Novel pharmacotherapy targeting the positive symptoms of schizophrenia

by Selleckchem | Nov 02 2023

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. 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 NaN Invalid Date 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 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.

Comments:

Title: Novel Pharmacotherapy for Targeting Positive Symptoms in Schizophrenia: An Updated Overview

Abstract:
Schizophrenia is a chronic psychiatric disorder characterized by positive symptoms such as hallucinations, delusions, and disorganized thinking. Despite the availability of antipsychotic medications, a significant proportion of patients with schizophrenia exhibit only partial response to treatment. This manuscript aims to provide an updated overview of novel pharmacological strategies targeting positive symptoms in schizophrenia. A comprehensive search of major databases was conducted to identify original articles published until the most recent date available. Promising compounds identified in the literature include lamotrigine, pro-cognitive compounds (such as donepezil, idazoxan, and piracetam), and drugs that act outside the Central Nervous System (CNS), such as anti-inflammatory drugs (celecoxib, methotrexate), cardiovascular compounds (L-theanine, mononitrate isosorbide, propentofylline, sodium nitroprusside), metabolic regulators (diazoxide, allopurinol), and others (bexarotene, raloxifene in women). The effectiveness of these compounds suggests that alternative biological systems, such as the immune or metabolic systems, may be potential targets for the treatment of positive symptoms in schizophrenia. Furthermore, mirtazapine may hold promise in treating negative symptoms without exacerbating delusions or hallucinations. However, the lack of study replication prevents definitive conclusions, and further research is needed to confirm the findings presented in this overview.

Keywords: schizophrenia, positive symptoms, antipsychotics, pharmacotherapy, novel compounds, pro-cognitive agents, anti-inflammatory drugs, cardiovascular compounds, metabolic regulators, immune system, metabolism, mirtazapine, negative symptoms.

1. Introduction

Schizophrenia is a debilitating psychiatric disorder characterized by a range of symptoms, including positive symptoms, negative symptoms, and cognitive impairments. While available antipsychotic medications have shown efficacy in managing symptoms, a significant proportion of patients experience only partial response or inadequate relief from positive symptoms. This manuscript aims to provide an updated overview of novel pharmacotherapy approaches for targeting positive symptoms in schizophrenia.

2. Methods
A comprehensive search of major databases including PubMed, PsychINFO, Isi Web of Knowledge, MEDLINE, and EMBASE was conducted to identify relevant original articles published until the most recent date available. The search focused on new pharmacological strategies for the treatment of positive symptoms in schizophrenia

3. Novel Pharmacotherapy Approaches
3.1 Lamotrigine
Lamotrigine, an anticonvulsant medication, has shown promise in reducing positive symptoms in schizophrenia. Studies suggest its potential as an adjunctive treatment to standard antipsychotics, although further research is needed to establish its efficacy and safety.

3.2 Pro-cognitive Compounds
Compounds with pro-cognitive effects, including donepezil, idazoxan, and piracetam, have shown potential in improving cognitive function and reducing positive symptoms. However, more research is necessary to validate their effectiveness in schizophrenia patients.

3.3 Drugs Acting Outside the CNS
Several compounds that act partially or completely outside the Central Nervous System (CNS) have demonstrated efficacy in alleviating positive symptoms. These include anti-inflammatory drugs (celecoxib, methotrexate), cardiovascular compounds (L-theanine, mononitrate isosorbide, propentofylline, sodium nitroprusside), metabolic regulators (diazoxide, allopurinol), and others (bexarotene, raloxifene in women). These findings suggest that targeting other biological systems, such as the immune or metabolic system, could be a potential avenue for future research.

4. Mirtazapine for Negative Symptoms
Mirtazapine, an antidepressant, shows promise in treating negative symptoms without exacerbating delusions or hallucinations. However, the lack of replication of studies hinders definitive conclusions, and further investigation is necessary.

5. Conclusion
Novel pharmacotherapy approaches offer potential for improving the treatment of positive symptoms in schizophrenia. Compounds such as lamotrigine, pro-cognitive agents, and drugs acting outside the CNS have shown promise in reducing positive symptoms. Additionally, alternative biological systems, including the immune and metabolic systems, warrant further exploration as potential targets. Mirtazapine may hold promise for alleviating negative symptoms. However, more research is required to replicate and confirm the findings presented in this overview, ultimately leading to improved treatment options for individuals with schizophrenia.