Clinical Question

Compared with other second-generation antipsychotics for schizophrenia, what is the effectiveness and tolerability of aripiprazole (Abilify)?

Evidence-Based Answer

Aripiprazole is less effective in treating schizophrenia than olanzapine (Zyprexa), but has fewer metabolic and sedative adverse effects. There is no difference in effectiveness between aripiprazole and risperidone (Risperdal); however, aripiprazole may be associated with less dystonia, smaller increases in prolactin, and less QTc prolongation, but more frequent tremor than risperidone. (Strength of Recommendation = B, based on inconsistent or limited-quality patient-oriented evidence)

Practice Pointers

Haloperidol (formerly Haldol) and chlorpromazine are effective first-generation medications for schizophrenia treatment. However, they have adverse effects such as movement disorders, sedation, anticholinergic effects, QTc prolongation, hyperprolactinemia, and metabolic syndrome.¹ Second-generation antipsychotic medications (i.e., atypical antipsychotics) have been developed to minimize these adverse effects.¹ The atypical antipsychotic aripiprazole differs from other second-generation antipsychotics because it is a dopamine-serotonin system stabilizer.²

This Cochrane review examined four drug company–sponsored randomized controlled trials (RCTs; n = 1,404) comparing the effectiveness of aripiprazole (15 to 30 mg per day) with second-generation antipsychotics olanzapine (10 to 20 mg per day) and risperidone (6 mg per day) in patients with acute or chronic schizophrenia. The trials ranged from four to 26 weeks in duration. The authors attempted an intention-to-treat analysis, but, overall, the discontinuation rate in the studies was high (38 percent), limiting the validity of the results.

Two of the studies (n = 1,020) evaluated the effectiveness and tolerability of aripiprazole compared with olanzapine. One study showed a statistically significant difference in mental state, as measured by the 30-item Positive and Negative Syndrome Scale (PANSS), favoring olanzapine at six weeks’ follow-up; no significant difference was noted at 26 weeks in the longer-term study. The clinical relevance of the PANSS is unclear. One of the RCTs showed that fewer patients in the aripiprazole group had increased cholesterol levels (number needed to harm [NNH] = 4; 95% CI, 3 to 6). One of the RCTs showed more sedation with olanzapine (NNH = 7; 95% CI, 4 to 13). There was no significant difference between aripiprazole and olanzapine for extrapyramidal adverse effects (e.g., akathisia, parkinsonism), glucose changes from baseline, or prolongation of QTc. There was a statistically significant difference in weight change that favored aripiprazole in one of the studies. In a separate Cochrane review of its treatment for schizophrenia,³ aripiprazole did not cause significant weight gain when compared with placebo.

The two RCTs (n = 384) of aripiprazole compared with risperidone showed no difference in global state or PANSS scores, QTc prolongation, change in glucose levels, or weight gain between the two treatments. There was no difference in extrapyramidal adverse effects other than dystonia, which was more frequent in the risperidone group (NNH = 8; 95% CI, 5 to 20), and tremor, which was more frequent in the aripiprazole group (NNH = 14; 95% CI, 8 to 50). More participants in the risperidone group had prolactin increases compared with the aripiprazole group.

The American Psychiatric Association does not recommend one specific medication for the treatment of schizophrenia, but does recommend using the lowest effective dosage while monitoring adverse effects, especially those that may threaten patient compliance.⁴ They also recommend surveillance for obesity-related health problems.