{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:02:51Z","timestamp":1788458571012,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"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>Schizophrenia is a chronic, invalidating, and polymorphic disease, characterized by relapses and remission periods. The main treatment option in schizophrenia are antipsychotics, administered as an oral or as a long-acting injectable (LAI) formulation. Although international guidelines rarely recommend it, mood stabilizers (MS) and\/or benzodiazepines (BZD) are frequently prescribed as adjunctive therapy in schizophrenia patients for various reasons. This is an observational, cross-sectional study including stabilized schizophrenia patients. A total of 315 patients were enrolled. Of these, 77 patients (24.44%) were stabilized on LAIs and 238 (75.56%) patients on oral antipsychotics (OAP). Eighty-four patients (26.66%) had concomitant treatment with MS and 119 patients (37.77%) had concomitant benzodiazepine treatment. No statistical significance was observed in MS or BZD use between LAIs and OAPs. In total, 136 patients (43.17%) were stabilized on antipsychotic monotherapy. Our study shows that the long-term use of benzodiazepines and mood stabilizers remains elevated among stabilized schizophrenia patients, regardless of the antipsychotic formulation (oral or LAI). Patients receiving second-generation LAI antipsychotics (SGA-LAI) seem to be more likely to be stabilized on monotherapy compared to those receiving oral antipsychotics. Further randomized controlled trials are necessary in order to clarify the benefits of the current drug polypharmacy trends.<\/jats:p>","DOI":"10.3390\/brainsci13020173","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:35:55Z","timestamp":1674182155000},"page":"173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Benzodiazepines and Mood Stabilizers in Schizophrenia Patients Treated with Oral versus Long-Acting Injectable Antipsychotics\u2014An Observational Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8697-1945","authenticated-orcid":false,"given":"Ana Aliana","family":"Miron","sequence":"first","affiliation":[{"name":"Facultatea de Medicin\u0103, Universitatea Transilvania din Bra\u0219ov, Bulevardul Eroilor nr. 29, 500036 Bra\u0219ov, Romania"},{"name":"Spitalul Clinic de Psihiatrie \u0219i Neurologie Bra\u0219ov, Str. Prundului nr. 7-9, 500123 Bra\u0219ov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Simina","family":"Petric","sequence":"additional","affiliation":[{"name":"Facultatea de Medicin\u0103, Universitatea Transilvania din Bra\u0219ov, Bulevardul Eroilor nr. 29, 500036 Bra\u0219ov, Romania"},{"name":"Spitalul Clinic de Psihiatrie \u0219i Neurologie Bra\u0219ov, Str. Prundului nr. 7-9, 500123 Bra\u0219ov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Teodorescu","sequence":"additional","affiliation":[{"name":"Facultatea de Medicin\u0103, Universitatea Transilvania din Bra\u0219ov, Bulevardul Eroilor nr. 29, 500036 Bra\u0219ov, Romania"},{"name":"Spitalul Clinic de Psihiatrie \u0219i Neurologie Bra\u0219ov, Str. Prundului nr. 7-9, 500123 Bra\u0219ov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petru","family":"Ifteni","sequence":"additional","affiliation":[{"name":"Facultatea de Medicin\u0103, Universitatea Transilvania din Bra\u0219ov, Bulevardul Eroilor nr. 29, 500036 Bra\u0219ov, Romania"},{"name":"Spitalul Clinic de Psihiatrie \u0219i Neurologie Bra\u0219ov, Str. Prundului nr. 7-9, 500123 Bra\u0219ov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Chele","sequence":"additional","affiliation":[{"name":"Facultatea de Medicin\u0103, Universitatea de Medicin\u0103 si Farmacie, Grigore T. Popa\u201d Ia\u0219i, Str. Universit\u0103\u021bii nr. 16, 700115 Ia\u0219i, Romania"},{"name":"Institutul de Psihiatrie <sub>\u201e<\/sub>Socola\u201d Ia\u0219i, \u015eoseaua Bucium nr. 36, 700282 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Silvana","family":"Szalontay","sequence":"additional","affiliation":[{"name":"Facultatea de Medicin\u0103, Universitatea de Medicin\u0103 si Farmacie, Grigore T. Popa\u201d Ia\u0219i, Str. Universit\u0103\u021bii nr. 16, 700115 Ia\u0219i, Romania"},{"name":"Institutul de Psihiatrie <sub>\u201e<\/sub>Socola\u201d Ia\u0219i, \u015eoseaua Bucium nr. 36, 700282 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15067","DOI":"10.1038\/nrdp.2015.67","article-title":"Schizophrenia","volume":"1","author":"Kahn","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/j.1600-0447.1994.tb05858.x","article-title":"How high is the relapse rate in schizophrenia?","volume":"382","author":"Johnstone","year":"1994","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/00004850-199501005-00002","article-title":"What is relapse in schizophrenia?","volume":"9","author":"Lader","year":"1995","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s40263-015-0282-7","article-title":"Anxiety in Patients with Schizophrenia: Epidemiology and Management","volume":"29","author":"Temmingh","year":"2015","journal-title":"CNS Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.psychres.2007.04.007","article-title":"Response inhibition and impulsivity in schizophrenia","volume":"157","author":"Enticott","year":"2008","journal-title":"Psychiatry Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1002\/jclp.23141","article-title":"Depressive symptoms, anxiety symptoms, and their co-occurrence among people living with schizophrenia in China: Prevalence and correlates","volume":"77","author":"Xi","year":"2021","journal-title":"J. Clin. Psychol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4088\/JCP.15032su1","article-title":"The Use of Long-Acting Injectable Antipsychotics in Schizophrenia: Evaluating the Evidence","volume":"77","author":"Correll","year":"2016","journal-title":"J. Clin. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.schres.2017.12.010","article-title":"Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia","volume":"197","author":"Taipale","year":"2018","journal-title":"Schizophr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S2215-0366(21)00039-0","article-title":"Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: A systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies","volume":"8","author":"Kishimoto","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s40263-021-00861-6","article-title":"Controversies Surrounding the Use of Long-Acting Injectable Antipsychotic Medications for the Treatment of Patients with Schizophrenia","volume":"35","author":"Kane","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"767756","DOI":"10.3389\/fpsyt.2021.767756","article-title":"Rating Opportunity for Long-Acting Injectable Antipsychotic Initiation Index (ROLIN)","volume":"12","author":"Ifteni","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_12","first-page":"i\u2013iv+1\u201356","article-title":"Practice guideline for the treatment of patients with schizophrenia, second edition","volume":"161","author":"Lehman","year":"2004","journal-title":"Am. J. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s40265-021-01556-4","article-title":"Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations","volume":"81","author":"Tiihonen","year":"2021","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/YCO.0b013e32835d9efb","article-title":"Polypharmacy for schizophrenia","volume":"26","author":"Ballon","year":"2013","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/bcpt.13384","article-title":"Polypharmacy in schizophrenia","volume":"126","author":"Baandrup","year":"2020","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_16","first-page":"345","article-title":"Benzodiazepines in combination with antipsychotic drugs for schizophrenia: GABA-ergic targeted therapy","volume":"29","author":"Szarmach","year":"2017","journal-title":"Psychiatr. Danub."},{"key":"ref_17","first-page":"349","article-title":"Benzodiazepines as adjunctive therapy in treatment refractory symptoms of schizophrenia","volume":"29","author":"Szarmach","year":"2017","journal-title":"Psychiatr. Danub."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"148S","DOI":"10.1002\/j.1875-9114.1996.tb03669.x","article-title":"Benzodiazepines in schizophrenia","volume":"16","author":"Stimmel","year":"1996","journal-title":"Pharmacotherapy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1176\/ajp.134.2.138","article-title":"gamma-Aminobutyric acid (Gaba) and the dopamine hypothesis of schizophrenia","volume":"134","year":"1977","journal-title":"Am. J. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1177\/0269881114541013","article-title":"Re-examining the role of benzodiazepines in the treatment of schizophrenia: A systematic review","volume":"29","author":"Sim","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/JCP.0000000000001497","article-title":"Use of Benzodiazepines and Antipsychotic Drugs Are Inversely Associated with Acute Readmission Risk in Schizophrenia","volume":"42","author":"Mellesdal","year":"2022","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"661","DOI":"10.4088\/JCP.15m10271","article-title":"Benzodiazepine use and risk of mortality among patients with schizophrenia: A retrospective longitudinal study","volume":"77","author":"Fontanella","year":"2016","journal-title":"J. Clin. Psychiatry"},{"key":"ref_23","first-page":"23","article-title":"Treatment-resistant schizophrenia: What role for mood stabilizers?","volume":"3","author":"Citrome","year":"2004","journal-title":"Curr. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1124\/pr.111.005512","article-title":"Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder","volume":"65","author":"Chiu","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_25","first-page":"CD003834","article-title":"Lithium for schizophrenia","volume":"10","author":"Leucht","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1176\/appi.ps.51.5.634","article-title":"Changes in use of valproate and other mood stabilizers for patients with schizophrenia from 1994 to 1998","volume":"51","author":"Citrome","year":"2000","journal-title":"Psychiatr. Serv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00228-020-02830-2","article-title":"Use of antidepressants and mood stabilizers in persons with first-episode schizophrenia","volume":"76","author":"Puranen","year":"2020","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/hup.2752","article-title":"Coprescription of mood stabilizers in schizophrenia, dosing, and clinical correlates: An international study","volume":"35","author":"Lim","year":"2020","journal-title":"Hum. Psychopharmacol."},{"key":"ref_29","first-page":"1809","article-title":"Har stemningsstabiliserende legemidler noen plass i behandlingen av schizofreni? [Are mood stabilizers beneficial in the treatment of schizophrenia?]","volume":"125","author":"Berle","year":"2005","journal-title":"Tidsskr Nor Laegeforen."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/sj.npp.1300023","article-title":"Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia","volume":"28","author":"Casey","year":"2003","journal-title":"Neuropsychopharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Puranen, A., Koponen, M., L\u00e4hteenvuo, M., Tanskanen, A., Tiihonen, J., and Taipale, H. (Acta Psychiatr. Scand., 2022). Real-world effectiveness of mood stabilizer use in schizophrenia, Acta Psychiatr. Scand., ahead of print.","DOI":"10.1111\/acps.13498"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2475","DOI":"10.1097\/MD.0000000000002475","article-title":"Significant Effect of Valproate Augmentation Therapy in Patients with Schizophrenia: A Meta-analysis Study","volume":"95","author":"Tseng","year":"2016","journal-title":"Medicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1192\/pb.21.4.224","article-title":"Chlorpromazine equivalents: A consensus of opinion for both clinical and research applications","volume":"21","author":"Atkins","year":"1997","journal-title":"Psychiatr. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/pcn.12275","article-title":"Psychotropic dose equivalence in Japan","volume":"69","author":"Inada","year":"2015","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1176\/appi.ajp.2009.09060802","article-title":"International consensus study of antipsychotic dosing","volume":"167","author":"Gardner","year":"2010","journal-title":"Am. J. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1093\/schbul\/sbv037","article-title":"Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method","volume":"41","author":"Leucht","year":"2015","journal-title":"Schizophr. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.2147\/NDT.S167394","article-title":"Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics\u2014Expert consensus survey part 1","volume":"14","author":"Sajatovic","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3111\/13696998.2012.751025","article-title":"Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral","volume":"16","author":"Offord","year":"2013","journal-title":"J. Med. Econ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1176\/appi.ps.202000932","article-title":"Variation in Psychotropic Medication Prescription for Adults with Schizophrenia in the United States","volume":"73","author":"Bareis","year":"2022","journal-title":"Psychiatr. Serv."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Reymann, S., Schoretsanitis, G., Egger, S.T., Mohonko, A., Kirschner, M., Vetter, S., Homan, P., Seifritz, E., and Burrer, A. (2022). Use of Long-Acting Injectable Antipsychotics in Inpatients with Schizophrenia Spectrum Disorder in an Academic Psychiatric Hospital in Switzerland. J. Pers. Med., 12.","DOI":"10.20944\/preprints202203.0099.v1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1177\/2045125318782694","article-title":"Real-world effectiveness of long-acting antipsychotic treatments in a nationwide cohort of 3957 patients with schizophrenia, schizoaffective disorder and other diagnoses in Quebec","volume":"8","author":"Stip","year":"2018","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2147\/PPA.S127623","article-title":"Treatment patterns in Medicaid patients with schizophrenia initiated on a first- or second-generation long-acting injectable versus oral antipsychotic","volume":"11","author":"Pilon","year":"2017","journal-title":"Patient Prefer. Adherence"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.eurpsy.2018.04.004","article-title":"Baseline results from the European non-interventional Antipsychotic Long acTing injection in schizOphrenia (ALTO) study","volume":"52","author":"Llorca","year":"2018","journal-title":"Eur. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.1007\/s12325-022-02232-z","article-title":"Systematic Review of Real-World Treatment Patterns of Oral Antipsychotics and Associated Economic Burden in Patients with Schizophrenia in the United States","volume":"39","author":"Martin","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_45","first-page":"117","article-title":"Treatment-resistant schizophrenia: Current insights on the pharmacogenomics of antipsychotics","volume":"9","author":"Lally","year":"2016","journal-title":"Pharm. Pers. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Miron, A.A., Ifteni, P.I., Teodorescu, A., and Petric, P.S. (2022). Long-Acting Injectable Antipsychotics (LAIs) Prescribing Trends during the COVID-19 Pandemic in Romania. Healthcare, 10.","DOI":"10.3390\/healthcare10071265"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s11126-021-09924-9","article-title":"Switch from Olanzapine Long-Acting Injectable to its Oral Equivalent during COVID-19 Pandemic: A Real World Observational Study","volume":"93","author":"Miron","year":"2022","journal-title":"Psychiatr. Q."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1097\/AOG.0000000000004893","article-title":"Valproate Teratogenicity: A Moving Target","volume":"140","author":"Gruppuso","year":"2022","journal-title":"Obstet. Gynecol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20451253221110016","article-title":"Who is prescribed valproate and how carefully is this treatment reviewed in UK mental health services? Data from a clinical audit","volume":"12","author":"Paton","year":"2022","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_50","first-page":"CD004028","article-title":"Valproate for schizophrenia","volume":"2016","author":"Wang","year":"2016","journal-title":"Cochrane Database Syst Rev."},{"key":"ref_51","first-page":"CD001258","article-title":"Carbamazepine for schizophrenia","volume":"2014","author":"Leucht","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_52","first-page":"CD005962","article-title":"Lamotrigine for schizophrenia","volume":"2006","author":"Premkumar","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1192\/pb.24.3.113","article-title":"Benzodiazepines in schizophrenia: Is there a trend towards long-term prescribing?","volume":"24","author":"Paton","year":"2000","journal-title":"Psychiatr. Bull."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.euroneuro.2013.03.001","article-title":"Benzodiazepine augmentation of antipsychotic drugs in schizophrenia: A meta-analysis and Cochrane review of randomized controlled trials","volume":"23","author":"Dold","year":"2013","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_55","first-page":"CD006391","article-title":"Benzodiazepines for schizophrenia","volume":"11","author":"Dold","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_56","first-page":"9","article-title":"The effects of benzodiazepines on cognition","volume":"66","author":"Stewart","year":"2005","journal-title":"J. Clin. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/7854_2015_425","article-title":"Benzodiazepines","volume":"34","author":"Nielsen","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cger.2012.01.008","article-title":"Medication adherence to multidrug regimens","volume":"28","author":"Marcum","year":"2012","journal-title":"Clin. Geriatr. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1176\/appi.ajp.2019.19010034","article-title":"Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia","volume":"177","author":"Leucht","year":"2020","journal-title":"Am. J. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2165\/00023210-200822010-00004","article-title":"Quetiapine: Dose-response relationship in schizophrenia","volume":"22","author":"Sparshatt","year":"2008","journal-title":"CNS Drugs"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.pnpbp.2004.05.048","article-title":"Effects of clozapine on sleep in bipolar and schizoaffective disorders","volume":"28","author":"Armitage","year":"2004","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ali, T., Sisay, M., Tariku, M., Mekuria, A.N., and Desalew, A. (2021). Antipsychotic-induced extrapyramidal side effects: A systematic review and meta-analysis of observational studies. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0257129"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1097\/JCP.0b013e3181f14098","article-title":"Incidence of extrapyramidal symptoms and tardive dyskinesia in schizophrenia: Thirty-six-month results from the European schizophrenia outpatient health outcomes study","volume":"30","author":"Novick","year":"2010","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"361","DOI":"10.9758\/cpn.2018.16.4.361","article-title":"Comparative Efficacy and Safety of Long-acting Injectable and Oral Second-generation Antipsychotics for the Treatment of Schizophrenia: A Systematic Review and Meta-analysis","volume":"16","author":"Park","year":"2018","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_65","first-page":"3","article-title":"Atypical antipsychotics: Sleep, sedation, and efficacy","volume":"6","author":"Miller","year":"2004","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1177\/070674370705200708","article-title":"Clozapine-induced seizures: Recognition and treatment","volume":"52","author":"Wong","year":"2007","journal-title":"Can. J. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/ijnp\/pyz068","article-title":"Antipsychotic Polypharmacy: A Dirty Little Secret or a Fashion?","volume":"23","author":"Lin","year":"2020","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1001\/jamapsychiatry.2018.4320","article-title":"Association of Antipsychotic Polypharmacy vs Monotherapy with Psychiatric Rehospitalization among Adults with Schizophrenia","volume":"76","author":"Tiihonen","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"860713","DOI":"10.3389\/fphar.2022.860713","article-title":"Long-Term Antipsychotic Effectiveness and Comparison of the Efficacy of Monotherapy and Polypharmacy in Schizophrenia: A 3-Years Follow-Up \u201cReal World\u201d Study in China","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/2\/173\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:11:45Z","timestamp":1760119905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/13\/2\/173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,20]]},"references-count":69,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["brainsci13020173"],"URL":"https:\/\/doi.org\/10.3390\/brainsci13020173","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,20]]}}}