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Original Research Early Career Psychiatrists September 5, 2022

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

Daniel Guinart, MD; Kaksha Varma, MD; Yarden Segal, MD; Nahal Talasazan; Christoph U. Correll, MD; John M. Kane, MD

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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  1. Leucht S, Tardy M, Komossa K, et al. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2012;(5):CD008016. PubMed CrossRef
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Miller RJ, Hiley CR. Anti-muscarinic properties of neuroleptics and drug-induced Parkinsonism. Nature. 1974;248(449):596–597. PubMed CrossRef
  9. 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
  10. 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
  11. 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
  12. Muench J, Hamer AM. Adverse effects of antipsychotic medications. Am Fam Physician. 2010;81(5):617–622. PubMed
  13. 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
  14. 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
  15. 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
  16. 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
  17. Buckley PF, Correll CU. Strategies for dosing and switching antipsychotics for optimal clinical management. J Clin Psychiatry. 2008;69(suppl 1):4–17. PubMed
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. Keks N, Schwartz D, Hope J. Stopping and switching antipsychotic drugs. Aust Prescr. 2019;42(5):152–157. PubMed CrossRef
  29. 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
  30. 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
  31. 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
  32. Cohen J. Statistical Power Analysis for the Behavioral Sciences. Routledge Academic; 1988.
  33. 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
  34. 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
  35. Divac N, Prostran M, Jakovcevski I, et al. Second-generation antipsychotics and extrapyramidal adverse effects. BioMed Res Int. 2014;2014:656370. PubMed CrossRef
  36. 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
  37. 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
  38. 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
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. 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
  45. Seeman MV. The pharmacodynamics of antipsychotic drugs in women and men. Front Psychiatry. 2021;12:650904. PubMed CrossRef
  46. Vargas A, Ormseth G, Seifi A. Gender and psychotropic poisoning in the USA. J Neurol Res. 2020;10(6):220–225. CrossRef
  47. 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
  48. 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
  49. 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
  50. 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
  51. 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
  52. Kane JM, Correll CU. The role of clozapine in treatment-resistant schizophrenia. JAMA Psychiatry. 2016;73(3):187–188. PubMed CrossRef
  53. 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
  54. 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
  55. 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
  56. 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
  57. Rubio JM, Kane JM. How and when to use clozapine. Acta Psychiatr Scand. 2020;141(3):178–189. PubMed CrossRef
  58. 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
  59. 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
  60. 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
  61. 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
  62. 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
  63. 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
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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
  69. 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
  70. 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
  71. 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
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