Can 5-HT3 antagonists contribute toward the treatment of schizophrenia?

Ellenbroek, Bart A.; Prinssen, Eric

doi:10.1097/fbp.0000000000000102

Cited by 23 publications

(14 citation statements)

References 102 publications

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“…Although agents with D2/5-HT2A antagonism and 5-HT1A partial agonism are currently available, efforts to develop agents with more potent 5-HT1A activity (targeting negative and cognitive symptoms) with better tolerability are ongoing. Recently, there is a renewed interest in the development of 5-HT3 antagonists (ondansetron, tropisetron and granisetron) as adjunctive agents for negative and cognitive symptoms [ 83 , 84 , 85 , 86 ]. For example, Ondansetron is a 5-HT3 receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer and is also potentially related to anti-inflammatory treatment strategy for schizophrenia.…”

Section: Novel Treatment Targetsmentioning

confidence: 99%

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

Yang

Tsai

2017

IJMS

233

129

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Schizophrenia has been primarily associated with dopamine dysfunction, and treatments have been developed that target the dopamine pathway in the central nervous system. However, accumulating evidence has shown that the core pathophysiology of schizophrenia might involve dysfunction in dopaminergic, glutamatergic, serotonergic, and gamma-aminobutyric acid (GABA) signaling, which may lead to aberrant functioning of interneurons that manifest as cognitive, behavioral, and social dysfunction through altered functioning of a broad range of macro- and microcircuits. The interactions between neurotransmitters can be modeled as nodes and edges by using graph theory, and oxidative balance, immune, and glutamatergic systems may represent multiple nodes interlocking at a central hub; imbalance within any of these nodes might affect the entire system. Therefore, this review attempts to address novel treatment targets beyond the dopamine hypothesis, including glutamate, serotonin, acetylcholine, GABA, and inflammatory cytokines. Furthermore, we outline that these treatment targets can be possibly integrated with novel treatment strategies aimed at different symptoms or phases of the illness. We anticipate that reversing anomalous activity in these novel treatment targets or combinations between these strategies might be beneficial in the treatment of schizophrenia.

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Section: Novel Treatment Targetsmentioning

confidence: 99%

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

Yang

Tsai

2017

IJMS

233

129

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“…In addition, 5-HT 2C agonists and 5-HT 6 antagonists have been proposed as clinically useful agents for the early or prodromal stage of schizophrenia, and 5-HT 3 antagonists have been evaluated as adjunctive treatments for negative and cognitive symptoms. However, lurasidone, which has a potent 5-HT 7 antagonism, has no clinical implications for treating negative and cognitive symptoms [16,39]. …”

Section: Unmet Needs In the Current Antipsychotic Medications For mentioning

confidence: 99%

A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia

Kim

Choi

Park

2017

IJMS

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Despite the substantial burden of illness in schizophrenia, there has been a discrepancy between the beneficial effects of an increased use of antipsychotic medications and achieving limited recovery or remission. Because the focus of the most common antipsychotic medications is on dopamine, which is associated with positive symptoms, there is an unmet need for patients with negative symptoms. Since cognitive and negative symptoms rather than positive symptoms are more closely associated with psychosocial impairments in patients with schizophrenia, the non-dopaminergic systems including glutamate and γ-aminobutyric acid (GABA) of the prefrontal cortex should be of concern as well. The balance of excitation and inhibition has been associated with epigenetic modifications and thus can be analyzed in terms of a neurodevelopmental and neural circuitry perspective. Hence, a novel bio-psychosocial-behavioral model for the treatment of schizophrenia is needed to account for the non-dopaminergic systems involved in schizophrenia, rather than dopaminergic mechanisms. This model can be understood from the viewpoint of neurodevelopment and neural circuitry and should include the staging care, personalized care, preventive care, reducing the cognitive deficits, and reducing stigma. Thomas R. Insel proposed this as a goal for schizophrenia treatment to be achieved by 2030.

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“…Although the underlying etiology of schizophrenia is still poorly understood, lines of evidence suggest that dysfunction in 5‐hydroxytryptamine (serotonin) processes involves in the pathophysiology of schizophrenia (Ellenbroek & Prinssen, 2015; Wooley & Shaw, 1954). Furthermore, another evidence is that the serotonin system plays a critical role in the efficiency of second generation antipsychotics, though binding much strongly with the serotonin system than dopamine system (Lieberman et al., 1998).…”

Section: Introductionmentioning

confidence: 99%

Successful treatment with risperidone increases 5‐HT 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

et al. 2017

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IntroductionThe relationship between peripheral 5‐HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown.MethodsA total 52 first‐episode and drug‐naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week.ResultsThere was no difference in 5‐HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline (p = .24). Among 47 patients who completed 8‐week naturalistic follow‐up, 37 were responders to risperidone treatment. 5‐HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8‐week treatment with risperidone (p = .29). However, 5‐HT3A receptor mRNA level in responders increased significantly (p = .04), but not in nonresponders (p = .81).ConclusionsSuccessful treatment with risperidone increases 5‐HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5‐HT3A receptor may be involved in the mechanism of risperidone effect.

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Can 5-HT3 antagonists contribute toward the treatment of schizophrenia?

Cited by 23 publications

References 102 publications

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

A Novel Bio-Psychosocial-Behavioral Treatment Model in Schizophrenia

Successful treatment with risperidone increases 5‐HT 3A receptor gene expression in patients with paranoid schizophrenia – data from a prospective study

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