title: A fixed-dose randomized controlled trial of olanzapine for psychosis in Parkinson disease.
abstract: BACKGROUND
  Psychosis is a common and debilitating side effect of long-term dopaminergic treatment of Parkinson disease (PD). While clozapine is an effective treatment, the need for blood monitoring has limited its first-line use.
  
  
  OBJECTIVE
  Since olanzapine shows similar receptor affinity to clozapine, we hypothesized that it might be an effective alternative to clozapine for treatment of drug-induced psychosis (DIP) in PD, and that lower doses than usual might make it tolerable.
  
  
  METHODS
  In 1998-2003 we conducted a four-week, double-blind, placebo-controlled, parallel group, fixed-dose trial of olanzapine (0, 2.5mg, or 5mg) in 23 PD patients with DIP while allowing for clinically realistic dose adjustments of dopaminomimetic mid-study. The primary outcome measures were Brief Psychiatric Rating Scale (BPRS) ratings scored from videotaped interviews after study termination by an observer blinded to dose assignment and to interview timing, and CGI (Clinical Global Impression). The Unified Parkinson's Disease Rating Scale motor subscale (UPDRS) was the primary measure of tolerability.
  
  
  RESULTS
  Intention-to-treat analysis found no significant differences among treatment groups in study completion or serious adverse events. However, a disproportionate number of olanzapine vs. placebo subjects reported mild side effects (p<0.04), many citing motor worsening. Fourteen patients completed the study (seven on placebo, two on 2.5mg olanzapine, five on 5mg olanzapine). In study completers, analysis by repeated measures ANOVA revealed no significant difference between olanzapine and placebo groups in BPRS psychosis reduction (p=0.536), parkinsonism (p=0.608), or any other measured parameters (CGI, MMSE, Beck Depression Inventory, Hamilton Depression score, PDQ‑39, Schwab-England ADL assessment, and sleep scores).
  
  
  CONCLUSIONS
  This study adds to other evidence that olanzapine is ineffective in treating medication-induced psychosis in Parkinson disease.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis MO, 63110, USA ; Current affiliation: UT Southwestern Medical Center, Dallas TX, 75390, USA.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Nichols
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis MO, 63110, USA ; Department of Neurology, Washington University School of Medicine, St. Louis MO, 63110, USA.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Hartlein
authors.affiliation: Department of Biology, Washington University, St. Louis MO, 63110, USA ; Current affiliation: Massachusetts General Hospital, Boston MA, 02114-2622, USA.
authors.forename: Meredith Ga
authors.initials: MG
authors.lastname: Eicken
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis MO, 63110, USA.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Racette
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis MO, 63110, USA ; Department of Neurology, Washington University School of Medicine, St. Louis MO, 63110, USA ; Department of Radiology, Washington University School of Medicine, St. Louis MO, 63110, USA ; Department of Anatomy & Neurobiology, Washington University School of Medicine, St. Louis MO, 63110, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Black