Perspective on Pimavanserin and the SAPS-PD: Novel Scale Development as a Means to FDA Approval

In 2016, pimavanserin, a 5-hydroxytryptamine 2A inverse agonist, became the first U.S. Food and Drug Administration (FDA) approved medication for Parkinson disease psychosis (PDP) after demonstrating modest clinical improvement in a single positive trial as assessed by a novel PDP scale, the Scale for the Assessment of Positive Symptoms for Parkinson's Disease Psychosis (SAPS-PD). This followed three trials that demonstrated negative findings on established measures of psychosis widely used in PDP research, including the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, the Parkinson Psychosis Rating Scale, and the Clinical Global Impression-Severity Scale. This review article provides an overview of the scale construction of the SAPS-PD, a measure which has yet to be established as valid, reliable, or sensitive to change in PDP. Furthermore, this article reviews analyses completed by an FDA statistical reviewer that call into question whether pimavanserin demonstrated a clinically significant difference from placebo on the SAPS-PD. These findings underscore concerns regarding the clinical efficacy of pimavanserin.