Bipolar Mania Monotherapy The efficacy of RISPERDAL ® in the treatment of acute manic or mixed episodes was established in 2 short-term ( 3-week) placebo-controlled trials in patients who met the DSM-IV criteria for Bipolar I Disorder with manic or mixed episodes. These trials included patients with or without psychotic features. The primary rating instrument used for assessing manic symptoms n these trials was the Young Mania Rating Scale ( Y-MRS) , an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology ( irritability, disruptive/ aggressive behavior, sleep, elevated mood, speech, increased activity, sexual nterest, language/ thought disorder, thought content, appearance, and insight) in a range from 0 ( no manic features) to 60 ( maximum score) . The primary outcome in these trials was change from baseline in the Y-MRS total score. The results of the trials follow: ( 1) In one 3-week placebo-controlled trial ( n= 246) , limited to patients with manic episodes, which involved a dose range of RISPERDAL ® 1-6 mg/ day, once daily, starting at 3 mg/ day ( mean modal dose was 4.1 mg/ day) , RISPERDAL ® was superior to placebo in the reduction of Y-MRS total score. ( 2) In another 3-week placebo-controlled trial ( n= 286) , which nvolved a dose range of 1-6 mg/ day, once daily, starting at 3 mg/ day ( mean modal dose was 5.6 mg/ day) , RISPERDAL ® was superior to placebo in the reduction of Y-MRS total score. Combination Therapy The efficacy of risperidone with concomitant lithium or valproate in the treatment of acute manic or mixed episodes was established in one controlled trial in patients who met the DSM-IV criteria for Bipolar I Disorder. This trial included patients with or without psychotic features and with or without a rapid-cycling course. ( 1) In this 3-week placebo-controlled combination trial, 148 in-or outpatients on lithium or valproate therapy with nadequately controlled manic or mixed symptoms were randomized to receive RISPERDAL ® , placebo, or an active comparator, in combination with their original therapy. RISPERDAL ® , in a dose range of 1-6 mg/ day, once daily, starting at 2 mg/ day ( mean modal dose of 3.8 mg/ day) , combined with lithium or valproate ( in a therapeutic range of 0.6 mEq/ L to 1.4 mEq/ L or 50 mcg/ mL to 120 mcg/ mL, respectively) was superior to lithium or valproate alone in the reduction of Y-MRS total score. ( 2) In a second 3-week placebo-controlled combination trial, 142 in-or outpatients on lithium, valproate, or carbamazepine therapy with inadequately controlled manic or mixed symptoms were randomized to receive RISPERDAL ® or placebo, in combination with their original therapy. RISPERDAL ® , in a dose range of 1-6 mg/ day, once daily, starting at 2 mg/ day ( mean modal dose of 3. 7 mg/ day) , combined with lithium, valproate, or carbamazepine ( in therapeutic ranges of 0. 6 mEq/ L to 1.4 mEq/ L for lithium, 50 mcg/ mL to 125 mcg/ mL for valproate, or 4-12 mcg/ mL for carbamazepine, respectively) was not superior to lithium, valproate, or carbamazepine alone in the reduction of Y-MRS total score. A possible explanation for the failure of this trial was induction of risperidone and 9-hydroxyrisperidone clearance by carbamazepine, leading to subtherapeutic levels of risperidone and 9-hydroxyrisperidone. | ||||
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