Subject:
Bipolar Disorder

Short Description:

Mood Stabilizer plus Antidepressant May Protect Against Mania

Background:

Most of you would hesitate to put a patient with bipolar I on antidepressants without adding a mood stabilizer, in order to prevent a switch to mania. If this is your clinical practice, you are following the recommendations of the APA consensus guidelines for the treatment of bipolar depression. But the hard data to support the danger of switching is surprisingly weak. Clinical trials have not yielded consistent results. This is why we read with interest a recent study providing a bit more evidence that unopposed antidepressants can indeed cause manic switches—but only in bipolar I, and only over the short-term.

Researchers in Sweden used a national database to identify all patients during the period of 2005 to 2009 who had been diagnosed with bipolar disorder I and who started antidepressants. Of the 3,240 patients identified, nearly 35% were on antidepressant monotherapy while the remainder were also prescribed a mood stabilizer in addition to the antidepressant (in this study, lithium, valproate, or lamotrigine). Importantly, the researchers excluded all patients who had taken antidepressants in the previous year, to better reveal new “switching” events.

Records were reviewed for the occurrence of mania during the period after the antidepressant was started. It turns out that antidepressant monotherapy was, indeed, linked to an increased risk of mania—but only in the short term (0 to 3 months after starting the antidepressant)—the hazard ratio (HR) was 2.83, meaning that these patients were almost three times more likely to become manic than those also taking a mood stabilizer. However, 3 to 9 months after starting the medication, there was no higher prevalence of mania (HR 0.71).

When researchers focused on patients who were prescribed mood stabilizers in addition to antidepressants, there was no increased risk of mania at all, either in the 0 to 3 month period or the 3 to 9 month period. In fact, for these patients the 3 to 9 month risk of mania was actually reduced (HR 0.63).

The researchers recommend the use of mood stabilizers when antidepressants are prescribed in bipolar disorder, and also point out that more options are necessary for the management of bipolar depression. It should be noted that the present study did not evaluate whether atypical antipsychotics, commonly used in all phases of bipolar disorder, can also prevent the switch to mania (Viktorin A et al, Am J Psychiatry 2014;online ahead of print).

TCPR’s Take: The researchers recommend that clinicians add mood stabilizers to antidepressants for bipolar disorder I. This is not a huge surprise and is in line with how most of us practice. But don’t be overly seduced by these results. This was a retrospective study that relied upon diagnoses given by non-researcher clinicians, and not on standardized interviews. Furthermore, it was limited by a non-standardized definition of “mania,” and it did not evaluate patients with bipolar II disorder. The best we can say is that at least these results don’t contradict standard practice.