Guidelines for treatment-resistant mania in children with bipolar disorder.

OBJECTIVE: To implement a treatment algorithm to operationalize treatment-resistance and improve patient outcomes in youth with pediatric bipolar disorder (PBD). The term "treatment resistance" was operationally defined as significant persistent symptoms following the application of a treatment algorithm. METHOD: Youth (6-17 years of age, n=120) with treatment-refractory bipolar I or II disorder, currently in a manic or mixed episode, were treated in accordance with the following 3 step algorithm: (1) removal of destabilizing agents (antidepressants, gamma aminobutyric acid [GABA]-agonists, and stimulants), (2) optimization of antimanic agents, and (3) use of a limited number (E 2) of mood stabilizers. The primary efficacy measure was change in scores on the Young Mania Rating Scale (YMRS) over the 6-month treatment course. Response was defined as repeated YMRS scores E 12. RESULTS: The sample was dichotomized into responders and non-responders. Both responders and non-responders improved significantly, with responders improving by a greater margin (d=3.2). At the end of 6 months, 75.8% of subjects demonstrated a significant and stable decrease in manic symptoms consistent with symptomatic remission (YMRS E 12). None of the subjects withdrew from the clinical process due to adverse events. CONCLUSION: The application of this proposed treatment algorithm allows for more accurate identification of true treatment resistance and can significantly reduce manic symptoms in patients previously described as having treatment-refractory bipolar disorder.