Significant Effect of Valproate Augmentation Therapy in Patients With Schizophrenia

Tseng, Po Chun; Chen, Yen Wen; Chung, Wen‐Hsin; Tu, Kun Yu; Wang, Hung-Yu; Wu, Ching Kuan; Lin, Pin‐Yao

doi:10.1097/md.0000000000002475

Cited by 31 publications

(17 citation statements)

References 63 publications

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“…The level of Lactobacillus phage phiadh was also relatively increased in individuals who were being treated with therapeutic valproate, a medication commonly used for the adjunctive treatment of schizophrenia (Tseng et al, 2016). This finding is of interest since valproate has been shown to modify the microbiome in mouse models of autism in the context of in utero exposure, probably related to us homology with short chain fatty acids(de Theije et al, 2014)).…”

Section: Resultsmentioning

confidence: 99%

The microbiome, immunity, and schizophrenia and bipolar disorder

Dickerson

Severance

Yolken

2017

Brain, Behavior, and Immunity

216

128

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Schizophrenia and bipolar disorder are serious neuropsychiatric disorders of uncertain etiology. Recent studies indicate that immune activation may contribute to the etiopathogenesis of these disorders. Numerous studies in animal models indicate that the mucosal microbiome may influence cognition and behavior by altering the functioning of the immune system. It is thus likely that the microbiome plays a role in human psychiatric disorders. The study of immune alterations and the microbiome in schizophrenia and bipolar disorder is in its infancy. Two recent investigations of the oro-pharyngeal microbiota in schizophrenia found differences between cases and controls. Other studies have found increased gastrointestinal inflammation in schizophrenia and bipolar disorder based on measures of microbial translocation. Several studies have also found an association between the receipt of antibiotics and an increased incidence of psychiatric disorders, perhaps due to alterations in the microbiome. Studies to characterize the intestinal microbiome of individuals with these disorders are in progress. The ultimate test of the role of the microbiome and immune-mediated pathology in schizophrenia and bipolar disorder will come from clinical trials of therapeutic agents which alter gut microbiota or gastrointestinal inflammation. The successful development of such modalities would represent a novel strategy to prevent and treat serious psychiatric disorders.

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Section: Resultsmentioning

confidence: 99%

The microbiome, immunity, and schizophrenia and bipolar disorder

Dickerson

Severance

Yolken

2017

Brain, Behavior, and Immunity

216

128

View full text Add to dashboard Cite

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“…These findings were consistent with those of Horowitz E et al 5 and Ananthavarathan 6 who showed that sodium valproate helps to reduce aggressiveness and hostility in schizophrenia. Tseng et al 7 also found effectiveness of adjunctive sodium valproate in patients of schizophrenia.…”

Section: Discussionmentioning

confidence: 95%

“…5,6 Tseng et al showed significantly better treatment effect with valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder. 7 Omranifard et al found that sodium valproate speeds up the recovery of positive symptoms of schizophrenia. 8 Only one case study in India reported beneficial effect of adjunctive sodium valproate in functional hallucinations in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Effect of Adjunctive Sodium Valproate in Patients of Acute Schizophrenia

Saini¹,

Aggarwal²,

Pardal³

et al. 2019

IJCMR

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introduction: Sodium valproate is an anticonvulsant widely prescribed as a mood stabilizer for treating bipolar disorders. It's role in treating schizoaffective disorders is well documented. There are controversies regarding sodium valproate efficacy in schizophrenia. Although, some studies have reported that it is effective in the management of positive symptoms in acute psychosis, others have not found such an association. Study aimed at assessment the effect of adjunctive sodium valproate in acute stage of schizophrenia. Material and Methods:A total of 60 schizophrenic patients (age 18-45 years) were taken. They were randomly allocated into two groups, A and B. Patients in group A received atypical antipsychotic with placebo and in group B atypical antipsychotic with adjunctive sodium valproate. Olanzapine was taken as atypical antipsychotic in both groups. A diagnosis of schizophrenia was established based on ICD-10 DCR criteria. All patients were assessed by PANSS and CGI-S at baseline and at 6 weeks. The collected data were analyzed by Student and Paired t-tests through SPSS. results: Comparison of mean PANSS scores showed statistically significant improvement in positive symptoms (p<0.014), general psychopathology (p<0.036) and total score (p<0.018) in group B patients as compared to group A. CGI-S scores were also statistically significantly less in (p<0.011) group B patients as compared to group A after 6 weeks. conclusion:Our study shows that if used as an adjunctive to antipsychotic in the management of acute psychosis, sodium valproate will speed up the recovery of positive symptoms.

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“…White matter loss and dysregulation of myelin modelling has been shown to contribute towards schizophrenia. Curcumin has been identified as a potent modifier of epigenetics signal pathways at multiple sites: HDAC (Histone Deacetylase) isoforms 1, 3, 8, HAT (histone acetyltransferase), non-coding RNA miRNA-22, miRNA186a and miRNA-199a ( Figure 2) [54,55]. In high throughput epigenetic screening assay using HeLa nuclear extract, curcumin was found to be more potent in inhibiting HDAC than valproic acid and sodium butyrate [56].…”

Section: Epigenetics Footprints and Curcuminmentioning

confidence: 99%

Targeting Epigenetics Signaling with Curcumin: A Transformative Drug Lead in Treatment of Schizophrenia?

Chiu¹,

Woodbury-Fariña²,

Terpstra³

et al. 2017

J Clin Epigenet

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While pharmacotherapy of second generation of atypical antipsychotics: clozapine, olanzapine, risperidol, quetiapine, ziprasidone, aripiprazole bring about significant improvement in the positive symptoms of schizophrenia [1], overall psychosocial outcomes in schizophrenia remain modest. Significant functional impairment related to negative symptoms (lack of volition, apathy, sociality, poverty of speech and affective flattening), active positive symptoms (delusions, hallucinations and bizarre behavioral disturbances) and neuro-cognition deficits, persists in 20-30% of patients with schizophrenia refractory to AbstractDespite advances in pharmacotherapy, schizophrenia continues to carry a high societal disease burden related to positive and negative symptoms, and neurocognitive deficits and severe functional impairment. Findings from epigenetics have yet to translate the epigenetics targets to efficacious drug therapy. We review the repertoire of CNS pharmacology of curcumin derived from Curcuma Longa, commonly known as "turmeric": the well-known curry extract. We highlight the body of evidence in support of the emerging role of curcumin as a panhistone deacetylase (HDAC) inhibitor regulating the expression of genes involved in inflammation and NMDA N-methyl-aspartic acid (NMDA)-glutamate systems, as related to schizophrenia. Based on the findings from translational studies of curcumin extracts, curcumin C-3 complex formulation (Supercurcumin TM ) and patented liposome-based curcumin (Lipocurc TM ), we propose that intravenous infusion of Lipocurc TM holds promise as the novel drug lead and preferred targeted brain delivery mode in reprogramming faculty epigenetics network and in remodeling restrictive chromatin configuration in schizophrenia. Phase II/Phase III epigenetics-biomarker-based randomized placebo-controlled trials in treatment resistant schizophrenia are warranted. Our approach of intravenous infusion of Lipocurc TM behaving as pan HDAC inhibitor represents a new paradigm of drug development in combining targeting epigenetics footprints with brain-specific drug delivery system in schizophrenia. Lipocurc TM can open the Pandora box in unexplored therapeutics vistas in modifying the phenotype of treatment resistant schizophrenia. [2]. Major breakthroughs in schizophrenia therapeutics are yet forthcoming. It becomes imperative to design molecular genetics and epigenetic tools to predict treatment responses, and to translate novel CNS drug targets for accelerating the development of new therapeutics for treatment refractory schizophrenia. Drug platforms require refinement of translational models of schizophrenia to catalyze clinical trials and to predict treatment responses. In the post-genomic era, deciphering the epigenetic code of the human genomes represents a major challenge in CNS disorders. A growing body of evidence supports dysregulation of epigenetics signaling: DNA methylation, histone modifications and microRNA, plays a significant role in schizophrenia [3][4][5]. Findings from studies of p...

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Significant Effect of Valproate Augmentation Therapy in Patients With Schizophrenia

Abstract: Supplemental Digital Content is available in the text

Cited by 31 publications

References 63 publications

The microbiome, immunity, and schizophrenia and bipolar disorder

The microbiome, immunity, and schizophrenia and bipolar disorder

Effect of Adjunctive Sodium Valproate in Patients of Acute Schizophrenia

Targeting Epigenetics Signaling with Curcumin: A Transformative Drug Lead in Treatment of Schizophrenia?

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