Safety and Efficacy of Ondansetron and Simvastatin as Potential Adjunctive Treatment for Patients With Schizophrenia: A Systematic Review of Randomized Controlled Trials

Abstract

In a generation where advancements in research and understanding have led to remarkable achievements in medicine, it is still unfathomable that, after more than a century, the cause of schizophrenia is still a mystery. While antipsychotics, without a doubt, have brought on an exemplary revolution in the way psychiatric disorders are now treated, there are still imperative deficits that need to be addressed to ultimately enable individuals with schizophrenia to function normally in society. However, without a definite cause of schizophrenia, even though speculation has been made on its inflammatory and neurodegenerative nature, it has provided an unnecessary hindrance to finding further potential treatment modalities for these patients. Nevertheless, some trials are investigating potential adjunctive treatment regimens to antipsychotics, which can help achieve complete remission. Exploring these drugs will have significant implications for managing schizophrenia in future clinical practices. This systematic review was conducted between January 2012 to July 2022 according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines to evaluate the safety and efficacy of ondansetron and simvastatin as adjunctive treatment to antipsychotics in adult patients with schizophrenia. This review included nine randomized controlled trials. Overall, both simvastatin and ondansetron, when used as adjunctive treatment in schizophrenia, appear to be safe. Ondansetron showed promising results, with all studies on this drug showing positive overall results on schizophrenia symptoms. On the other hand, simvastatin demonstrated mixed results, which can be attributed to the limited participants in the studies and the shorter duration of the trials. However, more extensive trials with uniform assessment tools are needed to demonstrate concrete evidence of the effectiveness of these drugs, whether alone or in combination with each other or perhaps another drug such as aspirin in schizophrenia.

The association between ondansetron use and mortality risk of traumatic brain injury patients: a population-based study

“…Two other studies found that 5-HT receptor antagonists, including sarpogrelate and tropisetron, could decrease the production of pro-inflammatory cytokines in shock models ( Nishiyama, 2009 ; Setoguchi et al, 2011 ). In addition, ondansetron has been used to control symptoms of neuropsychiatric diseases, including obsessive compulsive disorder, through decreasing the dopaminergic activity and the release of serotonin, norepinephrine, and acetylcholine, which also play an important role in the pathophysiological process of TBI ( Eissazade et al, 2023 ; Khan et al, 2023 ). Therefore, we reasonably hypothesize that ondansetron could improve the prognosis of TBI by regulating coagulation, inflammation, and immune status and protecting the kidney and brain after an injury.…”

Immunological Biomarkers as Predictors of Treatment Response in Psychotic Disorders

“…No significant difference were found for CRP > 1 mg/L, CRP >3.9 mg/L, CRP > 4 mg/L, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17a, TNF-α and IFN-γ, CD4+, CD8+, CD19+, and sIL-2R [ 48 , 60 , 63 , 64 , 71 , 73 , 74 , 80 ]. Several previous meta-analyses and systematic reviews on anti-inflammatory add-on drugs to antipsychotics exist, but none have investigated baseline immunological biomarkers and the prediction of treatment response [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 49 , 50 , 52 , 53 , 54 , 55 , 56 , 94 ].…”

“…A recent meta-analysis showed that drugs possessing either primary or pleiotropic anti-inflammatory properties, as an add-on to the antipsychotic treatment of psychotic disorders, improve the negative and positive symptoms and slow cognitive decline compared to placebos [ 38 ]. In addition, several previous meta-analyses on add-on drugs with either primary or pleiotropic anti-inflammatory properties have been performed, but none of the previous meta-analyses investigated baseline immune biomarkers and treatment effects [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ].…”