Successful Early Clozapine Trial in the Treatment of First-episode Schizophrenia: A Case Report

Kim, Yeon-Jin; No, Seung-Ho; Lee, Sangyeol

doi:10.9758/cpn.2013.11.3.168

Cited by 4 publications

(5 citation statements)

References 9 publications

(10 reference statements)

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“…Applying our inclusion and exclusion criteria reduced the number of relevant articles to fifteen , ten of which evaluated CLZ as a first‐line treatment , while five were clinical reports that evaluated CLZ as a second‐line treatment (Fig. ) . It is important to note that, from the articles excluded on the basis of criterion d1, nine articles (all published before 1990) seemed eligible at first sight because they investigated CLZ use in acutely psychotic patients (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…There were four case reports and one trial investigating CLZ as a second‐line treatment . Detailed information about the outcomes mentioned in these papers can be found in the Supplementary Results.…”

Section: Resultsmentioning

confidence: 99%

“…Fifteen articles were screened. Six case reports , two articles with overlapping study populations , and two articles without data to analyze/no active comparator were excluded. From the five articles that remained, three compared clozapine vs. risperidone , one compared clozapine vs. chlorpromazine , and one compared clozapine vs. thioridazine .…”

Section: Resultsmentioning

confidence: 99%

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Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Okhuijsen-Pfeifer

Huijsman

Hasan

et al. 2018

Acta Psychiatr Scand

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ObjectiveNo consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.MethodsArticles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.ResultsFifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).ConclusionThe few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Okhuijsen-Pfeifer

Huijsman

Hasan

et al. 2018

Acta Psychiatr Scand

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“…However, due to serious adverse drug reactions, including agranulocytosis, clozapine treatment is only indicated in patients who have failed at least two other antipsychotics. To minimize the risk of agranulocytosis, frequent blood monitoring is required which represents another restriction to its use in an often challenging population of patients 6 .…”

Section: Introductionmentioning

confidence: 99%

HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry

et al. 2021

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The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E−06) and agranulocytosis (OR = 10.49, P = 1.83E−06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E−08; agranulocytosis: OR = 16.31, P = 1.39E−06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.

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“…Natural products comprise a diverse array of biologically active compounds that have been studied extensively in the field of drug development, especially for cancer therapy (13,14). For example, erianin (ERN; 2-methoxy-5-[2- (3,4,5trimethoxyphenyl)-ethyl]-phenol, Figure S1) is isolated from Dendrobium chrysotoxum Lindl, a widely cultivated species of orchid, and has a variety of pharmacological activities, including anti-cancer activities (15,16).…”

Section: Introductionmentioning

confidence: 99%

Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress

Yang

Sun

et al. 2021

Front. Oncol.

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BackgroundLiver cancer is one of the most malignant human cancers, with few treatments and a poor prognosis. Erianin (ERN) is a natural compound with multiple pharmacological activities that has been reported to have numerous excellent effects against liver cancer in experimental systems. However, its application in vivo has been limited due to its poor aqueous solubility and numerous off-target effects. This study aimed to improve the therapeutic efficacy of ERN by developing novel ERN-loaded tumor-targeting nanoparticles.ResultsIn this study, ERN was loaded into liposomes by ethanol injection (LP-ERN), and the resulting LP-ERN nanoparticles were treated with transferrin to form Tf-LP-ERN to improve the solubility and enhance the tumor-targeting of ERN. LP-ERN and Tf-LP-ERN nanoparticles had smooth surfaces and a uniform particle size, with particle diameters of 62.60 nm and 88.63 nm, respectively. In HepG2 and SMMC-7721 cells, Tf-LP-ERN induced apoptosis, decreased mitochondrial membrane potentials and increased ERN uptake more effectively than free ERN and LP-ERN. In xenotransplanted mice, Tf-LP-ERN inhibited tumor growth, but had a minimal effect on body weight and organ morphology. In addition, Tf-LP-ERN nanoparticles targeted tumors more effectively than free ERN and LP-ERN nanoparticles, and in tumor tissues Tf-LP-ERN nanoparticles promoted the cleavage PARP-1, caspase-3 and caspase-9, increased the expression levels of Bax, Bad, PUMA, and reduced the expression level of Bcl-2. Moreover, in the spleen of heterotopic tumor model BALB/c mice, ERN, LP-ERN and Tf-LP-ERN nanoparticles increased the expression levels of Nrf2, HO-1, SOD-1 and SOD-2, but reduced the expression levels of P-IKKα+β and P-NF-κB, with Tf-LP-ERN nanoparticles being most effective in this regard. Tf-LP-ERN nanoparticles also regulated the expression levels of TNF-α, IL-10 and CCL11 in serum.ConclusionTf-LP-ERN nanoparticles exhibited excellent anti-liver cancer activity in vivo and in vitro by inducing cellular apoptosis, exhibiting immunoregulatory actions, and targeting tumor tissues, and did so more effectively than free ERN and LP-ERN nanoparticles. These results suggest that the clinical utility of a Tf-conjugated LP ERN-delivery system for the treatment of liver cancer warrants exploration.

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Successful Early Clozapine Trial in the Treatment of First-episode Schizophrenia: A Case Report

Cited by 4 publications

References 9 publications

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry

Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress

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