Adjunctive Use of Aripiprazole Approved for Bipolar I Disorder

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.