ABSTRACT
Schizophrenic patients resistant to antipsychotics are diagnosed as having treatment-refractory schizophrenia, and they are treated with clozapine. However, clozapine is sometimes combined with electroconvulsive therapy (ECT) if clozapine monotherapy fails. In this report, a severe treatment-refractory schizophrenic patient who did not respond to clozapine even with ECT, but who recovered with asenapine monotherapy, is presented. Asenapine, considered a serotonin spectrum dopamine modulator, is a new atypical antipsychotic with unique pharmacological features that is used not only for schizophrenia, but also for bipolar disorder. The unique features of asenapine may be effective for some treatment-refractory schizophrenic patients.
Subject(s)
Humans , Antipsychotic Agents , Bipolar Disorder , Clozapine , Dopamine , Electroconvulsive Therapy , Recurrence , Schizophrenia , Serotonin , SuicideABSTRACT
Introduction: For decades, the term refractory psychosis has been widely used, but not clearly defined. Although the exact mechanisms by which treatment-resistance is developed are unknown, some factors will lead to bigger vulnerability to present it. It remains unclear if it is just a severe extreme at the end of the psychosis spectrum, or a subtype of schizophrenia. Objective: To determine if there is current consensus in the concept of refractory psychosis. Methods: Review of different guidelines about it (EMEA, SIGN, NICE, BPA, APA, CPA and WFSBP) and comparison of their definitions and approach designs. Results: Consulted guidelines show differences in the way they define refractory psychosis, but uniformity in their management proposal. Conclusion: There is no consensus in the operational definition of treatment resistant psychosis.
Introducción: Por décadas, el término de esquizofrenia refractaria ha sido ampliamente usado, pero no adecuadamente definido. Aunque no se conocen los mecanismos exactos por los cuales se desarrolla resistencia a la terapia antipsicótica, algunos factores condicionarán mayor probabilidad de fallo terapéutico. No se sabe, a punto fijo, si el cuadro se trata sólo de un extremo severo al final del continuum del espectro psicótico, o si es un subtipo de esquizofrenia. Objetivo: Determinar si existe consenso actual sobre el concepto de esquizofrenia refractaria. Metodología: Revisión de distintas guías clínicas sobre el tema (EMEA, SIGN, NICE, BPA, APA, CPA y WFSBP) y comparación de sus definiciones y sus diseños de abordaje. Resultados: Las guías consultadas muestran diferencias respecto al modo en que definen esquizofrenia refractaria, pero uniformidad en su planteamiento de manejo. Conclusión: No existe consenso en la definición operacional de esquizofrenia resistente al tratamiento.
Subject(s)
Humans , Psychotic Disorders , Schizophrenia , Therapeutics , Consensus , Decision MakingABSTRACT
Objective To investigate the efficacy and side effects of aripiprazole combined with modified electroconvulsive therapy (MECT) in the treatment of female refractory schizophrenia.Methods One hundred and five female refractory schizophrenia patients in the Second Affiliated Hospital of Xinxiang Medical University from July 2014 to May 2016 were selected and divided into control group and observation group.Fifty-two patients in the control group were treated with aripiprazole.In the observation group,53 patients were treated with aripiprazole combined with MECT.All the patients were treated for eight weeks.Clinical efficacies were assessed with the positive and negative syndrome syndrome scale (PANSS);Wechsler memory scale (WMS) were used to evaluate the effect of MECT on memory.Adverse drug reactions were evaluated by treatment emergent symptom scale(TESS) before and after treatment in both groups.Results There was no significant difference in PANSS scores between the two groups before treatment (P ＞ 0.05).The positive symptom scores,the general mental pathology scores and the PANSS total scores in the two groups at the end of the second week were significantly lower than before treatment(P ＜ 0.05);at the end of fourth and eighth week of treatment,the negative symptom scores,the positive symptom scores,the general psychopathological scores and the PANSS total scores of the two groups were significantly lower than those before treatment (P ＜ 0.05 or P ＜ 0.01).The positive symptoms,the general psychopathological scores and the PANSS total score in the observation group were significantly lower than those in the control group at the end of fourth week of treatment (P ＜0.05).At the end of the eighth week of treatment,the negative symptom scores,the positive symptom scores,the general psychopathological scores and the PANSS total scores in the observation group were significant lower than those in the control group (P ＜ 0.05).At the end of the eighth week of treatment,the decreasing rates of PANSS score in the observation group and control group were (39.89-8.62) ％ and (31.97-± 8.17) ％,and the total effective rates were 66.67％ and 48.08％,respectively.The decreasing rates of PANSS score and total effective rates in the observation group were higher than those in the control group (P ＜ 0.05).The WMS score of the observation group decreased more significantly at the end of the second week of treatment compared with that before treatment;at the end of the fourth week of treatment,the score of the picture was louer than that before treatment(P ＜ O.05);but there was no significant difference in WMS score between that at the end of the eighth week and before treatment(P ＞ 0.05).There was no significant difference between the two groups in the TESS score and adverse reaction rate (P ＞ 0.05).Conclusion Compared with single application of aripiprazole,MECT combined with aripiprazole can significantly improve effects in treating female refractory schizophrenia and it can not increase the side effects.
ABSTRACT
OBJECTIVE: It is well documented that clozapine treatment causes agranulocytosis, but it can also induce drowsiness, constipation, and hypersalivation; however, these symptoms are usually less severe. It has been reported that clozapine-treated patients with schizophrenia and psychiatric healthcare professionals consider different side effects to be important. The aim of this study was to assess current practice related to the side effects of clozapine in clozapine-treated patients with schizophrenia and psychiatric healthcare professionals in Japan. METHODS: Data were collected from January 2014 to August 2015 in Okehazama Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated patients with schizophrenia and psychiatric healthcare professionals (psychiatrists and pharmacists) were enrolled in this study. RESULTS: Of the 106 patients and 120 psychiatric healthcare professionals screened, 100 patients and 104 healthcare professionals were included in this study. We asked the patients what side effects caused them trouble and we asked psychiatric healthcare professionals what side effects caused them concern. The patients and psychiatrists held similarly positive views regarding the efficacy of clozapine. The healthcare professionals were concerned about agranulocytosis (92.4%), blood routines (61.3%). On the other hand, the patients experienced hypersalivation (76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between patient satisfaction and DAI-10 score. CONCLUSION: Patients experienced more problems than healthcare professionals expected. However, usage experience of clozapine healthcare professionals tended to have similar results to patients. It is necessary that all healthcare professionals fully understand the efficacy and potential side effects of clozapine. This is very important for promoting clozapine treatment in Japan.
Subject(s)
Humans , Agranulocytosis , Clozapine , Constipation , Delivery of Health Care , Hand , Japan , Patient Satisfaction , Psychiatry , Schizophrenia , Sialorrhea , Sleep StagesABSTRACT
INTRODUCTION: Clozapine is the antipsychotic of choice in the treatment of refractory schizophrenia. However, its side effects, such as eosinophilia, may preclude its use. METHODS: Case report and literature review. RESULTS: Young woman, 19 years old, diagnosed with hebefrenic schizophrenia, admitted at Unicamp's psychiatry ward after psychotic symptoms relapse. Clozapine was started after unsuccessful attempts with risperidon and olanzapine. By the fourth week of clozapine use, eosinophils began to increase. Drug titration was stopped, but eosinophils counts continued to rise up, reaching the mark of 5200/mm³. Due to severity of psychotic symptoms and to the good response obtained with clozapine, we decided to investigate organs involvement before withdrawing the medication. As the patient had no organs involvement, clozapine was maintained and one month after eosinophils peak, it was already normalized. CONCLUSION: Eosinophilia should not necessarily lead to clozapine's withdrawal. Patients who present eosinophilia must be at rigorous observation for organs involvement, and if there is no such involvement, clozapine might be maintained, considering the possible benign and transitory nature of the eosinophils count elevation.
INTRODUÇÃO: Clozapina é o antipsicótico de escolha no tratamento de esquizofrenia refratária. No entanto, ela apresenta uma série de efeitos colaterais, como a eosinofilia, os quais podem inviabilizar sua continuação. MÉTODOS: Relato de caso e revisão da literatura. RESULTADOS: Jovem de 19 anos, com diagnóstico de esquizofrenia hebefrênica, internada na enfermaria de psiquiatra do HC-Unicamp por reagudização de sintomas psicóticos. Durante internação, após tentativas frustradas de uso de antipsicóticos como risperidona e olanzapina, iniciou-se clozapina. Na quarta semana após introdução, iniciou-se aumento de eosinófilos. Tendo em vista a gravidade do quadro e a ótima resposta obtida com relação aos sintomas psicóticos, o aumento de dose de clozapina foi interrompido, mas a medicação foi mantida. Mesmo com a dose estabilizada, a eosinofilia continuou a aumentar, chegando a 5.200/mm³. A paciente foi investigada para lesões de órgãos pela possível inflamação, mas nada foi encontrado. Assim, clozapina foi mantida e, um mês após seu pico, eosinófilos normalizaram-se. CONCLUSÃO: Eosinofilia não necessariamente impõe a interrupção de clozapina. O paciente deve ser mantido em observação rigorosa em busca de lesões de órgãos. Caso não haja indício de lesões, é justificável manter a clozapina, tendo em vista o possível caráter benigno e transitório da eosinofilia.
ABSTRACT
Objective To observe the effect of electroacupuncture(EA) in combination with small dose of clozapine on clinical symptoms of refractory schizophrenia patients so as to evaluate its validity and security.Methods Eighty schizophrenia patients were randomized into medication group and EA+medication group(n=40/group).Patients of medication group were treated with conventional oral administration of clozapine(50-100 mg/d to 200-500 mg/d,for 8 weeks) and those of EA+ medication group treated by EA of Baihui(GV 20) and bilateral Taiyang(EX-HN 5) and oral administration of clozapine(50 mg/d to 100-150 mg/d).EA was given to the patients,3 times a week for 8 weeks.Scores of the Positive and Negative Symptom Scale(PANSS) and the Untoward Effect Symptom Scale(TESS) were used to assess the therapeutic effect.Results Following treatment,PANSS scores for positive symptoms and the common psychiatric symptoms of the medication and EA+medication groups all decreased evidently from the 2rd week on(P0.05).But TESS score of EA+medication group was evidently lower than that of medication group(P
ABSTRACT
OBJECTIVE: The purpose of this study was to identify the predictors of one-year clozapine treatment in refractory schizophrenic patients. METHODS: We defined treatment response as the reduction of total PANSS scores by 20% or more and as the total PANSS scores below 60, or as the CGI severity score below 3, after one-year of clozapine treatment. We compared age, duration of illness, number of hospitalization, plasma monoamine metabolites, ventricle-brain ratio, and short-term treatment response between treatment response group and treatment non-response group. RESULTS: Among the total patients of 26, 12(46%) were categorized as treatment response group. In comparing between treatment response group(N=12) and treatment non-response group (N=14), there were no differences in age, onset age, duration of illness, but the number of hospitalization was significantly more frequent in treatment non-response group. There was no significant difference in total PANSS scores between the two groups before clozapine treatment. After 4 weeks of clozapine treatment, the changes of PANSS positive score was more higher in treatment response group. The baseline plasma HVA levels and HVA/5-HIAA ratio were significantly higher in treatment response group than in non-response group, but there was no significant difference in baseline plasma 5-HIAA levels between the two groups. No difference existed in ventricle-brain ratio between the two groups. CONCLUSION: This study suggests that number of hospitalization and short-term treatment response rate may be useful as the clinical predictors, and that plasma HVA levels also as a biological predictor of long term clozapine treatment.
Subject(s)
Humans , Age of Onset , Clozapine , Hospitalization , Hydroxyindoleacetic Acid , Plasma , SchizophreniaABSTRACT
OBJECTIVES: We attempted to investigate clinical efficacy of risperidone a new antipsychotic agent with high safety and without life-threatening side effect such as agranulocytosis, in refractory schizophrenia compared with a haloperidol, well-known antipsychotic agent. METHODS: Thirty-four subjects(risperidone group 16, haloperidol group 18), who had been proved to be refractory schizophrenics with prospective antipsychotic treatment with at least 2 antipsychotic agents belonging to different chemical groups from each other, were examined with Clinical Global Impression(CGI) and 18-item Brief Psychiatric Rating Scale(BPRS) at 0, 2nd, 4th, 8th, and 12th week from start of drug administration. Those scales were rated in the single-blind manner. RESULTS: End-point response rate of risperidone was 25%(4 subjects), and that of haloperidol was zero. Difference of the response rates between risperidone and haloperidol was statistically significant. Broader spectrum of symptoms was improved with risperidone treatment than with haloperidol. CONCLUSION: Risperidone is an antipsychotic agent that clinicians can primarily and effectively try in the refractory schizophrenics with high safety.
Subject(s)
Agranulocytosis , Antipsychotic Agents , Haloperidol , Prospective Studies , Risperidone , Schizophrenia , Weights and MeasuresABSTRACT
OBJECTIVE: Although antipsychotic treatments are effective for schizophrenia, at least 25% of schizophrenic patients have little response to conventional neuroleptics. Although patients respond well to antipsychotics initially, they often result in heavy loss of costs and social burden due to the frequent relapse which often require intensive institutional care while the patients experience significant social and functional disabilities. Many studies have come out recently concerning the cost of schizophrenia and its cost-effectiveness in treatment. Clozapine has the risk of agranulocytosis and greater initial cost, however, it has been reported to be cost-effective for the treatment of refractory schizophrenia because of its highly effectiveness, in addition, it has reduced rehospitalization rates and hospital stays. The purpose of this retrospective study was to ascertain the cost-effectiveness of clozapine treatment for patients with refractory schizophrenia in Korea. METHOD: We studied 17 patients with refractory schizophrenia treated by clozapine over a two year period. The numbers of hospitalization, hospital stays two years before clozapine treatment, and two years after clozapine treatment were investigated. Direct costs of psychiatric hospitalization, outpatient treatment, and other costs were estimated. Data on patients' clinical characteristics, use of mental health services and information about the cost of treatments were collected from psychiatric hospitalization records, outpatient records and hospital administration records. Some of the patient data information before the introduction of clozapine treatment were gathered through direct interviews of their families. Therapeutic outcome measures included the Clinical Global Impression (CGI) scale and Global Assessment of Functioning (GAF) score. RESULT: At the initial clozapine treatment, the mean age of subjects was 29 (+/- 7.9) years old. The mean duration of previous psychiatric treatment was 8 (+/- 3.0) years. Average total direct costs were reduced from \4,106,480 in the second pretreatment year to \2,338,427 in the second posttreatment year while the mean hospitalization costs, a percentage of total direct costs, were reduced from 82.9% to 27.4%. Also, the mean hospital stays per year were decreased from 83.4 days to 15.7 days, the mean numbers of hospitalization from 0.59 to 0.18. CGI scale scores and GAF scores showed a statistically significant clinical improvement between before and after clozapine treatment. CONCLUSION: These results suggest that a long-term treatment of clozapine for patients with refractory schizophrenia is indeed more cost-effective than conventional neuroleptic treatment. We suggest more comprehensive and prospective study due to the limitations of this retrospective study.