{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:19:53Z","timestamp":1793409593011,"version":"4.5.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>Clozapine is considered \u00ab the golden standard \u00bb for the management of treatment-resistant schizophrenia, but many patients do not present adequate responsivity even to this antipsychotic. If we add the need to strictly monitor the hematologic and cardiometabolic adverse events during each clozapine trial and the difficulty of preserving therapeutic adherence in patients with low insight, residual negative\/positive symptoms, or economic challenges, then the necessity of exploring alternative interventions for these patients becomes obvious. Also, in case of intolerance to clozapine or where clozapine did not induce remission, clinicians have to find new ways to help their patients. Switching to other antipsychotics or using these agents as add-ons to clozapine are the main interventions explored in this review, for patients with schizophrenia resistant to clozapine (ultra-resistant schizophrenia, URS). When clozapine intolerance is detected, conversion to another antipsychotic with distinct pharmacologic properties or formulation (e.g., long-acting intramuscular injectable agents, LAI) may be a useful option. Third-generation antipsychotics (TGA) have been selected for their distinct pharmacodynamically profile, which allows, at a theoretical level, their use in combination with clozapine. This narrative review is based on searching four electronic databases, that retrieved 19 primary and secondary reports on aripiprazole (seven case reports or case series presenting 24 patients; nine clinical trials, and three systematic reviews\/meta-analyses), two primary reports on brexpiprazole (case report and case series, <jats:italic>N<\/jats:italic> = 3 patients), and six primary reports on cariprazine (case reports and case series, <jats:italic>N<\/jats:italic> = 14 patients). Based on the information collected from these reports, which included oral and LAI formulations, the TGA most supported by evidence for the augmentation of clozapine is aripiprazole (high-and medium-quality data), followed by cariprazine (low-quality data). Brexpiprazole has not yet been systematically explored for this indication, and in the case of lumateperone, no report could be found. The efficacy of aripiprazole and cariprazine was supported in the domains of positive, negative, and general symptoms, and aripiprazole may positively impact the metabolic profile in patients with URS. Also, adding TGA may lead to a decrease in the dose of clozapine concomitantly administered. More data derived from good quality research are needed in order to confirm the circumstances of TGAs recommendation in patients with URS, either as monotherapy, or added to clozapine.<\/jats:p>","DOI":"10.3389\/fpsyt.2022.1069432","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T05:37:36Z","timestamp":1669700256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?"],"prefix":"10.3389","volume":"13","author":[{"given":"Octavian","family":"Vasiliu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"B1","first-page":"1099","article-title":"Treatment of resistant and ultra resistant schizophrenia.","volume":"33","author":"Medi\u0107","year":"2021","journal-title":"Psychiatr Danub."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11071030","article-title":"Clozapine: why is it so uniquely effective in the treatment of a range of neuropsychiatric disorders?","volume":"11","author":"Gammon","year":"2021","journal-title":"Biomolecules."},{"key":"B3","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1177\/0706743717718167","article-title":"Clozapine response rates among people with treatment-resistant schizophrenia: data from a systematic review and meta-analysis.","volume":"62","author":"Siskind","year":"2017","journal-title":"Can J Psychiatry."},{"key":"B4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.55453\/rjmm.2020.123.1.1","article-title":"Efficacy and tolerability of antibiotic augmentation in schizophrenia spectrum disorders- a systematic literature review.","author":"Vasiliu","year":"2020","journal-title":"RJMM."},{"key":"B5","doi-asserted-by":"publisher","first-page":"429","DOI":"10.5498\/wjp.v11.i8.429","article-title":"Clozapine resistant schizophrenia: newer avenues of management.","volume":"11","author":"Chakrabarti","year":"2021","journal-title":"World J Psychiatry."},{"key":"B6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1590\/s1516-44462007000300007","article-title":"Clinical aspects of super-refractory schizophrenia: a 6-month cohort observational study.","volume":"29","author":"Neto","year":"2007","journal-title":"Braz J Psychiatry."},{"key":"B7","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1176\/appi.ajp.2016.16050503","article-title":"Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology.","volume":"174","author":"Howes","year":"2017","journal-title":"Am J Psychiatry."},{"key":"B8","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1097\/00002826-200601000-00009","article-title":"Augmentation strategies of clozapine with antipsychotics in the treatment of ultra-resistant schizophrenia.","volume":"29","author":"Mouaffak","year":"2006","journal-title":"Clin Neuropharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.schres.2020.12.002","article-title":"Characteristics and definitions of ultra-treatment-resistant schizophrenia- a systematic review and meta-analysis.","volume":"228","author":"Campana","year":"2021","journal-title":"Schizophr Res."},{"key":"B10","first-page":"36","article-title":"Approaches for the treatment of people with schizophrenia that do not respond to clozapine or ultra-resistant schizophrenia. Review of the evidence.","author":"H\u00f6nig","year":"2019","journal-title":"Vertex."},{"key":"B11","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.schres.2019.08.001","article-title":"Clozapine, a controversial gold standard antipsychotic for the 21st century: switching to paliperidone palmitate 3-monthly improves the metabolic profiles and lowers antipsychotic dose equivalents in a treatment-resistant schizophrenia cohort.","volume":"212","author":"Mart\u00ednez-Andr\u00e9s","year":"2019","journal-title":"Schizophr Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.psc.2016.01.006","article-title":"Treatment-resistant schizophrenia.","volume":"39","author":"Elkis","year":"2016","journal-title":"Psychiatr Clin North Am."},{"key":"B13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3371\/CSRP.4.1.4","article-title":"Clozapine for treatment-resistant schizophrenia: national Institute of Clinical Excellence(NICE) guidance in the real world.","volume":"4","author":"Mortimer","year":"2010","journal-title":"Clin Schizophr Relat Psychoses."},{"key":"B14","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1111\/acps.13361","article-title":"Clozapine levels as a predictor for therapeutic response: a systematic review and meta-analysis.","volume":"144","author":"Siskind","year":"2021","journal-title":"Acta Psychiatr Scand."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1021\/cn400121z","article-title":"Classics in chemical neuroscience: clozapine.","volume":"4","author":"Wenthur","year":"2013","journal-title":"ACS Chem Neurosci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1007\/s13311-017-0552-9","article-title":"Clozapine as a model for antipsychotic development.","volume":"14","author":"Nucifora","year":"2017","journal-title":"Neurotherapeutics."},{"key":"B17","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1023\/a:1023228626309","article-title":"Clozapine: a clinical review of adverse effects and management.","volume":"15","author":"Iqbal","year":"2003","journal-title":"Ann Clin Psychiatry."},{"key":"B18","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1093\/oxfordjournals.schbul.a033333","article-title":"Management of the adverse effects of clozapine.","volume":"24","author":"Young","year":"1998","journal-title":"Schizophr Bull."},{"key":"B19","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/BF01064682","article-title":"Clinical profile of clozapine: adverse reactions and agranulocytosis.","volume":"63","author":"Lieberman","year":"1992","journal-title":"Psychiatr Q."},{"key":"B20","first-page":"14","article-title":"Review and management of clozapine side effects.","volume":"61","author":"Miller","year":"2000","journal-title":"J Clin Psychiatry."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1447-0349.2007.00506.x","article-title":"Side-effects and treatment with clozapine: a comparison between the views of consumers and their clinicians.","volume":"17","author":"Hodge","year":"2008","journal-title":"Int J Ment Health Nurs."},{"key":"B22","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/acps.13224","article-title":"Moving forward with clozapine.","volume":"142","author":"Schulte","year":"2020","journal-title":"Acta Psychiatr Scand."},{"key":"B23","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1111\/acps.13406","article-title":"Recognition and management of clozapine adverse effects: a systematic review and qualitative synthesis.","volume":"145","author":"Gurrera","year":"2022","journal-title":"Acta Psychiatr Scand."},{"key":"B24","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/schbul\/sby052","article-title":"Clozapine and long-term mortality risk in patients with: a systematic review and meta-analysis of studies lasting 1.1-12.5 years.","volume":"45","author":"Vermeulen","year":"2019","journal-title":"Schizophr Bull."},{"key":"B25","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1055\/a-1811-7318","article-title":"Clinical outcomes after clozapine discontinuation in patients with schizophrenia: a systematic review.","volume":"55","author":"Miura","year":"2022","journal-title":"Pharmacopsychiatry."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.4088\/JCP.09m05785yel","article-title":"An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis.","volume":"72","author":"Agid","year":"2011","journal-title":"J Clin Psychiatry."},{"key":"B27","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S2215-036630252-9","article-title":"Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study.","volume":"5","author":"Kahn","year":"2018","journal-title":"Lancet Psychiatry."},{"key":"B28","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1080\/14740338.2020.1795126","article-title":"Up-to-date expert opinion on the safety of recently developed antipsychotics.","volume":"19","author":"Orsolini","year":"2020","journal-title":"Expert Opin Drug Saf."},{"key":"B29","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1586\/14737175.5.3.297","article-title":"Aripiprazole: pharmacology, efficacy, safety and tolerability.","volume":"5","author":"Kinghorn","year":"2005","journal-title":"Expert Rev Neurother."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.876003","article-title":"Case report: L g-acting oral cariprazine.","volume":"13","author":"Dyrmishi","year":"2022","journal-title":"Front Psychiatry."},{"key":"B31","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1176\/appi.ajp.161.3.398","article-title":"The pathophysiology of schizophrenia disorders: perspectives from the spectrum.","volume":"161","author":"Siever","year":"2004","journal-title":"Am J Psychiatry."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.641319","article-title":"Evolving concepts of the schizophrenia spectrum: a research domain criteria perspective.","volume":"12","author":"Cuthbert","year":"2021","journal-title":"Front Psychiatry."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1016\/j.pnpbp.2006.03.024","article-title":"Benefits of combining aripiprazole to clozapine: three case reports.","volume":"30","author":"Rocha","year":"2006","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.pnpbp.2011.03.011","article-title":"Add-on of aripiprazole improves outcome in clozapine-resistant schizophrenia.","volume":"35","author":"De Risio","year":"2011","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry."},{"key":"B35","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1097\/JCP.0b013e318296884f","article-title":"Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: a 12-month, randomized, naturalistic trial.","volume":"33","author":"Cipriani","year":"2013","journal-title":"J Clin Psychopharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.pnpbp.2006.09.015","article-title":"Aripiprazole augmentation in the management of residual symptoms in clozapine-treated outpatients with chronic schizophrenia: an open-label pilot study.","volume":"31","author":"Mitsonis","year":"2007","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry."},{"key":"B37","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.schres.2010.12.011","article-title":"Effect of aripiprazole augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study.","volume":"127","author":"Muscatello","year":"2011","journal-title":"Schizophr Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"30","DOI":"10.2174\/1745017901006010030","article-title":"Augmentation of clozapine with aripiprazole in severe psychotic bipolar and schizoaffective disorders: a pilot study.","volume":"6","author":"Benedetti","year":"2010","journal-title":"Clin Pract Epidemiol Ment Health."},{"key":"B39","doi-asserted-by":"publisher","first-page":"117","DOI":"10.2165\/00044011-200626030-00001","article-title":"Aripiprazole augmentation of clozapine in treatment-resistant schizophrenia: a clinical observation.","volume":"26","author":"Ziegenbein","year":"2006","journal-title":"Clin Drug Investig."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1017\/S1461145710000490","article-title":"Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial.","volume":"13","author":"Fleischhacker","year":"2010","journal-title":"Int J Neuropsychopharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"720","DOI":"10.4088\/jcp.v69n0505","article-title":"Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial.","volume":"69","author":"Chang","year":"2008","journal-title":"J Clin Psychiatry."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD006324.pub2","article-title":"Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia.","volume":"3","author":"Cipriani","year":"2009","journal-title":"Cochrane Database Syst Rev."},{"key":"B43","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jpsychires.2015.01.004","article-title":"Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: a systematic review and meta-analysis of randomized-controlled trials.","volume":"62","author":"Srisurapanont","year":"2015","journal-title":"J Psychiatr Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jpsychires.2018.11.005","article-title":"Adjunctive second-generation antipsychotics for specific symptom domains of schizophrenia resistant to clozapine: a meta-analysis.","volume":"108","author":"Bartoli","year":"2019","journal-title":"J Psychiatr Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1097\/JCP.0000000000000794","article-title":"Effective switch from clozapine to aripiprazole in treatment-resistant schizophrenia and comorbid alcohol use disorder.","volume":"37","author":"Feeley","year":"2017","journal-title":"J Clin Psychopharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1097\/JCP.0b013e318193c765","article-title":"Successful switch from clozapine to aripiprazole: a case report.","volume":"29","author":"Jong-Yih","year":"2009","journal-title":"J Clin Psychopharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1345\/aph.1E682","article-title":"Clozapine-induced hyperlipidemia resolved after switch to aripiprazole therapy.","volume":"39","author":"Ball","year":"2005","journal-title":"Ann Pharmacother."},{"key":"B48","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1097\/WNF.0000000000000191","article-title":"A case of resistant schizophrenia successfully treated with clozapine\/long-acting injectable aripiprazole combination.","volume":"39","author":"Sepede","year":"2016","journal-title":"Clin Neuropharmacol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/WNF.0000000000000404","article-title":"One plus one sometimes equals more then two: long-acting injectable aripiprazole adjunction in clozapine-resistant schizophrenia.","volume":"43","author":"Balcioglu","year":"2020","journal-title":"Clin Neuropharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/YIC.0000000000000336","article-title":"The effects of adding long-acting injectable antipsychotic drugs to clozapine on relapse and hospitalization in patients with treatment-resistant schizophrenia: a mirror-image retrospective study.","volume":"36","author":"Caliskan","year":"2021","journal-title":"Int Clin Psychopharmacol."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.19m02560","article-title":"Comparison of clozapine with long-acting injectable antipsychotics in treatment-resistant schizophrenia: preliminary evidence from health care utilization indices.","volume":"22","author":"Grimminck","year":"2020","journal-title":"Prim Care Companion CNS Disord."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajp.2022.103121","article-title":"A case report of clozapine-treatment-resistant schizophrenia successfully managed with brexpiprazole combination therapy.","volume":"72","author":"Orsolini","year":"2022","journal-title":"Asian J Psychiatry."},{"key":"B53","doi-asserted-by":"publisher","first-page":"S355","DOI":"10.1192\/j.eurpsy.2022.903","article-title":"Clozapine-treatment-resistant schizophrenia successfully managed with brexpiprazole combination therapy: two case reports.","volume":"65","author":"Orsolini","year":"2022","journal-title":"Eur Psychiatry."},{"key":"B54","doi-asserted-by":"publisher","first-page":"174","DOI":"10.9758\/cpn.2021.19.1.174","article-title":"Cariprazine add-on in inadequate clozapine response: a report on two cases.","volume":"19","author":"De Berardis","year":"2021","journal-title":"Clin Psychopharmacol Neurosci."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1177\/20451253211066642","article-title":"Clozapine augmentation with cariprazine for negative symptoms: a case series and literature review.","volume":"12","author":"Oloyede","year":"2022","journal-title":"Ther Adv Psychopharmacol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.2147\/NDT.S315653","article-title":"Cariprazine: patients with treatment-resistant schizophrenia.","volume":"17","author":"Aubel","year":"2021","journal-title":"Neuropsychiatr Dis Treat."},{"key":"B57","doi-asserted-by":"publisher","first-page":"398","DOI":"10.9758\/cpn.2022.20.2.398","article-title":"Add-on cariprazine in patients with long-term clozapine treatment and treatment resistant schizophrenia: two cases of psychotic deterioration and Pisa syndrome.","volume":"20","author":"Weise","year":"2022","journal-title":"Clin Psychopharmacol Neurosci."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.887547","article-title":"Remission of persistent negative symptoms and psychosocial consequences by combined clozapine and cariprazine treatment in a patient with long-standing treatment-resistant schizoaffective disorder.","volume":"13","author":"Bogren","year":"2022","journal-title":"Front Psychiatry."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.2147\/NDT.S367922","article-title":"Switching clozapine to cariprazine in three patients with persistent symptoms of schizophrenia: a case series.","volume":"18","author":"Duque-Yemail","year":"2022","journal-title":"Neuropsychiatr Dis Treat."},{"key":"B60","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1097\/JCP.0b013e318219cba3","article-title":"Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial.","volume":"31","author":"Barbui","year":"2011","journal-title":"J Clin Psychopharmacol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1080\/13543784.2016.1175431","article-title":"Aripiprazole for relapse prevention and craving in alcohol use disorder: current evidence and future perspectives.","volume":"25","author":"Martinotti","year":"2016","journal-title":"Expert Opin Investig Drugs."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.786171","article-title":"Case report: cariprazine efficacy in young patients diagnosed with schizophrenia with predominantly negative symptoms.","volume":"12","author":"Vasiliu","year":"2021","journal-title":"Front Psychiatry."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1177\/20451253211034019","article-title":"The role of lumateperone in the treatment of schizophrenia.","volume":"11","author":"Syed","year":"2021","journal-title":"Ther Adv Psychopharmacol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1001\/jamapsychiatry.2019.4379","article-title":"Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical trial.","volume":"77","author":"Correll","year":"2020","journal-title":"JAMA Psychiatry."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.884143","article-title":"Investigational drugs for the treatment of depression (part 1): monoaminergic, orexinergic, GABA-ergic, and anti-inflammatory agents.","volume":"13","author":"Vasiliu","year":"2022","journal-title":"Front Pharmacol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1176\/appi.ajp.2021.20091339","article-title":"Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial.","volume":"178","author":"Calabrese","year":"2021","journal-title":"Am J Psychiatry."},{"key":"B67","year":"2022","journal-title":"Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder. NCT05061706."}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.1069432\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T05:37:41Z","timestamp":1669700261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2022.1069432\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,29]]},"references-count":67,"alternative-id":["10.3389\/fpsyt.2022.1069432"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2022.1069432","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,29]]},"article-number":"1069432"}}