{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:26:12Z","timestamp":1792463172981,"version":"4.5.0"},"reference-count":130,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords \u201cclozapine\u201d and \u201cschizophrenia\u201d, \u201cside effects\u201d, \u201cagranulocytosis\u201d, \u201cTRS\u201d, or \u201cbipolar affective disorder (BAF)\u201d for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: we selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions\u2019 severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.<\/jats:p>","DOI":"10.3390\/brainsci10110840","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T19:08:28Z","timestamp":1605121708000},"page":"840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety\u2014Particularities in the Context of COVID-19"],"prefix":"10.3390","volume":"10","author":[{"given":"Ana","family":"Dragoi","sequence":"first","affiliation":[{"name":"Department of Psychiatry, \u201cAlexandru Obregia\u201d Clinical Hospital for Psychiatry, 10 Berceni St., 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Radulescu","sequence":"additional","affiliation":[{"name":"Department of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu St., 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5682-0225","authenticated-orcid":false,"given":"Bogdana","family":"N\u0103sui","sequence":"additional","affiliation":[{"name":"Department of Community Health, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1448-1928","authenticated-orcid":false,"given":"Anca","family":"Pop","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Food Safety, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 6 Traian Vuia St., 020945 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Varlas","sequence":"additional","affiliation":[{"name":"Department of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu St., 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-4669","authenticated-orcid":false,"given":"Simona","family":"Trifu","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu St., 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"ref_1","first-page":"89","article-title":"Do antidepressants really work?","volume":"33","author":"Blier","year":"2008","journal-title":"J. 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