Rapid Titration of Mood Stabilizers Predicts Remission From Mixed or Pure Mania in Bipolar Patients

Joseph F. Goldberg; Jessica L. Garno; Andrew C. Leon; James H. Kocsis; Laura Portera

J Clin Psychiatry 1998;59(4):151-158

Article Abstract

Background: Recent investigations have suggestedthat the antimanic agents divalproex sodium and carbamazepine mayeach hasten hospital discharge and be especially beneficial intreating mixed-state mania. This study retrospectively comparedthe time to remission for pure versus mixed manic bipolarinpatients who were taking lithium, divalproex, or carbamazepine,or their combination, under naturalistic conditions.

Method: Records were reviewed for 120 bipolarinpatients from 1991 to 1995. Research DSM-III-R diagnoses ofpure or mixed mania were assigned along standardized guidelines.Data were obtained on daily symptoms, medication doses, and bloodlevels. Weekly improvement was evaluated by Kaplan-Meier survivalanalysis of Clinical Global Impressions scale scores. Variablesassociated with “remission” versus”nonremission” were examined by logistic regression.

Results: Mixed mania (N=70) was more common thanpure mania (N=50). No significant differences were observed inthe time to remission for mixed or pure manic bipolar patientswho took lithium compared with those who took divalproex orcarbamazepine. In patients who remained symptomatic with lithiumas a single-agent mood stabilizer despite therapeutic serumlithium levels, the addition of a second mood stabilizer led torapid symptom improvement. Among all medication subgroups, thespeed with which patients achieved therapeutic blood levels ofany of these agents significantly affected the time to remission.

Conclusion: Mixed manic bipolar patients takinglithium, divalproex, or carbamazepine under naturalisticconditions remit at comparable rates. Those failing to respond tosingle-agent mood stabilizers often receive combinations of moodstabilizers. However, delays in optimizing
a medication regimen may attenuate short-term outcome, regardlessof the mood stabilizer selected. Rapid achievement of therapeuticblood levels of any antimanic agent appears to be stronglyrelated to swift symptom remission.