Adherence to Background Antipsychotic and Pimavanserin in Patients with Schizophrenia: Post Hoc Analyses from the ENHANCE and ADVANCE Studies.

Background: In patients with schizophrenia, study design to optimize adherence and objective measurement of adherence is critical for interpreting results. Two randomized, double-blind studies evaluating adjunctive pimavanserin in patients with schizophrenia who received stable antipsychotic treatment included measures to encourage and assess treatment adherence. Objective: This post hoc analysis evaluated adherence levels achieved in the Phase III ENHANCE study (NCT02970292) and the Phase II ADVANCE study (NCT02970305). Methods: Blood levels of participants receiving adjunctive treatment with pimavanserin or placebo added to their ongoing antipsychotic medication were tested and evaluated regularly throughout both studies. For both the background antipsychotic and pimavanserin, treatment adherence was defined as a blood sample test result above the lower limit of quantification. Results: Overall, 392 of 633 screened patients and 403 of 608 screened patients were in the safety populations in ENHANCE and ADVANCE, respectively. In ENHANCE, at weeks 1, 3, and 6/early termination (ET), the adherence rates remained ≥ 95.1% for the background antipsychotic in both pimavanserin and placebo treatment groups and ≥ 96.8% for pimavanserin. In ADVANCE, high adherence rates (≥90.6%) with the background antipsychotic (for both treatment groups) and pimavanserin (≥95.0%) were observed at weeks 2, 8, 14, and 26/ET. Conclusion: Rigorous screening was performed to exclude patients not adherent to their background antipsychotic before enrollment and to pimavanserin during study visits by using regular blood sampling. Mandatory caregiver participation further supported adherence to study treatment and procedures. These efforts may have contributed to the high levels of adherence to both background antipsychotic and pimavanserin reported in ENHANCE and ADVANCE.