98
Views
0
CrossRef citations to date
0
Altmetric
Review

A review on side effect management of second-generation antipsychotics to treat schizophrenia: a drug safety perspective

ORCID Icon, , &
Pages 715-729 | Received 09 Nov 2023, Accepted 24 Apr 2024, Published online: 06 May 2024

References

  • Stahl SM, Sy S, Maguire GA. How and when to treat the most common adverse effects of antipsychotics: expert review from research to clinical practice. Acta Psychiatr Scand. 2021 Feb;143(2):172–180. doi: 10.1111/acps.13266
  • Schneider-Thoma J, Chalkou K, Dorries C, et al. Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis. Lancet. 2022 Feb 26;399(10327):824–836. doi: 10.1016/S0140-6736(21)01997-8
  • Beaudoin M, Hudon A, Giguere CE, et al. Prediction of quality of life in schizophrenia using machine learning models on data from clinical antipsychotic trials of intervention effectiveness (CATIE) schizophrenia trial. Schizophrenia (Heidelb). 2022 Mar 21;8(1):29. doi: 10.1038/s41537-022-00236-w
  • Dibonaventura M, Gabriel S, Dupclay L, et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry. 2012 Mar 20;12(1):20. doi: 10.1186/1471-244X-12-20
  • Grunder G, Heinze M, Cordes J, et al. Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of life in schizophrenia: a double-blind, randomised study. Lancet Psychiatry. 2016 Aug;3:(8):717–729.
  • Lally J, MacCabe JH. Antipsychotic medication in schizophrenia: a review. Br Med Bull. 2015 Jun;114(1):169–179. doi: 10.1093/bmb/ldv017
  • German Society for Psychiatry, Psychotherapy and Neurology (DGPPN e.V.) (ed.) for the guideline group: S3 guideline schizophrenia. Long version, 2019, version 1.0, last modified March 15, 2019.
  • SIGN G. Scottish intercollegiate guidelines network (SIGN). Management of attention deficit and hyperkinetic disorders in children and young people: a national clinical guideline. 2009:112.
  • Health NCCfM. Psychosis and schizophrenia in adults: treatment and management. 2014.
  • Barnes TR, Drake R, Paton C, et al. Evidence-based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the british association for psychopharmacology. J Psychopharmacol. 2020 Jan;34:(1):3–78.
  • Salzmann-Erikson M, Sjodin M. A narrative meta-synthesis of how people with schizophrenia experience facilitators and barriers in using antipsychotic medication: implications for healthcare professionals. Int J Nurs Stud. 2018 Sep;85:7–18. doi: 10.1016/j.ijnurstu.2018.05.003
  • Hasan A, Falkai P, Lehmann I, et al. Schizophrenia. Dtsch Arztebl Int. 2020 Jun 12;117(24):412–419. doi: 10.3238/arztebl.2020.0412
  • Huhn M, Nikolakopoulou A, Schneider-Thoma J, et al. 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. Lancet. 2019 Sep 14;394(10202):939–951. doi: 10.1016/S0140-6736(19)31135-3
  • Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013 Sep 14;382(9896):951–962. doi: 10.1016/S0140-6736(13)60733-3
  • Sabe M, Zhao N, Crippa A, et al. Antipsychotics for negative and positive symptoms of schizophrenia: dose-response meta-analysis of randomized controlled acute phase trials. NPJ Schizophr. 2021 Sep 13;7(1):43. doi: 10.1038/s41537-021-00171-2
  • Zhu Y, Li C, Huhn M, et al. How well do patients with a first episode of schizophrenia respond to antipsychotics: a systematic review and meta-analysis. Eur Neuropsychopharmacol. 2017 Sep;27:(9):835–844.
  • Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005 Sep 22;353(12):1209–1223. doi: 10.1056/NEJMoa051688
  • Kahn RS, Fleischhacker WW, Boter H, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 2008 Mar 29;371(9618):1085–1097. doi: 10.1016/S0140-6736(08)60486-9
  • Jones PB, Barnes TR, Davies L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: cost utility of the latest antipsychotic drugs in schizophrenia study (CUtLASS 1). Arch Gen Psychiatry. 2006 Oct;63:(10):1079–1087.
  • Chen Z, Fan L, Wang H, et al. Structure-based design of a novel third-generation antipsychotic drug lead with potential antidepressant properties. Nat Neurosci. 2022 Jan;25:(1):39–49.
  • Vasiliu O. Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: what is the evidence? Front Psychiatry. 2022;13:1069432. doi: 10.3389/fpsyt.2022.1069432
  • McCutcheon RA, Harrison PJ, Howes OD, et al. Data-driven taxonomy for antipsychotic medication: a new classification system. Biol Psychiatry. 2023 Oct 1;94(7):561–568. doi: 10.1016/j.biopsych.2023.04.004
  • Correll CU, Abi-Dargham A, Howes O. Emerging treatments in schizophrenia. J Clin Psychiatry. 2022 Feb 15;83(1). doi: 10.4088/JCP.SU21024IP1
  • Brannan SK, Sawchak S, Miller AC, et al. Muscarinic cholinergic receptor agonist and peripheral antagonist for schizophrenia. N Engl J Med. 2021 Feb 25;384(8):717–726. doi: 10.1056/NEJMoa2017015
  • Dean B. Muscarinic M1 and M4 receptor agonists for schizophrenia: promising candidates for the therapeutic arsenal. Expert Opin Investig Drugs. 2023 Jul;32(12):1113–1121. doi: 10.1080/13543784.2023.2288074
  • Siafis S, Wu H, Wang D, et al. Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis. Mol Psychiatry. 2023 Aug;28:(8):3267–3277.
  • Rummel-Kluge C, Komossa K, Schwarz S, et al. Second-generation antipsychotic drugs and extrapyramidal side effects: a systematic review and meta-analysis of head-to-head comparisons. Schizophr Bull. 2012 Jan;38:(1):167–177.
  • Chang C-C, Chen H-K. The prevalence of constipation and its risk factors in patients with schizophrenia. Taiwan J Psychiatry. 2021;35(2):95–98. doi: 10.4103/tpsy.tpsy_20_21
  • Chiappini S, Mosca A, Miuli A, et al. Misuse of anticholinergic medications: a systematic review. Biomedicines. 2022 Feb 1;10(2):355. doi: 10.3390/biomedicines10020355
  • Haddad C, Salameh P, Sacre H, et al. Effects of antipsychotic and anticholinergic medications on cognition in chronic patients with schizophrenia. BMC Psychiatry. 2023 Jan 24;23(1):61. doi: 10.1186/s12888-023-04552-y
  • Joshi YB, Thomas ML, Braff DL, et al. Anticholinergic medication burden-associated cognitive impairment in schizophrenia. Am J Psychiatry. 2021 Sep 1;178(9):838–847. doi: 10.1176/appi.ajp.2020.20081212
  • Caroff SN, Citrome L, Meyer J, et al. A modified delphi consensus study of the screening, diagnosis, and treatment of Tardive Dyskinesia. J Clin Psychiatry. 2020 Jan 28;81(2). doi: 10.4088/JCP.19cs12983
  • Marzoughi S, Banerjee A, Jutzeler CR, et al. Tardive neurotoxicity of anticholinergic drugs: a review. J Neurochem. 2021 Sep;158:(6):1334–1344.
  • Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989;154(5):672–676. doi: 10.1192/bjp.154.5.672
  • Barnes TR. The Barnes akathisia rating scale–revisited. J Psychopharmacol. 2003;17(4):365–370. doi: 10.1177/0269881103174013
  • Gerlach J, Korsgaard S, Clemmesen P, et al. The st. Hans rating scale for extrapyramidal syndromes: reliability and validity. Acta Psychiatr Scand. 1993;87(4):244–252. doi: 10.1111/j.1600-0447.1993.tb03366.x
  • Onishi H, Yoshioka A, Sato I, et al. Akathisia, an easily overlooked side effect. J Clin Oncol: Off J Am Society Clin Oncol. 2023 Jun 23;41(25):4184–4185. doi: 10.1200/jco.23.00853
  • Thompson H. Implementation of an akathisia scale into the mental health assessment to screen for early-onset akathisia. 2021.
  • Bjarke J, Gjerde HN, Jorgensen HA, et al. Akathisia and atypical antipsychotics: relation to suicidality, agitation and depression in a clinical trial. Acta Neuropsychiatr. 2022 Oct;34:(5):282–288.
  • Wu H, Siafis S, Wang D, et al. Antipsychotic-induced akathisia in adults with acute schizophrenia: a systematic review and dose-response meta-analysis. Eur Neuropsychopharmacol. 2023 Jul;72:40–49. doi: 10.1016/j.euroneuro.2023.03.015
  • Demyttenaere K, Detraux J, Racagni G, et al. Medication-induced akathisia with newly approved antipsychotics in patients with a severe mental illness: a systematic review and meta-analysis. CNS Drugs. 2019 Jun;33:(6):549–566.
  • Salem H, Nagpal C, Pigott T, et al. Revisiting antipsychotic-induced akathisia: Current issues and prospective challenges. Curr Neuropharmacol. 2017;15(5):789–798. doi: 10.2174/1570159X14666161208153644
  • Musco S, McAllister V, Caudle I. Dopamine-receptor blocking agent-associated akathisia: a summary of current understanding and proposal for a rational approach to treatment. Ther Adv Psychopharmacol. 2020;10:2045125320937575. doi: 10.1177/2045125320937575
  • Poyurovsky M, Weizman A. Treatment of Antipsychotic-Induced Akathisia: role of serotonin 5-HT(2a) receptor antagonists. Drugs. 2020 Jun;80(9):871–882. doi: 10.1007/s40265-020-01312-0
  • Pringsheim T, Gardner D, Addington D, et al. The assessment and treatment of antipsychotic-induced akathisia. Can J Psychiatry. 2018 Nov;63:(11):719–729.
  • Zareifopoulos N, Katsaraki M, Stratos P, et al. Pathophysiology and management of akathisia 70 years after the introduction of the chlorpromazine, the first antipsychotic. Eur Rev Med Pharmacol Sci. 2021 Jan;25:(14):4746–4756.
  • Shams-Alizadeh N, Bakhshayesh H, Rezaei F, et al. Effect of vitamin B6 versus propranolol on antipsychotic-induced akathisia: a pilot comparative double-blind study. Iran J Pharm Res. 2018 Winter;17(Suppl):130–135.
  • Carbon M, Hsieh CH, Kane JM, et al. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017 Mar;78:(3):e264–e278.
  • Carbon M, Kane JM, Leucht S, et al. Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis. World Psychiatry. 2018 Oct;17:(3):330–340.
  • Stegmayer K, Walther S, van Harten P. Tardive dyskinesia associated with atypical antipsychotics: prevalence, mechanisms and management strategies. CNS Drugs. 2018 Feb;32(2):135–147. doi: 10.1007/s40263-018-0494-8
  • Mentzel TQ, van der Snoek R, Lieverse R, et al. Clozapine monotherapy as a treatment for Antipsychotic-Induced Tardive Dyskinesia: a meta-analysis. J Clin Psychiatry. 2018 Sep 18;79(6). doi: 10.4088/JCP.17r11852
  • Pardis P, Remington G, Panda R, et al. Clozapine and tardive dyskinesia in patients with schizophrenia: a systematic review. J Psychopharmacol. 2019 Oct;33:(10):1187–1198.
  • Wong J, Pang T, Cheuk NKW, et al. A systematic review on the use of clozapine in treatment of tardive dyskinesia and tardive dystonia in patients with psychiatric disorders. Psychopharmacol (Berl). 2022 Nov;239:(11):3393–3420.
  • Dorfman BJ, Jimenez-Shahed J. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia. Expert Rev Neurother. 2021 Jan;21(1):9–20. doi: 10.1080/14737175.2021.1848548
  • Solmi M, Pigato G, Kane JM, et al. Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2018;12:1215–1238. doi: 10.2147/DDDT.S133205
  • Takeuchi H, Mori Y, Tsutsumi Y. Pathophysiology, prognosis and treatment of tardive dyskinesia. Ther Adv Psychopharmacol. 2022;12:20451253221117313. doi: 10.1177/20451253221117313
  • Szczakowska A, Gabryelska A, Gawlik-Kotelnicka O, et al. Deep brain stimulation in the treatment of tardive dyskinesia. J Clin Med. 2023;12(5):1868. doi: 10.3390/jcm12051868
  • Castle DJ, Buckley PF, Gaughran FP. Physical health and schizophrenia. Oxford: Oxford University Press; 2017. https://global.oup.com/academic/product/physical-health-and-schizophrenia-9780198811688?lang=en&cc=us
  • Correll CU, Solmi M, Croatto G, et al. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 2022 Jun;21:(2):248–271.
  • Doane MJ, Bessonova L, Friedler HS, et al. Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder. BMC Psychiatry. 2022 Feb 14;22(1):114. doi: 10.1186/s12888-022-03758-w
  • Rummel-Kluge C, Komossa K, Schwarz S, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010 Nov;123:(2–3):225–233.
  • Annamalai A, Tek C. An overview of diabetes management in schizophrenia patients: office based strategies for primary care practitioners and endocrinologists. Int J Endocrinol. 2015;2015:969182. doi: 10.1155/2015/969182
  • Bernardo M, Rico-Villademoros F, Garcia-Rizo C, et al. Real-world data on the adverse metabolic effects of second-generation antipsychotics and their potential determinants in adult patients: a systematic review of population-based studies. Adv Ther. 2021 May;38:(5):2491–2512.
  • Hirsch L, Patten SB, Bresee L, et al. Second-generation antipsychotics and metabolic side-effects: Canadian population-based study. BJPsych Open. 2018 Jul;4:(4):256–261.
  • Musil R, Obermeier M, Russ P, et al. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf. 2015 Jan;14:(1):73–96.
  • Galling B, Roldan A, Nielsen RE, et al. Type 2 diabetes mellitus in youth exposed to antipsychotics: a systematic review and meta-analysis. JAMA Psychiatry. 2016 Mar;73:(3):247–259.
  • Garrido-Torres N, Rocha-Gonzalez I, Alameda L, et al. Metabolic syndrome in antipsychotic-naive patients with first-episode psychosis: a systematic review and meta-analysis. Psychol Med. 2021 Oct;51:(14):2307–2320.
  • Misiak B, Frydecka D, Laczmanski L, et al. Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients. Eur J Clin Pharmacol. 2014 Dec;70:(12):1433–1441.
  • Plosker GL, Deeks ED. Asenapine: a review in schizophrenia. CNS Drugs. 2016 Jul;30(7):655–666. doi: 10.1007/s40263-016-0363-2
  • Durgam S, Landbloom RP, Mackle M, et al. Exploring the long-term safety of asenapine in adults with schizophrenia in a double-blind, fixed-dose, extension study. Neuropsychiatr Dis Treat. 2017;Volume 13:2021–2035. doi: 10.2147/NDT.S130211
  • Meyer JM, Ng-Mak DS, Chuang C-C, et al. Weight changes before and after lurasidone treatment: a real-world analysis using electronic health records. Ann Gen Psychiatry. 2017;16(1):1–9. doi: 10.1186/s12991-017-0159-x
  • Pochiero I, Calisti F, Comandini A, et al. Impact of lurasidone and other antipsychotics on body weight: real-world, retrospective, comparative study of 15,323 adults with schizophrenia. Int J Gene Med. 2021;Volume 14:4081–4094. doi: 10.2147/IJGM.S320611
  • Barton BB, Segger F, Fischer K, et al. Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis. Expert Opin Drug Saf. 2020 Mar;19:(3):295–314.
  • De Hert M, Yu W, Detraux J, et al. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs. 2012 Sep 1;26(9):733–759. doi: 10.2165/11634500-000000000-00000
  • Cimo A, Stergiopoulos E, Cheng C, et al. Effective lifestyle interventions to improve type II diabetes self-management for those with schizophrenia or schizoaffective disorder: a systematic review. BMC Psychiatry. 2012 Mar 23;12(1):24. doi: 10.1186/1471-244X-12-24
  • Marteene W, Winckel K, Hollingworth S, et al. Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia. Expert Opin Drug Saf. 2019 Dec;18:(12):1149–1160.
  • Alvarez-Jimenez M, Hetrick SE, Gonzalez-Blanch C, et al. Non-pharmacological management of antipsychotic-induced weight gain: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry. 2008;193(2):101–107. doi: 10.1192/bjp.bp.107.042853
  • Teasdale SB, Ward PB, Rosenbaum S, et al. Solving a weighty problem: systematic review and meta-analysis of nutrition interventions in severe mental illness. Br J Psychiatry. 2017;210(2):110–118. doi: 10.1192/bjp.bp.115.177139
  • Rosenbaum S, Tiedemann A, Sherrington C, et al. Physical activity interventions for people with mental illness: a systematic review and meta-analysis. J Clin Psychiatry. 2014;75(9):14465. doi: 10.4088/JCP.13r08765
  • Speyer H, Christian Brix Nørgaard H, Birk M, et al. The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity. World Psychiatry. 2016;15(2):155–165. doi: 10.1002/wps.20318
  • Green CA, Yarborough BJH, Leo MC, et al. The STRIDE weight loss and lifestyle intervention for individuals taking antipsychotic medications: a randomized trial. Am J Psychiatry. 2015;172(1):71–81. doi: 10.1176/appi.ajp.2014.14020173
  • Ostuzzi G, Vita G, Bertolini F, et al. Continuing, reducing, switching, or stopping antipsychotics in individuals with schizophrenia-spectrum disorders who are clinically stable: a systematic review and network meta-analysis. Lancet Psychiatry. 2022 Aug;9:(8):614–624.
  • Bak M, Drukker M, Cortenraad S, et al. Antipsychotics result in more weight gain in antipsychotic naive patients than in patients after antipsychotic switch and weight gain is irrespective of psychiatric diagnosis: a meta-analysis. PLoS One. 2021;16(2):e0244944. doi: 10.1371/journal.pone.0244944
  • Leucht S, Corves C, Arbter D, et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009 Jan 3;373(9657):31–41. doi: 10.1016/S0140-6736(08)61764-X
  • de Silva VA, Suraweera C, Ratnatunga SS, et al. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016 Oct 3;16(1):341. doi: 10.1186/s12888-016-1049-5
  • Mizuno Y, Suzuki T, Nakagawa A, et al. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull. 2014 Nov;40:(6):1385–1403.
  • Siskind DJ, Leung J, Russell AW, et al. Metformin for clozapine associated obesity: a systematic review and meta-analysis. PLoS One. 2016;11(6):e0156208. doi: 10.1371/journal.pone.0156208
  • Fitzgerald I, O’Connell J, Keating D, et al. Metformin in the management of antipsychotic-induced weight gain in adults with psychosis: development of the first evidence-based guideline using GRADE methodology. Evid Based Ment Health. 2022 Feb;25:(1):15–22.
  • Goh KK, Chen CH, Lu ML. Topiramate mitigates weight gain in antipsychotic-treated patients with schizophrenia: meta-analysis of randomised controlled trials. Int J Psychiatry Clin Pract. 2019 Mar;23(1):14–32. doi: 10.1080/13651501.2018.1449864
  • Okuyama Y, Oya K, Matsunaga S, et al. Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat. 2016;12:3221–3236. doi: 10.2147/NDT.S125367
  • Zheng W, Xiang YT, Xiang YQ, et al. Efficacy and safety of adjunctive topiramate for schizophrenia: a meta-analysis of randomized controlled trials. Acta Psychiatr Scand. 2016 Nov;134:(5):385–398.
  • Kouidrat Y, Amad A. GLP-1 agonists for metabolic disorders in schizophrenia. Schizophr Res. 2019 Feb;204:448–449. doi: 10.1016/j.schres.2018.09.019
  • Kouidrat Y, Amad A, Stubbs B, et al. Surgical management of obesity among people with schizophrenia and bipolar disorder: a systematic review of outcomes and recommendations for future research. Obes Surg. 2017 Jul;27:(7):1889–1895.
  • Noda K, Kato T, Nomura N, et al. Semaglutide is effective in type 2 diabetes and obesity with schizophrenia. Diabetol Int. 2022 Oct;13:(4):693–697.
  • Prasad F, De R, Korann V, et al. Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin – a case series. Ther Adv Psychopharmacol. 2023;13:20451253231165169. doi: 10.1177/20451253231165169
  • Gupta D, Singh A. Olanzapine-samidorphan for schizophrenia: a systematic review and meta-analysis. Indian J Psychol Med. 2023;46(1):14–23. doi: 10.1177/02537176231201326
  • Corrao MM, Nelson LA. Olanzapine/Samidorphan: a new combination treatment for schizophrenia and bipolar I disorder intended to reduce weight gain. CNS Drugs. 2022 Jun;36(6):605–616. doi: 10.1007/s40263-022-00923-3
  • Jawad MY, Alnefeesi Y, Lui LMW, et al. Olanzapine and samidorphan combination treatment: a systematic review. J Affect Disord. 2022 Mar 15;301:99–106. doi: 10.1016/j.jad.2022.01.004
  • Peng Z, Jia Q, Mao J, et al. Effects of combined therapy of olanzapine and Samidorphan on safety and metabolic parameters in schizophrenia patients: a meta-analysis. Neuropsychiatr Dis Treat. 2023;19:2295–2308. doi: 10.2147/NDT.S426481
  • Tse L, Procyshyn RM, Fredrikson DH, et al. Pharmacological treatment of antipsychotic-induced dyslipidemia and hypertension. Int Clin Psychopharmacol. 2014;29(3):125–137. doi: 10.1097/YIC.0000000000000014
  • Jiang W-L, Cai D-B, Yin F, et al. Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials. Transl Psychiatry. 2020;10(1):117. doi: 10.1038/s41398-020-0785-y
  • Marvanova M. Strategies for prevention and management of second generation antipsychotic-induced metabolic side effects. Mental Health Clinician. 2013;3(3):154–161. doi: 10.9740/mhc.n166832
  • Souaiby L, Kazour F, Zoghbi M, et al. Sexual dysfunction in patients with schizophrenia and schizoaffective disorder and its association with adherence to antipsychotic medication. J Ment Health. 2020 Dec;29:(6):623–630.
  • Montejo ÁL, Majadas S, Rico-Villademoros F, et al. Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics. J Sex Med. 2010;7(10):3404–3413. doi: 10.1111/j.1743-6109.2010.01709.x
  • Rodrigues C. Management of antipsychotic-related sexual dysfunction. Eur Psychiatry. 2022;65(S1):S712–S712. doi: 10.1192/j.eurpsy.2022.1836
  • Allen K, Baban A, Munjiza J, et al. Management Of antipsychotic-related sexual dysfunction: systematic review. J Sex Med. 2019 Dec;16:(12):1978–1987.
  • Gonzalez-Blanco L, Greenhalgh AMD, Garcia-Rizo C, et al. Prolactin concentrations in antipsychotic-naïve patients with schizophrenia and related disorders: a meta-analysis. Schizophrenia Research. 2016 Jul;174:(1–3):156–160.
  • Aymerich C, Pedruzo B, Pacho M, et al. Prolactin and morning cortisol concentrations in antipsychotic naive first episode psychosis: a systematic review and meta-analysis. Psychoneuroendocrinology. 2023 Apr;150:106049. doi: 10.1016/j.psyneuen.2023.106049
  • Bargiota SI, Bonotis KS, Messinis IE, et al. The effects of antipsychotics on prolactin levels and Women’s menstruation. Schizophr Res Treatment. 2013;2013:1–10. doi: 10.1155/2013/502697
  • Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the pituitary society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006 Aug;65:(2):265–273.
  • Gorobets LN, Semenova ND, Litvinov AV. Application of antipsychotic medication: gender differences in tolerance and medication response. Jour. 2022;2(2):57–66. doi: 10.52667/2712-9179-2022-2-2-57-66
  • Andrade C. Prolactin-raising and prolactin-sparing antipsychotic drugs and the risk of fracture and fragility fracture in patients with schizophrenia, dementia, and other disorders. J Clin Psychiatry. 2023 Jan 30;84(1). doi: 10.4088/JCP.23f14790
  • Gonzalez-Rodriguez A, Labad J, Seeman MV. Antipsychotic-induced hyperprolactinemia in aging populations: prevalence, implications, prevention and management. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jul 13;101:109941. doi: 10.1016/j.pnpbp.2020.109941
  • Rahman T, Sahrmann JM, Olsen MA, et al. Risk of breast cancer with prolactin elevating antipsychotic drugs: an observational study of US women (ages 18–64 years). J Clin Psychopharmacol. 2022 Jan 1;42(1):7–16. doi: 10.1097/JCP.0000000000001513
  • Taipale H, Solmi M, Lahteenvuo M, et al. Antipsychotic use and risk of breast cancer in women with schizophrenia: a nationwide nested case-control study in Finland. Lancet Psychiatry. 2021 Oct;8:(10):883–891.
  • Montejo AL, Arango C, Bernardo M, et al. Multidisciplinary consensus on the therapeutic recommendations for iatrogenic hyperprolactinemia secondary to antipsychotics. Front Neuroendocrinol. 2017 Apr;45:25–34. doi: 10.1016/j.yfrne.2017.02.003
  • Rusgis MM, Alabbasi AY, Nelson LA. Guidance on the treatment of antipsychotic-induced hyperprolactinemia when switching the antipsychotic is not an option. Am J Health Syst Pharm. 2021 May 6;78(10):862–871. doi: 10.1093/ajhp/zxab065
  • Keks N, Hope J, Schwartz D, et al. Comparative tolerability of dopamine D2/3 receptor partial agonists for schizophrenia. CNS Drugs. 2020 May;34:(5):473–507.
  • Jiang Q, Li T, Zhao L, et al. Treatment of antipsychotic-induced hyperprolactinemia: a systematic review of systematic reviews and meta-analyses. 2023.
  • Labad J, Montalvo I, Gonzalez-Rodriguez A, et al. Pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia: a systematic review and meta-analysis. Schizophr Res. 2020 Aug;222:88–96. doi: 10.1016/j.schres.2020.04.031
  • Fan Z, Wu Y, Shen J, et al. Schizophrenia and the risk of cardiovascular diseases: a meta-analysis of thirteen cohort studies. J Psychiatr Res. 2013 Nov;47:(11):1549–1556.
  • Hennekens CH, Hennekens AR, Hollar D, et al. Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005 Dec;150:(6):1115–1121.
  • Li M, Fan YL, Tang ZY, et al. Schizophrenia and risk of stroke: a meta-analysis of cohort studies. Int J Cardiol. 2014 May 15;173(3):588–590. doi: 10.1016/j.ijcard.2014.03.101
  • Westman J, Eriksson SV, Gissler M, et al. Increased cardiovascular mortality in people with schizophrenia: a 24-year national register study. Epidemiol Psychiatr Sci. 2018 Oct;27:(5):519–527.
  • Sweeney M, Whiskey E, Patel RK, et al. Understanding and managing cardiac side-effects of second-generation antipsychotics in the treatment of schizophrenia. BJPsych Adv. 2020;26(1):26–40. doi: 10.1192/bja.2019.49
  • Rotella F, Cassioli E, Calderani E, et al. Long-term metabolic and cardiovascular effects of antipsychotic drugs. A meta-analysis of randomized controlled trials. Eur Neuropsychopharmacol. 2020 Mar;32:56–65. doi: 10.1016/j.euroneuro.2019.12.118
  • Wagle A. Psychotropic medications and heart. Open Acc J Biomed Sci. 2022;4(1). doi: 10.38125/OAJBS.000385
  • Huhn M, Arndt T, Schneider-Thoma J, et al. Effects of antipsychotics on heart rate in treatment of schizophrenia: a systematic review and meta-analysis. Ther Adv Psychopharmacol. 2022;12:20451253221097261. doi: 10.1177/20451253221097261
  • Ali Z, Ismail M, Nazar Z, et al. Prevalence of QTc interval prolongation and its associated risk factors among psychiatric patients: a prospective observational study. BMC Psychiatry. 2020 Jun 3;20(1):277. doi: 10.1186/s12888-020-02687-w
  • Du W, Ge MW, Hu FH, et al. Qtc prolongation in patients with schizophrenia taking antipsychotics: prevalence and risk factors. J Psychopharmacol. 2023 Oct;37:(10):971–981.
  • Vohra J. Sudden cardiac death in schizophrenia: a review. Heart Lung Circ. 2020 Oct;29(10):1427–1432. doi: 10.1016/j.hlc.2020.07.003
  • Bordet C, Garcia P, Salvo F, et al. Antipsychotics and risk of QT prolongation: a pharmacovigilance study. Psychopharmacol (Berl). 2023 Jan;240:(1):199–202.
  • Fanoe S, Kristensen D, Fink-Jensen A, et al. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management. Eur Heart J. 2014 May 21;35(20):1306–1315. doi: 10.1093/eurheartj/ehu100
  • Ruiz Diaz JC, Frenkel D, Aronow WS. The relationship between atypical antipsychotics drugs, QT interval prolongation, and torsades de pointes: implications for clinical use. Expert Opin Drug Saf. 2020 May;19(5):559–564. doi: 10.1080/14740338.2020.1745184
  • Gurrera RJ, Gearin PF, Love J, et al. Recognition and management of clozapine adverse effects: a systematic review and qualitative synthesis. Acta Psychiatr Scand. 2022 May;145:(5):423–441.
  • de Filippis R, De Fazio P, Kane JM, et al. Pharmacovigilance approaches to study rare and very rare side-effects: the example of clozapine-related DiHS/DRESS syndrome. Expert Opin Drug Saf. 2022 May;21:(5):585–587.
  • Correll CU, Agid O, Crespo-Facorro B, et al. A guideline and checklist for initiating and managing clozapine treatment in patients with treatment-resistant schizophrenia. CNS Drugs. 2022 Jul;36:(7):659–679.
  • Oloyede E, Blackman G, Whiskey E, et al. Clozapine haematological monitoring for neutropenia: a global perspective. Epidemiol Psychiatr Sci. 2022 Nov 25;31:e83. doi: 10.1017/S204579602200066X
  • Manu P, Sarvaiya N, Rogozea LM, et al. Benign ethnic neutropenia and clozapine use: a systematic review of the evidence and treatment recommendations. J Clin Psychiatry. 2016 Jul;77:(7):e909–16.
  • Aydin M, Ilhan BC, Calisir S, et al. Continuing clozapine treatment with lithium in schizophrenic patients with neutropenia or leukopenia: brief review of literature with case reports. Ther Adv Psychopharmacol. 2016 Feb;6:(1):33–38.
  • Corbeil O, Bechard L, Fournier E, et al. Clozapine rechallenge or continuation despite neutropenia or agranulocytosis using colony-stimulating factor: a systematic review. J Psychopharmacol. 2023 Apr;37:(4):370–377.
  • Myles N, Myles H, Xia S, et al. A meta-analysis of controlled studies comparing the association between clozapine and other antipsychotic medications and the development of neutropenia. Aust N Z J Psychiatry. 2019 May;53:(5):403–412.
  • Myles N, Myles H, Xia S, et al. Meta-analysis examining the epidemiology of clozapine-associated neutropenia. Acta Psychiatr Scand. 2018 Aug;138:(2):101–109.
  • Ronaldson KJ, Fitzgerald PB, Taylor AJ, et al. Rapid clozapine dose titration and concomitant sodium valproate increase the risk of myocarditis with clozapine: a case-control study. Schizophr Res. 2012 Nov;141:(2–3):173–178.
  • Vickers M, Ramineni V, Malacova E, et al. Risk factors for clozapine-induced myocarditis and cardiomyopathy: a systematic review and meta-analysis. Acta Psychiatr Scand. 2022 May;145:(5):442–455.
  • Yuen JW, Kim DD, Procyshyn RM, et al. A focused review of the metabolic side-effects of clozapine. Front Endocrinol. 2021;12:67. doi: 10.3389/fendo.2021.609240
  • Williams AM, Park SH. Seizure associated with clozapine: incidence, etiology, and management. CNS Drugs. 2015;29(2):101–111. doi: 10.1007/s40263-014-0222-y
  • Zheng W, Xiang Y-T, Yang X-H, et al. Clozapine augmentation with antiepileptic drugs for treatment-resistant schizophrenia: a meta-analysis of randomized controlled trials. J Clin Psychiatry. 2017;78(5):3011. doi: 10.4088/JCP.16r10782
  • Solmi M, Tiihonen J, Lahteenvuo M, et al. Antipsychotics use is associated with greater adherence to cardiometabolic medications in patients with schizophrenia: results from a nationwide, within-subject design study. Schizophr Bull. 2022 Jan 21;48(1):166–175. doi: 10.1093/schbul/sbab087
  • Guinart D, Taipale H, Rubio JM, et al. Risk factors, incidence, and outcomes of neuroleptic malignant syndrome on long-acting injectable vs oral antipsychotics in a nationwide schizophrenia cohort. Schizophr Bull. 2021 Oct 21;47(6):1621–1630. doi: 10.1093/schbul/sbab062
  • Guinart D, Misawa F, Rubio JM, et al. A systematic review and pooled, patient-level analysis of predictors of mortality in neuroleptic malignant syndrome. Acta Psychiatr Scand. 2021 Oct;144:(4):329–341.
  • Chilari M, Chianu M. Malignant neuroleptic syndrome in the use of atypical neuroleptics in the treatment of schizophrenia. 2020.
  • Tse L, Barr AM, Scarapicchia V, et al. Neuroleptic malignant syndrome: a review from a clinically oriented perspective. Curr Neuropharmacol. 2015;13(3):395–406. doi: 10.2174/1570159X13999150424113345
  • Strawn JR, Keck PE Jr., Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007 Jun;164(6):870–876. doi: 10.1176/ajp.2007.164.6.870
  • Belvederi Murri M, Guaglianone A, Bugliani M, et al. Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs In R&D. 2015;15(1):45–62. doi: 10.1007/s40268-014-0078-0
  • Lao KS, Zhao J, Blais JE, et al. Antipsychotics and risk of neuroleptic malignant syndrome: a population-based cohort and case-crossover study. CNS Drugs. 2020;34(11):1165–1175. doi: 10.1007/s40263-020-00767-9
  • Misawa F, Okumura Y, Takeuchi Y, et al. Neuroleptic malignant syndrome associated with long-acting injectable versus oral second-generation antipsychotics: analyses based on a spontaneous reporting system database in Japan. Schizophr Res. 2021 May;231:42–46. doi: 10.1016/j.schres.2021.02.016
  • Langan J, Martin D, Shajahan P, et al. Antipsychotic dose escalation as a trigger for neuroleptic malignant syndrome (NMS): literature review and case series report. BMC Psychiatry. 2012 Nov 29;12(1):214. doi: 10.1186/1471-244X-12-214
  • Schonfeldt-Lecuona C, Kuhlwilm L, Cronemeyer M, et al. Treatment of the neuroleptic malignant syndrome in international therapy guidelines: a comparative analysis. Pharmacopsychiatry. 2020 Mar;53:(2):51–59.
  • Pileggi DJ, Cook AM. Neuroleptic malignant syndrome: focus on treatment and rechallenge. Ann Pharmacother. 2016;50(11):973–981. doi: 10.1177/1060028016657553
  • Lang FU, Lang S, Becker T, et al. Neuroleptic malignant syndrome or catatonia? Trying to solve the catatonic dilemma. Psychopharmacology. 2015;232(1):1–5. doi: 10.1007/s00213-014-3807-8
  • Davis JM, Janicak PG, Sakkas P, et al. Electroconvulsive therapy in the treatment of the neuroleptic malignant syndrome. J Ect. 1991;7(2):111–120.
  • Morcos N, Rosinski A, Maixner DF. Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. J Ect. 2019;35(4):225–230. doi: 10.1097/YCT.0000000000000600
  • Henshall C, Cipriani A, Ruvolo D, et al. Implementing a digital clinical decision support tool for side effects of antipsychotics: a focus group study. Evid Based Ment Health. 2019 May;22:(2):56–60.
  • Pillinger T, Howes OD, Correll CU, et al. Antidepressant and antipsychotic side-effects and personalised prescribing: a systematic review and digital tool development. Lancet Psychiatry. 2023 Nov;10:(11):860–876.
  • van Dijk F, de Wit I, Blankers M, et al. The personal antipsychotic choice index. Pharmacopsychiatry. 2018 May;51:(3):89–99.
  • Leucht S, Siafis S, Rodolico A, et al. Shared decision making Assistant (SDMA) and other digital tools for choosing antipsychotics in schizophrenia treatment. Eur Arch Psychiatry Clin Neurosci. 2023 Dec;273(8): 1629–1631. doi: 10.1007/s00406-023-01712-9
  • Drake RJ, Husain N, Marshall M, et al. Effect of delaying treatment of first-episode psychosis on symptoms and social outcomes: a longitudinal analysis and modelling study. Lancet Psychiatry. 2020 Jul;7:(7):602–610.
  • Joo SW, Kim H, Jo YT, et al. Delay in psychiatric hospitalization from the diagnosis of first-episode schizophrenia and its association with clinical outcomes and direct medical costs: a nationwide, health insurance data-based study. BMC Psychiatry. 2022 Oct 8;22(1):636. doi: 10.1186/s12888-022-04292-5
  • Yu M, Tan Q, Wang Y, et al. Correlation between duration of untreated psychosis and long-term prognosis in chronic schizophrenia. Front Psychiatry. 2023;14:1112657. doi: 10.3389/fpsyt.2023.1112657
  • Correll CU, Martin A, Patel C, et al. Systematic literature review of schizophrenia clinical practice guidelines on acute and maintenance management with antipsychotics. Schizophrenia (Heidelb). 2022 Feb 24;8(1):5. doi: 10.1038/s41537-021-00192-x
  • Muller K, Schuster F, Rodolico A, et al. How should patient decision aids for schizophrenia treatment be designed? - a scoping review. Schizophr Res. 2023 May;255:261–273. doi: 10.1016/j.schres.2023.03.025
  • Blackman G, Oloyede E, Horowitz M, et al. Reducing the risk of withdrawal symptoms and relapse following clozapine discontinuation-is It feasible to develop evidence-based guidelines? Schizophr Bull. 2022 Jan 21;48(1):176–189. doi: 10.1093/schbul/sbab103
  • Luykx JJ, Stam N, Tanskanen A, et al. In the aftermath of clozapine discontinuation: comparative effectiveness and safety of antipsychotics in patients with schizophrenia who discontinue clozapine. Br J Psychiatry. 2020 Sep;217:(3):498–505.
  • Miura G, Tanaka K, Kemuriyama T, et al. Clinical outcomes after clozapine discontinuation in patients with schizophrenia: a systematic review. Pharmacopsychiatry. 2022 Jul;55:(4):181–192.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.