Affiliation:
1. Division of Drug Informatics, Keio University Faculty of Pharmacy,
Tokyo, Japan
2. Department of Neuropsychiatry, Keio University School of Medicine,
Tokyo, Japan
Abstract
Abstract
Introduction Conventional antipsychotic drugs that attenuate dopaminergic
neural transmission are ineffective in approximately one-third of patients with
schizophrenia. This necessitates the development of non-dopaminergic agents.
Methods A systematic search was conducted for completed phase II and III
trials of compounds for schizophrenia treatment using the US Clinical Trials
Registry and the EU Clinical Trials Register. Compounds demonstrating
significant superiority over placebo in the primary outcome measure in the
latest phase II and III trials were identified. Collateral information on the
included compounds was gathered through manual searches in PubMed and press
releases.
Results Sixteen compounds were identified; four compounds (ulotaront,
xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated
as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809,
encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone,
valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy.
Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin,
bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for
positive symptoms; roluperidone and pimavanserin were effective for negative
symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and
valacyclovir improved cognitive function.
Discussion Compounds that function differently from existing antipsychotics
may offer novel symptom-specific therapeutic strategies for patients with
schizophrenia.