Novel pharmaceutical treatment approaches for schizophrenia: a systematic literature review

Purpose Schizophrenia is a chronic and debilitating neuropsychiatric disorder afecting approximately 1% of the global
population. Traditional antipsychotic treatments, while efective for positive symptoms, often have signifcant side efects and
fail to address cognitive and negative symptoms. Novel pharmacological treatments targeting muscarinic receptors, TAAR1
agonists, serotonergic pathways, and glutamate modulation have emerged as promising alternatives.
Aim This systematic literature review aims to critically evaluate the efcacy, safety, and mechanisms of action of novel
pharmacological agents in the treatment of schizophrenia.
Methods A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Scopus, and Web of Science
for randomized controlled trials (RCTs) and clinical trials published between April 2014 and March 2024. Studies evaluating novel treatments targeting muscarinic receptors, TAAR1 agonists, serotonergic agents, and glutamate modulation were
included. Primary outcomes focused on symptom reduction and quality of life, while secondary outcomes included cognitive
function and adverse events. The Joanna Briggs Institute (JBI) tool was used for quality assessment.
Results Eleven studies involving 4614 participants (mean age 37–43 years, predominantly male) were included. Drugs evaluated included xanomeline-trospium (KarXT), pimavanserin, ulotaront, emraclidine, and bitopertin. Signifcant improvements
in PANSS and CGI-S scores were observed, with xanomeline-trospium showing a mean reduction of 17.4 points (p 0.001).
Adverse events were mostly mild and transient, with nausea, constipation, and somnolence being common.
Conclusion Novel treatments for schizophrenia show promise in managing both positive and negative symptoms, with
generally favorable safety profles. Future studies should focus on large-scale, long-term trials to refne their efcacy, safety,
and clinical applicability.