Patients with bipolar depression who exhibit even minimal manic symptoms are at heightened risk for switching into mania if they receive antidepressant medication, according to a new report from the Bipolar Collaborative Network.1
This finding from the multinational sites of the former Stanley Foundation Bipolar Network emerged in a post hoc analysis of 176 patients who participated in a 10-week controlled trial of adjunctive antidepressant medication for bipolar I or II depression. The investigators sought to identify clinical correlates for the development of treatment-emergent affective switching from patient demographics and baseline symptoms.
Possible risk factors for affective switch, which have been previously suggested, include comorbid substance abuse, younger age, decreased thyroid-stimulating hormone, and rapid cycling. Although none of these factors were predictive in this study, the investigators acknowledged that their modest effect size precluded ruling these out in other populations. They characterize this study, however, as the first controlled assessment of antidepressant treatment in bipolar depression to correlate a specific phenomenological presentation at baseline with affective switching in subsequent antidepressant treatment.
Of the clinical variables considered, a higher baseline score on 3 items of the Young Mania Rating Scale (YMRS)—related to increased motor activity, pressured speech, and distractibility or racing thoughts—was associated with a greater likelihood of developing hypomania or mania in the course of antidepressant treatment, whether or not depressive symptoms improved. This finding prompted the investigators to advise that “careful examination for these specific symptoms of mania is warranted prior to antidepressant treatment for patients with bipolar depression.”
Lead author Mark Frye, MD, elaborated on this recommendation in comments to Psychiatric Times. “If I’ve got . . . bipolar depressed patient[s] in my office, while there is clear evidence of them being depressed, if I notice that they’re significantly activated or they’ve got pressured speech or they’re distractible—those might be signs, now, for me to really stay away from an antidepressant for that depressive episode.”
Although study participants had higher baseline YMRS scores, the average total score of approximately 4 was below diagnostic threshold for “mixed state,” a subtype of mania. The presentation is consistent with some descriptions of a “mixed depression.”2
In an editorial accompanying the published report of the study, Christopher Schneck, MD,3 indicated that the distinct clinical course found in this group reflects the complexity of bipolar disorder and the inadequacy of existing bipolar nosology. He considers the possibility of future classifications, perhaps in DSM-V or the upcoming revision to the International Classification of Diseases (ICD-11), reminiscent of those described by Emil Kraepelin, which distinguished between pure depression, mixed depression, mixed hypomania, mixed mania, and pure mania.
1. Frye MA, Helleman G, McElroy SL, et al. Correlates of treatment-emergent mania associated with antidepressant treatment in bipolar depression. Am J Psychiatry. 2009;166:164-172.
2. Benazzi F, Akiskal HS. Psychometric delineation of the most discriminant symptoms of depressive mixed states. Psychiatry Res. 2006;141:81-88.
3. Schneck CD. Mixed depression: the importance of rediscovering subtypes of mixed mood states. Am J Psychiatry. 2009;166:127-130.
4. Bottlender R, Rudolf D, Strauss A, Möller HJ. Moodstabilisers reduce the risk of developing antidepressant- induced maniform states in acute treatment of bipolar I depressed patients. J Affect Disord. 2001; 63:79-83.
5. Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006;163:232-239.
6. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356:1711-