CLONAZEPAM IN ACUTE MANIA - TIME-BLIND EVALUATION OF CLINICAL-RESPONSE AND CONCENTRATIONS IN PLASMA

This study was performed to evaluate the optimal doses and clinical ef ficacy of clonazepam as a first-line drug in acute mania, as well as t o determine its effective plasma concentrations. Clonazepam was admini stered orally to 11 newly admitted inpatients. On day 0, the loading d ose was titrated upward according to the clinical global impression; t he maintenance dose was calculated with intent to maintain the plasma level that had been achieved after initial dose escalation. Clinically based dose adjustments were allowed on days 4 and 7. Manic symptoms w ere scored on days 0, 4 and 14 according to a time-blind procedure; cl onazepam plasma levels were measured by HPLC. On day 14, there was a s ignificant decrease in manic symptoms and 66.7% of the patients who co mpleted the trial were markedly improved. Steady-state plasma levels o f clonazepam were significantly correlated with daily doses (r(s) = 0. 795, P < 0.005) and therapeutic concentrations ranged between 6.5-83.9 mu g/l. At the onset of therapy, the clinically titrated loading dose resulted in plasma concentrations within the narrow range of 18.9-34. 0 mu g/l. These results support the potential value of clonazepam in t he short-term management of acute mania; the initial control of agitat ion was achieved with plasma drug levels in a remarkably narrow range as compared with the further control of mania.