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Clozapine

Clozapine is an atypical antipsychotic medication used to treat schizophrenia, particularly in patients who have not responded well to other antipsychotic drugs.
It works by modulating the activity of neurotransmitters in the brain, such as dopamine and serotonin, to alleviate psychotic symptoms.
Clozapine has been shown to be effective in reducing the positive and negative symptoms of schizophrenia, and may also have neuroprotective effects.
However, its use is associated with a risk of serious side effects, including agranulocytosis, and requires close monitoring.
Reserach into optimizing clozapine treatment and improving its safety profile is an active area of investigation.

Most cited protocols related to «Clozapine»

1
Developing Consensus Criteria for Treatment-Resistant Schizophrenia
Cited 64 times
An iterative approach was adopted to develop criteria for treatment resistance in schizophrenia. Initially, a systematic review of definitions of treatment resistant schizophrenia used in clinical trials was conducted. A literature search of PubMed, PsycINFO, and Embase from January 1980 to January 2016 was undertaken using the search string: “(randomized or random or randomly) and (resistant or refractory or clozapine) and (schizophrenia)”. Titles and abstracts were reviewed to initially determine eligibility. The reference lists of each relevant paper were also searched, as were reference lists of relevant review papers, to further identify potential studies. Studies were included if they were randomized controlled trials of a pharmacological intervention in adults with treatment resistant schizophrenia. Studies were excluded if they were naturalistic, or purely of biomarkers such as neuroimaging measures, studies of adjuvant treatments or non-pharmacological interventions, studies of childhood onset or late onset schizophrenia.
The data extracted were: the prerequisites for previous antipsychotic treatment (requirements of different antipsychotics, minimum treatment duration, dose); the specified severity of symptoms; and whether there was a stipulation for resistance to be prospectively demonstrated. Additionally, whether criteria were operationalized or not was recorded. To be considered as operationalized, the study had to report criteria that met the following characteristics: 1) The use of a validated rating scale to determine symptom severity; 2) A specification of minimum symptom duration; and 3) A definition of adequate treatment that specified minimum dose, duration, and number of previous antipsychotics.
Subsequently, a working group - consisting of expert researchers and clinicians, scientists from the pharmaceutical industry and other specialists with experience and expertise in the area of schizophrenia - was identified by the co-chairs of the Treatment Response and Resistance in Psychosis working group (OH, JMK, CUC). This was augmented by attendees at TRRIP meetings held at international conferences in the field. Members of the final working group included researchers who had published recently in the field and researchers who attended the inaugural TRRIP meeting at the Schizophrenia International Research Society Biennial meeting in 2014. The working group mapped out the key criteria and operationalized them.
Second, members of the TRRIP working group were contacted and invited to take part in an on-line survey to identify key areas of agreement and disagreement. The survey was developed by the TRRIP co-chairs and modified with input from TRRIP work group members. In its final version (see Appendix 1), the survey was conducted using SurveyMonkey (www.surveymonkey.com). 48 researchers and clinicians were invited by email to take part in the survey. Over the 30-day collection period, 29 responses (60%), covering 13 countries, were received to the on-line survey; 3 (10%) responses were incomplete. See supplementary information for a summary of the responses to individual items. These responses were synthesized and refined during subsequent discussions amongst the whole group to derive the consensus recommendations for both minimum and optimum criteria.
Third, the working group met to consider and revise criteria for which there was a lack of consensus. The revised criteria were circulated to the TRRIP working group members, and presented as part of an open workshop at an international meeting in the field for further discussion, input and refinement. Finally, consensus was reached regarding this publication through review by all authors.
Howes O.D., McCutcheon R., Agid O., de Bartolomeis A., van Beveren N.J., Birnbaum M.L., Bloomfield M.A., Bressan R.A., Buchanan R.W., Carpenter W.T., Castle D.J., Citrome L., Daskalakis Z.J., Davidson M., Drake R.J., Dursun S., Ebdrup B.H., Elkis H., Falkai P., Fleischacker W.W., Gadelha A., Gaughran F., Glenthøj B.Y., Graff-Guerrero A., Hallak J.E., Honer W.G., Kennedy J., Kinon B.J., Lawrie S.M., Lee J., Leweke F.M., MacCabe J.H., McNabb C.B., Meltzer H., Möller H.J., Nakajima S., Pantelis C., Reis Marques T., Remington G., Rossell S.L., Russell B.R., Siu C.O., Suzuki T., Sommer I.E., Taylor D., Thomas N., Üçok A., Umbricht D., Walters J.T., Kane J, & Correll C.U. (2016). Treatment resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. The American journal of psychiatry, 174(3), 216-229.
Publication 2016
Adult Antipsychotic Agents ARID1A protein, human Biological Markers Clozapine Conferences Eligibility Determination Pharmaceutical Adjuvants Psychotic Disorders Schizophrenia Schizophrenia, Treatment-Resistant Specialists
2
Pharmacological Preparation and Administration
Cited 14 times
Clozapine was provided as a generous gift to J.H.P. from Novartis (Hanover, NJ, USA). Olanzapine was provided as a generous gift to J.H.P. from Eli Lilly (Indianapolis, IN, USA). Clozapine, olanzapine, and risperidone were supplied to D.W. by the National Institute of Mental Health’s Chemical Synthesis and Drug Supply Program. Haloperidol, prazosin, propranolol, and ritanserin were purchased from Sigma-Aldrich (St. Louis, MO, USA). J.H.P. and M.S.F. obtained CNO from the Rapid Access to Investigative Drug Program funded by the National Institute of Neurological Disorders and Stroke. D.W. obtained CNO from the National Institute on Drug Abuse Drug Supply Program.
Clozapine, olanzapine, risperidone, haloperidol, prazosin, propranolol, and ritanserin were each dissolved in distilled water with 2–3 drops of lactic acid and pH-adjusted to 6.0–7.0 with NaOH. For mouse drug discrimination studies, CNO was also dissolved in this vehicle. For rat drug discrimination studies and for mouse and rat pharmacokinetic analyses, CNO was dissolved in bacteriostatic saline containing v/v 2.5–5.0% dimethyl sulfoxide (Sigma-Aldrich) and 10% Cremophor EL (Sigma-Aldrich).
For mouse drug discrimination studies, all drugs were administered s.c. at a volume of 10 ml/kg, 30 min prior to session onset. For rat drug discrimination studies, all drugs were administered i.p. at a volume of 1 ml/kg. Clozapine was administered 60 min prior to session onset, while olanzapine, risperidone, prazosin, and propranolol were administered 30 min prior to session onset. CNO was tested at both 30 and 60 min pretreatment times. All drug doses are expressed as the salt weight.
Manvich D.F., Webster K.A., Foster S.L., Farrell M.S., Ritchie J.C., Porter J.H, & Weinshenker D. (2018). The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. Scientific Reports, 8, 3840.
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Publication 2018
Anabolism Clozapine cremophor EL Discrimination, Psychology Haloperidol Lactic Acid Mice, House Olanzapine Pharmaceutical Preparations Prazosin Propranolol Risperidone Ritanserin Saline Solution Sodium Chloride Sulfoxide, Dimethyl
3
Genetic Study of Treatment-Resistant Schizophrenia
Cited 11 times
We collected data on patients with schizophrenia (case group) in two waves, which we call (a) CLOZUK and (b) CardiffCOGS (Cardiff Cognition in Schizophrenia). The CLOZUK sample (n = 6558) consists of individuals taking the antipsychotic clozapine. In the UK, clozapine is reserved for patients with treatment-resistant schizophrenia, who provide regular blood samples to allow detection of adverse drug effects. Through collaboration with Novartis, the manufacturer of a proprietary form of clozapine, we acquired anonymised blood samples from people on clozapine. Participants (71% male) were aged 18-90, with a recorded diagnosis of treatment-resistant schizophrenia according to the clozapine registration forms completed by their psychiatrists. The use of these anonymised samples for genetic association studies was approved by the local ethics committee. The CLOZUK sample has been described elsewhere.21 (link) The CardiffCOGS (n = 571) is a sample of patients with clinically diagnosed schizophrenia recruited from community, in-patient and voluntary sector mental health services in the UK. Interview with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) instrument22 (link) and case-note review was used to arrive at a best-estimate lifetime diagnosis according to DSM-IV criteria.23
Rees E., Walters J.T., Georgieva L., Isles A.R., Chambert K.D., Richards A.L., Mahoney-Davies G., Legge S.E., Moran J.L., McCarroll S.A., O’Donovan M.C., Owen M.J, & Kirov G. (2014). Analysis of copy number variations at 15 schizophrenia-associated loci. The British Journal of Psychiatry, 204(2), 108-114.
Publication 2014
Antipsychotic Agents BLOOD Clozapine Cognition Diagnosis Genetic Association Studies Males Mental Health Services Patients Psychiatrist Regional Ethics Committees Schizophrenia Schizophrenia, Treatment-Resistant Substance Abuse Detection
4
Modeling Individual Treatment Effects
Cited 10 times

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Publication 2008
Clozapine Olanzapine Patients Perphenazine Pharmaceutical Preparations Quetiapine Risperidone Specimen Handling ziprasidone
5
Metabolic Side Effects of Antipsychotics
Cited 9 times
The meta-analysis was conducted and reported according to recommendations of the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group [36] (link). A review protocol was construed following the MOOSE guidelines. This was not published but only for internal use of this study.
A PubMed and Embase search was conducted for articles on metabolic side effect profiles of antipsychotic medication. The search term used was: ((“weight gain” OR “BMI” OR “7% weight”) AND (chlorpromazine OR haloperidol OR bromperidol OR fluphenazine OR zuclopenthixol OR pentixol OR flupentixol OR levopromazine OR perphenazine OR pimozide OR penfluridol OR sulpiride OR amisulpride OR amoxapine OR asenapine OR aripiprazole OR blonanserine OR clozapine OR iloperidone OR melperone OR olanzapine OR risperidone OR paliperidone OR quetiapine OR sertindole OR lurasidone OR ziprasidone)) NOT (addition OR additive OR adjunctive OR augmentation OR lithium OR valproate OR carbamazepine OR metformin OR topiramate OR ramelteon OR rimonabant OR modafinil OR sibutramine OR genetics OR pharmacokinetics OR vomiting OR nausea OR review OR “cognitive behavioural therapy” OR “cognitive behavioral therapy” OR delirium OR steroids OR ropinirole OR sleep OR “brain volume”)
Limits Activated: Humans, Clinical Trial, Randomized Controlled Trial, Clinical Trial, Phase IV, Controlled Clinical Trial, English, German, All Adult: 18+ years, Publication Date from 1999/01/01 to 2011/12/31.
Bak M., Fransen A., Janssen J., van Os J, & Drukker M. (2014). Almost All Antipsychotics Result in Weight Gain: A Meta-Analysis. PLoS ONE, 9(4), e94112.
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Publication 2014
Adult Amisulpride Amoxapine Antipsychotic Agents Aripiprazole asenapine Brain bromperidol Carbamazepine Chlorpromazine Clozapine Cognitive Therapy Delirium Drug Kinetics Drug Reaction, Adverse Flupenthixol Fluphenazine Haloperidol Homo sapiens iloperidone Lithium Lurasidone Metformin Methotrimeprazine metylperon Modafinil Nausea Olanzapine Paliperidone Penfluridol Perphenazine Pimozide Quetiapine ramelteon Rimonabant Risperidone ropinirole sertindole sibutramine Sleep Steroids Sulpiride Topiramate Valproate ziprasidone Zuclopenthixol

Most recents protocols related to «Clozapine»

1
Water-Soluble DREADD Agonist CNO Protocol
To avoid the use of the toxic solvent dimethyl sulfoxide (DMSO), which is typically used for the preparation of CNO products in concentrations of up to 15% (Campbell and Marchant, 2018 (link)), we opted for the use of a water-soluble salt preparation of CNO, CNO dihydrochloride (Tocris, Bio-Techne LTD, Abingdon, UK, catalog no.: 6329) dissolved in sterile saline. The dihydrochloride preparation of CNO undergoes less back-metabolism to clozapine but has a higher bioavailability compared to CNO-DMSO as indicated by pharmacokinetic work in rhesus macaques (Allen et al., 2019 (link)). This product has previously been used in sleep studies on mice at concentrations between 1 and 5 mg/kg (Fernandez et al., 2018 (link); Stucynski et al., 2021 (link)). For C21 injections we used the water-soluble version of DREADD agonist C21 (C21 dihydrochloride, Tocris, Bio-Techne LTD, Abingdon, UK, catalog no.: HB6124). We chose a dose of 3 mg/kg because a detailed pharmacokinetic assessment of this product at this specific concentration as well as behavioural testing in a five-choice serial-reaction-time task did not reveal any behavioural effects at this dose (Jendryka et al., 2019 (link)).
Traut J., Mengual J.P., Meijer E.J., McKillop L.E., Alfonsa H., Hoerder-Suabedissen A., Song S.H., Fehér K.D., Riemann D., Molnar Z., Akerman C.J., Vyazovskiy V.V, & Krone L.B. (2023). Effects of clozapine-N-oxide and compound 21 on sleep in laboratory mice. eLife, 12, e84740.
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Publication 2023
Clozapine Macaca mulatta Metabolism Mice, House Polysomnography Saline Solution Sodium Chloride Solvents Sterility, Reproductive Sulfoxide, Dimethyl
2
Restless Legs Syndrome and Dementia Risk
Chi-square for categorical variables and Mann–Whitney U test for continuous variables due to non-normality were used to compare the baseline characteristics between patients with RLS and RLS-free controls. Cox proportional hazards regression models were applied to explore the association between RLS and the risk of dementia after adjusting for age, sex, income, residence, CCI, and history of other comorbidities. Among the Cox regression models, we used the Fine–Gray subdistribution hazard model with mortality as a competing risk given the old age of the study population. The proportional hazard assumption was satisfied in our Cox model (Schoenfeld individual test p-value > 0.05).
Sensitivity analyses were performed using four different models. In model 1, dementia was defined as the prescription of anti-dementia medications (donepezil, rivastigmine, galantamine, and memantine) at least twice and a diagnosis of the ICD-code of dementia. Although these medications were approved for only AD (rivastigmine additionally for Parkinson’s disease dementia), they can be used for cognitive symptoms in other types of dementia based on recommendations from multiple guidelines [31 (link)–33 (link)]. The previous study revealed that the definition of all-cause dementia by ICD-10 code plus anti-dementia medications had a positive predictive value of 94.7% when reviewing the medical records of 972 patients in two hospitals [34 (link)]. In model 2, medication history was added to the ICD code to define RLS. Patients with RLS ICD-code (G25.8) who had taken dopamine agonists (ropinirole or pramipexole) twice or more were regarded as patients with RLS (n = 1458). In this sensitivity model, we excluded patients with Parkinson’s disease because they could also take dopamine agonists. In model 3, patients taking antipsychotic agents were excluded because the antidopaminergic property of antipsychotic agents could lead to a misdiagnosis of RLS (n = 2482). The following antipsychotic agents approved in South Korea were used in this study: haloperidol, sulpiride, chlorpromazine, perphenazine, pimozide, risperidone, olanzapine, quetiapine, paliperidone, amisulpride, aripiprazole, ziprasidone, clozapine, blonanserin, and zotepine. In model 4, patients with RLS only diagnosed by psychiatrists or neurologists were included (n = 1154) to preclude the possible misdiagnosis by non-expert physicians.
To evaluate the effect of dopamine agonists (pramipexole and ropinirole) on the development of dementia, the risk of dementia was compared after dividing RLS patients by dopamine agonist use. Patients with RLS who were prescribed pramipexole or ropinirole at least once were considered dopamine agonist users. All missing data were addressed using listwise deletion. Data processing and statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA). Statistical significance was set at a two-tailed p-value of < 0.05.
Kim K.Y., Kim E.H., Lee M., Ha J., Jung I, & Kim E. (2023). Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study. Alzheimer's Research & Therapy, 15, 46.
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Publication 2023
Age Groups agonists Amisulpride Antipsychotic Agents Aripiprazole blonanserin Chlorpromazine Clozapine Deletion Mutation Donepezil Dopamine Agonists Dopamine Effect Galantamine Haloperidol Hypersensitivity Memantine Neurobehavioral Manifestations Neurologists Olanzapine Paliperidone Parkinson Disease Patients Perphenazine Pharmaceutical Preparations Physicians Pimozide Pramipexole Prescription Drugs Presenile Dementia Psychiatrist Quetiapine Risperidone Rivastigmine ropinirole Sulpiride ziprasidone zotepine
3
Foraging Behavior Post-Predator Encounter
Mice completed two consecutive foraging sessions after the live predator encounter. These sessions were identical in structure to baseline foraging. No clozapine was administered in the foraging sessions post-live predator exposure.
Ly A., Barker A., Prévost E.D., McGovern D.J., Kilpatrick Z, & Root D.H. (2023). Bed Nucleus of the Stria Terminalis GABA neurons are necessary for changes in foraging behavior following an innate threat. bioRxiv.
Publication Preprint 2023
Clozapine Mice, House
4
Clozapine Modulation of Predator Avoidance
Mice were exposed to the robotic predator in a single session in the last trial, in which the food pellet was located 70cm away from the nesting zone. Mice were intraperitoneally injected with a behaviorally-subthreshold dose of clozapine (Caymen Chemical, 0.1mg/kg) to activate the hM4Di receptor at least 10 minutes before the foraging session. The robotic predator was positioned behind the 70cm mark where the food pellet was located. The trial ended after the mouse consumed the pellet and returned to the nesting zone or 5 minutes after the trial began with no successful consumption of the food pellet. Following 24hrs, mice completed two consecutive post-encounter foraging sessions without the presence of the robogator. These post-encounter sessions were identical in structure to baseline foraging. No clozapine was administered in the foraging sessions post-robotic predator exposure.
Ly A., Barker A., Prévost E.D., McGovern D.J., Kilpatrick Z, & Root D.H. (2023). Bed Nucleus of the Stria Terminalis GABA neurons are necessary for changes in foraging behavior following an innate threat. bioRxiv.
Publication Preprint 2023
Clozapine Food Mice, House
5
Clozapine Modulates Foraging Under Predation
After a return to baseline foraging, mice were exposed to a live predator in a single session in the last trial, in which the food pellet was located 70cm away from the nesting zone. Mice were intraperitoneally injected with clozapine (0.1mg/kg) at least 10 minutes before the foraging session. The live predator was positioned behind the 70cm mark with the small circular opening pointed towards the nesting zone. The trial ended after the mouse consumed the pellet and returned to the nesting zone or 5 minutes after the trial began with no successful consumption of the food pellet.
Ly A., Barker A., Prévost E.D., McGovern D.J., Kilpatrick Z, & Root D.H. (2023). Bed Nucleus of the Stria Terminalis GABA neurons are necessary for changes in foraging behavior following an innate threat. bioRxiv.
Publication Preprint 2023
Clozapine Food Mice, House

Top products related to «Clozapine»

1
Clozapine by Merck Group
Sourced in United States, United Kingdom, Germany, Sao Tome and Principe, Israel, Macao
Clozapine is a laboratory instrument used for the detection and quantification of the antipsychotic drug clozapine. It is designed to provide accurate and reliable measurements of clozapine concentrations in biological samples, such as blood or plasma.
2
Haloperidol by Merck Group
Sourced in United States, United Kingdom, Sao Tome and Principe, Germany, France, Japan, Spain
Haloperidol is a laboratory reagent used in various research and analytical applications. It is a butyrophenone-class antipsychotic drug that acts as a dopamine D2 receptor antagonist. Haloperidol is commonly used as a reference standard and in the development and validation of analytical methods.
3
Clozapine by Bio-Techne
Sourced in United Kingdom
Clozapine is a laboratory product manufactured by Bio-Techne. It is a tricyclic dibenzodiazepine compound used for research purposes.
4
Risperidone by Merck Group
Sourced in United States, United Kingdom, France, Germany
Risperidone is a medication used to treat various psychiatric conditions, including schizophrenia, bipolar disorder, and certain symptoms of autism. It is an antipsychotic drug that works by affecting the balance of certain natural substances in the brain.
5
Olanzapine by Merck Group
Sourced in United States, United Kingdom
Olanzapine is a pharmaceutical compound used as a laboratory standard in research and development. It is a white crystalline powder that is soluble in organic solvents. Olanzapine is commonly used as a reference substance in analytical and bioanalytical methods for the identification and quantification of related substances.
6
Aripiprazole by Merck Group
Sourced in United States
Aripiprazole is a laboratory reagent manufactured by Merck Group. It is a synthetic compound used in various research applications, including pharmaceutical development and biological studies. Aripiprazole functions as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors.
7
Dimethyl sulfoxide (dmso) by Merck Group
Sourced in United States, Germany, United Kingdom, China, Italy, Sao Tome and Principe, France, Macao, India, Canada, Switzerland, Japan, Australia, Spain, Poland, Belgium, Brazil, Czechia, Portugal, Austria, Denmark, Israel, Sweden, Ireland, Hungary, Mexico, Netherlands, Singapore, Indonesia, Slovakia, Cameroon, Norway, Thailand, Chile, Finland, Malaysia, Latvia, New Zealand, Hong Kong, Pakistan, Uruguay, Bangladesh
DMSO is a versatile organic solvent commonly used in laboratory settings. It has a high boiling point, low viscosity, and the ability to dissolve a wide range of polar and non-polar compounds. DMSO's core function is as a solvent, allowing for the effective dissolution and handling of various chemical substances during research and experimentation.
8
Sch23390 by Merck Group
Sourced in United States, United Kingdom
SCH23390 is a laboratory reagent used for scientific research. It is a specific antagonist of the D1 dopamine receptor, and is commonly used as a tool compound in neuroscience and biochemistry studies. The core function of SCH23390 is to selectively bind to and block the activity of the D1 dopamine receptor in in vitro and in vivo experimental settings.
9
Haloperidol by Bio-Techne
Sourced in United Kingdom, United States
Haloperidol is a laboratory reagent manufactured by Bio-Techne. It is a neuroleptic medication commonly used in research applications. The core function of Haloperidol is to act as a potent dopamine D2 receptor antagonist, which can be used to study dopaminergic signaling pathways and related biological processes.
10
Clozapine by Abcam
Sourced in United Kingdom
Clozapine is a laboratory product used for research purposes. It is a chemical compound with specific properties and functions, without providing any interpretation or extrapolation on its intended use.

More about "Clozapine"

Clozapine is an atypical or second-generation antipsychotic medication primarily used to treat schizophrenia, particularly in patients who have not responded well to other antipsychotic drugs like Haloperidol, Risperidone, Olanzapine, or Aripiprazole.
It works by modulating the activity of neurotransmitters in the brain, such as dopamine and serotonin, to alleviate positive and negative psychotic symptoms.
Clozapine has also shown neuroprotective effects and may have benefits for cognition.
However, the use of Clozapine is associated with a risk of serious side effects, including agranulocytosis, a potentially life-threatening condition.
This requires close monitoring of patients during treatment.
DMSO and SCH23390 are compounds that have been studied in relation to Clozapine, with potential applications in optimizing its treatment and improving its safety profile.
Researchers are actively investigating ways to enhance Clozapine therapy, such as developing better dosing protocols, identifying predictive biomarkers, and exploring adjunctive treatments.
Advanced tools like PubCompare.ai can help streamline this research by facilitating the discovery of the best protocols from literature, preprints, and patents, while promoting reproducibility and accuracy through intelligent analysis.