Combination Therapy in Dual Diagnosis Bipolar Rapid Cycling

Once a therapeutic blood level of lithium was achieved, Divalproex was initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL.

Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL.

Subjects who did not respond to the combination of Lithium and Divalproex were then randomly assigned in a 1:1 ratio to adjunctive lamotrigine versus placebo after stratification by illness type (bipolar I versus bipolar II), historical response to lithium (response versus oon-response), and the length of current exposure to the combination treatment with lithium and divalproex (\<2 months versus ≥2 months).