Emerging 5-HT receptor antagonists for the treatment of Schizophrenia

ABSTRACT

Introduction

While antipsychotics have been generally successful in treating psychosis in schizophrenia, there is a major treatment gap for negative symptoms and cognitive deficits. Given that these aspects of the disease contribute to poor functional outcomes independently of positive symptoms, treatments would have profound implications for quality of life. The 5-HT_2A- receptor has been considered a potential target for interventions aimed at negative and cognitive symptoms and multiple antagonists and inverse agonists of this receptor have been tested.

Areas covered

Ritanserin and volinanserin, are historically important compounds in this area, while pimavanserin, roluperidone, and lumateperone are either newly approved, in late stages of development, or currently being tested for efficacy in schizophrenia-related features. The focus will be on their efficacy in the treatment of negative symptoms, with a limited secondary discussion of cognition.

Expert opinion

In addition to their efficacy in treating negative symptoms and cognition, these compounds may also have a role in modulating antipsychotic-induced dopamine super-sensitivity and preventing relapse. They may also show efficacy in treating patients with milder symptoms such as patients with schizotypal personality disorder and attenuated psychosis syndrome. Their utility may also expand outside the spectrum of schizophrenia to encompass Parkinson’s Disease psychosis, major depression, bipolar depression, and dementia-associated apathy.

KEYWORDS:

• Cognition
• negative symptoms
• pharmacology
• psychosis
• schizophrenia
• serotonin
• treatment

Article highlights

• Treatments targeting the 5HT–2A receptor are being developed for treatment of schizophrenia.

• Although these treatments have been considered before, there are two drugs currently approved by the US Food and Drug Administration and one in development that have shown promise for targeting previously poorly treated features of the illness.

• These three drugs, Lumateperone, Pimavanserin, and Roluperidone have all shown promise for treating negative symptoms in particular.

Declaration of interest

PD Harvey has received consulting fees or travel reimbursements from Acadia Pharma, Alkermes, Bio Excel, Boehringer Ingelheim, Intra-Cellular Therapies, Minerva Pharma, Otsuka Pharma, Regeneron Pharma, Roche Pharma, Sunovion Pharma, Takeda Pharma, and Teva during the past year. PD Harvey receives royalties from the Brief Assessment of Cognition in Schizophrenia. He is chief scientific officer of i-Function, Inc. He had a research grant from Takeda and from the Stanley Medical Research Foundation. None of these companies provided any information to the authors that is not in the public domain. MT Strassnig has received consulting fees or travel reimbursements from Signant Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.