Long-Term Treatment with Asenapine Safe and Effective for Schizophrenia and Schizoaffective Disorder

New Orleans—An extension study that looked at the safety and efficacy of asenapine to treat patients with schizophrenia or schizoaffective disorder found that asenapine remains well tolerated and effective for up to 3 years of treatment. The study, presented in a poster at the recent APA meeting by Joep Schoemaker, MSc, of Merck Sharp & Dohme, confirmed previously published results that showed the safety and efficacy of asenapine for schizophrenia or schizoaffective disorder after 1 year of treatment.

The 1-year, double-blind, phase 3, randomized trial tested the safety and efficacy of asenapine (5 or 10 mg twice daily, administered sublingually) versus olanzapine (10-20 mg, 4 times daily, administered orally) in 1225 patients with schizophrenia or schizoaffective disorder.

Patients eligible for the study were at least 18 years of age, had a diagnosis of schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, had a Positive and Negative Syndrome Scale (PANSS) of ≥60 (including scores of ≥4 on at least 2 of 5 prespecified items on the PANSS positive subscale at screening and baseline), and a Clinical Global Impresssion-Severity of Illness score of ≥4 at baseline. Patients were excluded if they had a history of inadequate therapeutic response or intolerable adverse events (AEs) with olanzapine.

The core study found that asenapine was well tolerated over 1 year and caused no serious metabolic changes and less weight gain than olanzapine. However, asenapine was associated with a higher incidence of extrapyramidal symptoms (EPS) than olanzapine. The study also found that the PANSS improved with both treatments.

The double-blind, phase 3a extension trial, conducted at 75 sites between October 2004 and October 2006, assessed the long-term safety and efficacy of asenapine for up to 2 additional years in patients who completed the core trial. Patients eligible for the extension study included those who completed the core trial, had benefited from treatment, and provided informed consent to participate in the extension trial.

A total of 440 patients participated in the extension trial. All patients continued on the same treatment regimen as in the core study. Of the 440 patients, 290 continued on asenapine and 150 continued on olanzapine. The mean daily dose for the core and extension trials was 13.4 mg for both asenapine and olanzapine. Total exposure duration, including the core and extension studies, was 676 days for asenapine and 692 days for olanzapine.

No differences were seen between the 2 treatment groups in terms of sex, age, race, or weight: 55.5% of patients were men, the mean age at baseline was 36.9 years, the mean weight was 74.2 kg, and 94.5 were white. Patients were diagnosed with paranoid type schizophrenia (79.5%), schizoaffective disorder (12.3%), and other schizophrenia types (8.2%).

The extension study found that 62.1% of patients treated with asenapine and 54.7% of patients treated with olanzapine had treatment-emergent AEs, and 26.9% and 22.7%, respectively, had treatment-related AEs. AEs that occurred in at least 5% of patients in either treatment group included weight gain, insomnia, worsening schizophrenia, depression, anxiety, headache, influenza, nasopharyngitis, and agitation.

In terms of weight gain, the mean body weight during the extension study did not change beyond the weight gain in the core study. Weight gain in the core study was 76.3 kg for asenapine and 78.8 kg for olanzapine. In the extension study, weight gain was 76.3 kg for asenapine and 78.4 for olanzapine.

No change in the scores on EPS rating scales occurred during the extension study. Over the entire treatment period the incidence of EPS-related AEs was 20% with asenapine and 11% with olanzapine. During the extension period the incidence of EPS-related AEs was 4.5% and 3.3%, respectively, in the asenapine and olanzapine groups. Other changes in measures of safety and tolerability (eg, vital signs and laboratory measures of cholesterol, prolactin, and liver enzymes) were small and comparable between treatment groups.

Overall, 114 patients (87 treated with asenapine and 27 with olanzapine) discontinued treatment during the extension study because of AEs.

Based on observed case analysis, the extension study found that asenapine had comparable efficacy to olanzapine, with the mean change in PANSS total score over the entire treatment period of −35.4 for patients treated with asenapine and −36.1 for those treated with olanzapine. On last observation carried forward analysis, olanzapine was associated with greater improvements than asenapine: mean change in PANSS total score of −18.8 for asenapine and −26.2 for olanzapine.

According to the authors, the greater improvements with olanzapine are most likely due to lower dropout rates with olanzapine compared with asenapine. However, they add, “although overall dropout rates were higher for subjects on asenapine than on olanzapine, there were no meaningful between-group differences in main reasons for discontinuation; withdrawal of consent occurred most frequently.”

Based on these results, the authors conclude that “asenapine and olanzapine [are] well tolerated and maintained efficacy in patients receiving up to 3 years of treatment.”—Mary Beth Nierengarten