SSRI antidepressant medications contribute to a significant worsening of emotional “rapid cycling” in patients diagnosed with bipolar disorder, according to a study published in the Journal of Affective Disorders. The authors described the study as the first-ever randomized clinical trial to test whether the finding from previous observational studies was true, and stated that the study clarified the “lack of safety” of antidepressants for some people with bipolar.
Involving psychiatric researchers from the University of Louisville, Tufts, Stanford and the University of Pennsylvania, the study described rapid cycling as a tendency among some patients with bipolar to have four or more episodes of mania or depression in a 12-month period. The researchers did a secondary analysis from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) with 68 people diagnosed with bipolar, including 18 identified rapid cyclers, who had already “achieved clinical recovery” for at least two months while taking both an antidepressant and a mood stabilizer. These people were then randomized into antidepressant continuation or discontinuation groups while their mood stabilizer was continued.
“(I)n all groups except the rapid cyclers maintained on antidepressants, distributions were skewed toward zero, meaning most patients had few if any depressive episodes,” the researchers wrote. “In the (rapid cyclers) group maintained on antidepressants, the distribution was normal, meaning most patients had 2-4 depressive episodes.”
“In this sample, long-term continuation of antidepressants was associated with more mood episodes in patients with rapid-cycling bipolar disorder, particularly with three-fold increased rate of depressive episodes in the first year of follow-up,” they stated. “These data represent the first randomized data with new generation antidepressants, and they confirm the only other randomized study, conducted with tricyclic antidepressants.”
The researchers conceded that their sample size was limited, but they said they attempted to compensate for that by using descriptive measurements — such as numbers of episodes — rather than relying on p-value estimates of effects.
Conversely, they noted that their sample consisted of “a selected population of patients who had responded to antidepressants for acute bipolar depression, without manic switch. Thus, this was an ‘enriched’ sample of antidepressant-responsive patients. Even so, there appeared to be worsening of depressive episodes over time in subjects with a history of rapid-cycling bipolar disorder… Further, all patients took baseline mood stabilizers, indicating that mood stabilizers were not protective against such antidepressant-related worsening of mood episodes in rapid-cycling bipolar disorder, at least in the depressive pole.”
They concluded: “Even with pre-selection for good antidepressant response and absence of acute mania related to antidepressants, and despite concurrent mood stabilizer treatment, a priori analysis of rapid cycling status predicted more depressive episode criteria in those who continued antidepressant treatment as opposed to discontinued antidepressant treatment. This decreased efficacy of antidepressants supports previous claims of limited clinical utility and lack of safety in long term treatment of (bipolar disorder) patients with (antidepressants).”
An analysis of the study is also available on Medscape Medical News.
El-Mallakh, Rif S., Paul A. Vöhringer, Michael M. Ostacher, Claudia F. Baldassano, Niki S. Holtzman, Elizabeth A. Whitham, Sairah B. Thommi, Frederick K. Goodwin, and S. Nassir Ghaemi. “Antidepressants Worsen Rapid-Cycling Course in Bipolar Depression: A STEP-BD Randomized Clinical Trial.” Journal of Affective Disorders 0, no. 0. Accessed June 29, 2015. doi:10.1016/j.jad.2015.04.054. (Abstract)
Discontinue Antidepressants in Rapid-Cycling Bipolar Disorder (Medscape Medical News, June 22, 2015) (Registration required)