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Pardis, Parnian, Gary Remington, Roshni Panda, Milan Lemez, and Ofer Agid. "Clozapine and tardive dyskinesia in patients with schizophrenia: A systematic review." Journal of Psychopharmacology 33, no. 10 (July 26, 2019): 1187–98. http://dx.doi.org/10.1177/0269881119862535.
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Background: It is commonly recommended that a switch to clozapine be implemented in the face of tardive dyskinesia, even if current treatment involves another “atypical” agent. However, reports do indicate clozapine carries a liability for tardive dyskinesia. Aims: This review sought to evaluate clozapine in relation to tardive dyskinesia in the context of available evidence. Methods: Medline, Embase, and PsycINFO databases were searched for studies published in English, using the keywords: clozapine AND tardive dyskinesia OR TD. References from major review articles were searched for additional relevant publications. Studies were included if they investigated: tardive dyskinesia in clozapine-treated patients diagnosed with schizophrenia spectrum disorders, and reported on two or more assessments of tardive dyskinesia severity measured by the Abnormal Involuntary Movement Scale; or clozapine’s tardive dyskinesia liability. Results: In total, 513 unique citations were identified and 29 reports met the inclusion criteria. Thirteen studies suggest clozapine reduces dyskinetic symptoms over time ( n=905 clozapine-treated participants); however, the minimum required dose and effect of withdrawal requires further investigation. The majority of reports which address clozapine’s liability for tardive dyskinesia are case studies (11 of 14 reports, 79%), and clozapine was only the first-line treatment in one of the remaining three studies reporting treatment-emergent dyskinetic symptoms with clozapine in 12% of patients. No significant between-drug differences were identified comparing clozapine’s risk to other atypical antipsychotics. Conclusions: Research to date supports switching to clozapine for the purpose of reducing tardive dyskinesia risk and/or treating existing tardive dyskinesia, but prospective randomized controlled trials are necessary if we are to substantiate existing recommendations.
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Qubad, Mishal, and Robert A. Bittner. "Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia." Therapeutic Advances in Psychopharmacology 13 (January 2023): 204512532311581. http://dx.doi.org/10.1177/20451253231158152.
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Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.
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Rajkumar, Anto P., B. Poonkuzhali, Anju Kuruvilla, Alok Srivastava, Molly Jacob, and K. S. Jacob. "Association betweenCYP1A2gene single nucleotide polymorphisms and clinical responses to clozapine in patients with treatment-resistant schizophrenia." Acta Neuropsychiatrica 25, no. 1 (February 2013): 2–11. http://dx.doi.org/10.1111/j.1601-5215.2012.00638.x.
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ObjectivesDespite clozapine's superior clinical efficacy in treatment-resistant schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes mandate a clinical need to predict its treatment response. Although cytochrome P450 1A2 (CYP1A2) is the principal determinant of metabolism of clozapine, the role ofCYP1A2gene in the clinical response to clozapine is uncertain. Hence, we investigated its association with treatment responses and adverse events of clozapine in TRS.MethodsWe evaluated four single nucleotide polymorphisms (SNP) in theCYP1A2gene, clinical responses and serum clozapine levels in 101 consecutive patients with TRS on stable doses of clozapine. We defined clozapine responsea prioriand investigated allelic and genotypic associations. We assessed the socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition and disability of the participants, using standard assessment schedules for appropriate multivariate analyses.ResultsOur results revealed thatCYP1A2gene SNP (*1C, *1D, *1Eand*1F) were not associated with clozapine treatment response, adverse effects, serum clozapine levels or with disability (pvalues > 0.10).ConclusionAsCYP1A2gene SNP do not help to predict the clinical response to clozapine, routine screening for them prior to start clozapine is currently unwarranted. We suggest future longitudinal genome-wide association studies investigating clinical and pharmacogenetic variables together.
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Lieberman, Jeffrey A., Bruce L. Saltz, Celeste A. Johns, Simcha Pollack, Michael Borenstein, and John Kane. "The Effects of Clozapine on Tardive Dyskinesia." British Journal of Psychiatry 158, no. 4 (April 1991): 503–10. http://dx.doi.org/10.1192/bjp.158.4.503.
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This article reviews eight published studies that describe clozapine's effects on TD and examines the outcome of 30 patients with TD treated with clozapine for up to 36 months. These data indicate that TD response to clozapine is variable but that approximately 43% of cases, particularly those with dystonic features, improved after clozapine treatment. Methodological limitations of the studies described, however, preclude definitive conclusions, which must await appropriately controlled trials.
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Coward, D. M. "General Pharmacology of Clozapine." British Journal of Psychiatry 160, S17 (May 1992): 5–11. http://dx.doi.org/10.1192/s0007125000296840.
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Clozapine shows neuroleptic-like inhibition of locomotor activity and conditioned avoidance responding in rodents, although tolerance develops on repeated treatment. EEG-based studies show strong arousal-inhibiting activity of clozapine as well as neuroleptic-like effects on both caudate spindle duration and rat sleep-waking patterns. Effects such as apomorphine blockade, catalepsy and strong increases of plasma prolactin levels are not seen, however, and chronic treatment does not lead to dopamine D2 receptor supersensitivity. Binding studies show clozapine's highest affinities to be for dopamine D4, 5-HT1c, 5-HT2, α1, muscarinic and histamine H1 receptors, but moderate affinity is also seen for many other receptor subtypes. Microdialysis studies indicate a preferential interaction with striatal D1 receptors, whereas autoradiographical studies indicate upregulation of D1 and downregulation of 5-HT2 receptors after chronic clozapine. Clarification of the mechanisms underlying clozapine's special attributes is often hampered by a failure to examine compounds which show a close chemical relationship to clozapine, but which produce extrapyramidal side-effects in man, such as clothiapine, loxapine and amoxapine.
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Oliveira-Souza, Ricardo de, Rogério Paysano Marrocos, and Jorge Moll. "Clozapine for severe ("kraepelinian") schizophrenia: Sustained improvement over 5 years." Dementia & Neuropsychologia 2, no. 1 (March 2008): 71–75. http://dx.doi.org/10.1590/s1980-57642009dn20100014.
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Abstract Clozapine has become a keystone in the treatment of schizophrenia because of its efficacy as an antipsychotic with negligible neuroleptic effects. The long-term stability of its effects, however, is poorly understood, because most studies have probed the usefulness of clozapine over a period of weeks to several months at the most. Knowing whether clozapine's benefits are sustained over the very long-term, i.e., more than 5 years, may be critical for cost-benefit analyses. Objective: To report the results of an open study on the efficacy of clozapine over the very long-term. Methods: Thirty-three adults (26 men) with severe (kraepelinian) schizophrenia were assessed at regular intervals using a brief neuropsychiatric battery over a 5-year period. Results: A significant improvement was observed between the pre-clozapine and the first "on-clozapine" evaluation. This improvement was paralleled by a remarkable conversion of schizophrenia from "active" (mostly paranoid) into "residual" in 70% of all patients. Eight patients became functionally productive to the point of being capable of living an independent life. Roughly one-third of our cases showed no improvement. Conclusions: Clozapine is a safe and effective drug for patients with severe schizophrenia who have failed to improve on other antipsychotic drugs. Clozapine's maximal benefit is established by the end of the first year of treatment and continues unabated for many years thereafter. Clozapine-resistant patients remain a major challenge calling for the discovery of new treatments for schizophrenia.
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Dell’Osso, Liliana, Chiara Bonelli, Benedetta Nardi, Federico Giovannoni, Cristiana Pronestì, Ivan Mirko Cremone, Giulia Amatori, Stefano Pini, and Barbara Carpita. "Rethinking Clozapine: Lights and Shadows of a Revolutionary Drug." Brain Sciences 14, no. 1 (January 20, 2024): 103. http://dx.doi.org/10.3390/brainsci14010103.
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The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice. For this work, a search was performed on PubMed using the terms “Clozapine indications”, “Clozapine adverse effects”, “Clozapine regenerative effects”, and “Clozapine neuroplasticity” with the aim of reviewing the scientific literature on Clozapine’s treatment indications, adverse effects and potential regenerative role. The results confirmed the efficacy of clozapine in clinical practice, although limited by its adverse effects. It appears crucial to raise awareness among clinicians about the potential benefits of using Clozapine, as well educating medical personnel about its risks and the early identification of possible adverse effects and their management.
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Orejas, O., C. Masferrer Herrera, C. Macías Castellví, and P. Flores Martínez. "Subacute psychiatric hospitalization unit: The role of clozapine." European Psychiatry 33, S1 (March 2016): S548—S549. http://dx.doi.org/10.1016/j.eurpsy.2016.01.2026.
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IntroductionSeveral studies report that Clozapine is more effective in reducing symptoms of schizophrenia, producing clinically meaningful improvements and postponing relapse than other antipsychotic strategies.ObjectivesTo analyze the prescription of Clozapine in a sample of 88 inpatients admitted to a subacute psychiatric hospitalization unit.MethodsThis is a transversal study. All patients admitted for a medium-term psychiatric treatment since 01/06/2014 to 30/11/2015 were included. Data about socio-demographical status and clinical situation were obtained and compiled in a database. This study compares patients receiving clozapine treatment with those who receive other psychopharmacologic treatment. Statistics were performed using SPSS Software.ResultsEighty-eight patients (52% men; mean age: 48.6 years) composed the sample. In 58% of cases, schizophrenia and schizoaffective disorder were the diagnoses motivating the admission. Within the 51 patients with Schizophrenia o Schizoaffective Disorder, 16 of them (31.4%) received Clozapine. Comparing clozapine group vs non-clozapine group, there were no significant differences between the groups in terms of sex, civil state or working state. Instead, Clozapine group patients were older, had a major number of previous hospitalization admissions and had a larger trajectory of their disorder.ConclusionsPatients requiring treatment with Clozapine had a major number of hospital admissions and had more often committed suicide attempts, suggesting a more severe course of the disorder. They were older than the non-clozapine group. Clozapine is delayed in its use among resistant-treatment patients. It is worth highlighting that only 16 cases of Schizophrenia inpatients received Clozapina. It could mean that Clozapine is underprescribed.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Stanton, Robert J., Chris Paxos, Werner J. Geldenhuys, B. Pharm, Jessica L. Boss, Mark Munetz, Altaf S. Darvesh, and M. Pharm. "Clozapine underutilization in treatment-resistant schizophrenia." Mental Health Clinician 5, no. 2 (March 1, 2015): 63–67. http://dx.doi.org/10.9740/mhc.2015.03.063.
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Abstract It has been shown that up to one third of patients with schizophrenia do not respond to antipsychotic therapy. Thus, treatment-resistant schizophrenia (TRS) remains a major mental health care challenge. Clozapine has been shown to provide superior therapeutic benefits and is approved as first-line therapy for TRS. These benefits include improvement in both positive and negative symptoms, and reduction of suicidal behavior in patients with schizophrenia. Clozapine, however, remains significantly underused for TRS. A major reason for clozapine's underuse is its substantial adverse effect profile, mainly the risk of life-threatening agranulocytosis which necessitates regular hematologic monitoring. Another factor contributing to reduced clozapine prescribing is the increased use of other second-generation antipsychotics. In TRS patients, there is often a considerable delay in clozapine use, which is prescribed only after other unsuccessful second-generation antipsychotic trials. To combat this trend, there is a push for increased awareness to optimize clozapine prescribing. An important aspect in improving the use of clozapine therapy is physician and patient education. Furthermore, pharmacist involvement can improve clozapine prescription trends in TRS.
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Fehsel, K., K. Schwanke, BA Kappel, E. Fahimi, E. Meisenzahl-Lechner, C. Esser, K. Hemmrich, T. Haarmann-Stemmann, G. Kojda, and C. Lange-Asschenfeldt. "Activation of the aryl hydrocarbon receptor by clozapine induces preadipocyte differentiation and contributes to endothelial dysfunction." Journal of Psychopharmacology 36, no. 2 (January 3, 2022): 191–201. http://dx.doi.org/10.1177/02698811211055811.
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Background: The superior therapeutic benefit of clozapine is often associated with metabolic disruptions as obesity, insulin resistance, tachycardia, higher blood pressure, and even hypertension. Aims: These adverse vascular/ metabolic events under clozapine are similar to those caused by polycyclic aromatic hydrocarbons (PAHs), and clozapine shows structural similarity to well-known ligands of the aryl hydrocarbon receptor (AhR). Therefore, we speculated that the side effects caused by clozapine might rely on AhR signaling. Methods: We examined clozapine-induced AhR activation by luciferase reporter assays in hepatoma HepG2 cells and we proved upregulation of the prototypical AhR target gene Cyp1A1 by realtime-PCR (RT-PCR) analysis and enzyme activity. Next we studied the physiological role of AhR in clozapine’s effects on human preadipocyte differentiation and on vasodilatation by myography in wild-type and AhR-/- mice. Results: In contrast to other antipsychotic drugs (APDs), clozapine triggered AhR activation and Cyp1A1 expression in HepG2 cells and adipocytes. Clozapine induced adipogenesis via AhR signaling. After PGF2α-induced constriction of mouse aortic rings, clozapine strongly reduced the maximal vasorelaxation under acetylcholine in rings from wild-type mice, but only slightly in rings from AhR-/- mice. The reduction was also prevented by pretreatment with the AhR antagonist CH-223191. Conclusion: Identification of clozapine as a ligand for the AhR opens new perspectives to explain common clozapine therapy-associated adverse effects at the molecular level.
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Davis, Erica A. K., and Deanna L. Kelly. "Clozapine-associated renal failure: A case report and literature review." Mental Health Clinician 9, no. 3 (May 1, 2019): 124–27. http://dx.doi.org/10.9740/mhc.2019.05.124.
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Abstract One of clozapine's unrecognized potential side effects is renal insufficiency and nephritis. Although most clinicians are aware of the possibility of clozapine-induced myocarditis, less is known about other inflammatory disorders due to clozapine treatment. This patient was started on lithium and clozapine within 4 days of each other although lithium was discontinued after 7 days due to tremor. Routine labs showed an increase in serum creatinine, which was initially attributed to the recent lithium. However, the patient's kidney function continued to worsen, requiring discontinuation of clozapine despite a robust response to a low dose. Several years later, the patient's kidney function improved but has not returned to baseline. This literature review and case report illustrates the similarities in diagnostic presentation of clozapine-associated renal insufficiency as well as potential risk factors. More research should be conducted into the role concomitant sodium valproate and/or lithium play in the risk of clozapine-associated renal insufficiency.
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Jalenques, Isabelle, and André-Julien Coudert. "Clozapine for the treatment of levodopa-induced psychosis and dyskinesia in Parkinson's disease." Irish Journal of Psychological Medicine 11, no. 2 (June 1994): 83–88. http://dx.doi.org/10.1017/s0790966700012404.
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AbstractThe treatment of psychosis in patients with Parkinson's disease (PD) is one of the most difficult problems in clinical psychiatry. Clozapine's low propensity to induce extrapyramidal side effects makes it an attractive treatment for psychotic patients with PD. A number of published uncontrolled studies suggest that low-dose clozapine is effective in these patients. However, the dose range, side effect profiles and length of treatment have varied in these reports. In this article, the authors review the literature and report on the effects of clozapine in a patient with Parkinson's disease and psychosis. Clozapine (50mg per day) resulted in a complete resolution of psychosis, improvement of motor function, reduction of “off” time and a major improvement in levodopa-induced dystonic dyskinesias. The only adverse effect was mild sedation during the first two weeks of clozapine treatment. The lack of acute blockade of striatal D2 receptors by clozapine and the failure of chronic clozapine treatment to suppress striatal dopamine release may account for its beneficial effect in Parkinson's disease. Additionally, an ameliorating effect of clozapine on parkinsonism might be due to its action on serotonergic systems leading to release of striatal dopamine.
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Kenton, Emma M., Samantha M. Zoellner, and Leigh Anne Nelson. "Diltiazem for clozapine-induced generalized hyperhidrosis." Mental Health Clinician 13, no. 4 (August 1, 2023): 193–95. http://dx.doi.org/10.9740/mhc.2023.08.193.
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Abstract Background Clozapine can be associated with significant side effects and tolerability issues. Hyperhidrosis occurs less commonly and is unanticipated by clinicians because of clozapine's significant anticholinergic activity. Case Report A 34-year-old female developed clozapine-induced nocturnal, generalized hyperhidrosis following initial titration to 400 mg/day. Dose reduction did not decrease the side effect. Treatment with an anticholinergic medication could not be initiated because of constipation. Treatment with a beta blocker resulted in worsening of asthma. Treatment with a calcium channel blocker, diltiazem CD 180 mg/day, resulted in a significant reduction in hyperhidrosis. Conclusion This case supports the use of calcium channel blockers to reduce clozapine-induced hyperhidrosis and offers an alternative to anticholinergic medications that may negatively impact clozapine tolerability.
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Marcelino, Carla R. B., and Clarissa de R. Dantas. "Clozapine-induced severe eosinophilia: report of a case with good outcome." Jornal Brasileiro de Psiquiatria 62, no. 3 (September 2013): 240–43. http://dx.doi.org/10.1590/s0047-20852013000300009.
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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.
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Sulejmanpasic, G., and S. Bise. "Clozapine augmented with risperidone in treatment-resistant schizophrenia." European Psychiatry 41, S1 (April 2017): S385. http://dx.doi.org/10.1016/j.eurpsy.2017.02.424.
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IntroductionThe evolution of various pharmacological therapies for schizophrenia has given rise to several pharmacological models for the neuroreceptor targets of antipsychotics and the influence of various neuroreceptors on specific symptoms and side effects.ObjectivesExperience in clinical practice affirms clozapine's position as the treatment of choice for patients with treatment-refractory schizophrenia. Unlike clozapine, risperidone has a more targeted profile of neurotransmitter binding, with particular predilection for dopamine and serotonin receptors. Risperidone is, to date, the most extensively documented clozapine augmentation agent.AimThe aim was to evaluate clinical efficacy, safety and tolerability of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia.MethodsIn a randomized, double-blind, placebo-controlled 8-week trial, 10 patients unresponsive or partially responsive to 300 mg/day of clozapine monotherapy (n = 5) received a steady dose of 450 mg/day clozapine combined with or up to 4 mg/day of risperidone (n = 5). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS) and Clinical Global Impression (CGI) improvement scale.ResultsFrom baseline to week 4 and week 8, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine monotherapy group. Clozapine/risperidone treatment did not induce additional weight gain or agranulocytosis compared with clozapine monotherapy treatment.ConclusionsClozapine augmentation with risperidone appears to be well tolerated, safe and may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Kirwan, P., L. O’Connor, K. Sharma, and C. McDonald. "The impact of switching to clozapine on psychiatric hospital admissions: a mirror-image study." Irish Journal of Psychological Medicine 36, no. 4 (July 18, 2017): 259–63. http://dx.doi.org/10.1017/ipm.2017.28.
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BackgroundClozapine is an atypical antipsychotic agent used primarily in the management of treatment-resistant schizophrenia. Previous studies have demonstrated clozapine’s superior efficacy over other antipsychotic medications in treating this population of patients. The aim of this study was to assess if the number of hospital admissions and days spent in hospital reduced with the initiation of clozapine, compared with when the same sample of patients were prescribed other antipsychotics prior to clozapine initiation.MethodA mirror-image study design was adopted. In this case the intervention under study was the initiation of clozapine. Information was collected retrospectively from the charts of patients attending the University Hospital Galway clozapine clinic. The number of admissions and number of hospital days were collected for each patient over the 3 years before and after clozapine initiation. Wilcoxon’s signed-rank test was used to test for statistical significance.ResultsThe total sample size comprised of 62 patients, of which the majority were male (74.2%) and had a diagnosis of schizophrenia (82.3%). The mean dose of clozapine was 417 mg, and mean age of the sample was 38 years. Mean number of hospital admissions reduced from 2.8 to 0.8 (p<0.0001) following initiation of clozapine. Mean number of days spent in hospital reduced from 116.4 to 17.1 (p<0.0001).ConclusionAfter initiation of clozapine treatment, patients experience a substantial reduction in number of hospital admissions and number of days spent in hospital when compared with a similar period prior to clozapine initiation.
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Kumar Agrawal, Adesh, Soumitra Das, Lorenzo Abednego B. Adre, Nakka Raghuma, Sharanya Kaushik, and Adarsha Adhikari. "A Case Report of a Patient with Soaring Clozapine Levels after Developing a Urinary Tract Infection." Case Reports in Psychiatry 2024 (February 20, 2024): 1–4. http://dx.doi.org/10.1155/2024/9147674.
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Clozapine is an antipsychotic medicine used to treat mental illnesses that is resistant to therapy. It can induce dose-dependent adverse effects such as increased susceptibility to infections and hematological irregularities. In this case report, we present a 37-year-old woman with schizoaffective disorder who experienced clozapine side effects following a moderate urinary tract infection (UTI). Her serum clozapine levels and side effects were increased throughout her UTI but resolved once the UTI was managed conservatively. We reviewed clozapine’s pharmacokinetic properties to understand why serum levels rose during infection. While we could not definitely explain the mechanism of elevation, we emphasize the importance of monitoring serum clozapine levels and keeping watchful for adverse effects, as well as heightened scrutiny, evaluation for recent infections, and regular monitoring of patients.
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Kubota, Takashi, Itsuki Jibiki, Akira Ishikawa, Tomomi Kawamura, Sonoko Kurokawa, and Man Wang. "Increase in extracellular dopamine levels during clozapine-induced potentiation in the hippocampal dentate gyrus of chronically prepared rabbits." Canadian Journal of Physiology and Pharmacology 86, no. 5 (May 2008): 249–56. http://dx.doi.org/10.1139/y08-036.
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We previously found that 20 mg/kg clozapine i.p. potentiated the excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path in chronically prepared rabbits. We called this phenomenon clozapine-induced potentiation and proved that it was an NMDA receptor-mediated event. This potentiation is presumably related to clozapine’s clinical effect on negative symptoms and cognitive dysfunctions in schizophrenia. In the present study, to investigate the mechanisms underlying clozapine-induced potentiation, we examined whether extracellular dopamine and 5-HT levels changed during the potentiation by using a microdialysis technique in the dentate gyrus. The extracellular concentrations of dopamine and 5-HT levels were measured every 5 min during all experiments. Extracellular 5-HT levels did not change, but dopamine levels eventually increased significantly during clozapine-induced potentiation. The increase in the dopamine levels occurred almost simultaneously with the induction of clozapine-induced potentiation. These results suggest that clozapine-induced potentiation is at least partly attributable to a dopamine-mediated potentiation of excitatory synaptic transmission. The present study implies that such phenomena occur also in the perforant path–dentate gyrus pathway.
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Freudenreich, O. "Augmentation strategies for treatment-refractory clozapine patients." European Psychiatry 64, S1 (April 2021): S31. http://dx.doi.org/10.1192/j.eurpsy.2021.109.
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BackgroundClozapine can be a life-saving and course-altering treatment for patients with psychosis, particularly treatment-resistant schizophrenia. Unfortunately, clozapine monotherapy rarely leads to a full symptomatic remission.AimsThis talk outlines key decision points in the use of clozapine: how to select patients for clozapine treatment and how to optimize clozapine’s efficacy in patients with a poor response to an adequate clozapine monotherapy trial.ConclusionsClozapine’s main indication is for treatment-resistant schizophrenia. Therapeutic drug monitoring (TDM) should be used to optimize clozapine dosing during a clozapine trial and to rule-out pseudo-resistance. Up to 50% of patients do not respond to clozapine monotherapy and augmentation strategies can be utilized in such cases. Pharmacological add-on treatments are selected based on the most prominent symptom cluster (refractory psychosis, negative symptoms, depression and suicidality, aggression). Electroconvulsive therapy is the most effective augmentation strategy for refractory psychosis and suicidality. Non-pharmacological interventions and a focus on quality of life become important considerations in clozapine non-responders.CommentsClozapine is an important and underutilized tool in the management of treatment-resistant schizophrenia. It should be offered timely, as soon as treatment-resistance becomes apparent. Clinicians can use personalized augmentation strategies as part of a comprehensive treatment plan in order to achieve improvements even in patients with a poor response to clozapine alone. However, polypharmacy should be used judiciously, keeping in mind medical morbidity and quality of life.DisclosureI have the following financial relationship with a commercial interest to disclose (recipient SELF; content area SCHIZOPHRENIA): Alkermes – Research grant (to institution), consultant honoraria (Advisory Board); Avanir – Research grant (to institution);
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Nasyrova, R. F., A. V. Kidyaeva, V. V. Grechkina, M. M. Petrova, and N. A. Shnayder. "Personalized Approach to Prediction and Prevention Clozapine-Induced QT Prolongation." Psychiatry (Moscow) (Psikhiatriya) 22, no. 5 (January 9, 2025): 75–86. https://doi.org/10.30629/2618-6667-2024-22-5-75-86.
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Background: antipsychotics are widely used in psychiatry. Clozapine remains an indispensable antipsychotic due to its effectiveness. However, it has a wide range of undesirable effect, including an increased risk of QT prolongation, a potentially fatal complication that can lead to Torsade de Pointes (TdP) and sudden cardiac death. Objective: to systematize information for practicing psychiatrists about a personalized approach to the prevention of QT interval prolongation in patients with mental disorders when taking clozapine. Methods: a search for full-text articles published from 02/01/2014 to 02/01/2024 was carried out in PubMed, eLIBRARY.RU, Google Scholar. Results: this review analyzed and summarized the results of studies on the effect of clozapine on the QT interval, the role of risk factors and hereditary predisposition in the development of clozapine-induced prolongation of the QT interval and Torsade de Pointes in patients with mental disorders. The main mechanism of clozapine’s cardiotoxic effect is dose-dependent inhibition of potassium channels in the cardiomyocyte membrane. Clozapine is extensively metabolized in the liver, which may cause significant interindividual variability in its pharmacokinetics. A decrease in the rate of metabolism of clozapine may lead to an increase in its concentration in the blood, and thereby increase the risk of developing cardiotoxic adverse reactions. To reduce the risk of clozapine-induced QT prolongation, it is advisable to use predictive pharmacogenetic testing. Conclusion: Generalized data on the effect of clozapine on the duration of the QT interval and the risk of developing TdP in patients with mental disorders may be needed by psychiatrists when selecting the dose and duration of clozapine. Predictive pharmacogenetic testing can help reduce the incidence of potentially fatal ventricular arrhythmias.
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Bunney, Benjamin S. "Clozapine: A Hypothesised Mechanism for its Unique Clinical Profile." British Journal of Psychiatry 160, S17 (May 1992): 17–21. http://dx.doi.org/10.1192/s0007125000296864.
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Clozapine's clinical profile is unique among antipsychotic drugs. What makes it different? For almost two decades researchers have been attempting to answer this question. Based on various data, many hypotheses have been proposed. Using electrophysiological techniques we have found that clozapine, like typical antipsychotic drugs, inactivates most midbrain dopamine cells secondary to the induction of depolarisation block. However, unlike classical antipsychotic drugs, clozapine does not inactivate the nigrostriatal dopamine system. Based on these and other findings the hypothesis of ‘depolarisation block‘ is reviewed and presented as an explanation for clozapine's unique clinical profile. Research data both for and against the hypothesis are then discussed.
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Fernando, Tharushi, and Ritesh Bhandarkar. "Consumer Survey on the Experience of Clozapine Treatment and Monitoring Process in an Australian Community Mental Health Service." BJPsych Open 10, S1 (June 2024): S135—S136. http://dx.doi.org/10.1192/bjo.2024.363.
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AimsClozapine is a well-established and widely practiced treatment for treatment-resistant schizophrenia. Due to its significant side effect profile, it requires intense monitoring, including monthly blood tests and medical reviews. A patient's attitude towards clozapine can impact compliance with treatment and its monitoring process. This survey intended to identify the community mental health patients' perception of the clozapine treatment and its monitoring process and to help improve current practices of the service.MethodsA structured survey with 17 questions was administered to patients registered at the community clozapine clinic via face-to-face or phone conversation at an Australian Community Mental Health Service by the principal researcher and clozapine coordinators.Results17 out of 25 eligible patients (68%) participated; the mean age was 39.7 years. There were nine female and eight male participants. 94% of patients were on clozapine for more than one year. 70.5% agreed that clozapine helped to improve mental health, and they understand clozapine side effects and monitoring process. 76.5% agreed that the treating team provided psychoeducation. Seven participants reported clozapine improved side effects compared with previous medications. Three disagreed that clozapine improved side effects, and six remained neutral. Hypersalivation (35.2%), constipation (23.5%) and weight gain (17.6%) were identified as the worst side effects. Nine (52.9%) participants reported that they make healthy life choices. Factors affecting motivation for a healthy lifestyle are mental health symptoms (47%), finances (47%) and physical health well-being (52.9%). Only 35% identified motivation from others as necessary for a healthy lifestyle. Fatigue/poor motivation (47%) and mental health (35.2%) prevent them from making healthy choices. Side effects and finances equally (23.5%) impact healthy choices. Eleven participants (64.7%) felt clozapine monitoring was a positive experience, and 88.2% felt they had enough support during the clozapine monitoring process and were adequately informed about their treatment plan. Two participants disagreed that they were informed of their treatment plan. The majority (82.3%) said no change was needed in the monthly medical officer-led clozapine clinic or six-monthly psychiatrist-led clozapine clinics. Text messages (88.2%) and phone conversations (47%) were the most preferred method for treating team communication about treatment.ConclusionThe majority of patients identified that clozapine helped to improve mental health, and the monitoring process was a positive experience. Most participants were aware of clozapine and its monitoring process. Psychosocial support will be essential to improve quality of life and might improve the negative perception of clozapine's side effects.
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Cairns, Rebecca, and Stephen Guy. "Clozapine initiation in the Belfast Health and Social Care Trust (BHSCT)." BJPsych Open 7, S1 (June 2021): S177. http://dx.doi.org/10.1192/bjo.2021.482.
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AimsThe aim of this project is to improve the quality of documentation and recording of the assessment and monitoring of patients commencing clozapine in BHSCT.BackgroundClozapine is an effective treatment for patients with schizophrenia who have not responded to at least two other antipsychotics. Due to clozapine's significant side effect profile patients must be carefully assessed prior to treatment initiation with close monitoring of their physical observations and reported side effects during initiation.The BHSCT Clozapine Pathway currently uses a Clozapine Assessment Integrated Care Pathway (ICP) common to inpatient and outpatient clozapine titrations and a Clozapine Titration ICP which varies slightly between inpatient and outpatient titrations.MethodThe Clozapine ICPs of patients commenced on clozapine in BHSCT in a 9 month period commencing January 2019 were reviewed. Handwritten clinical records were used to collect data on rates of completion of all aspects of the pathway.These results were used to identify areas of the pathway that were being poorly completed and the “Method for Improvement Model” used to trial changes to the pathway using Plan-Do-Study-Act (PDSA) cycles.Result20 patients in BHSCT were commenced on clozapine in the 9 month period. 1 Clozapine Initiation Pathway could not be located; therefore data were collected on 19 patients. 2 patients were initiated in the community and 17 patients initiated as inpatients.The results showed that sections of the Clozapine Assessment ICP were poorly completed; for example only 27% of the “Patient Baseline Preparation Checklist” were complete, with 60% partially complete and 13% completely blank.In the inpatient clozapine titration ICP the physical observations record was complete in only 20% of patients and the side effects monitoring record complete in only 13% of patients. Conversely the physical observations and side effects monitoring records were complete in 100% (n = 2) of patients.ConclusionBHSCT Clozapine Pathways were being poorly completed, with outpatient pathways being completed better than inpatient pathways. Analysis of the data shows that repetition of information in various parts of the pathway leads to gaps in documentation.Parts of the pathway that were poorly completed have been redesigned and the impact of these changes assessed using the PDSA cycle method. It is hoped that this along with education of staff will lead to an improvement in the assessment and monitoring of patients being commenced on clozapine.
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Chang, Geng-Ruei, Hsien-Yueh Liu, Wei-Cheng Yang, Chao-Min Wang, Ching-Fen Wu, Jen-Wei Lin, Wei-Li Lin, et al. "Clozapine Worsens Glucose Intolerance, Nonalcoholic Fatty Liver Disease, Kidney Damage, and Retinal Injury and Increases Renal Reactive Oxygen Species Production and Chromium Loss in Obese Mice." International Journal of Molecular Sciences 22, no. 13 (June 22, 2021): 6680. http://dx.doi.org/10.3390/ijms22136680.
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Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine’s adverse metabolic effects—such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy—was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.
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Gire, Nadeem, Atta Asif, and Nusrat Husain. "Longitudinal Trend Evaluation and Prescription Cost Analysis (PCA) of Clozapine in the United Kingdom." BJPsych Open 10, S1 (June 2024): S37. http://dx.doi.org/10.1192/bjo.2024.150.
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AimsSevere Mental Illnesses (SMI) are a group of disorders which can have a debilitating impact on an individual's daily life functioning. The National Institute for Health and Care Excellence (NICE) has set out clinical guidelines for the treatment of SMI including the use of Second Generation Antipsychotic (SGA) medication as well as psychological therapies. However, Treatment Resistant Schizophrenia (TRS) affects approximately 34% of patients with schizophrenia. Clozapine, a SGA, has shown superiority in treatment resistant schizophrenia as well as its potential benefits in reducing suicidality and improving functioning.MethodsThe following study aimed to examine the longitudinal trends in prescribing clozapine based on the NHS Digital prescription cost analysis (PCA) between 2015–2023.ResultsThe results show that a number of prescriptions decrease simultaneously from the financial year 2015 (n = 5536) to 2023 (n = 3059). The cost was also found to be reducing until the financial year 2018–19 where there was an increase in costs which reached the maximum (14%) despite the number of prescriptions being lower as compared with 2015–16. In addition, it was found that clozapine prescribing trends have been reducing over time, despite a large proportion of service users with schizophrenia experiencing TRS (34%). Overall, since 2015–2023 a total of n = 34,440 items of clozapine were prescribed costing £1,252,052.27.ConclusionConsidering clozapine's superior efficacy in the treatment of TRS, further research is required to better understand prescribing practices, monitoring compliance of clozapine and treatment adherence. Further qualitative research is needed to better understand the views and perspectives of both service users and prescribers in the clinical use of clozapine. Future research may also look at referrals of clozapine-prescribed patients to psychological services, the impact of clozapine in TRS patients who are offered psychological therapy, and the potential clinical and cost implications of not prescribing clozapine.
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Hirsch, Steven R., Christopher G. G. Link, Jeffrey M. Goldstein, and Lisa A. Arvanitis. "ICI 204, 636: A New Atypical Antipsychotic Drug." British Journal of Psychiatry 168, S29 (May 1996): 45–56. http://dx.doi.org/10.1192/s0007125000298310.
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The therapeutic effects of ‘classic’ (typical) antipsychotic agents lie in their ability to block central dopaminergic receptors – a property that is also responsible for the frequent occurrence of undesirable extrapyramidal side-effects (EPS). In contrast to these typical agents, clozapine alone has distinguished itself in humans – by virtue of its enhanced antipsychotic action and lack of concurrent EPS – as an atypical antipsychotic. However, the use of clozapine has been limited by the occurrence of agranulocytosis and, to a lesser extent, seizures (Alvir et al, 1993; Haring et al, 1994). The mechanism underpinning the atypical profile of clozapine remains elusive. One hypothesis suggests that it lies in clozapine's higher serotonin 5-HT2: D2 binding ratio, when compared with typical agents – a factor being considered as a predictor of atypicality (Meltzer, this issue; Meltzer et al, 1989). However, an emerging view is that it is not a single pharmacological action, but rather multiple properties that may define an atypical, clozapine-like compound (Lieberman, 1993).
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Haile, Kibrom, and Halima Umer. "The use of clozapine and clonazepam co-administration in the treatment of a severe tardive dyskinesia: A case report." SAGE Open Medical Case Reports 7 (January 2019): 2050313X1983325. http://dx.doi.org/10.1177/2050313x19833254.
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This is a case report of a patient who was treated with clozapine and clonazepam after he developed neuroleptic-induced tardive dyskinesia following treatment for schizophrenia. There are reports of clozapine treatment itself causing tardive dyskinesia; however, more reports have shown clozapine’s benefit for patients with neuroleptic-induced tardive dyskinesia. This is a case report of a patient with neuroleptic-induced tardive dyskinesia who benefitted from clozapine treatment with adjuvant use of clonazepam – the first such case report from Ethiopia. A 43-year-old male patient developed severe involuntary abnormal body movements mainly involving the trunk after he received chlorpromazine for 8 years for the diagnosis of schizophrenia. When the movement disorder became intolerable and disabling, the diagnosis of severe neuroleptic-induced tardive dyskinesia was established and the patient was started on clozapine with adjuvant clonazepam treatment. Following such management, the patient responded well and the dyskinetic movements were fully controlled, and the patient was able to work. Patients with severe and disabling neuroleptic-induced tardive dyskinesia can be treated and be productive if they receive treatment with clozapine, with adjuvant use of clonazepam.
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Murphy, Kate, Ian Coombes, Sara McMillan, and Amanda J. Wheeler. "Clozapine and shared care: the consumer experience." Australian Journal of Primary Health 24, no. 6 (2018): 455. http://dx.doi.org/10.1071/py18055.
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Clozapine is a high-risk medication with restrictions that may increase consumer treatment burden. Shared care may improve access, reduce burden and promote primary care management. However, knowledge about the consumer experience of clozapine treatment within a shared-care setting has not been previously reported to the authors’ knowledge. The aim of this study was to explore the consumer experience within the shared-care setting. This mixed-methods study examined consumers’ experiences with a clozapine shared-care program in an urban setting in Queensland, Australia. Eligible consumers (n=35) participated in a semi-structured interview, including a survey. Analysis was descriptive and thematic. Ten (28.6%) consumers participated. Survey results found a strong belief in the necessity for clozapine, with a low level of reported treatment burden and minimal adverse effects. Four themes were identified from the interviews: (i) understanding of illness and recovery; (ii) positive outcomes of treatment; (iii) acceptance of treatment burden; and (iv) communication pathways. Participants reported positive experiences in the clozapine shared-care program, citing clozapine’s efficacy and the GP relationship as key benefits, however communication between clinicians and consumers must be enhanced to reduce risk of suboptimal treatment and adverse drug events.
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Peinado, A. Gomez, P. Cano Ruiz, S. Cañas Fraile, M. Gonzalez Cano, and G. E. Barba Fajardo. "Clozapine induced blood dyscrasias and a therapeutical approach." European Psychiatry 33, S1 (March 2016): S613. http://dx.doi.org/10.1016/j.eurpsy.2016.01.2293.
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IntroductionClozapine is a neuroleptic commonly used in treatments resistant to schizophrenia. However, despite the benefits, clozapine might cause some serious side effects. Hence, it is of the utmost necessity to keep an exacting control of the patients.ObjectivesTo study some of the therapeutical approaches to the treatment of clozapine induced neutropenia and agranulocytosis.MethodsReview of some articles in Mental Health Journals.ResultsThe treatment with clozapine, substratum of aminergic and muscarinic receptors, entails a 0.9% risk of causing agranulocytosis, and approximately a 2.7% risk of causing neutropenia. Both occur, over 80% of them, during the first 18 weeks of treatment. Thus, before starting it, it is necessary to draw some blood and analyze the complete blood count (CBC). Also, we must analyze CBCs weekly during the first 18 weeks. Other dyscrasias like leukopenia, leukocytosis, anaemia, eoshinophilia, thrombocythaemia or thrombocytopenia can also be observed. When agranulocytosis appears, it can be treated by discontinuing the clozapine treatment, but also using granulocyte-colony stimulating factor or lithium, both separated or combined with clozapine. Lithium produces reversible leukocytosis onceplasma levels of > 0.4 mmol/L are reached. Despite the simultaneous treatment with lithium, clozapine can trigger some neurological side effects, it seems that seizure risk remains invariable.ConclusionsSome of the clozapine's side effects, like neutropenia or agranulocytosis, are potentially lethal. Their treatment consists of discontinuing clozapine or initiating granulocyte-colony stimulating factor or lithium. These are good options that can give rise to a later continued treatment with clozapine.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Fernando, Tharushi, Ritesh Bhandarkar, and Graham Meadows. "Clinical Audit of Clozapine Prescribing Practice and Monitoring Process in an Australian Community Mental Health Service." BJPsych Open 8, S1 (June 2022): S4—S5. http://dx.doi.org/10.1192/bjo.2022.83.
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AimsClozapine, a well-established treatment of choice for treatment-resistant schizophrenia is known to reduce suicidality, lessen the risk of tardive dyskinesia and reduce relapse risk. It contributes to a higher quality of life by reducing cognitive clouding. Patients taking Clozapine have improved social and work functioning. But Clozapine's significant side effects require regular, intense monitoring to minimize mortality and morbidity. To improve current practice of clozapine prescribing and monitoring, a systematic audit of service practices against guidelines of local hospital / Monash Health Clozapine patient management guidelines and the Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines will identify any deficits and inform measures to overcome them.MethodsAn audit was conducted to compare the current clozapine prescribing practice and monitoring process compared with local hospital / Monash Health Clozapine patient management guidelines and RANZCP clinical practice guidelines among clozapine prescribed patients in an Australian community mental health service.ResultsMedical records of thirty-three eligible adult patients on clozapine were audited. All the patients were prescribed dosages within the recommended daily clozapine range. Clozapine was used for appropriate indications (treatment of treatment resistant-schizophrenia or schizoaffective disorder). Of the 33 patients, clozapine level was subtherapeutic on 54.5% of patients. 54.5% of patients were on an adjunct psychotropic with clozapine. Aripiprazole and sodium valproate were used by eight patients each, and nine patients were identified using selective serotonin reuptake inhibitors. The most common side effect was hypersalivation (57.6%), followed by weight gain (39.4%), sedation (21.2%) and constipation (12.1%). Monthly weight monitoring, physical examination, medical officer monthly review and full blood examination, at 97% compliance met these standards. However, monitoring of Body Mass Index (BMI) (66.7%) and six-monthly consultant reviews (42.4%) showed poor compliance (<70%) with the standards. Most metabolic blood investigations were in moderate compliance (70–90%) except for relatively high compliance for lipid profile (90.1%). Monitoring cardiac functions by echocardiogram were only 75.8% met the standard.ConclusionMost patients in this clinic receive recommended monthly monitoring practice but for BMI monitoring, six-monthly consultant review, most blood investigations and annual or 2 yearly echocardiogram findings indicated need for improvement. Polypharmacy of psychotropics increases the side effect burden and further increases the need to closely monitor the physical health and prescriptions of this cohort of patients. The next stage of this project will involve a codesign approach to developing a response to these findings that will be outlined here.
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Dickson, Ruth A., Richard Williams, and J. Thomas Dalby. "The Clozapine Experience from a Family Perspective." Canadian Journal of Psychiatry 40, no. 10 (December 1995): 627–29. http://dx.doi.org/10.1177/070674379504001010.
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Objective To examine how the lives of family members of clozapine-treated patients with schizophrenia have been affected by this treatment. Methods Through the use of a questionnaire and an interview of family members, this qualitative study focused on the families' perceptions of change in their family member and the impact on the family unit. Results Fourteen patients and their family members participated. The family interview was conducted an average of 1.78 years after clozapine inititation (range 0.58 years to 3.73 years). Global ratings of behavioural change were positively and significantly correlated between all raters: patients, family members, and clinicians. Family members were positive about clozapine's effect on their relatives and the impact on the family. Conclusion A positive response to clozapine decreases the burden on the family. This is in part the result of a decreased need for rehospitalization.
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Muñoz-Manchado, L. I., F. González-Saiz, J. I. Pérez-Revuelta, N. Laherrán-Cantera, and R. J. Pardo-Velasco. "Analysis of the predictive potential of good clinical response of plasma levels of clozapine in patients with resistant schizophrenia in an area of southern Spain." European Psychiatry 66, S1 (March 2023): S446. http://dx.doi.org/10.1192/j.eurpsy.2023.959.
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IntroductionResistant schizophrenia is a schizophrenia subtype characterized by a non-ability to respond to an appropriate antipsychotic treatment in dosage and duration by the patients. These patients show a lower prognostic and symptomatology. The unique drug which has shown efficacy for resistant schizophrenia treatment is clozapine, which is effective in suicide and aggressive behaviour prevention too. Whereas clozapine has numerous and serious adverse effects such as agranulocytosis risk. Because of this, and for guaranteeing an accurate diagnosis of resistant schizophrenia, distinguishing this from pseudo-resistance due to a poor tracing of schizophrenia, clozapine’s plasmatic levels monitoring is recommended in Spain by many clinical practise-guidelines.ObjectivesThis studio has the objective of determining if altered clozapine’s plasmatic levels have predictive potential of therapeutical response and answering what clinical and sociodemographic variables are associated to these anormal plasmatic levels.MethodsIn this work, a cross-sectional observational study was carried out in which clinical and sociodemographic data obtained by the Mental Health Unit of the Jerez de la Frontera University Hospital were collected within the research project entitled: "Role of social cognition as a factor psychosocial functioning of the schizophrenic patient” (ECOFUN), of all the participating patients (in total the sample was 141 patients, of which 40 are in treatment with clozapine).ResultsThe sample of patients has a mean age of 44 years and medium-high educational levels. The vast majority are men and do not currently consume substances of abuse, and when this consumption occurs, tobacco and alcohol are the most consumed substances. Their total scores on the PANSS and Markova Barrios scales are generally very disparate, but with average values of 55 and 16. It has been obtained as results that there is no significant statistical correlation between the plasma levels of clozapine and the values of the PANSS scale and its subscales in the patients. On the other hand, patients treated with clozapine would present clinical and sociodemographic characteristics practically identical to those of patients treated with other antipsychotics, especially their values on the PANSS scale. In addition, plasma levels of clozapine are correlated, although not significantly, with an improvement in the positive symptomatology of schizophrenia.ConclusionsAs a conclusion, unusually higher values of clozapine are correlated significantly with lower values in positive symptomatology in schizophrenia, but plasmatic levels are not correlated significantly with values of PANSS scale.Disclosure of InterestNone Declared
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&NA;. "Clozapine see Imipramine/clozapine." Reactions Weekly &NA;, no. 309 (July 1990): 4. http://dx.doi.org/10.2165/00128415-199003090-00013.
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Remington, Gary J., Donald Addington, Evan J. Collins, Barry D. Jones, Pierre Lalonde, Duncan J. MacCrimmon, and G. William MaCewan. "Clozapine: Current Status and Role in the Pharmacotherapy of Schizophrenia." Canadian Journal of Psychiatry 41, no. 3 (April 1996): 161–66. http://dx.doi.org/10.1177/070674379604100306.
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Objective: This study evaluates clozapine and its present role in the pharmacotherapy of schizophrenia. Method: Clozapine's current clinical status is reviewed, as is its position with respect to other treatment options. Results: Clozapine represents the prototype of “atypical” neuroleptics, with evidence of clinical efficacy in both positive and negative symptoms, as well as a diminished risk of extrapyramidal side effects. It is the only neuroleptic to date that has established itself as having little, if any, risk of tardive dyskinesia. More recent research has focused on its potential for overall savings in health care costs, as well as possible benefits in the area of neuropsychological functioning. Conclusion: Evidence suggesting that the course of schizophrenia can be altered by effective treatment favours a systematic approach that optimizes treatment options. While clozapine does not represent a 1st-line agent because of its risk of agranulocytosis, it has an integral role to play in treatment-resistant schizophrenia or in individuals experiencing intolerable side effects with conventional neuroleptics. Objectif: La présente étude vise à évaluer la clozapine et son rôle actuel dans la pharmacothérapie de la schizophrénie. Méthode: On évalue l'emploi clinique actuel de la clozapine ainsi que sa position par rapport à d'autres options de traitement. Résultats: La clozapine constitue le prototype des neuroleptiques «atypiques,» révélant une efficacité clinique autant sur les symptômes positifs que négatifs ainsi qu'un risque réduit d'effets secondaires extrapyramidaux. Elle constitue le seul neuroleptique à ce jour associé à peu, voire pas du tout, de risque de dyskinésie tardive. De récentes recherches se sont penchées sur son potentiel d'économies globales en soins de santé ainsi que sur ses avantages en matière de fonctionnement neuropsychologique. Conclusion: L'information qui suggère que l'évolution de la schizophrénie peut être modifiée par un traitement efficace encourage une approche systématique optimisant les options de traitement. Bien que la clozapine ne soit pas un médicament d'élection étant donné le risque d'agranulocytose, elle joue un rôle important dans le traitement de la schizophrénie résistante au traitement ou chez les personnes pour qui les effets secondaires des neuroleptiques conventionnels sont intolérables.
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Edinoff, Amber N., Emily Sauce, Carolina O. Ochoa, Jordan Cross, Mark Cogburn, Elyse M. Cornett, Adam M. Kaye, Alex D. Pham, and Alan D. Kaye. "Clozapine and Constipation: A Review of Clinical Considerations and Treatment Options." Psychiatry International 2, no. 3 (September 1, 2021): 344–52. http://dx.doi.org/10.3390/psychiatryint2030026.
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Psychosis, a break in reality which is manifested as hallucinations, delusions or the disruption in thought process, is the hallmark of schizophrenia. Despite novel pharmacotherapy advancements of antipsychotic medications that have resulted in some patients having the ability to return to social settings and thereby decreasing psychotic symptoms and reducing hospital admissions, there is still a sub-population of patients who remain symptomatic. Treatment-resistant schizophrenia is defined as failure of treatment with at least two different antipsychotics with the proper length of treatment and titration. Clozapine has been heralded as a drug to resolve the puzzle of treatment-resistant schizophrenia. Clozapine has one side effect that is well known, being the development of agranulocytosis. However, there is another side effect that can limit clozapine’s use and can also be life-threatening. Recently, at the end of January 2020, the FDA issued a communications statement which “[strengthened] an existing warning that constipation caused by the schizophrenia medicine clozapine can, uncommonly, progress to serious bowel complications.” After identifying ten cases of constipation from between 2006 to 2016 that progressed to hospitalization, surgery, and even death, the FDA focused their attention on this often overlooked, common side effect, especially when considering the strong anticholinergic effects of clozapine. Although patients are screened by their physicians for agranulocytosis by weekly lab monitoring, constipation is also a complication that needs to be identified and treated. Much like opioid-induced constipation, constipation can also be reduced with the use of laxatives and reduction in the co-prescribing of anticholinergic therapies with clozapine.
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Shih, Yu-Ju, Ching-Hua Lin, and Li-Shiu Chou. "The factors associated with clozapine polypharmacy for schizophrenia patients discharged from a large public psychiatric hospital in Taiwan, 2006–2021." Medicine 103, no. 51 (December 20, 2024): e40897. https://doi.org/10.1097/md.0000000000040897.
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Clozapine treatment continues to be recognized as the gold standard for managing treatment-resistant schizophrenia. Combining clozapine with other antipsychotics (i.e., clozapine polypharmacy) has emerged as an option for clozapine-resistant schizophrenia. We aimed to investigate the factors associated with clozapine polypharmacy in schizophrenia patients discharged on clozapine from a public psychiatric hospital. The analysis included patients with schizophrenia who were discharged between 2006 and 2021 and prescribed clozapine upon discharge. All patients were divided into 2 groups: clozapine monotherapy and clozapine polypharmacy. Multivariate logistic regression was used to identify factors associated with clozapine polypharmacy. A total of 1396 (42.7%) schizophrenia patients discharged on clozapine polypharmacy. In a multivariate logistic regression model, the clozapine polypharmacy was more likely to be male gender, to be younger, to be earlier age of onset, to have a greater number of previous hospitalizations, to have a shorter length of hospital stay, and to have a lower clozapine daily dose. The prevalence of clozapine significantly increased from 22.4% in 2006 to 50% in 2021. Compared with clozapine monotherapy, clozapine polypharmacy was associated with male gender, younger, earlier age of onset, a greater number of previous hospitalizations, shorter length of hospital stay, and lower clozapine daily dose. The utilization of clozapine polypharmacy has seen a significant increase over time. Further research is necessary to clarify its efficacy, safety, and overall risk/benefit ratio.
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de Leon, Jose, Can-Jun Ruan, Hélène Verdoux, and Chuanyue Wang. "Clozapine is strongly associated with the risk of pneumonia and inflammation." General Psychiatry 33, no. 2 (April 2020): e100183. http://dx.doi.org/10.1136/gpsych-2019-100183.
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Clinicians need to remember that (1) systemic inflammations can increase clozapine level; (2) clozapine, by itself, can cause inflammation, particularly during titration that is too rapid for that patient; (3) clozapine may increase the risk of infection; and (4) more specifically, clozapine may be particularly strongly associated with the risk of pneumonia. Pneumonia appears to be associated with high mortality in clozapine patients around the world. Clinicians who are alert to the risk of pneumonia in clozapine patients may significantly decrease mortality in clozapine patients. There is no data on COVID-19 infections in clozapine patients, but based on what we know about clozapine pharmacology, we can hypothesise that clozapine, possibly by impairing immunological mechanisms, may increase the risk of pneumonia in infected patients. More importantly, once fever and/or pneumonia develops, the clozapine dose should be cut in half to decrease the risk of clozapine intoxication. If there is any doubt that in spite of halving the dose there are still signs of clozapine intoxication, completely stopping clozapine may be indicated. Once the signs of inflammation and fever have disappeared, the clozapine dose can be increased to the prior dosage level.
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de Leon, Jose, Violet Henighan, Joseph K. Stanilla, and George M. Simpson. "Clozapine Levels After Clozapine Discontinuation." Journal of Clinical Psychopharmacology 16, no. 2 (April 1996): 193–94. http://dx.doi.org/10.1097/00004714-199604000-00016.
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lu, Hatice, i. kc, Canan l, and Yasemin ek. "Potential Indicators of Bone Marrow Suppression in Patients with Schizophrenia Receiving Clozapine: Platelet-Large Cell Ratio and Immature Granulocytes." Psychiatry and Behavioral Sciences 14, no. 4 (2024): 140. http://dx.doi.org/10.5455/pbs.20240301055535.
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Aim/background: The use of clozapine is restricted due to its serious side effects, particularly bone marrow suppression, which occurs at an average rate of 1%. These side effects are markedly related to blood concentrations of clozapine and its metabolite nor-clozapine. Therefore, therapeutic drug monitoring is recommended for clozapine. Currently, laboratory monitoring of bone marrow suppression includes neutrophil count follow-up. However, using early-changing biomarkers may be more effective in detecting and preventing this side effect before neutropenia develops. Therefore, we aimed to evaluate serum clozapine and nor-clozapine levels and their relationship with early parameters reflecting bone marrow activity in complete blood count (CBC), immature granulocyte (IG) for neutrophils, mean platelet volume (MPV) and platelet-to-large cell ratio (P-LCR) for platelets in patients with schizophrenia receiving clozapine. Methods: Fifty-one patients with schizophrenia receiving clozapine were included in the study. Of these, 49% (n=25) were on a low dose (<300 mg/day), 49% (n=25) on a middle dose (300-600 mg/day), and one patient was on a high dose (>600 mg/day) clozapine. CBC parameters—especially IG, MPV and P-LCR—and serum clozapine/nor-clozapine levels along with clozapine doses were recorded on the same day. The relationship between serum drug concentrations and CBC parameters was evaluated separately for the total patients and dose groups. Results: There was no correlation between clozapine dose and serum clozapine or nor-clozapine concentrations. None of the patients had neutropenia or agranulocytosis. Serum clozapine and nor-clozapine levels negatively correlated with P-LCR (r=-0.402, p=0.006 and r=-0.465, p=0.001, respectively) and MPV (r=-0.294, p=0.036 and r=-0.397, p=0.004, respectively); positively correlated with neutrophil (r=0.381, p=0.011 and r=0.387, p=0.009, respectively) and IG counts (r=0.346, p=0.018 and r=0.335, p=0.023, respectively); but not with other CBC sub-parameters. Although the clozapine dosing differed between the two groups, the serum levels of clozapine and nor-clozapine were not significantly different (p=0.078 and p=0.058, respectively). Furthermore, in the middle dose group, serum clozapine and nor-clozapine levels were negatively correlated with P-LCR (rho=-0.547, p=0.007 and rho=-0.636, p=0.001, respectively), consistent with the total group. Conclusion: Monitoring early biomarkers reflecting bone marrow activity, such as P-LCR for platelets and IG for neutrophils, alongside serum clozapine and nor-clozapine levels, is promising for predicting and preventing bone marrow suppression in patients receiving clozapine, thereby protecting against this serious side effect. However, our findings need to be supported by further research.
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Buckley, Peter F., Philip Cola, Mitsuru Hasegawa, Christine Lys, and Paul Thompson. "Clozapine plasma levels and dosing strategies in patients with treatment-refractory schizophrenia." Irish Journal of Psychological Medicine 14, no. 3 (September 1997): 85–88. http://dx.doi.org/10.1017/s0790966700003165.
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AbstractObjective: To determine the effect on clinical response to clozapine of increasing the plasma levels of clozapine and its major metabolite N-desmethylclozapine in 19 patients with schizophrenia who had plasma clozapine levels ≤ 370ng/ml, a level previously determined to identify patients who were unlikely to have an adequate response to clozapine.Method: The dosage of clozapine was increased by 20% in 11 patients and left unaltered in the other eight patients. Clozapine and N-desmethylclozapine plasma levels were measured after six weeks at the higher dose.Results: Nine of the 11 patients in whom clozapine dosage was increased subsequently achieved plasma clozapine levels ≥ 370ng/ml. However, in this group of patients who already had partially responded to clozapine, increasing the dosage of clozapine did not produce additional clinical improvement.Conclusion: Clozapine plasma levels are useful in clinical practice to guide dosage strategies. However, these results suggest that increasing the dosage of clozapine to achieve plasma levels ≥ 370ng/ml is unlikely to produce further improvement in patients who have already achieved a partial response to clozapine at plasma levels ≤ 370ng/ml.
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Taylor, D., L. Shapland, G. Laverick, J. Bond, and J. Munro. "Clozapine – a survey of patient perceptions." Psychiatric Bulletin 24, no. 12 (December 2000): 450–52. http://dx.doi.org/10.1192/pb.24.12.450.
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Aims and MethodWe aimed to find out how patients on clozapine felt about clozapine treatment. A structured questionnaire was given to 1284 consecutive patients attending 27 clozapine clinics in the UK.ResultsThe response rate was 44.4% (570 forms returned). This cohort of responders to the questionnaire consisted, for the most part, of Caucasian males who had been taking clozapine for more than 2 years. Respondents expressed largely favourable views on clozapine treatment. For example, 86.1% claimed to feel better on clozapine and 88.6% claimed to prefer to remain on clozapine than to change to another drug. Many patients stated that they disliked having to undergo blood testing, but a large majority (87.0%) felt that the advantages of clozapine outweighed disadvantages. All other responses supported this overall favourable view of clozapine therapy.Clinical ImplicationsPatients stabilised on clozapine are largely content with their treatment. These results suggest that clozapine is effective as assessed by patients' own standards and that adherence to therapy is likely to be good.
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Jagota, Gopika, and Sandeep Grover. "Clozapine Withdrawal Catatonia: A Case Series and Review of Literature." Annals of Indian Psychiatry 8, no. 3 (June 20, 2024): 246–54. http://dx.doi.org/10.4103/aip.aip_177_23.
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Background: Catatonia has been reported with withdrawal of medications. Among the various psychotropics, clozapine has been implicated to cause catatonia when abruptly withdrawn. The data regarding clozapine withdrawal catatonia are scarce and are mostly available in the form of case reports and series. Aim: In this case series, we present three cases of clozapine withdrawal catatonia and review the available literature on clozapine withdrawal clozapine. Results: All the three patients developed catatonia within 48 h to 14 days of stoppage of clozapine in the doses of 100–350 mg/day. Two of the patients experiencing clozapine withdrawal improved with reinstitution of clozapine in the previous doses along with benzodiazepines. However, one patient additionally required electroconvulsive therapy (ECT) for the management of withdrawal catatonia. A review of literature showed that clozapine withdrawal catatonia has male preponderance and has been reported with withdrawal of clozapine doses of 50–550 mg/day. The catatonia usually starts in 48 h to 2 weeks of stopping clozapine. Available literature suggests that most of the patients have been managed with restarting of clozapine, along with lorazepam and occasional patients require ECT. Conclusions: To conclude our case series and the available review of literature suggests that sudden discontinuation of clozapine can lead to withdrawal catatonia. Our cases also highlight the importance of reviewing treatment history, especially of abrupt discontinuation of clozapine when a patient on clozapine present with catatonia. This can be very helpful in deciding about further management.
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Gessner, Brooke, Michelle Carter, Alberto Almeida, Colleen Borralho, Kiana Rahnama, Tamara Mihic, Joan C. Y. Ng, Joseph H. Puyat, Angela Russolillo, and Katelyn C. Halpape. "Clozapine clinical toolkit optimizes inpatient clozapine monitoring." Mental Health Clinician 14, no. 2 (April 1, 2024): 85–91. http://dx.doi.org/10.9740/mhc.2024.04.085.
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Abstract Introduction Clozapine is the most effective antipsychotic in the management of treatment-resistant schizophrenia; however, its use is challenging due to the risk of severe adverse effects. Despite the risks associated with clozapine, there is no mandatory monitoring in Canada beyond hematologic testing for agranulocytosis surveillance. This study focuses on the development, implementation, and evaluation of a clozapine clinical toolkit (CTK) targeted at optimizing inpatient clozapine use. Methods A comprehensive literature review was conducted to identify clozapine best practices, experts were consulted, and a comprehensive clozapine CTK was developed and implemented at a large Canadian tertiary hospital in December 2018. To evaluate the CTK, a retrospective chart review was conducted to assess for change in guideline-concordant monitoring pre- and post- CTK implementation. Patients were included if they were &gt; 18 years of age and received clozapine during inpatient admission. Results were analyzed using descriptive and inferential statistics. Results Among the charts reviewed, 185 and 113 admissions met the pre- and post-CTK inclusion criteria, respectively. Staff used the CTK in the care of 96% of clozapine patients post implementation, and its use resulted in improvements in guideline-concordant monitoring for agranulocytosis and myocarditis. Discussion Implementation of the clozapine CTK increased the concordance of clozapine monitoring with best practice recommendations. Future research is necessary to assess the impact of the CTK on clinical outcomes and patient satisfaction.
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Jakobsen, Michelle Iris, H. Grønborg, H. V. Hansen, and A. Fink-Jensen. "Clozapine-associated neutropenia following augmentation with sodium valproate." SAGE Open Medical Case Reports 9 (January 2021): 2050313X2110197. http://dx.doi.org/10.1177/2050313x211019791.
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Clozapine is gold standard for the management of treatment-resistant schizophrenia. It can offer life-changing symptom reduction where other antipsychotics have failed, and for these patients, treatment with clozapine should be maintained, if in any possible way. However, treatment with clozapine comes with a risk of developing potentially fatal adverse reactions, for example, severe neutropenia or agranulocytosis, in which case, treatment must be discontinued. Here, we present a case of clozapine-related neutropenia that commenced after the addition of sodium valproate. A subsequent re-challenge to clozapine resulted in severe neutropenia and led to the permanent cessation of clozapine treatment. The patient had been tolerating clozapine for more than a year before the addition of sodium valproate. The awareness of an interaction between clozapine and sodium valproate could help reduce the risk of clozapine-induced neutropenia and subsequent clozapine discontinuation.
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Griffiths, Kira, Edward Millgate, Alice Egerton, and James H. MacCabe. "Demographic and clinical variables associated with response to clozapine in schizophrenia: a systematic review and meta-analysis." Psychological Medicine 51, no. 3 (February 2021): 376–86. http://dx.doi.org/10.1017/s0033291721000246.
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AbstractClozapine is the only licensed pharmacotherapy for treatment-resistant schizophrenia. However, response to clozapine is variable. Understanding the demographic and clinical features associated with response to clozapine may be useful for patient stratification for clinical trials or for identifying patients for earlier initiation of clozapine. We systematically reviewed the literature to investigate clinical and demographic factors associated with variation in clozapine response in treatment-resistant patients with schizophrenia spectrum disorders. Subsequently, we performed a random-effects meta-analysis to evaluate differences in duration of illness, age at clozapine initiation, age of illness onset, body weight and years of education between clozapine responders and non-responders. Thirty-one articles were eligible for qualitative review and 17 of these were quantitatively reviewed. Shorter duration of illness, later illness onset, younger age at clozapine initiation, fewer hospitalisations and fewer antipsychotic trials prior to clozapine initiation showed a trend to be significantly associated with a better response to clozapine. Meta-analysis of seven studies, totalling 313 subjects, found that clozapine responders had a significantly shorter duration of illness compared to clozapine non-responders [g = 0.31; 95% confidence interval (CI) 0.06–0.56; p = 0.01]. The results imply that a delay in clozapine treatment may result in a poorer response and that a focus on prompt treatment with clozapine is warranted.
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Stark, Anne, and James Scott. "A review of the use of clozapine levels to guide treatment and determine cause of death." Australian & New Zealand Journal of Psychiatry 46, no. 9 (February 10, 2012): 816–25. http://dx.doi.org/10.1177/0004867412438871.
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Objective: To review the literature to examine the use of clozapine levels to (i) guide therapy and prevent toxicity in clinical care and (ii) determine cause of death in post-mortem examination of patients who were treated with clozapine. Methods: MEDLINE was searched in December 2010 using the following keywords: ‘clozapine levels’, ‘clozapine and toxicity’, ‘clozapine and death’, ‘clozapine and mortality’ and ‘post-mortem redistribution’. Data was also collected from the 2010 MIMS Annual. Results: The literature reported significant variation in clozapine levels attained with any given dose, and considerable variability in the clinical response achieved at any given clozapine level. The lowest effective clozapine levels ranged from 250 to 550 µg/L, while the recommended upper limit to prevent toxicity varied from 600 to 2000 µg/L. There was minimal correlation between clozapine levels and side effects, with the exception of sedation, hypotension and seizure activity. The risk of seizures increased with plasma clozapine levels greater than 600 µg/L or rapid upward titration. In addition to prescribed dose, there are many factors that influence plasma clozapine levels. After death, the process of post-mortem drug redistribution resulted in 3.00 to 4.89 times increases in clozapine levels in central blood vessels and 1.5 fold increases in peripheral vessels compared to ante-mortem levels. Conclusions: The exact range of clozapine levels that corresponds to toxicity remains unclear. However, levels between 350 µg/L and 1000 µg/L achieved with gradual upward titration are more likely to be effective and less likely to cause toxicity. Ongoing clozapine level monitoring is indicated, especially when (i) prescribing higher doses (> 600 mg/day) of clozapine, (ii) there has been a change in a patient’s concomitant pharmacotherapy or cigarette use and (iii) there has been a suboptimal response to treatment. The use of post-mortem clozapine levels to determine clozapine toxicity as a cause of death is unreliable.
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Goudie, Andrew J., Gillian D. Cooper, Jon C. Cole, and Harry R. Sumnall. "Cyproheptadine resembles clozapine in vivo following both acute and chronic administration in rats." Journal of Psychopharmacology 21, no. 2 (March 2007): 179–90. http://dx.doi.org/10.1177/0269881107067076.
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Cyproheptadine is a cheap, widely available anti-allergy drug with a broad receptor binding profile which resembles that of clozapine. In rats discriminating clozapine from vehicle cyproheptadine mimicked clozapine very closely. Acutely it induced full generalization in the absence of response suppression, as observed with clozapine. Chronic administration of clozapine and cyproheptadine induced tolerance and cross-tolerance respectively to the clozapine stimulus. This was characterized by circa 3.5-fold parallel shifts to the right in the clozapine generalization curves. Such tolerance and cross-tolerance was spontaneously reversible, suggesting that it was pharmacodynamic, and that clozapine and cyproheptadine induce similar neuroadaptations when administered chronically. Administration of chlordiazepoxide at a very high dose induced no cross-tolerance to the clozapine stimulus showing the pharmacological specificity of tolerance. The clozapine stimulus is a compound cue involving actions at various receptors, and various clozapine-like antipsychotic (APD) drugs generalize fully to it. These data demonstrate that in vivo cyproheptadine resembles clozapine both acutely and chronically. Our findings, in conjunction with other actions of cyproheptadine - induction of weight gain, alleviation of clozapine withdrawal, anxiolytic actions, alleviation of ‘typical’ APD-induced motoric side effects, and some preliminary clinical findings - suggest that further study of cyproheptadine in conjunction with a ‘typical’ APD for the possible treatment of schizophrenia is merited at both pre-clinical and clinical levels.
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Chtibi, M., H. Zarouf, I. Hanine, S. Belbachir, and A. Ouanass. "Ultra-Resistant Schizophrenia Comorbid with Temporal Epilepsy: A Case Report." Scholars Journal of Medical Case Reports 11, no. 09 (September 6, 2023): 1603–7. http://dx.doi.org/10.36347/sjmcr.2023.v11i09.009.
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Resistant schizophrenia is a significant public health issue due to high treatment costs and institutional dependence of patients. Despite the various definitions currently available to define resistant schizophrenia, along with existing clinical guidelines, their impact on daily clinical practice remains limited. While clozapine has been endorsed by national clinical guidelines, its utilization remains suboptimal, with delays in initiation and instances of ineffectiveness. Ultra-resistant schizophrenia is defined by clozapine's inefficacy even after a well-conducted treatment. The relationship between epilepsy and epilepsy-related psychoses is intricate. Individuals with epilepsy are more likely to develop psychotic disorders, while those suffering from primary psychotic disorders also have an increased risk of epilepsy. These findings suggest the presence of shared predisposing factors. We present the case of a patient with clozapine-resistant schizophrenia associated with temporal epilepsy.
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Ktari, H., A. Ouertani, S. Madouri, A. Aissa, Y. Zgueb, U. Ouali, and R. Jomli. "Clozapine cessation." European Psychiatry 65, S1 (June 2022): S730. http://dx.doi.org/10.1192/j.eurpsy.2022.1884.
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Introduction Approximately 30% of individuals diagnosed with schizophrenia suffer from treatment-resistant or refractory schizophrenia. The gold standard for treatment is clozapine. However, a significant number of patients discontinue clozapine treatment and this carries a poor prognosis. Objectives This study explores patients’ motives for cessation of clozapine therapy and its prevalence. Methods A longitudinal, retrospective and descriptive study on a period of 20 years, at the psychiatry department A of the Razi hospital in Tunisia. Data was collected from the medical files of patients trated by clozapine using a pre-established sheet. Results The studied sample included 64 patient records. Treatment with clozapine was stopped spontaneously or following a medical decision in 37 patients (57.8%). The total number of clozapine stops in these 37 patients was 70. Indeed, each one of these patients had stopped treatment at least once. Clozapine was discontinued by some patients in the study sample for poor compliance(45.9%), for adverse side effects of treatment (16.2%) and by treating physicians for poor response treatment (8.1%). Clozapine was discontinued by 11 patients for hematological adverse reactions, representing 27.9% of the total number of clozapine discontinuations. Withdrawal of clozapine was indicated in 2 cases of agranulocytosis(18.2%), in 2 cases of moderate neutropenia(18.2%), in 3 cases of eosinophilia (27.2%), in 3 cases of thrombocytopenia (27.2%) and in 1 case of severe anemia (9.2%). Conclusions Clozapine discontinuation was essentially caused by poor patients’ observation and hematological adverse reactions appearance.Future research should seek to further investigate clozapine cessation factors in order to better benefit from the medical virtues of this molecule. Disclosure No significant relationships.
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Bonany, J. Marti, E. Pérez Sánchez, M. Pérez Carre, M. I. Martínez Casamitjana, J. R. Fortuny Olive, C. Macias Castellví, E. Carrió Diez, F. Lana Moliner, and R. Sánchez González. "Elevated clozapine levels in patients with COVID-19 infection." European Psychiatry 64, S1 (April 2021): S299. http://dx.doi.org/10.1192/j.eurpsy.2021.803.
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IntroductionClozapine is the most effective antipsychotic for treatment resistant schizophrenia. In patients treated with clozapine, COVID-19 infection may result in complications including an increased risk of pneumonia, clozapine toxicity, and disruption to clozapine treatment by COVID-19 induced lymphopenia.ObjectivesWe report 5 cases of elevated clozapine levels occurring in patients with COVID-19 infection who had been previously managed for several years on stable doses.MethodsSubjects: 48 admitted patients to a long-stay psychiatric unit. COVID-19 infection confirmed by positive nasopharyngeal swab for viral ribonucleic acid of SARS-CoV-2. Hematological controls between March and April 2020.Results16 patients (33%) treated with clozapine.18 patients (37’5%) had COVID-19 infection, of which 5 (10’4%) were treated with clozapine. Results are presented in table 1. Increases in plasma clozapine levels were observed in all cases (49’38 to 307.5%). We don’t have the clozapine levels of a patient who presented a pneumonia requiring admission and treatment in the general hospital. Two cases of neutropenia were observed, of which one had to discontinue treatment with clozapine. In the other three patients the dose of clozapine was reduced and they did not present haematological or intoxication complications that required further adjustments.ConclusionsCovid-19 infection is associated with increased serum clozapine levels by probably multifactorial mechanisms (systemic infection, reduced smoking). Importance of full clinical assessment of suspected COVID-19 infection in clozapine treated patients, including assessment clozapine level, and full blood count. The general recommendation is to reduce the dose of clozapine in this patients.