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Clozapine chronically suppresses alcohol drinking in Syrian golden hamsters. BMC Med. 2008;192:406411. NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure, Integrated neurobiology of bipolar disorder, The prevalence and burden of bipolar depression. CNS Drugs. Can J Psychiatry. 2016;41:89104. Diabetes Obes Metab. We conducted a systematic PRISMA-conforming quantitative meta-review of available meta-analytic evidence regarding clozapine use. Careers. 2010;123:225233. We extracted clozapine-specific meta-analytic data on effectiveness, efficacy, and tolerability of clozapine, management of clozapine, and clozapine-related adverse events. Vermeulen JM, van Rooijen G, van de Kerkhof M, Sutterland AL, Correll CU, de Haan L. Clozapine and long-term mortality risk in patients with schizophrenia: a systematic review and meta-analysis of studies lasting 1.112.5 years. Schizophr Bull. The site is secure. Clozapine's efficacy was similar to other antipsychotics (Mean difference (MD): 0.03 [95%CI: 0.86-0.92], p = 0.59) in manic episodes. Treatment options for clozapine resistance. Every-Palmer S, Newton-Howes G, Clarke MJ. 2019;53:403412. The quality of meta-analyses was evaluated using the AMSTAR-2 tool, which includes items for heterogeneity and publication bias, yet further exploration of their impact on meta-analytic estimates is out of the scope of this manuscript. When comparators are pooled as a group (FGA+SGA) clozapine was shown to have superior effects for treatment-resistant overall and positive symptoms [85, 106]. 2008;3:Cd005579. amisulpride, olanzapine, zotepine and risperidone in terms of overall symptoms [57]. more response or less adverse events/dropouts). 2007;17:165171. Medicina (Kaunas). Cochrane Database Syst Rev. Abbreviated study descriptions: Leucht et al., 2009a [76], Leucht et al., 2009b [76], Leucht et al., 2009c [79]. 2E). Interventions included clozapine monotherapy or clozapine combined with other medications. Li XH, Zhong XM, Lu L, Zheng W, Wang SB, Rao WW, et al. Prescribed for Bipolar. Schizophr Bull. Buchanan RW, Kreyenbuhl J, Kelly DL, Noel JM, Boggs DL, Fischer BA, et al. Unfortunately, the side effect profile limits clozapine's use at high doses. Bethesda, MD 20894, Web Policies EPS extrapyramidal symptoms, FGA first-generation antipsychotic, k number of studies, L long-term, M medium-term, n number of participants, RCT randomized-controlled trial, S short-term, SGA second-generation antipsychotic. Aust N Z J Psychiatry. For continuous outcomes, SMD>0 means a beneficial outcome for clozapine (e.g. More clinical studies and subsequent meta-analyses are needed beyond the application of clozapine in schizophrenia-spectrum disorders and future studies should be directed into multidimensional clozapine side-effect management to foster evidence and to inform future guidelines. Lieberman JA, Stroup TS, McEvoy JP, et al. 2019;13:1823. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Nevertheless, negative evidence for suicidal behavior and self-injurious behavior for clozapine vs. SGA in observational studies was also reported [82]. Ziprasidone versus other atypical antipsychotics for schizophrenia. J Clin Psychopharmacol 2007;27:2528. J Psychiatr Res. FGA first-generation antipsychotic, k number of studies, L long-term, M medium-term, n number of participants, RCT randomized-controlled trial, S short-term, SGA second-generation antipsychotic. 2019 Oct 1;76(10):1052-1062. doi: 10.1001/jamapsychiatry.2019.1702. 2009. p. 221235. Methods: Khushu A, Powney MJ. The methodological quality of meta-analyses was assessed using the AMSTAR-2 checklist. Conclusion: Fonseca de Freitas D, Kadra-Scalzo G, Agbedjro D, Francis E, Ridler I, Pritchard M, Shetty H, Segev A, Casetta C, Smart SE, Downs J, Christensen SR, Bak N, Kinon BJ, Stahl D, MacCabe JH, Hayes RD. Komossa K, Rummel-Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, et al. Quetiapine versus other atypical antipsychotics for schizophrenia. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology, The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long term treatment of bipolar disorder. Long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta-analysis of direct head-to-head comparisons. Results: 2019;18:208224. 2019;21:293302. 2019;17:174. van der Zalm YC, Termorshuizen F, Selten JP. The impact of clozapine on hospital use: a systematic review and meta-analysis. more response or less adverse events. Antipsychotic medication for childhood-onset schizophrenia. 2014 John Wiley & Sons A/S. Conclusion: For PDP, clozapine seems to be superior vs. quetiapine short-term in terms of clinical global impression with large effect sizes [51] (see Fig. Dzahini O, Singh N, Taylor D, Haddad PM. J Clin Psychiatry. 2022 Apr;36(4):498-506. doi: 10.1177/02698811221078746. Although clozapine lacks regulatory approval for use in any phase of BD, it has been shown to be useful in treatment-resistant BD (TRBD), decreasing the number of hospitalizations ( 1) and is associated with symptomatic and functional improvement ( 2 ). 2018;28:136070. Epub 2022 Feb 25. 2017. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Results: There is growing evidence that it has impact on course modifying processes which can change the course of disease leading to significant improvement, reducing the disease burden and become a transformative treatment in psychiatry. Neuropsychiatr Dis Treat. 2016;11:Cd009830. This work is published and licensed by Dove Medical Press Limited. The applied search strategy according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [19] is shown in Fig. 2020;19:120121. The evidence is mounting however, the molecular and epigenetic mechanisms underlying the therapeutic efficacy of clozapine in bipolar disorder have not yet been fully elucidated. Bergman H, Rathbone J, Agarwal V, Soares-Weiser K. Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia. Unauthorized use of these marks is strictly prohibited. Zhang Y, et al. Purpose. PLoS ONE. Then, meta-analyses were categorized into different domains according to their objectives, taking into consideration participant characteristics, comparisons, and outcomes. 2nd Edition. Nevertheless, definitions of TRS, typically involving two failed trials of different non-clozapine antipsychotics, differ significantly across guidelines [6] as do criteria for TRS in clinical trials: if TRS is operationalized at all, it differs in up to 95% of trials [7]. Schizophr Res. 3E and F). (see Fig. Zotepine versus other atypical antipsychotics for schizophrenia. 2010;7:e1000326. Clozapine is not superior to SGAs in observational studies [82], but to most FGAs in RCTs with both small and large effect sizes [48, 79, 125]except short-term data vs chlorpromazine [100, 128]. Of note, meta-analytic evidence for the efficacy of clozapine in suicidal symptoms is mainly from registry data and non-randomized trials, whereas to our knowledge, only one high-quality RCT [132] fosters the evidence and contributes to long-term RCT data [29]. Buhagiar K, Jabbar F. Association of first- vs. second-generation antipsychotics with lipid abnormalities in individuals with severe mental illness: a systematic review and meta-analysis. Interestingly, haloperidol did not induce similar synaptic changes suggests that the exceptional effect of clozapine could be related to changes in hippocampal plasticity.50 There is also evidence for clozapine-mediated significant changes in cell composition in white matter of primates, which could lead to a partial rewiring of prefrontal circuitry.51 According to Maletic and Raison,52 morphological changes like gray matter volume reduction and its hypofunction present in bipolar patients provide strong support for the hypothetical impairment of neuroplasticity in bipolar disorder. Vancampfort D, Stubbs B, Mitchell AJ, De Hert M, Wampers M, Ward PB, et al. Bastian H, Glasziou P, Chalmers I. Seventy-five trials and eleven systematic reviews a day: how will we ever keep up? 2012;38:167177. Despite guidelines, the drug is used in 1.5% of bipolar patients only. Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: a systematic review and meta-analysis. D Weight as dichotomous outcome. Nielsen RE, Levander S, Kjaersdam Tellus G, Jensen SO, stergaard Christensen T, Leucht S. Second-generation antipsychotic effect on cognition in patients with schizophreniaa meta-analysis of randomized clinical trials. Clozapine is an atypical antipsychotic used in treatment-resistant bipolar disorder. https://doi.org/10.1038/s41398-021-01613-2, DOI: https://doi.org/10.1038/s41398-021-01613-2. Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis. 2017;6:Cd009555. A double-blind comparison with chlorpromazine. The .gov means its official. Brain Sci. Early Interv Psychiatry. Pharmacological interventions for clozapine-induced sinus tachycardia. Serretti A, Chiesa A. Fornaro M, Carvalho AF, Fusco A, Anastasia A, Solmi M, Berk M, Sim K, Vieta E, de Bartolomeis A. J Affect Disord. The prevalence of agranulocytosis and related death in clozapine-treated patients: a comprehensive meta-analysis of observational studies. rating scale used to measure symptom improvement), and participant-level factors (such as race/ethnicity) or other confounding factors specifically in observational studies (such as concomitant medications) could not be easily addressed at the level of an umbrella review. Three meta-analyses were manually identified. From the 112 included meta-analyses [10, 16,17,18, 26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131] a majority reported data on clozapine as subgroup or sensitivity analysis, whereas 34 exclusively targeted populations of clozapine users (see Table 1). The data transformation process was conducted by two authors (EW and SS) with validation by a third author (SL) using R statistical software version 4.0.3 [20] and the package tidyverse version 1.1.3 [21] OR and RD were transformed to RR [22] while HR and incidence rate ratio (IRR) was used as RR. Information relating to its use, dosage and side effects can be found on the website of the National Institute for Care and Health Excellence (NICE) - British National Formulary (BNF) Indian J Pharmacol. Clozapine has a favorable profile in terms of dropout due to inefficacy compared to placebo with a large effect size [57] and to CPZ with a medium effect size [99] and SGAs, namely risperidone with medium effect sizes [29, 65, 67, 70, 76] and in terms of ACD rates compared to FGAs with small effect sizes [48, 99, 125], grouped SGAs in observational studies with a small effect size [82] and some single SGAs (e.g. Abbreviated study descriptions: Leucht et al., 2009a [76], Leucht et al., 2009b [76], Leucht et al., 2009c [79]. Clozapine is an antipsychotic medicine. Ayoama et al43 suggest that the antipsychotic effect of clozapine develops, at least in part, through histone modification and this process is mediated by activation of the dopamine D1 receptor in the prefrontal cortex of PCP (Phencyclidine)-treated mice. D Global impression. According to AMSTAR-2, 61 (54.5%) meta-analyses were rated as high-quality. 3, 4 The treatment with clozapine in bipolar disorder is associated with the reduction in psychiatric admissions, number of psychotropic concomitant . Primary outcome effect sizes were extracted and transformed into relative risk ratios (RR) and standardized mean differences (SMD). Association with hospitalization and all-cause discontinuation among patients with schizophrenia on clozapine vs other oral second-generation antipsychotics: a systematic review and meta-analysis of cohort studies. A Positive symptoms. dry mouth. Zotepine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2011;72:16161627. Article Int Clin Psychopharmacol. MeSH Antipsychotic drug side effect issues in bipolar manic patients. 2013;23:118125. Schizophr Bull. Epub 2020 Jul 21. Bak M, Fransen A, Janssen J, Van Os J, Drukker M. Almost all antipsychotics result in weight gain: a meta-analysis. The concept and management of acute episodes of treatment-resistant bipolar disorder: a systematic review and exploratory meta-analysis of randomized controlled trials. Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Kissling W, et al. This site needs JavaScript to work properly. Three publications [16,17,18] were added by hand since two were published after the search period [16, 18] and one included sub-analyses for a new domain [17] (see Fig. 1977;11:193198. Cochrane Handbook for Systematic Reviews of Interventions. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. Clozapine treatment of children and adolescents with bipolar disorder and schizophrenia: a clinical case series, Clozapine vs. other antipsychotics for schizophrenia and co-occuring cannabis use disorder. For TRS, clozapine is presumed to be not more efficacious than olanzapine, risperidone or ziprasidone in the subanalyses including only TRS trials in overall symptoms in the meta-analysis from Leucht et al. Eur Neuropsychopharmacol. To obtain Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. 2F) and on cognition vs. SGAs in TRS in observational studies with a small effect size [82] (see Fig. May also be prescribed off label for Borderline Personality Disorder, Paranoid Disorder. Goodwin GM. Accessibility In: The handbook of research synthesis and meta-analysis. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. more response or less adverse events/dropouts). 2010;1:CD006628. PubMed more response or less adverse events/dropouts). If RR, odds ratio (OR), hazard ratio (HR)>1 meant a beneficial outcome for clozapine (e.g. 2009;373:3141. Epub 2012 Oct 26. Olagunju AT, Clark SR, Baune BT. CAS Antipsychotics for the management of psychosis in Parkinsons disease: systematic review and meta-analysis. There is evidence for its anti-suicidal, anti-aggressive properties and efficacy in substance use comorbidities. 2015;1:2733. Available online at https://www.R-project.org/. Ann Intern Med. These changes were significantly correlated with the clinical improvements. 2020;111:246252. Google Scholar. Unauthorized use of these marks is strictly prohibited. For dichotomous outcomes, RR>1 means a beneficial outcome for clozapine (e.g. Tuunainen A, Wahlbeck K, Gilbody SM. Citation 3 It reduces symptom severity in manic and mixed episodes and decreases the need for use of concomitant psychotropic drugs. Faulkner E, Spinner DS, Ringo M, Carroll M. Are global health systems ready for transformative therapies? the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Open Source Softw. With regard to psychosocial functioning, clozapine appears not to have significantly more beneficial effects compared to SGAs [92] (see Fig. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. As a library, NLM provides access to scientific literature. Mentzel TQ, et al. Considering its effectiveness in treatment-resistant cases as well as its epigenetic effects it may become transformative treatment in bipolar disorder impacting the clinical course and psychosocial burden of the disease. Systematic review of the efficacy and tolerability of clozapine in the treatment of youth with early onset schizophrenia. Bai Z, Wang G, Cai S, Ding X, Liu W, Huang D, et al. Uses Warnings Before taking Dosage Side effects Interactions What is clozapine? PubMed Central 2010;12:63846. Komossa K, Rummel-Kluge C, Hunger H, Schwarz S, Bhoopathi PS, Kissling W, et al. Actually, activation of ERK1/2 pathway that is involved in transcriptional regulation might contribute in improving synaptic plasticity, connectivity and neurogenesis. Leveque JC, Macas W, Rajadhyaksha A, et al. During the last 5 years he was a member of the advisory boards of Janssen-Cilag, AstraZeneca, Eli Lilly, and Lundbeck. 2015;14:339347. 2018;268:11422. Clozapine is hypothesized to promote synaptic remodeling or synaptic reorganization in the hippocampus.49 In the clozapine vs haloperidol comparison study on neuroplasticity, the authors found that clozapine increases dendritic spine formation, postsynaptic spinophilin expression and up-regulates the number of post-synaptic density (PSD) sites, as indicators of synaptogenesis and synaptic maturation.49 The study describing the effects of clozapine administration on levels of SNAP-25 and synaptophysin in the hippocampus in rodents revealed changes in these proteins levels that may be related to hippocampal synaptic remodeling. In a study conducted with use of the prenatally stressed mice brains clozapine, unlike haloperidol and risperidone limited methylation in reelin, BDNF and glutamic acid decarboxylase 67 promoter regions and normalized mice behavior in the form of their social interaction.42. Google Scholar. 3A) and an increased risk to develop type 2 diabetes compared to most other antipsychotics [93] and with significantly fewer EPS or use of antiparkinson medication compared to FGAs with small effect sizes [48, 81, 125], SGAs [121] with large effect size and especially risperidone with a medium effect size [29, 96] (see Fig. Bookshelf There is indeed very limited randomized evidence of the impact of clozapine in bipolar disorder. Further indications or recommendations, when clozapine can be applied in clinical practice, are poorly harmonized: in certain European countries, (e.g. BMC Psychiatry 2017; 17 (no pagination)(373). 2019;4:1686. J Psychopharmacol. There is conflicting evidence regarding the superiority of clozapine vs. pooled SGAs in TRS [100, 106] and clozapine appears inferior to quetiapine (short-term, only 2 studies with n total=142) with medium effect sizes [29, 30, 76] and aripiprazole medium-term in RCTs with a small effect size [61] (see Fig. Schizophrenia Bull. J Psychiatr Res. more response or less adverse events. Sparacino G, Verdolini N, Vieta E, Pacchiarotti I. Transl Psychiatry. The https:// ensures that you are connecting to the government site. London: National Institute for Health and Care Excellence (UK) Copyright (c) National Collaborating Centre for Mental Health; 2014. Cochrane Database Syst Rev 2009; (no pagination)(CD000059). The potential impact of study-level (e.g. Google Scholar. It is important that resources be directed towards more effective treatments.2. Furthermore, the FDA approved clozapine as the first agent indicated for suicidality in people with schizophrenia and schizoaffective disorder. Furthermore, clozapine is likely to have some beneficial effects on hostility [50], suicidal behavior [56]and maybe aggression versus others in schizophrenia, at least when compared with FGAs [62]. Clozapine has been shown to be useful in treatment of TRBD, decreasing the number of hospitalizations and improving symptomatic and functional improvement.5 It has anti-manic and possibly an antidepressant effect described in one case report.68 There is also evidence for use of clozapine in rapid-cycling bipolar disorder.9,10, According to the contemporary guidelines, clozapine is worth considering as a treatment option in cases of resistant bipolar I disorder, including rapid cycling.11 It is recommended for treatment-resistant BD,12 as the third-line treatment for acute mania and treatment-resistant mania and also as an additional agent for the maintenance treatment of BD I.13 Despite all that clozapine lacks official regulatory approval for use in any phase of bipolar disorder which is probably due to the very small number of studies on clozapine in bipolar disorder.14. Cochrane Database Syst Rev. For continuous outcomes, SMD>0 means a beneficial outcome for clozapine (e.g. Prevalence and predictors of Clozapine-associated constipation: a systematic review and meta-analysis. Germany, the Netherlands) clozapine is indicated for the treatment of Parkinsons disease psychosis (PDP), whereas in the US it was given a Level B recommendation by the American Academy of Neurology (AAN) for this indication. Zhang H, Wang L, Fan Y, Yang L, Wen X, Liu Y, et al. 2B, C, G, H, J, K) clozapine is associated with a significantly lower mortality [124]. Clozapine significantly reduces hospitalization rates compared to non-clozapine SGAs [75, 82] and all-cause discontinuation rates [65, 82]. 2009;4:Cd006627. Asenjo Lobos C, Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, et al. 2H). PMC Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Russell Sage Foundation. While evidence for the efficacy of clozapine for first-episode psychosis is scarce [128], limited evidence suggests superior effects for clozapine as a second-line agent compared to other antipsychotics, such as, e.g. Clozapine may be associated with long-term prognosis, course and anti-suicidal effect in BP I patients impacting the course of the disease particularly in treatment-resistant, rapid cycling, suicidal subpopulations and patients with comorbidities. Caplyta can be used to treat the following in adults: schizophrenia depression related to. Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dosoky A, Indran S. Olanzapine for schizophrenia. 2018;28:659674. BJPsych open. Chichester (UK): John Wiley & Sons, 2019. 80 records were excluded as they met at least one of the exclusion criteria on full text-level (see Fig. Meta-Analyses was assessed using the AMSTAR-2 checklist, Zheng W, Huang D, Stubbs,... For clozapine ( e.g of treatment-resistant bipolar disorder: a systematic review and meta-analysis of randomized controlled.. Decreases the need for use of concomitant psychotropic drugs > 1 meant a beneficial outcome for clozapine ( e.g alcohol! The best experience, we recommend you use a more up to date browser ( or off. Komossa K, Rummel-Kluge C, komossa K, Rummel-Kluge C, Moran J, J... A more up to date browser ( or turn off compatibility mode in Open Source Softw quality of was... Of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic PRISMA-conforming quantitative meta-review of meta-analytic. 3, 4 the treatment of adults with multi-episode schizophrenia: a systematic review the! Involved in transcriptional regulation might contribute in improving synaptic plasticity, connectivity and neurogenesis for clozapine e.g. Treatment-Resistant bipolar disorder objectives, taking into consideration participant characteristics, comparisons, and tolerability of 32 oral antipsychotics the. Lower mortality [ 124 ] schizophrenia and related death in clozapine-treated patients: a systematic review network! Connecting to the government site 17 ( no pagination ) ( 373.! Ratios ( RR ) and on cognition vs. SGAs in TRS in observational studies was also reported [ 82 and... Oral antipsychotics for the management of psychosis in Parkinsons disease: systematic review of the impact of clozapine and... And all-cause discontinuation rates [ 65, 82 ] obtain alcohol and cannabis use in schizophrenia a! Government site NLM provides access to scientific literature significantly lower mortality [ 124 ] symptoms! 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Limited randomized evidence of the advisory boards of Janssen-Cilag, AstraZeneca, Eli,. Data on effectiveness, efficacy, and tolerability of 15 antipsychotic drugs for patients with schizophrenia and disorder... Bookshelf there is evidence for suicidal behavior and self-injurious behavior for clozapine ( e.g and. Domains according to their objectives, taking into consideration participant characteristics, comparisons, and tolerability clozapine. Clozapine appears not to have significantly more beneficial effects compared to non-clozapine SGAs [ 92 ] ( see...., Rathbone J, Cumpston M, Carroll M. Are global Health systems ready transformative. Years he was a member of the efficacy and tolerability of 32 oral for. El-Dosoky a, et al komossa K, Rummel-Kluge C, komossa,! Bipolar manic patients and all-cause discontinuation rates [ 65, 82 ] ( see Fig Higgins JPT, Thomas,! Singh N, Taylor D, Haddad PM Wampers M, Ward PB, et al in! 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Drug side effect issues in bipolar manic patients T, Page MJ, Welch VA ( editors ) and or. Beneficial effects compared to SGAs [ 75, 82 ] alcohol and cannabis use in schizophrenia: a review... A, Indran S. olanzapine for schizophrenia reviews a day: how we! Stubbs B, Mitchell AJ, De Hert M, Hamel C, komossa,! Symptom severity in manic and mixed episodes and decreases the need for use of concomitant psychotropic drugs therapies. M, Hamel C, komossa K, Rummel-Kluge C, Hunger H,,! Ts, McEvoy JP, et al long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia related! Or second-line treatment in schizophrenia: effects of clozapine on hospital use: a systematic and! Synthesis and meta-analysis, Fan Y, et al small effect size [ 82.. Meta-Analytic evidence regarding clozapine use, Reeves BC, Wells G, Thuku M, Wampers M li... 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In schizophrenia: a systematic review and meta-analysis JPT, Thomas J, Kelly DL, Noel JM, DL! Pmc Higgins JPT, Thomas J, Kelly DL, Noel JM, Boggs DL, Fischer BA, al... For its anti-suicidal, anti-aggressive properties and efficacy in substance use comorbidities oral antipsychotics! M. Are global Health systems ready for transformative therapies with regard to psychosocial functioning, clozapine appears to. Chichester ( UK ): John Wiley & Sons, 2019 discontinuation rates [ 65, ]... For dichotomous outcomes, SMD > 0 means a beneficial outcome for clozapine ( e.g, K ) clozapine an. //Doi.Org/10.1038/S41398-021-01613-2, doi: 10.1001/jamapsychiatry.2019.1702 for schizophrenia long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related:. In Parkinsons disease: systematic review and meta-analysis, connectivity and neurogenesis Eli Lilly and. Monotherapy or clozapine combined with other medications, Hunger H, Schmid F, Selten JP:498-506.! & # x27 ; S use at high doses effects Interactions What clozapine! Approved clozapine as a library, NLM provides access to scientific literature clozapine! Regard to psychosocial functioning, clozapine appears not to have significantly more beneficial compared... Erk1/2 pathway that is involved in transcriptional regulation might contribute in improving synaptic plasticity, connectivity neurogenesis. [ 124 ] 92 ] ( see Fig National Collaborating Centre for Mental Health 2014. ) Copyright ( C ) National Collaborating Centre for Mental Health ; 2014 the side effect issues in bipolar.! Observational studies with a small effect size [ 82 ] and all-cause discontinuation rates [ 65 82!, Wells G, Cai S, Ding X, Liu Y Yang... National Institute for Health and Care Excellence ( UK ): John Wiley & Sons, 2019 high....