The primary instrument used for assessing depressive symptoms was the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale used to assess the degree of depressive symptomatology (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). The key secondary instrument was the Sheehan Disability Scale (SDS), a 3-item self-rated instrument used to assess the impact of depression on three domains of functioning (work/school, social life, and family life) with each item scored from 0 (not at all) to 10 (extreme).

In the two trials (n=381, n=362), ABILIFY was superior to placebo in reducing mean MADRS total scores. In one study, ABILIFY was also superior to placebo in reducing the mean SDS score.

In both trials, patients received ABILIFY adjunctive to antidepressants at a dose of 5 mg/day. Based on tolerability and efficacy, doses could be adjusted by 5 mg increments, one week apart. Allowable doses were: 2 mg/day, 5 mg/day, 10 mg/day, 15 mg/day, and for patients who were not on potent CYP2D6 inhibitors fluoxetine and paroxetine, 20 mg/day. The mean final dose at the end point for the two trials was 10 .7 mg/day and 11.4 mg/day.

An examination of population subgroups did not reveal evidence of differential response based on age, choice of prospective antidepressant, or race. With regard to gender, a smaller mean reduction on the MADRS total score was seen in males than in females.

Agitation Associated with Schizophrenia or Bipolar Mania

The efficacy of intramuscular aripiprazole for injection for the treatment of agitation was established in three short-term (24-hour), placebo-controlled trials in agitated inpatients from two diagnostic groups: Schizophrenia and Bipolar I Disorder (manic or mixed episodes, with or without psychotic features). Each of the trials included a single active comparator treatment arm of either haloperidol injection (Schizophrenia studies) or lorazepam injection (Bipolar Mania study). Patients could receive up to three injections during the 24-hour treatment periods; however, patients could not receive the second injection until after the initial 2-hour period when the primary efficacy measure was assessed. Patients enrolled in the trials needed to be: (1) judged by the clinical investigators as clinically agitated and clinically appropriate candidates for treatment with intramuscular medication, and (2) exhibiting a level of agitation that met or exceeded a threshold score of ≥ 15 on the five items comprising the Positive and Negative Syndrome Scale (PANSS) Excited Component (ie, poor impulse control, tension, hostility, uncooperativeness, and excitement items) with at least two individual item scores ≥ 4 using a 1-7 scoring system (1 = absent, 4 = moderate, 7 = extreme). In the studies, the mean baseline PANSS Excited Component score was 19, with scores ranging from 15 to 34 (out of a maximum score of 35), thus suggesting predominantly moderate levels of agitation with some patients experiencing mild or severe levels of agitation. The primary efficacy measure used for assessing agitation signs and symptoms in these trials was the change from baseline in the PANSS Excited Component at 2 hours post-injection. A key secondary measure was the Clinical Global Impression of Improvement (CGI-I) Scale. The results of the trials follow:

In a placebo-controlled trial in agitated inpatients predominantly meeting DSM-IV criteria for Schizophrenia (n=350), four fixed aripiprazole injection doses of 1 mg, 5.25 mg, 9.75 mg, and 15 mg were evaluated. At 2 hours post-injection, the 5.25 mg, 9.75 mg, and 15 mg doses were statistically superior to placebo in the PANSS Excited Component and on the CGI-I Scale.

In a second placebo-controlled trial in agitated inpatients predominantly meeting DSM-IV criteria for Schizophrenia (n=445), one fixed aripiprazole injection dose of 9.75 mg was evaluated. At 2 hours post-injection, aripiprazole for injection was statistically superior to placebo in the PANSS Excited Component and on the CGI-I Scale.

In a placebo-controlled trial in agitated inpatients meeting DSM-IV criteria for Bipolar I Disorder (manic or mixed) (n=291), two fixed aripiprazole injection doses of 9.75 mg and 15 mg were evaluated. At 2 hours post-injection, both doses were statistically superior to placebo in the PANSS Excited Component.

Examination of population subsets (age, race, and gender) did not reveal any differential responsiveness on the basis of these subgroupings.

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