Novel pharmacotherapy targeting the positive symptoms of schizophrenia

ABSTRACT

Introduction

The severity of positive symptoms in schizophrenia is associated with poor prognosis. About one-third of schizophrenia patients partially respond to treatment with available antipsychotics. The purpose of the present manuscript is to provide an updated overview of novel pharmacotherapy targeting positive symptoms in schizophrenia.

Areas covered

A comprehensive research on the main database sources (PubMed, PsychINFO, Isi Web of Knowledge, MEDLINE, and EMBASE) was performed to obtain original articles published till 31^st January 2023 about new pharmacological strategies for the treatment of positive symptoms in schizophrenia.

Expert opinion

The most promising compounds include: lamotrigine, pro-cognitive-compounds (donepezil – in the short term, idazoxan and piracetam) and drugs acting partially or totally outside the Central Nervous System (CNS) (anti-inflammatory drugs: celecoxib, methotrexate; cardiovascular compounds: L-theanine, mononitrate isosorbide, propentofylline, sodium nitroprusside; metabolic regulators: diazoxide, allopurinol; others: bexarotene, raloxifene [in women]). The effectiveness of the latter compounds indicates that other biological systems, such as immunity or metabolism can be object of future research to identify pharmacological targets for positive symptoms of schizophrenia. Mirtazapine could be useful for treating negative symptoms without increasing the risk of a worsening of delusions/hallucinations. Nevertheless, the lack of replication of studies prevents to draw definitive conclusions and future studies are needed to confirm the findings presented in this overview.

KEYWORDS:

• Schizophrenia
• positive symptoms
• new pharmacological strategies
• delusions
• hallucinations

Article highlights

• Schizophrenia is a chronic and highly disabling mental disorder which is related to low rates of functional recovery.

• Current pharmacological treatment of schizophrenia is based on antipsychotics, which can be partly effective on positive symptoms.

• Different off-label compounds were tested for a better management of positive symptoms of subjects affected by schizophrenia.

• Among the numerous off-label pharmacologic strategies targeting the positive symptoms of schizophrenia, only few compounds resulted in improved positive symptoms, with findings coming from single studies.

• Promising results regard molecules not acting exclusively on the central nervous system (CNS), suggesting that other biological systems, such as immunity or metabolism could be the object of future research to identify pharmacological targets for positive symptoms of schizophrenia.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Author contributions

E Capuzzi and A Caldiroli: Conceptualization, Investigation, Methodology, Writing – original draft, Data curation.

F Butturini: Conceptualization, Formal analysis, Methodology

C Quitadamo: Conceptualization, Writing – review & editing.

T Surace: Writing – review & editing.

M Buoli: Conceptualization, Formal analysis, Writing – review & editing, Supervision.

M Clerici: Supervision.

Additional information

Funding

This paper was not funded.