Schizophrenia is a severe, often chronic mental disorder, characterized by positive and
negative symptoms and cognitive deficits. The serotonin hypothesis of schizophrenia was
proposed in the 1950s, but only recently, pimavanserin, the first antipsychotic medication
with selective affinity for the serotonin 2A receptor was approved.
The aim of this translational proposal is to test the clinical validity of the serotonin
hypothesis of schizophrenia and to guide development of operational, objective criteria for
stratification of first-episode schizophrenia spectrum patients before antipsychotic
treatment.
Our previous data have strongly suggested, that a subgroup of antipsychotic-naïve patients
will respond to serotonin 2A receptor (2AR) blockade. This treatment will cause minimal
side-effects compared with conventional dopamine D2/3 receptor blockade.
In this Danish, investigator-initiated trial, we will establish a cohort of 40
antipsychotic-free, first-episode schizophrenia spectrum patients and enrol them in a 6-week
open label, one-armed trial with selective serotonin 2AR blockade (pimavanserin).
Before initiation of pimavanserin patients will undergo: positron emission tomography (PET)
imaging of the serotonin 2AR binding potential using the radioligand [¹¹C]Cimbi-36; magnetic
resonance spectroscopy (MRS) of cerebral glutamate levels; structural Magnetic Resonance
imaging (MRI), including Diffusion Tensor Imaging (DTI); cognitive and psychopathological
examinations; Electrocardiography (ECG), and blood sampling for genetic- and metabolic
analyses.
Matched healthy controls will undergo parallel examinations, but not medical treatment and
PET .
ACADIA Pharmaceuticals Inc. provides the study medication (pimavanserin). ACADIA had no
influence on study design and will not take part in data processing or publication of the
results of the study.
Phase:
Phase 2
Details
Lead Sponsor:
Bjorn H. Ebdrup
Collaborators:
ACADIA Pharmaceuticals Inc. GCP unit, Copenhagen University Hospital Rigshospitalet, Denmark