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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. 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. 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.

Novel pharmacotherapy targeting the positive symptoms of schizophrenia