ghaemi’s group undertook a randomized controlled trial that examined citalopram as a maintenance treatment for bipolar depression. After 12 months, there was no benefit of citalopram over placebo in improving depressive symptoms. In addition to its ineffectiveness, he argued, it can cause a switch to mania-particularly when used with TCAs and SNRIs. This switching can occur in patients treated acutely and in those receiving maintenance therapy. The rate to manic switch is typically highest in bipolar I disorder, followed by mixed states, bipolar II disorder and, finally, unipolar depression.

In the EMBOLDEN II study, quetiapine was found to be effective in acute bipolar depression, as measured by the Montgomery-Asberg Depression Rating Scale response.4 Paroxetine was found to be no better than placebo. In addition to manic switching, some patients with bipolar mixed presentations who received antidepressants experienced an up to 3-fold increase in depressive episodes.


On the basis of the above evidence, it appears that antidepressants should be avoided in most patients with bipolar disorder. As argued by Dr McIntyre, however, clinical wisdom suggests that some patients with a diagnosis of bipolar depression seem to improve with antidepressants. There is also some evidence to suggest improvement.5

Until there is a biomarker for bipolar disorder, the debate about antidepressants in patients with the disorder will likely continue. In the meantime, clinical features can be used to better predict those patients with bipolar disorder. As always, more research is required to elucidate the etiology of manic, mixed, and depressive episodes to better guide diagnosis and treatment.


This article was originally posted on 6/15/2015 and has since been updated.


Dr Naidoo is a fourth year psychiatry resident in the Department of Psychiatry and Behavioral Neurosciences at Wayne State University in Detroit.


1. Marwaha S, He Z, Broome M, et al. How is affective instability defined and measured? A systematic review. Psychol Med. 2014;44:1793-1808.

2. Goldberg JF, Garno JL, Callahan AM, et al. Overdiagnosis of bipolar disorder among substance use disorder inpatients with mood instability. J Clin Psychiatry. 2008;69:1751-1757.

3. Glauser TA, Cerenzia W, Wiley S, et al. Identifying psychiatrists’ practice patterns when managing depression in patients with bipolar I disorder: a descriptive study to inform education needs. Postgrad Med. 2013;125:144-153.

4. Ghaemi SN, Ostacher MM, El-Mallakh RS, et al. Antidepressant discontinuation in bipolar depression: a Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) randomized clinical trial of long-term effectiveness and safety. J Clin Psychiatry. 2010;71:372-380.

5. Sidor MM, Macqueen GM. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry. 2010;72:156-167.

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