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Updated: Mar 26, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Rapid versus non-rapid cycling bipolar II depression: response to venlafaxine and lithium and hypomanic risk
L Lorenzo-Luaces1,2, J D Amsterdam1, I Soeller1,3
1Depression Research Unit, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA.
Objective:
To examine the safety and effectiveness of antidepressant versus mood stabilizer monotherapy in rapid versus non-rapid cycling bipolar II disorder.
Method:
Subjects ≥18 years old with bipolar II depression (n = 129) were randomized to double-blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n = 59) received continuation monotherapy for six additional months.
Results:
Rapid cycling did not affect frequency of response or change over time in depressive symptoms. Rapid cycling status did not affect frequency of depressive relapse or sustained treatment response. Rapid cyclers were more likely to experience hypomanic symptoms (P = 0.005) during continuation monotherapy; however, rates were similar in venlafaxine (17.6%) and lithium (42.9%) (P = 0.31).
Conclusion:
Rapid cycling status may not be associated with an increased risk of diminished response or greater depressive relapse during venlafaxine, relative to lithium monotherapy, in bipolar II subjects. Additional randomized studies are needed to confirm these findings.
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