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.

The role of executive functions and psychiatric symptom severity in the Allen Cognitive Levels.

This study examined the relationship between Allen Cognitive Level (ACL) and psychiatric symptom severity, level of nursing support required to complete activities of daily living (ADLs), and post-hospitalization discharge disposition in a sample of 193 acute psychiatric inpatients. A subsample of 31 participants with acute psychotic disorders were administered three measures of executive functioning in order to examine the convergent validity between ACL and basic sequencing and shifting, phonemic fluency, and visuospatial construction. Findings indicated significant moderate positive correlations between ACL and motor processing speed, basic sequencing and shifting, and phonemic fluency, and a nonsignificant relationship with visuospatial construction. A subsample of 166 participants were administered the Brief Psychiatric Rating Scale-Expanded (BPRS-E) to assess psychiatric symptom severity. Results indicated a significant weak negative correlation between ACL and total psychiatric symptomatology, as well as significant weak negative correlations with specific symptoms. In contrast with prior research, there was no significant correlation between ACL and level of nursing assistance required to complete ADLs. A logistic regression did not identify ACL as a contributing factor to post-hospitalization discharge disposition. These findings call into question the clinical utility of the ACLS-5 as an assessment of functional cognition for those experiencing acute psychiatric illness.