Background:Although clozapine is an effective option for treatment-resistant schizophrenia(TRS),there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine.The main purpose of this randomized,double-bli...Background:Although clozapine is an effective option for treatment-resistant schizophrenia(TRS),there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine.The main purpose of this randomized,double-blind,placebocontrolled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia(CTRS)patients.Methods:A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride(amisulpride group)or clozapine plus placebo(placebo group).Positive and Negative Syndrome Scale(PANSS),Scale for the Assessment of Negative Symptoms(SANS),Clinical Global Impression(CGI)scale scores,Repeatable Battery for the Assessment of Neuropsychological Status(RBANS),Treatment Emergent Symptom Scale(TESS),laboratory measurements,and electrocardiograms(ECG)were performed at baseline,week 6,and week 12.Results:Compared with the placebo group,amisulpride group had a lower PANSS total score,positive subscore,and general psychopathology subscore at week 6 and week 12(PBonferroni<0.01).Furthermore,compared with the placebo group,the amisulpride group showed an improved RBANS language score at week 12(PBonferroni<0.001).Amisulpride group had a higher treatment response rate(P=0.04),lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group(PBonferroni<0.05).There were no differences between the groups in body mass index(BMI),corrected QT(QTc)intervals,and laboratory measurements.This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients.展开更多
Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cogni...Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population. Aim To provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES. Methods An independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size. Results 56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as 'high quality' according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=-1.60,95% Cl -1.82 to -1.38,厂=67%) and all seven cognitive domains, with the SMD ranging from -0.87 to -1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=-1.90), Trail Making Test (TMT)(SMD=-1.36), Continuous Performance Test-Identical Pairs (SMD=-1.33), Hopkins Verbal Learning Test (SMD=-1.24), Brief Visuospatial Memory Test (SMD=-1.18), Mazes (SMD=-1.16), Category Fluency (SMD=-1.01), Spatial Span (SMD=-0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=-0.38). Conclusions Our meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.展开更多
Objective To investigate the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice and an-tagonistic action ...Objective To investigate the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice and an-tagonistic action of clozapine.Methods Immunohistochemistry was used to detect the expression of c-Fos protein.Results MK-801(0.6 mg·kg-1)acute administration produced a significant increase in the expression of c-Fos protein in the layers Ⅲ-Ⅳ of posterior cingulate and retrosplenial(PC/RS)cortex,which was consistent with the previous reports.Moreover,we presented a new finding that MK-801(0.6 mg·kg-1)chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex,prefrontal cortex(PFC)and hypothalamus of mice.Among that,c-Fos protein expression in the PC/RS cortex of mice was most significant.Compared acute administration with chronic administration,we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/RS cortex,PFC and hypothalamus.Furthermore,pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration.Conclusions Marked expression of c-Fos protein induced by MK-801 is associated with neurotransmitters' change noted in our previous studies,and c-Fos protein,the marker of neuronal activation,might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist.展开更多
Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and s...Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and several pharmacological strategies are used to augment it. Several reviews including meta-analyses have been published, but the efficacy of augmentation therapy for clozapine-resistant patients is not adequately supported. Though there is a weak connection between the oral dose and plasma concentration of clozapine, there is no report of augmentation therapy considering the plasma concentration of clozapine. Blonanserin is reported to be effective in treatment of both positive and negative symptoms of schizophrenia and well tolerated. Methods: We obtained consent to evaluate clinical presentations and clozapine plasma concentrations at the Okayama Psychiatric Medical Center and had not identified the individual for ethical reasons. This is a case report. Results: This case fulfilled the diagnostic criteria of neuroleptic-induced dopamine supersensitivity psychosis. Monotherapy with blonanserin was not effective, but augmentation of blonanserin with clozapine was effective and well tolerated by a clozapine-resistant schizophrenia patient. Conclusion: Because clozapine may ameliorate dopamine supersensitivity psychosis, the addition of blonanserin to clozapine may be effective even if monotherapy with blonanserin was not.展开更多
We read the impressive review article“Clozapine resistant schizophrenia:Newer avenues of management”with great enthusiasm and appreciation.The author believes that preventing clozapine resistance from developing may...We read the impressive review article“Clozapine resistant schizophrenia:Newer avenues of management”with great enthusiasm and appreciation.The author believes that preventing clozapine resistance from developing may be the most effective treatment strategy for patients with clozapine-resistant schizophrenia(CRS),and optimizing clozapine treatment is a key component.Disentangling the differences between treatment-resistant schizophrenia and CRS is important for studies addressing treatment strategies for these difficult-to-treat populations.展开更多
[Objectives]To observe the clinical effect of Fuzi Lizhong pills for salivation after taking clozapine in schizophrenia.[Methods]A total of 45 cases of schizophrenia patients with salivation after taking clozapine onl...[Objectives]To observe the clinical effect of Fuzi Lizhong pills for salivation after taking clozapine in schizophrenia.[Methods]A total of 45 cases of schizophrenia patients with salivation after taking clozapine only were selected as the study subjects and randomly divided into two groups according to enrollment order.The control group(22 cases)was treated with propantheline bromide tablets and the treatment group(23 cases)were treated with Fuzi Lizhong pills combined with propantheline bromide tablets.Clinical effects and adverse reactions were compared between the two groups.Chinese medicine syndrome scores,scores of severe degree of salivation and levels of serum cholinesterase were compared between the two groups before treatment,after one-week treatment and after two-week treatment.[Results]The total clinical effective rate was 86.96%in the treatment group,higher than that of 59.09%in the control group(P<0.05).When compared with those before treatment,Chinese medicine syndrome scores of short breath and lack of strength,lassitude of spirit and somnolence,poor appetite,spontaneous sweating and dyspnea,and salivation as well as scores of salivation in Rating Scale for Extrapyramdal Side Effects(RSESE)and the severe degree of salivation in the two groups were decreased after 1 week and 2 weeks treatment(P<0.05),and levels of serum cholinesterase were increased(P<0.05).When compared with those in the control group after one-week and two-week treatment,Chinese medicine syndrome scores of short breath and lack of strength,lassitude of spirit and somnolence,poor appetite,spontaneous sweating and dyspnea,and salivation as well as scores of salivation in RSESE and the severe degree of salivation in the treatment group at the same period were lower(P<0.05),and level of serum cholinesterase was higher(P<0.05).There was no significant difference in the comparison of incidence of adverse reactions between the two groups(P>0.05).[Conclusions]Fuzi Lizhong pills combined with propantheline bromide tablets can improve clinical symptoms of schizophrenia patients with salivation after taking clozapine,and enhance level of serum cholinesterase and clinical effect.展开更多
Objective: Clozapine is regarded as the most effective drug for treatment of schizophrenia but has complex adverse effects associated with hyperglycemia and diabetes mellitus. Method: We report that clozapine was very...Objective: Clozapine is regarded as the most effective drug for treatment of schizophrenia but has complex adverse effects associated with hyperglycemia and diabetes mellitus. Method: We report that clozapine was very effective to treat positive, negative, and cognitive symptoms and well tolerated to a treatment-resistant schizophrenia patient with severe type 2 diabetes mellitus (DM) under cautious blood-sugar monitoring. Results: Clozapine itself and discontinuation of other psychotropic and anticholinergic agents after switching may improve cognitive function and adherence to the treatment regimens for schizophrenia and DM. Conclusion: Clozapine can be administered to treatment-resistant schizophrenia patients even with severe DM with caution.展开更多
Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-...Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-episode schizophrenia,and evaluate the effect size of PPI deficits between patients and healthy controls.Methods:The effect size of PPI deficits was evaluated for PPI%by calculating standard mean differences(SMDs)between patients with antipsychotic-na-ve,first-episode schizophrenia and healthy controls.Results:Twelve studies met the inclusion criteria,consisting390antipsychotic-na-ve,first-episode schizophrenia and406healthy controls.The effect sizes of76dB PPI in60ms and120ms interstimulus interval(ISI)were-0.19and-0.41respectively,and the76dB PPI overall effect size was-0.30.The effect sizes of85/86dB PPI in30ms,60ms and120ms ISI were-0.25,-0.42and-0.59respectively,and the85/86dB PPI overall effect size was-0.46.One study were excluded due to heterogeneity in the85/86dB,120ms ISI group,the pooled effect size of the PPI differences between patient group and health control dropped to-0.42,and the overall effect size changed to-0.39.There were no statistical differences in startle magnitude(overall effect size=-0.18)and habituation%(overall effect size=-0.17)between patients and healthy controls.Conclusions:Antipsychotic-na-ve,first-episode schizophrenia patients exhibit robust and reliable deficits in PPI,85/86dB PPI deficit was more severe than76dB PPI,and85/86dB,60-ms ISI PPI was more likely to be a biomarker for schizophrenia,it suggested that the parameters of PPI are particularly significant to affect the effect size so that should be interpreted with cautions in the future studies.展开更多
Clozapine has been recognized as the best drug for the treatment of refractory schizophrenia,but its clinical use is very cautious.Clozapine has many side effects,among which agranulocytosis is fatal.And it often caus...Clozapine has been recognized as the best drug for the treatment of refractory schizophrenia,but its clinical use is very cautious.Clozapine has many side effects,among which agranulocytosis is fatal.And it often causes glucose intolerance,leading to type 2 di-abetes.The treatment plan for elevated blood glucose in clozapine patients is still unclear.This paper will report one case of glucose intolerance caused by clozapine and its alternative treatment,and discuss the treatment plan.展开更多
基金supported by the National Natural Science Foundation of China(81401127)the Clinical Research Project of Shanghai Municipal Health Commission(20204Y0173)+4 种基金the Open Project Program of State Key Laboratory of Virtual Reality Technology and Systems,Beihang University(VRLAB2022 B02)the Shanghai Key Laboratory of Psychotic Disorders Open Grant(21-K03)the Scientific Research Project of Traditional Chinese Medicine of Guangdong(20192070)the Guangzhou Municipal Key Discipline in Medicine(2021–2023)the Science and Technology Plan Project of Guangdong Province(2019B030316001).
文摘Background:Although clozapine is an effective option for treatment-resistant schizophrenia(TRS),there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine.The main purpose of this randomized,double-blind,placebocontrolled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia(CTRS)patients.Methods:A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride(amisulpride group)or clozapine plus placebo(placebo group).Positive and Negative Syndrome Scale(PANSS),Scale for the Assessment of Negative Symptoms(SANS),Clinical Global Impression(CGI)scale scores,Repeatable Battery for the Assessment of Neuropsychological Status(RBANS),Treatment Emergent Symptom Scale(TESS),laboratory measurements,and electrocardiograms(ECG)were performed at baseline,week 6,and week 12.Results:Compared with the placebo group,amisulpride group had a lower PANSS total score,positive subscore,and general psychopathology subscore at week 6 and week 12(PBonferroni<0.01).Furthermore,compared with the placebo group,the amisulpride group showed an improved RBANS language score at week 12(PBonferroni<0.001).Amisulpride group had a higher treatment response rate(P=0.04),lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group(PBonferroni<0.05).There were no differences between the groups in body mass index(BMI),corrected QT(QTc)intervals,and laboratory measurements.This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients.
文摘Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population. Aim To provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES. Methods An independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size. Results 56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as 'high quality' according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=-1.60,95% Cl -1.82 to -1.38,厂=67%) and all seven cognitive domains, with the SMD ranging from -0.87 to -1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=-1.90), Trail Making Test (TMT)(SMD=-1.36), Continuous Performance Test-Identical Pairs (SMD=-1.33), Hopkins Verbal Learning Test (SMD=-1.24), Brief Visuospatial Memory Test (SMD=-1.18), Mazes (SMD=-1.16), Category Fluency (SMD=-1.01), Spatial Span (SMD=-0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=-0.38). Conclusions Our meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.
文摘Objective To investigate the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice and an-tagonistic action of clozapine.Methods Immunohistochemistry was used to detect the expression of c-Fos protein.Results MK-801(0.6 mg·kg-1)acute administration produced a significant increase in the expression of c-Fos protein in the layers Ⅲ-Ⅳ of posterior cingulate and retrosplenial(PC/RS)cortex,which was consistent with the previous reports.Moreover,we presented a new finding that MK-801(0.6 mg·kg-1)chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex,prefrontal cortex(PFC)and hypothalamus of mice.Among that,c-Fos protein expression in the PC/RS cortex of mice was most significant.Compared acute administration with chronic administration,we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/RS cortex,PFC and hypothalamus.Furthermore,pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration.Conclusions Marked expression of c-Fos protein induced by MK-801 is associated with neurotransmitters' change noted in our previous studies,and c-Fos protein,the marker of neuronal activation,might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist.
文摘Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and several pharmacological strategies are used to augment it. Several reviews including meta-analyses have been published, but the efficacy of augmentation therapy for clozapine-resistant patients is not adequately supported. Though there is a weak connection between the oral dose and plasma concentration of clozapine, there is no report of augmentation therapy considering the plasma concentration of clozapine. Blonanserin is reported to be effective in treatment of both positive and negative symptoms of schizophrenia and well tolerated. Methods: We obtained consent to evaluate clinical presentations and clozapine plasma concentrations at the Okayama Psychiatric Medical Center and had not identified the individual for ethical reasons. This is a case report. Results: This case fulfilled the diagnostic criteria of neuroleptic-induced dopamine supersensitivity psychosis. Monotherapy with blonanserin was not effective, but augmentation of blonanserin with clozapine was effective and well tolerated by a clozapine-resistant schizophrenia patient. Conclusion: Because clozapine may ameliorate dopamine supersensitivity psychosis, the addition of blonanserin to clozapine may be effective even if monotherapy with blonanserin was not.
文摘We read the impressive review article“Clozapine resistant schizophrenia:Newer avenues of management”with great enthusiasm and appreciation.The author believes that preventing clozapine resistance from developing may be the most effective treatment strategy for patients with clozapine-resistant schizophrenia(CRS),and optimizing clozapine treatment is a key component.Disentangling the differences between treatment-resistant schizophrenia and CRS is important for studies addressing treatment strategies for these difficult-to-treat populations.
基金Supported by Project of Science and Technology Bureau of Jiande City,Zhejiang Province(2018JYW14)。
文摘[Objectives]To observe the clinical effect of Fuzi Lizhong pills for salivation after taking clozapine in schizophrenia.[Methods]A total of 45 cases of schizophrenia patients with salivation after taking clozapine only were selected as the study subjects and randomly divided into two groups according to enrollment order.The control group(22 cases)was treated with propantheline bromide tablets and the treatment group(23 cases)were treated with Fuzi Lizhong pills combined with propantheline bromide tablets.Clinical effects and adverse reactions were compared between the two groups.Chinese medicine syndrome scores,scores of severe degree of salivation and levels of serum cholinesterase were compared between the two groups before treatment,after one-week treatment and after two-week treatment.[Results]The total clinical effective rate was 86.96%in the treatment group,higher than that of 59.09%in the control group(P<0.05).When compared with those before treatment,Chinese medicine syndrome scores of short breath and lack of strength,lassitude of spirit and somnolence,poor appetite,spontaneous sweating and dyspnea,and salivation as well as scores of salivation in Rating Scale for Extrapyramdal Side Effects(RSESE)and the severe degree of salivation in the two groups were decreased after 1 week and 2 weeks treatment(P<0.05),and levels of serum cholinesterase were increased(P<0.05).When compared with those in the control group after one-week and two-week treatment,Chinese medicine syndrome scores of short breath and lack of strength,lassitude of spirit and somnolence,poor appetite,spontaneous sweating and dyspnea,and salivation as well as scores of salivation in RSESE and the severe degree of salivation in the treatment group at the same period were lower(P<0.05),and level of serum cholinesterase was higher(P<0.05).There was no significant difference in the comparison of incidence of adverse reactions between the two groups(P>0.05).[Conclusions]Fuzi Lizhong pills combined with propantheline bromide tablets can improve clinical symptoms of schizophrenia patients with salivation after taking clozapine,and enhance level of serum cholinesterase and clinical effect.
文摘Objective: Clozapine is regarded as the most effective drug for treatment of schizophrenia but has complex adverse effects associated with hyperglycemia and diabetes mellitus. Method: We report that clozapine was very effective to treat positive, negative, and cognitive symptoms and well tolerated to a treatment-resistant schizophrenia patient with severe type 2 diabetes mellitus (DM) under cautious blood-sugar monitoring. Results: Clozapine itself and discontinuation of other psychotropic and anticholinergic agents after switching may improve cognitive function and adherence to the treatment regimens for schizophrenia and DM. Conclusion: Clozapine can be administered to treatment-resistant schizophrenia patients even with severe DM with caution.
基金supported by researchgrants from the National Natural Science foundationof China (81471365, 81601169) Major Brain Program of Beijing Science and Technology Plan (Z161100002616017)Beijing Municipal Administration of Hospitals ClinicalMedicine Development of Special Funding Support(ZYLX201807).
文摘Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-episode schizophrenia,and evaluate the effect size of PPI deficits between patients and healthy controls.Methods:The effect size of PPI deficits was evaluated for PPI%by calculating standard mean differences(SMDs)between patients with antipsychotic-na-ve,first-episode schizophrenia and healthy controls.Results:Twelve studies met the inclusion criteria,consisting390antipsychotic-na-ve,first-episode schizophrenia and406healthy controls.The effect sizes of76dB PPI in60ms and120ms interstimulus interval(ISI)were-0.19and-0.41respectively,and the76dB PPI overall effect size was-0.30.The effect sizes of85/86dB PPI in30ms,60ms and120ms ISI were-0.25,-0.42and-0.59respectively,and the85/86dB PPI overall effect size was-0.46.One study were excluded due to heterogeneity in the85/86dB,120ms ISI group,the pooled effect size of the PPI differences between patient group and health control dropped to-0.42,and the overall effect size changed to-0.39.There were no statistical differences in startle magnitude(overall effect size=-0.18)and habituation%(overall effect size=-0.17)between patients and healthy controls.Conclusions:Antipsychotic-na-ve,first-episode schizophrenia patients exhibit robust and reliable deficits in PPI,85/86dB PPI deficit was more severe than76dB PPI,and85/86dB,60-ms ISI PPI was more likely to be a biomarker for schizophrenia,it suggested that the parameters of PPI are particularly significant to affect the effect size so that should be interpreted with cautions in the future studies.
文摘Clozapine has been recognized as the best drug for the treatment of refractory schizophrenia,but its clinical use is very cautious.Clozapine has many side effects,among which agranulocytosis is fatal.And it often causes glucose intolerance,leading to type 2 di-abetes.The treatment plan for elevated blood glucose in clozapine patients is still unclear.This paper will report one case of glucose intolerance caused by clozapine and its alternative treatment,and discuss the treatment plan.
