Emerging drugs for schizophrenia: an update

Abstract

Introduction: Schizophrenia is one of the most serious mental disorders. Its treatment remains challenging, as existing antipsychotic antidopaminergic medications improve only/predominantly positive symptoms, agitation and aggression but have limited/insignificant efficacy for negative and cognitive symptoms, which strongly affect functional outcome. Therefore, new therapeutic agents are urgently needed that treat aspects of the spectrum of schizophrenia symptomatology and improve functional outcome.

Areas covered: The authors review the mechanisms of action and key clinical results of drug development targets currently in Phase II and III clinical testing for schizophrenia. They further discuss potential barriers to the successful development of these targets and summarize the drug development status of emerging treatments for various aspects of schizophrenia.

Expert opinion: Although modifications and variations of antidopaminergic mechanisms are expected to be successful, the added benefits will likely remain small, at least regarding enhanced efficacy for negative symptoms, cognition and functional outcomes. Greater innovation will likely come from further and deeper exploration of extra-dopaminergic mechanisms. Investment is needed to develop clinically meaningful animal paradigms probing the different symptom domains, to discover more efficient in vivo screening methods for novel drug targets, to optimize clinical trial design and trial conduct, and to parse the heterogeneous groups of schizophrenias into biologically more homogeneous subgroups.

Keywords::

• agonist
• antagonist
• dopamine
• mechanisms of action
• medications
• non-dopaminergic
• psychosis
• schizophrenia

Acknowledgement

We thank the following people who we contacted and who confirmed the correctness of publically available information and/or who provided us with additional information relevant for this article: E Ehrich, MD (Alkermes); Y Lavrovsky, PhD (Avineuro Pharmaceuticals, Inc.); I Lombardo, MD and N Ortiz, PhD (Forum Pharmaceuticals); M Rogerson (GW Pharmaceuticals); C O'Gorman, MD, MBA, N Schrameijer, MD, D Bugarski-Kirola, MD, T Haigh, DPhil, CMPP (Hoffmann-La Roche Ltd./Genentech); K Vanover, PhD (Intracellular Therapies); P Hertel, PhD (Lundbeck); R Sanchez, MD (Otsuka Pharmaceutical); Dean Mastrojohn (Pfizer); L Bhat, PhD (Reviva Pharmaceuticals, Inc.); L Rovati, MD (Rottapharm Madaus). We also thank R Goodwin for comments on an earlier draft of this paper.