Clozapine in bipolar disorder: A systematic review and meta-analysis

Delgado, André; Velosa, J.; Zhang, Junyu; Dursun, Serdar; Kapczinski, Flávio; Cardoso, Taiane de Azevedo

doi:10.1016/j.jpsychires.2020.02.026

Cited by 45 publications

(27 citation statements)

References 30 publications

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“…CLZ was the first atypical antipsychotic showing cognitive promoting functions in patients with schizophrenia [ 133 , 134 ]. A recent systematic review and meta-analysis study demonstrated that the efficacy of CLZ was almost equal to other antipsychotics in manic episodes, but was superior to other antipsychotics against treatment-resistant bipolar disorder [ 135 ]. The clinical prognosis of treatment-resistant bipolar disorder is considered to be heterogeneous and not a general rule [ 136 , 137 ], therefore, improvement of cognitive impairment is an important outcome [ 135 ].…”

Section: Candidate Pathomechanisms Of Clz Associated With Cx43mentioning

confidence: 99%

“…A recent systematic review and meta-analysis study demonstrated that the efficacy of CLZ was almost equal to other antipsychotics in manic episodes, but was superior to other antipsychotics against treatment-resistant bipolar disorder [ 135 ]. The clinical prognosis of treatment-resistant bipolar disorder is considered to be heterogeneous and not a general rule [ 136 , 137 ], therefore, improvement of cognitive impairment is an important outcome [ 135 ]. A model of imbalances in the tripartite synapses responsible for the pathophysiology of bipolar disorder has been proposed [ 138 , 139 ].…”

Section: Candidate Pathomechanisms Of Clz Associated With Cx43mentioning

confidence: 99%

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A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

Okada

Fukuyama

Shiroyama

et al. 2020

IJMS

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Clozapine (CLZ) is an approved antipsychotic agent for the medication of treatment-resistant schizophrenia but is also well known as one of the most toxic antipsychotics. Recently, the World Health Organization’s (WHO) global database (VigiBase) reported the relative lethality of severe adverse reactions of CLZ. Agranulocytosis is the most famous adverse CLZ reaction but is of lesser lethality compared with the other adverse drug reactions of CLZ. Unexpectedly, VigiBase indicated that the prevalence and relative lethality of pneumonia, cardiotoxicity, and seizures associated with CLZ were more serious than that of agranulocytosis. Therefore, haematological monitoring in CLZ patients monitoring system provided success in the prevention of lethal adverse events from CLZ-induced agranulocytosis. Hereafter, psychiatrists must amend the CLZ patients monitoring system to protect patients with treatment-resistant schizophrenia from severe adverse CLZ reactions, such as pneumonia, cardiotoxicity, and seizures, according to the clinical evidence and pathophysiology. In this review, we discuss the mechanisms of clinical efficacy and the adverse reactions of CLZ based on the accumulating pharmacodynamic findings of CLZ, including tripartite synaptic transmission, and we propose suggestions for amending the monitoring and medication of adverse CLZ reactions associated with pneumonia, cardiotoxicity, and seizures.

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Section: Candidate Pathomechanisms Of Clz Associated With Cx43mentioning

confidence: 99%

Section: Candidate Pathomechanisms Of Clz Associated With Cx43mentioning

confidence: 99%

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

Okada

Fukuyama

Shiroyama

et al. 2020

IJMS

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“…50 Furthermore, clozapine is often associated with sedation. 51,52 In total, 49.6-64.7% of patients taking clozapine experienced sedation associated with clozapine. 51,52 The effect of sedation induced by clozapine could decrease benzodiazepine use, which may be used for insomnia and the agitated behavior of patients with schizophrenia.…”

Section: Dovepressmentioning

confidence: 99%

“…51,52 In total, 49.6-64.7% of patients taking clozapine experienced sedation associated with clozapine. 51,52 The effect of sedation induced by clozapine could decrease benzodiazepine use, which may be used for insomnia and the agitated behavior of patients with schizophrenia. A previous study also reported that benzodiazepine use declined in a group of outpatients with schizophrenia after initiating clozapine.…”

Section: Dovepressmentioning

confidence: 99%

<p>Clozapine Use in Patients with Early-Stage Schizophrenia in a Chinese Psychiatric Hospital</p>

Yi¹,

She

Zhang

et al. 2020

NDT

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Objective: Previous studies suggest that clozapine is commonly underutilized and that its initiation is delayed in patients with first-episode schizophrenia. Knowledge regarding clozapine use among Chinese patients with early-stage schizophrenia is limited. The aim of the present study was to investigate the point prevalence of and patterns and factors associated with clozapine use in patients with early-stage schizophrenia discharged from a psychiatric hospital in China. Methods: A retrospective study was conducted to analyze the prescriptions of 867 consecutive patients with early-stage schizophrenia who were admitted to the Affiliated Brain Hospital of Guangzhou Medical University between Jan 1, 2011 and Dec 31, 2016. Results: At discharge from the hospital, 114 (13.1%) patients were prescribed clozapine. Among the patients taking clozapine, 93 patients (81.6%) were prescribed clozapine polypharmacy, and only 21 patients (18.4%) were prescribed clozapine monotherapy. None of the patients were prescribed an overdose of clozapine. The mean daily dosage of clozapine was 160.97 mg, 149.05 mg and 213.69 mg among all patients taking clozapine, patients taking clozapine polypharmacy and patients taking clozapine monotherapy, respectively. The antipsychotic most frequently combined with clozapine was risperidone. Logistic regression suggested that the length of hospital stay, high school education, lower benzodiazepine use and antipsychotic polypharmacy were independently and significantly associated with clozapine use (P<0.05). Conclusion: Although clozapine has been commonly used in China in recent years, the present study found that clozapine was not commonly used in patients with early-stage schizophrenia. An underutilization and delayed initiation of clozapine may exist in a portion of patients with early-stage schizophrenia. Given the unfavorable outcomes of underutilized and delayed clozapine use, future studies may be needed to assess and increase clozapine use in this population.

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“…It is con rmed that antipsychotics have a signi cant effect on improving the positive symptoms of schizophrenia and no determined curative effect in improving negative symptoms [2] and cognitive function [3]. Meanwhile, antipsychotics wil bring numerous adverse effects, such as cardiovascular symptoms, metabolic syndrome, hyperprolactinemia, tardive dyskinesia, extrapyramidal reactions, obesity, constipation and so on [4][5][6][7]. It seriously affects both recovery and quality of life.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of Jie-du-qing-nao granules for first-episode schizophrenics: study protocol for a randomized controlled trial

Ning

Chen

et al. 2020

Preprint

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BackgroundAt present, the focus and difficulty of schizophrenia (SCZ) treatment is to improve cognitive function and negative symptoms. Jie-du-qing-nao granules(JQG) , a traditional Chinese medicine(TCM) prescription , has a good clinical effectiveness in enhancing the cognition and negative symptoms of patients with SCZ. However, its clear effectiveness and safety have not been adequately supported by clinical studies. The main objective of this study is to explore the efficacy and safety of JQG for first-episode schizophrenics.Methods/designThis trial is a prospective, randomized, single-centered, parallel-controlled clinical study with double-blind design. A total of 96 eligible participants will be randomly assigned to either the study group or the control group in a ratio of 1:1. Participants allocated to the study group will receive JQG and aripiprazole, control group will receive placebo and aripiprazole. The treatment course will last 12 weeks, with follow-up every 4 weeks. Outcome measurements include Positive and Negative Syndrome Scale (PANSS), self face test , MATRICS Consensus Cognitive Battery (MCCB), TNFα, IL-6, IL-1β, BDNF, vital signs, complete blood count, liver and kidney function tests, urinalysis, and electrocardiograph. Adverse reactions will be evaluated using the Treatment Emergent Symptom Scale (TESS).DiscussionThis study will provide evidence for the efficacy and safety of JQG as a complementary approach, which can be initiated following with antipsychotics therapy. Trial registration Chinese Clinical Trial Registry, ID: ChiCTR1900028250 . Registered on December 16, 2019, http://www.chictr.org.cn/edit.aspx?pid=41880&htm=4 .

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Clozapine in bipolar disorder: A systematic review and meta-analysis

Cited by 45 publications

References 30 publications

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43

<p>Clozapine Use in Patients with Early-Stage Schizophrenia in a Chinese Psychiatric Hospital</p>

Efficacy and safety of Jie-du-qing-nao granules for first-episode schizophrenics: study protocol for a randomized controlled trial

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