Clozapine in Treatment-Resistant Patients With Schizophrenia, Schizoaffective Disorder, or Psychotic Bipolar Disorder

Ciapparelli, Antonio; Dell’Osso, Liliana; Poggio, Adolfo Bandettini di; Carmassi, Claudia; Cecconi, D.; Fenzi, Melania; Chiavacci, Maria Cristina; Bottai, Matteo; Ramacciotti, Carla Emilia; Cassano, Giovanni Battista

doi:10.4088/jcp.v64n0416

Cited by 101 publications

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“…Good results have been achieved in all patients and this is consistent with previous studies reporting high rates of positive results [7,9,11]. In spite of these positive results, clozapine is prescribed only if other maintenance strategies fail because of its some serious side effects such as agranulocytosis.…”

Section: Discussionsupporting

confidence: 89%

“…For instance 30-40% of the patients are reported to be non-responsive to lithium, which is still gold standard in prophylactic treatment of bipolar disorder (BD) [2,3]. Studies demonstrating effectiveness of clozapine, an antipsychotic drug, especially in resistant bipolar patients for prophylaxis were reported [4,5,6,7,8,9,10,11]. However, they are limited to open-labeled studies with small sample sizes or case reports [12,13].…”

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confidence: 99%

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Clozapine Therapy for Long-Term Prophylaxis in Bipolar Patients; Prescription Rates and Efficacy

Berkol¹

2015

Ann Clin Anal Med

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Anahtar KelimelerBipolar Bozukluk; Klozapin; Profilaksi Abstract Aim: It is reported that clozapine maintenance treatment could be effective in treatment-resistant bipolar patients. The aim of this study is to evaluate the prescription rates of clozapine, features of patients on clozapine prophylaxis and efficacy of clozapine prophylaxis in patients with bipolar disorder. Material and Method: 280 patients with DSM-IV diagnostic criteria for bipolar disorder, type I were included in the study. The patients' medical records and life-charts were reviewed retrospectively and patients who took clozapine for maintenance treatment for at least one year were identified. Results: Twelve of 280 patients (4.8 %) took clozapine for prophylaxis for at least one period during lifetime. Among them 7 patients have only received clozapine, while 5 patients have used combination of clozapine and valproic acid. All of these twelve patients had resistance to at least two different maintenance treatments before clozapine prophylaxis. However, positive results were observed in all of the patients with clozapine prophylaxis. Discussion: These findings suggest that clozapine is regarded as an effective prophylactic choice for treatment of resistant patients with bipolar disorder. Consequently, this study demonstrates effectiveness and safety of clozapine use even in severe patients refractory to various strategies of prophylaxis. Retrospective nature of our study constitutes a limitation. However, when considering limited number of studies on this subject, it may still have a significant contribution. But more comprehensive prospective controlled studies are still needed.

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Section: Discussionsupporting

confidence: 89%

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confidence: 99%

Clozapine Therapy for Long-Term Prophylaxis in Bipolar Patients; Prescription Rates and Efficacy

Berkol¹

2015

Ann Clin Anal Med

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“…The study was conducted during the period between 1998 and2003 at the Psychiatry Clinic of the Clinical Center Kragujevac. The allocation of the patients in three study arms followed pragmatic (naturalistic) design 11 . It means that treatment allocation of study subjects was only governed by clinical practice criteria in our country, not by subject study status.…”

Section: Methodsmentioning

confidence: 99%

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period

Ravanic

Dejanovic

Janjić

et al. 2009

Arq. Neuro-Psiquiatr.

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-Objective: The aim of our study was to evaluate the effects of low doses of clozapine in flexible regime in comparison with haloperidol and chlorpromazine in long term. Method: The naturalistic study was prospective, active-controlled with 325 adult outpatients of both genders (140 females), with mean year age of 34.8 (range 21-57), suffering from chronic schizophrenia. The first onset of illness was at the mean of 27.9 years (range 17-38), and subjects had the mean year age of 4.1±0.5 previous relapses. The patients were allocated to receive haloperidol (105 subjects, dose range 2-15 mg), chlorpromazine (n=105, 100-400 mg) or clozapine (n=115, 75-600 mg). The scores of psychometric instruments (GWB, PANSS, CGI) were regularly assessed during 5 year period. Results: The sixty-six responders were included in per-protocol analysis: 12, 10 and 16 with positive and 7, 6 and 15 with negative schizophrenic syndrome in haloperidol, chlorpromazine and clozapine group, respectively. The statistically significant differences in all psychometric scores was found, for both schizophrenic syndromes, favoring clozapine. The distribution of eighteen different types of adverse events, which we noted, were significantly different among treatment groups (χ 2 =315.7, df=34, p<0.001). Clozapine was safer and had fewer adverse effects (average of 0.9 adverse events per patient) than haloperidol (2.7) and chlorpromazine (3.2). Conclusions: Clozapine, in low doses of flexible regime, in long term (five years) showed better effectiveness in chronic schizophrenics with positive and negative symptoms than typical antipsychotics.Key WordS: schizophrenia, antipsychotics drugs, long-term outcomes, clinical practice. Eficácia da clozapina, haloperidol e clorpromazina na esquizofrenia em um período de cinco anosResumo -Objetivo: o propósito deste estudo foi avaliar os efeitos de baixas doses de clozapina em regime flexível comparando com o uso de haloperidol e clorpromazina por período de 5 anos. Método: Um estudo prospectivo naturalístico, ativo-controlado foi realizado com 325 pacientes com idade média de 34,8 (variância 21-57). Todos com diagnóstico de esquizofrenia. No primeiro surto da doença os pacientes apresentavam idade média de 27,9 anos (variância 17-38) e os surtos subsequentes apareceram em média 4,1±0,5 anos após. os pacientes foram orientados a receberem haloperidol (105 pacientes com dose entre 2 e 15 mg), clorpromazina (105 pacientes com dose entre 100 e 400 mg) e clozapina (115 pacientes com dose entre 75 e 600 mg). os instrumentos psicométricos utilizados (GWB, PANSS e CGI) foram regularmente empregados durante os 5 anos do estudo. Resultados: os 66 pacientes respondedores ao tratamento foram incluídos no protocolo de análise: 12, 10 e 16 apresentavam síndrome esquizofrênica positiva e 7, 6 e 15 síndrome negativa esquizofrênica com haloperidol, clorpromazina e clozapina, respectivamente. diferenças estatísticas significantes foram observadas em todas as avaliações psicométricas em ambas síndromes esquizofrênicas f...

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“…Furthermore, among treatment-resistant patients, compared to schizophrenic patients, those with bipolar disorder may be more responsive to clozapine. 63 Required doses for optimal effect in bipolar disorder may be less than for treatment-resistant schizophrenia. 64 Only one study has systematically compared clozapine as an add-on study to a treatment as usual group using a random assignment but not blinded design.…”

Section: High-dose Thyroid Augmentationmentioning

confidence: 99%

Treatment-resistant bipolar disorder

2006

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Despite the remarkable increase in medications validated as effective in bipolar disorder, treatment is still plagued by inadequate response in acute manic or depressive episodes or in long-term preventive maintenance treatment. Established first-line treatments include lithium, valproate and second-generation antipsychotics (SGAs) in acute mania, and lithium and valproate as maintenance treatments. Recently validated treatments include extended release carbamazapine for acute mania and lamotrigine, olanzapine and aripiprazole as maintenance treatments. For treatment-resistant mania and as maintenance treatments, a number of newer anticonvulsants, and one older one, phenytoin, have shown some promise as effective. However, not all anticonvulsants are effective and each agent needs to be evaluated individually. Combining multiple agents is the most commonly used clinical strategy for treatment resistant bipolar patients despite a relative lack of data supporting its use, except for acute mania (for which lithium or valproate plus an SGA is optimal treatment). Other approaches that may be effective for treatment-resistant patients include high-dose thyroid augmentation, clozapine, calcium channel blockers and electroconvulsive therapy (ECT). Adjunctive psychotherapies show convincing efficacy using a variety of different techniques, most of which include substantial attention to education and enhancing coping strategies. Only recently, bipolar depression has become a topic of serious inquiry with the dominant controversy focusing on the place of antidepressants in the treatment of bipolar depression. Other than mood stabilizers alone or the combination of mood stabilizers and antidepressants, most of the approaches for treatment-resistant bipolar depression are relatively similar to those used in unipolar depression, with the possible exception of a more prominent place for SGAs, prescribed either alone or in combination with antidepressants. Future work in the area needs to explore the treatments commonly used by clinicians with inadequate research support, such as combination therapy and the use of antidepressants as both acute and adjunctive maintenance treatments for bipolar disorder. With the first report of lithium's efficacy in 1949 by Cade, bipolar disorder has the longest record of treatment efficacy among the major Axis I disorders. Furthermore, after more than half a century of clinical research, multiple agents from many different pharmacological classes have shown at least some efficacy, while many other agents (albeit without a consistent database demonstrating their utility) are prescribed regularly by clinicians. Yet, despite this plethora of choices, treatment of bipolar disorder remains suboptimal from the points of view of clinicians and patients alike. Whether measured by recovery time from manic or depressive episodes or preventive efficacy of maintenance treatments, bipolar disorder is characterized by sluggish responses, inadequate responses, poor compliance and recurrences in controlled cli...

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Clozapine in Treatment-Resistant Patients With Schizophrenia, Schizoaffective Disorder, or Psychotic Bipolar Disorder

Cited by 101 publications

References 0 publications

Clozapine Therapy for Long-Term Prophylaxis in Bipolar Patients; Prescription Rates and Efficacy

Clozapine Therapy for Long-Term Prophylaxis in Bipolar Patients; Prescription Rates and Efficacy

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period

Treatment-resistant bipolar disorder

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