Reasons for Antipsychotic Treatment Switch: A Systematic Retrospective Review of Prescription Records and Prescriber Notes

Daniel Guinart, MD^a,b,c,d ; Kaksha Varma, MD^a ; Yarden Segal, MD^a ; Nahal Talasazan^a ; Christoph U. Correll, MD^a,b,c,e ; John M. Kane, MD^a,b,c

J Clin Psychiatry 2022;83(5):21m14272

ABSTRACT

Objective: Switching of antipsychotic medications, which are used for many psychiatric conditions, is common. However, reasons and clinical documentation of such switches have scarcely been studied.

Methods: A systematic, retrospective review of prescription records and prescriber notes was conducted to characterize reasons for and types of antipsychotic switches at one hospital during inpatient or outpatient care, starting August 1, 2017, until 270 antipsychotic switches with type and reasons were collected, as required by power analysis.

Results: After removing 7 cases in which quetiapine was switched to a non-antipsychotic agent, 263 antipsychotic switches involving 195 unique subjects (median age = 31 [interquartile range, 24–47] years; schizophrenia = 36.9%, bipolar disorder = 27.7%, schizoaffective disorder = 18.5%) were analyzed. Frequent reasons for antipsychotic switch were intolerability (45.7%) and inefficacy/clinical worsening (17.6%). Reasons did not differ by race (P = .2644), age (P = .0621), or insurance type (P = .2970), but differed heterogeneously regarding different reasons by sex (P = .004). The most common reported switches were from second-generation oral antipsychotics (SGA-OAPs) to other SGA-OAPs (N = 155, 58.9%), mostly due to tolerability or inefficacy; second-generation long-acting injectable antipsychotics (SGA-LAIs) to SGA-OAPs (11%), mostly due to intolerability, patient preference, or insurance coverage problems; and SGA-OAPs to SGA-LAIs (10.7%) due to nonadherence. Reasons for antipsychotic switch were properly documented in 208 (79.1%) of the prescriber notes.

Conclusions: In this retrospective chart review, switching varied by sex regarding reasons and occurred almost in half of the cases due to intolerability. Different reasons predominated in switches from SGA-OAP to SGA-OAP, SGA-LAI to SGA-OAP, and SGA-OAP to SGA-LAI. One in 5 switches were not properly documented, requiring attention.

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References (71)

Leucht S, Tardy M, Komossa K, et al. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2012;(5):CD008016. PubMed CrossRef
Keating D, McWilliams S, Schneider I, et al. Pharmacological guidelines for schizophrenia: a systematic review and comparison of recommendations for the first episode. BMJ Open. 2017;7(1):e013881. PubMed CrossRef
Kishimoto T, Hagi K, Nitta M, et al. Long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta-analysis of direct head-to-head comparisons. World Psychiatry. 2019;18(2):208–224. PubMed CrossRef
Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry. 2018;17(2):149–160. PubMed CrossRef
Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther. 1989;251(1):238–246. PubMed
Roth BL, Ciaranello RD, Meltzer HY. Binding of typical and atypical antipsychotic agents to transiently expressed 5-HT1C receptors. J Pharmacol Exp Ther. 1992;260(3):1361–1365. PubMed
Canton H, Verrièle L, Colpaert FC. Binding of typical and atypical antipsychotics to 5-HT1C and 5-HT2 sites: clozapine potently interacts with 5-HT1C sites. Eur J Pharmacol. 1990;191(1):93–96. PubMed CrossRef
Miller RJ, Hiley CR. Anti-muscarinic properties of neuroleptics and drug-induced Parkinsonism. Nature. 1974;248(449):596–597. PubMed CrossRef
Correll CU. From receptor pharmacology to improved outcomes: individualising the selection, dosing, and switching of antipsychotics. Eur Psychiatry. 2010;25(suppl 2):S12–S21. PubMed CrossRef
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;394(10202):939–951. PubMed CrossRef
Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757–777. PubMed CrossRef
Muench J, Hamer AM. Adverse effects of antipsychotic medications. Am Fam Physician. 2010;81(5):617–622. PubMed
Pillinger T, McCutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(1):64–77. PubMed CrossRef PubMed
Guinart D, Kane JM. Use of behavioral economics to improve medication adherence in severe mental illness. Psychiatr Serv. 2019;70(10):955–957. PubMed CrossRef
Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry. 2013;12(3):216–226. PubMed CrossRef
Newcomer JW, Weiden PJ, Buchanan RW. Switching antipsychotic medications to reduce adverse event burden in schizophrenia: establishing evidence-based practice. J Clin Psychiatry. 2013;74(11):1108–1120. PubMed CrossRef
Buckley PF, Correll CU. Strategies for dosing and switching antipsychotics for optimal clinical management. J Clin Psychiatry. 2008;69(suppl 1):4–17. PubMed
Takeuchi H, Kantor N, Uchida H, et al. Immediate vs gradual discontinuation in antipsychotic switching: a systematic review and meta-analysis. Schizophr Bull. 2017;43(4):862–871. PubMed CrossRef
Takeuchi H, Thiyanavadivel S, Agid O, et al. Gradual vs wait-and-gradual discontinuation in antipsychotic switching: a meta-analysis. Schizophr Res. 2017;189:4–8. PubMed CrossRef
Takeuchi H, Remington G. Immediate versus wait-and-gradual discontinuation in antipsychotic switching: a meta-analysis. J Psychopharmacol. 2020;34(8):914–919. PubMed CrossRef
Takeuchi H, Thiyanavadivel S, Agid O, et al. Rapid vs slow antipsychotic initiation in schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2018;193:29–36. PubMed CrossRef
Ayyagari R, Thomason D, Mu F, et al. Association of antipsychotic treatment switching in patients with schizophrenia, bipolar, and major depressive disorders. J Med Econ. 2020;23(2):204–212. PubMed CrossRef
Hugenholtz GWK, Heerdink ER, Nolen WA, et al. Less medication switching after initial start with atypical antipsychotics. Eur Neuropsychopharmacol. 2004;14(1):1–5. PubMed CrossRef
Nyhuis AW, Faries DE, Ascher-Svanum H, et al. Predictors of switching antipsychotic medications in the treatment of schizophrenia. BMC Psychiatry. 2010;10(1):75. PubMed CrossRef
Fulone I, Silva MT, Lopes LC. Switching between second-generation antipsychotics in patients with schizophrenia and schizoaffective disorder: 10-year cohort study in Brazil. Front Pharmacol. 2021;12:638001. PubMed CrossRef
Murru A, Hidalgo D, Bernardo M, et al. Antipsychotic switching in schizoaffective disorder: a systematic review. World J Biol Psychiatry. 2016;17(7):495–513. PubMed CrossRef
Hugenholtz GW, Heerdink ER, Meijer WE, et al. Reasons for switching between antipsychotics in daily clinical practice. Pharmacopsychiatry. 2005;38(3):122–124. PubMed CrossRef
Keks N, Schwartz D, Hope J. Stopping and switching antipsychotic drugs. Aust Prescr. 2019;42(5):152–157. PubMed CrossRef
Kishi T, Oya K, Iwata N. Long-acting injectable antipsychotics for prevention of relapse in bipolar disorder: a systematic review and meta-analyses of randomized controlled trials. Int J Neuropsychopharmacol. 2016;19(9):pyw038. PubMed CrossRef
Kishimoto T, Robenzadeh A, Leucht C, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014;40(1):192–213. PubMed CrossRef
Correll CU, Citrome L, Haddad PM, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1–24. PubMed CrossRef
Cohen J. Statistical Power Analysis for the Behavioral Sciences. Routledge Academic; 1988.
Labad J, Montalvo I, González-Rodríguez 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;222:88–96. PubMed CrossRef
Dumontaud M, Korchia T, Khouani J, et al. Sexual dysfunctions in schizophrenia: Beyond antipsychotics: a systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2020;98:109804. PubMed CrossRef
Divac N, Prostran M, Jakovcevski I, et al. Second-generation antipsychotics and extrapyramidal adverse effects. BioMed Res Int. 2014;2014:656370. PubMed CrossRef
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;12(1):20. PubMed CrossRef
Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry. 2015;72(4):334–341. PubMed CrossRef
Correll CU, Solmi M, Veronese N, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry. 2017;16(2):163–180. PubMed CrossRef
Vancampfort D, Stubbs B, Mitchell AJ, et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015;14(3):339–347. PubMed CrossRef
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;123(2-3):225–233. PubMed CrossRef
Shapiro DA, Renock S, Arrington E, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003;28(8):1400–1411. PubMed CrossRef
Stroup TS, McEvoy JP, Ring KD, et al; Schizophrenia Trials Network. A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: Comparison of Antipsychotics for Metabolic Problems (CAMP). Am J Psychiatry. 2011;168(9):947–956. PubMed CrossRef
Kim DD, Barr AM, Lian L, et al. Efficacy and tolerability of aripiprazole versus D₂ antagonists in the early course of schizophrenia: a systematic review and meta-analysis. NPJ Schizophr. 2021;7(1):29. PubMed CrossRef
Marazziti D, Baroni S, Picchetti M, et al. Pharmacokinetics and pharmacodynamics of psychotropic drugs: effect of sex. CNS Spectr. 2013;18(3):118–127. PubMed CrossRef
Seeman MV. The pharmacodynamics of antipsychotic drugs in women and men. Front Psychiatry. 2021;12:650904. PubMed CrossRef
Vargas A, Ormseth G, Seifi A. Gender and psychotropic poisoning in the USA. J Neurol Res. 2020;10(6):220–225. CrossRef
Iversen TSJ, Steen NE, Dieset I, et al. Side effect burden of antipsychotic drugs in real life: impact of gender and polypharmacy. Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:263–271. PubMed CrossRef
Sørup FKH, Eriksson R, Westergaard D, et al. Sex differences in text-mined possible adverse drug events associated with drugs for psychosis. J Psychopharmacol. 2020;34(5):532–539. PubMed CrossRef
Samara MT, Dold M, Gianatsi M, et al. Efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia: a network meta-analysis. JAMA Psychiatry. 2016;73(3):199–210. PubMed CrossRef
Stroup TS, Gerhard T, Crystal S, et al. Comparative effectiveness of clozapine and standard antipsychotic treatment in adults with schizophrenia. Am J Psychiatry. 2016;173(2):166–173. PubMed CrossRef
Tiihonen J, Mittendorfer-Rutz E, Majak M, et al. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29,823 patients with schizophrenia. JAMA Psychiatry. 2017;74(7):686–693. PubMed CrossRef
Kane JM, Correll CU. The role of clozapine in treatment-resistant schizophrenia. JAMA Psychiatry. 2016;73(3):187–188. PubMed CrossRef
Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatment-resistant schizophrenic. a double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45(9):789–796. PubMed CrossRef
Howes OD, McCutcheon R, Agid O, et al. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry. 2017;174(3):216–229. PubMed CrossRef
Bachmann CJ, Aagaard L, Bernardo M, et al. International trends in clozapine use: a study in 17 countries. Acta Psychiatr Scand. 2017;136(1):37–51. PubMed CrossRef
Correll CU, Brevig T, Brain C. Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists. BMC Psychiatry. 2019;19(1):362. PubMed CrossRef
Rubio JM, Kane JM. How and when to use clozapine. Acta Psychiatr Scand. 2020;141(3):178–189. PubMed CrossRef
Verdoux H, Quiles C, Bachmann CJ, et al. Prescriber and institutional barriers and facilitators of clozapine use: a systematic review. Schizophr Res. 2018;201:10–19. PubMed CrossRef
Guinart D, Misawa F, Rubio JM, et al. Outcomes of neuroleptic malignant syndrome with depot versus oral antipsychotics: a systematic review and pooled, patient-level analysis of 662 case reports. J Clin Psychiatry. 2020;82(1):20r13272. PubMed CrossRef
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;47(6):1621–1630. PubMed CrossRef
Kishimoto T, Hagi K, Kurokawa S, et al. 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. Lancet Psychiatry. 2021;8(5):387–404. PubMed CrossRef
Kishi T, Matsunaga S, Iwata N. Mortality risk associated with long-acting injectable antipsychotics: a systematic review and meta-analyses of randomized controlled trials. Schizophr Bull. 2016;42(6):1438–1445. PubMed CrossRef
Misawa F, Kishimoto T, Hagi K, et al. Safety and tolerability of long-acting injectable versus oral antipsychotics: a meta-analysis of randomized controlled studies comparing the same antipsychotics. Schizophr Res. 2016;176(2-3):220–230. PubMed CrossRef
Velligan DI, Weiden PJ, Sajatovic M, et al. Strategies for addressing adherence problems in patients with serious and persistent mental illness: recommendations from the expert consensus guidelines. J Psychiatr Pract. 2010;16(5):306–324. PubMed CrossRef
Kane JM, Kishimoto T, Correll CU. Assessing the comparative effectiveness of long-acting injectable vs oral antipsychotic medications in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry. J Clin Epidemiol. 2013;66(suppl):S37–S41. PubMed CrossRef
Sajatovic M, Ross R, Legacy SN, et al. Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics: expert consensus survey part 1. Neuropsychiatr Dis Treat. 2018;14:1463–1474. PubMed CrossRef
Sajatovic M, Ross R, Legacy SN, et al. Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder: expert consensus survey part 2. Neuropsychiatr Dis Treat. 2018;14:1475–1492. PubMed CrossRef
Robinson DG, Subramaniam A, Fearis PJ, et al. Focused ethnographic examination of barriers to use of long-acting injectable antipsychotics. Psychiatr Serv. 2020;71(4):337–342. PubMed CrossRef
Potkin S, Bera R, Zubek D, et al. Patient and prescriber perspectives on long-acting injectable (LAI) antipsychotics and analysis of in-office discussion regarding LAI treatment for schizophrenia. BMC Psychiatry. 2013;13(1):261. PubMed CrossRef
Iyer S, Banks N, Roy MA, et al. A qualitative study of experiences with and perceptions regarding long-acting injectable antipsychotics: part II-physician perspectives. Can J Psychiatry. 2013;58(suppl 1):23S–29S. PubMed CrossRef
Patel RS, Bachu R, Adikey A, et al. Factors related to physician burnout and its consequences: a review. Behav Sci (Basel). 2018;8(11):98. PubMed CrossRef