A new era for schizophrenia drug development – Lessons for the future

Granger, Kiri; Sand, Michael; Caswell, Sheryl; Lizarraga, Lorena; Barnett, Jennifer H.; Moran, Paula M.

doi:10.1016/j.drudis.2023.103603

Cited by 12 publications

(5 citation statements)

References 75 publications

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“…Schizophrenia is classified as one of the most serious mental disorders due to its complicated behavioural and cognitive symptoms ( Gao et al, 2023 ) and the reduced life expectancy of individuals diagnosed with this disorder, which is 10–25 years less compared to the general population ( Sheybani-Arani et al, 2023 ). The symptoms of this disorder include hallucinations and delusions (positive symptoms), asociality, anhedonia, blunted affect and alogia (negative symptoms) and impairment of working memory, attention and executive function (cognitive symptoms) ( Granger et al, 2023 ). According to Ngubane and De Gama (2023) , the symptoms of schizophrenia may overlap with the symptoms observed in patients reported to be bewitched or who have an ancestral calling.…”

Section: Introductionmentioning

confidence: 99%

The antipsychotic potential of Salix Mucronata on ketamine-induced rats

Ngubane,

Mabandla,

De Gama

2024

IBRO Neuroscience Reports

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Section: Introductionmentioning

confidence: 99%

The antipsychotic potential of Salix Mucronata on ketamine-induced rats

Ngubane,

Mabandla,

De Gama

2024

IBRO Neuroscience Reports

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“…Density functional theory has also been used in building QSAR models for schizophrenia drugs along with multilinear regression of the genetic function approximation method for building the model . Recently, different QSAR/QSPR models and other clinical techniques have been used to develop potent and efficient drugs for the disorder. − …”

Section: Introductionmentioning

confidence: 99%

“… 6 Recently, different QSAR/QSPR models and other clinical techniques have been used to develop potent and efficient drugs for the disorder. 7 − 11 …”

Section: Introductionmentioning

confidence: 99%

QSPR Analysis of Drugs for Treatment of Schizophrenia Using Topological Indices

Zhang,

Saif,

Idrees

et al. 2023

ACS Omega

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Schizophrenia is a chronic psychotic disorder characterized primarily by cognitive deficits. Drugs and therapies are helpful in managing the symptoms, mostly with long-term compliance. There is a pressing need to design more efficient drugs with fewer adverse effects. Solubility, metabolic stability, toxicity, permeability, and transporter effects are important parameters in the efficacy of drug design, which in turn depend upon different physical and chemical characteristics of drugs. In recent years, there has been growing interest in developing computational tools for the discovery and development of drugs for schizophrenia. Some of these methods use machine learning algorithms to predict the efficacy and side effects of the potential drugs. Other studies have used computer simulations to understand the molecular mechanisms underlying the disease and identify new targets for drug development. Topological indices are numeric quantities linked to the chemical structure of drugs and predict the properties, reactivity, and stability of drugs through the quantitative structure−property relationship (QSPR). This work is aimed at using statistical techniques to link QSPR correlating properties with connectivity indices using linear regression. The QSPR model gives quite a better estimation of the properties of drugs, such as melting point, boiling point, enthalpy, flash point, molar refractivity, refractive index, complexity, molecular weight, and refractivity. Results are validated by comparing actual values to estimated values for the drugs.

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“…Currently, there are more than 20 pharmacotherapeutic options to treat schizophrenia symptoms ( 27 , 28 ) and some focus on non-dopaminergic mechanisms ( 29 ), although these mechanisms ultimately affect dopaminergic transmission ( 30 ). When choosing a prescription, clinicians should balance efficacy with safety and adverse events.…”

Section: Introductionmentioning

confidence: 99%

Brexpiprazole in patients with schizophrenia with or without substance use disorder: an observational study

Lombardozzi,

Trovini,

Amici

et al. 2023

Front. Psychiatry

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BackgroundPartial dopamine D2 receptor agonists are used for psychotic symptoms in adults with schizophrenia spectrum disorders. Recently, interest surged for partial dopamine D2 receptor agonists in substance use disorders (SUDs). Since it is believed that SUDs decrease the efficacy of pharmacotherapy of underlying psychiatric disorders, we tested the efficacy of the partial D2 agonist brexpiprazole in patients with schizophrenia who were either comorbid with a SUD (SUD group) or not comorbid (non-SUD) to assess treatment response and the effect of brexpiprazole on substance craving in SUD.MethodsWe included patients with DSM-5/DSM-5-TR schizophrenia (using SCID-5-CV) aged 18–66 years with either comorbid SUD or non-SUD to treat with brexpiprazole 4 mg/day for 6 months during February–October 2022. Patients were assessed with the Clinical Global Impressions–Severity (CGI-S) scale, the 24-item Brief Psychiatric Rating Scale (BPRS), and the Positive And Negative Syndrome Scale (PANSS) at baseline, weekly for the first 2 months and monthly for the next four. Furthermore, we assessed substance craving in SUD with a visual analog scale for craving (VAScrav) at the same timepoints.ResultsThe total sample was 86 (85 analysable) 18- to 64-year-old (mean 39.32 ± 14.09) patients with schizophrenia [51 men (59.3%) and 35 women (40.7%)], of whom 48 SUD (55.8%) (37 men and 11 women) and 38 non-SUD (44.2%) (14 men and 24 women). No serious or persistent adverse events developed over the study period, but one patient dropped out for subjective akathisia. Results indicated the main effects of time with improvements over the course of the study for CGI-S, BPRS, and PANSS in both SUD and non-SUD groups and the entire sample, and for VAScrav in SUD. Brexpiprazole was associated with similar significant improvements in both groups at the 6 month endpoint compared to baseline.ConclusionTreatment with brexpiprazole for 6 months improved psychotic symptoms in patients with schizophrenia, independently from whether they belonged to the SUD or the non-SUD group; hence, SUD comorbidity did not confer treatment resistance to brexpiprazole. Furthermore, in the SUD group, we observed reduced substance craving.

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A new era for schizophrenia drug development – Lessons for the future

Cited by 12 publications

References 75 publications

The antipsychotic potential of Salix Mucronata on ketamine-induced rats

The antipsychotic potential of Salix Mucronata on ketamine-induced rats

QSPR Analysis of Drugs for Treatment of Schizophrenia Using Topological Indices

Brexpiprazole in patients with schizophrenia with or without substance use disorder: an observational study

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