Real‐world effectiveness of antipsychotics

Tiihonen, Jari

doi:10.1111/acps.12641

Cited by 15 publications

(11 citation statements)

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“…We found majority of the risperidone induced DNA methylation changes had treatment effect. This result supports the clinal studies that antipsychotic drugs do more good than harm [58] for the patients in a molecular aspect. The comparison between the pre-treatment FES associated CpG sites and the post-treatment associated CpG sites showed us different effect pattern with majority of treatment effect in the pre-treatment FES and majority of side effect in the post-treatment FES.…”

Section: Discussionsupporting

confidence: 89%

Risperidone-induced changes in DNA methylation from peripheral blood in first-episode schizophrenia parallel neuroimaging and cognitive phenotype

Xia

Zong

et al. 2020

Preprint

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Today, second generation anti-psychotics such as clozapine and risperidone are the favored treatment for schizophrenia. Yet, the absence of relevant biomarkers that can decode their neurobiological effect shackles our ability to accurately predict and track response to treatment. While researchers have investigated DNA methylation as a biomarker for schizophrenia risk, none have performed a systematic analysis of the effect of antipsychotics upon DNA methylation. We hypothesize that disease-related methylation changes occur before treatment, and that acute antipsychotic treatment may affect DNA methylation. We designed a longitudinal DNA methylation study to estimate risperidone's effect on DNA methylation and how changes in DNA methylation might influence risperidone's therapeutic effect on behavioral and neuroimaging phenotypes. Thirty-eight patients with first-episode drug-naïve schizophrenia (FES) and 38 demographically-matched individuals (healthy controls) participated. We identified brain related pathways enriched in 8,204 FES-associated methylation sites. Risperidone administration altered methylation in 6,143 CpG DNA sites. Post-treatment FES associated with methylation in 6760 CpG sites. Majority of the DNA methylation changes were treatment effect in the overall CpG sites, the FES associated CpG sites, and risperidone associated CpG sites, except for the post-treatment FES associated CpG sites. There were 590 DNA methylation cites normalized by risperidone treatment. The methylation changes of these 590 CpG sites were related to alterations in symptom severity, spontaneous neurophysiological activity, and cognitive function. To our knowledge, this is the first longitudinal methylation study of drug treatment effect and side effect in psychiatric disorders to include parallel studies of neuroimaging and cognitive phenotypes. We identified FES-associated CpG sites not confounded by drug treatment as potential SCZ biomarkers. The normalization effect of risperidone monotherapy suggests that DNA methylation changes may serve as a predictive biomarker for treatment effect. The constructed methylation-phenotype network revealed a relationship between methylation and a wide range of biological and psychological variables.Analysis and interpretation of data:

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Section: Discussionsupporting

confidence: 89%

Risperidone-induced changes in DNA methylation from peripheral blood in first-episode schizophrenia parallel neuroimaging and cognitive phenotype

Xia

Zong

et al. 2020

Preprint

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“…We found that discontinuation because of nonefficacy or insufficient efficacy was higher in quetiapine (50.0%) compared with aripiprazole (15.38%) and ziprasidone (20.97%). Effectiveness studies using standard dosage ranges pointed out that quetiapine may be less effective than some other widely used SGAs ( Ciudad et al, 2008 ; Asmal et al, 2013 ; Leucht et al, 2013 ; Tiihonen, 2016 ) and FGAs ( Vanasse et al, 2016 ). Regarding the latter study, the authors also warned about a higher risk for health events related to quetiapine.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Antipsychotic Effectiveness in First Episode of Psychosis: A 3-Year Follow-Up Randomized Clinical Trial Comparing Aripiprazole, Quetiapine, and Ziprasidone

Gómez-Revuelta

Pelayo-Terán

Ruíz

et al. 2018

International Journal of Neuropsychopharmacology

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BackgroundDifferent effectiveness profiles among second-generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to affect long-term outcome. The aim of this study was to compare the clinical effectiveness of aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.MethodFrom October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. Two hundred-two first-episode, drug-naïve patients were randomly assigned to aripiprazole (n=78), ziprasidone (n =62), or quetiapine (n=62) and followed-up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on the intention-to-treat principle was conducted in the analysis for clinical efficacy.ResultsThe overall dropout rate at 3 years reached 19.3%. Treatment discontinuation rates were significantly different among treatment groups (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (χ2=11.680; P=.001). Statistically significant differences in terms of nonefficacy, nonadherence, and side effects were observed among treatment groups along the 3-year follow-up determining significant differences in time to all-cause discontinuation (log-rank=32.260; P=.001). Significant differences between treatments were found in the categories of sleepiness/sedation (χ2=9.617; P=.008) and increased sleep duration (χ2=6.192; P=.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines.ConclusionsFirst-episode psychosis patients on quetiapine were more likely to discontinue treatment due to nonefficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.

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“…These have explored hospitalisation, mortality, and filled prescriptions. A review of seven large cohort studies indicated that the use of antipsychotics is associated with a lower risk of death or severe health problem when compared with no use, suggesting that antipsychotics do more good than harm …”

Section: Relationship Between Diabetes and Schizophreniamentioning

confidence: 99%