Korean J Schizophr Res.  2023 Apr;26(1):1-11. 10.16946/kjsr.2023.26.1.1.

Breakthrough Psychosis and Long-Acting Injectable Antipsychotics

• Joo EJ
• Lee KY
• Jeong SH
• Kim YS

• KMID: 2542194
• DOI: http://doi.org/10.16946/kjsr.2023.26.1.1

Abstract

“Breakthrough” of psychosis despite good compliance of antipsychotics medication for a long time is a major obstacle to the treatment of schizophrenia, whether the mechanism is caused by dopamine hypersensitivity or insufficient dose of antipsychotics. Researchers advocating “Dopamine Supersensitivity Psychosis” (DSP) emphasize to avoid excessive inhibition of dopamine 2 receptors from the beginning of treatment. On the other hand, researchers advocating “Breakthrough psychosis on Antipsychotic Maintenance Medication” (BAMM) in which psychosis recurs due to insufficient medication despite continuous administration of antipsychotics without non-adherence argue that dose of antipsychotics should be increased to enhance therapeutic effect. In patients using long-acting antipsychotics injection (LAI), non-compliance can be ruled out. We believe that in treating non-affective psychosis, it is necessary to continuously maintain the lowest dose possible using the optimal dose considering the side effects of second-generation antipsychotics and the cycle and stage of psychosis, and the optimal formulation such as LAI.

Keyword

Antipsychotics; Breakthrough psychosis (BAMM); Dopamine supersensitivity psychosis (DSP); Long-acting injectable antipsychotics (LAI); Schizophrenia; 도파민 초민감성 정신병; 돌파정신병; 조현병; 항정신병약물 장기지속형 주사제; 항정신병약물

Reference

1. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012; 379:2063–2071.

2. Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. 2014; 16:505–524.

3. Rubio JM, Taipale H, Correll CU, Tanskanen A, Kane JM, Tiihonen J. Psychosis breakthrough on antipsychotic maintenance: results from a nationwide study. Psychol Med. 2020; 50:1356–1367.

4. Emsley R, Chiliza B, Asmal L, Harvey BH. The nature of relapse in schizophrenia. BMC Psychiatry. 2013; 13:50.

5. Fellner C. New Schizophrenia Treatments Address Unmet Clinical Needs. P T. 2017; 42:130–134.

6. Robinson D, Woerner MG, Alvir JM, Bilder R, Goldman R, Geisler S, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999; 56:241–247.

7. Valenstein M, Copeland LA, Blow FC, McCarthy JF, Zeber JE, Gillon L, et al. Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission. Med Care. 2002; 40:630–639.

8. Morken G, Widen JH, Grawe RW. Non-adherence to antipsychotic medication, relapse and rehospitalisation in recent-onset schizophrenia. BMC Psychiatry. 2008; 8:32.

9. Alphs L, Nasrallah HA, Bossie CA, Fu DJ, Gopal S, Hough D, et al. Factors associated with relapse in schizophrenia despite adherence to long-acting injectable antipsychotic therapy. Int Clin Psychopharmacol. 2016; 31:202–209.

10. Kishimoto T, Nitta M, Borenstein M, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013; 74:957–965.

11. 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:S37–S41.

12. Adams CE, Fenton MK, Quraishi S, David AS. Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. Br J Psychiatry. 2001; 179:290–299.

13. Haddad PM, Taylor M, Niaz OS. First-generation antipsychotic long-acting injections v. oral antipsychotics in schizophrenia: systematic review of randomised controlled trials and observational studies. Br J Psychiatry Suppl. 2009; 52:S20–S28.

14. Waddell L, Taylor M. Attitudes of patients and mental health staff to antipsychotic long-acting injections: systematic review. Br J Psychiatry Suppl. 2009; 52:S43–S50.

15. Correll CU, Citrome L, Haddad PM, Lauriello J, Olfson M, Calloway SM, et al. The Use of Long-Acting Injectable Antipsychotics in Schizophrenia: Evaluating the Evidence. J Clin Psychiatry. 2016; 77:1–24.

16. Doolabh U, Yeap S. Examining long-acting injectable antipsychotic (depot) medication in the elderly: a five-year retrospective cross-sectional study evaluating depot use in an Australian psychogeriatric service. Australas Psychiatry. 2022; 30:31–36.

17. Paton C, Okocha CI, Patel MX. Can the use of long-acting injectable antipsychotic preparations be increased in routine clinical practice and the benefits realised? Ther Adv Psychopharmacol. 2022; 12:20451253211072347.

18. Chouinard G, Jones BD, Annable L. Neuroleptic-induced supersensitivity psychosis. Am J Psychiatry. 1978; 135:1409–1410.

19. Rubio JM, Kane JM. Psychosis breakthrough on antipsychotic maintenance medication (BAMM): what can we learn? NPJ Schizophr. 2017; 3:36.

20. Davis KL, Rosenberg GS. Is there a limbic system equivalent of tardive dyskinesia? Biol Psychiatry. 1979; 14:699–703.

21. Nakata Y, Kanahara N, Iyo M. Dopamine supersensitivity psychosis in schizophrenia: Concepts and implications in clinical practice. J Psychopharmacol. 2017; 31:1511–1518.

22. Chouinard G, Chouinard VA. Atypical antipsychotics: CATIE study, drug-induced movement disorder and resulting iatrogenic psychiatric-like symptoms, supersensitivity rebound psychosis and withdrawal discontinuation syndromes. Psychother Psychosom. 2008; 77:69–77.

23. Iyo M, Tadokoro S, Kanahara N, Hashimoto T, Niitsu T, Watanabe H, et al. Optimal extent of dopamine D2 receptor occupancy by antipsychotics for treatment of dopamine supersensitivity psychosis and late-onset psychosis. J Clin Psychopharmacol. 2013; 33:398–404.

24. Kimura H, Kanahara N, Komatsu N, Ishige M, Muneoka K, Yoshimura M, et al. A prospective comparative study of risperidone long-acting injectable for treatment-resistant schizophrenia with dopamine supersensitivity psychosis. Schizophr Res. 2014; 155:52–58.

25. Suzuki T, Kanahara N, Yamanaka H, Takase M, Kimura H, Watanabe H, et al. Dopamine supersensitivity psychosis as a pivotal factor in treatment-resistant schizophrenia. Psychiatry Res. 2015; 227:278–282.

26. Takase M, Kanahara N, Oda Y, Kimura H, Watanabe H, Iyo M. Dopamine supersensitivity psychosis and dopamine partial agonist: a retrospective survey of failure of switching to aripiprazole in schizophrenia. J Psychopharmacol. 2015; 29:383–389.

27. Fallon P, Dursun SM. A naturalistic controlled study of relapsing schizophrenic patients with tardive dyskinesia and supersensitivity psychosis. J Psychopharmacol. 2011; 25:755–762.

28. Chouinard G, Samaha AN, Chouinard VA, Peretti CS, Kanahara N, Takase M, et al. Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy. Psychother Psychosom. 2017; 86:189–219.

29. Emsley R, Asmal L, Rubio JM, Correll CU, Kane JM. Predictors of psychosis breakthrough during 24 months of long-acting antipsychotic maintenance treatment in first episode schizophrenia. Schizophr Res. 2020; 225:55–62.

30. Takekita Y, Kinoshita T. New developments in long-acting injectable antipsychotics LAI. Jpn J Clin Psychopharmacol. 2021; 24:1079–1087.

31. Smith RC, Davis JM. Behavioral evidence for supersensitivity after chronic administration of haloperidol, clozapine, and thioridazine. Life Sci. 1976; 19:725–731.

32. Grace AA. Dopamine System Dysregulation and the Pathophysiology of Schizophrenia: Insights From the Methylazoxymethanol Acetate Model. Biol Psychiatry. 2017; 81:5–8.

33. Samaha AN, Seeman P, Stewart J, Rajabi H, Kapur S. “Breakthrough” dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci. 2007; 27:2979–2986.

34. Ginovart N, Wilson AA, Hussey D, Houle S, Kapur S. D2-receptor upregulation is dependent upon temporal course of D2-occupancy: a longitudinal [11C]-raclopride PET study in cats. Neuropsychopharmacology. 2009; 34:662–671.

35. Murugaiah K, Theodorou A, Mann S, Clow A, Jenner P, Marsden CD. Chronic continuous administration of neuroleptic drugs alters cerebral dopamine receptors and increases spontaneous dopaminergic action in the striatum. Nature. 1982; 296:570–572.

36. Seeman P, Schwarz J, Chen JF, Szechtman H, Perreault M, McKnight GS, et al. Psychosis pathways converge via D2high dopamine receptors. Synapse. 2006; 60:319–346.

37. Murray RM, Quattrone D, Natesan S, van Os J, Nordentoft M, Howes O, et al. Should psychiatrists be more cautious about the longterm prophylactic use of antipsychotics? Br J Psychiatry. 2016; 209:361–365.

38. Wada M, Noda Y, Iwata Y, Tsugawa S, Yoshida K, Tani H, et al. Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment. Mol Psychiatry. 2022; 27:2950–2967.

39. Sachdev PS. The current status of tardive dyskinesia. Aust N Z J Psychiatry. 2000; 34:355–369.

40. Catts SV, O’Toole BI. Reducing long-term antipsychotic use: a therapeutic dead end? Br J Psychiatry. 2017; 210:368.

41. Caroff SN. Recent Advances in the Pharmacology of Tardive Dyskinesia. Clin Psychopharmacol Neurosci. 2020; 18:493–506.

42. Seifert R. Drugs for treatment of schizophrenia. Seifert R, editor. Basic Knowledge of Pharmacology: Springer;2019.

43. Kolakowska T, Williams AO, Jambor K, Ardern M. Schizophrenia with good and poor outcome. III: Neurological ‘soft’ signs, cognitive impairment and their clinical significance. Br J Psychiatry. 1985; 146:348–357.

44. Wistedt B, Ranta J. Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology. Acta Psychiatr Scand. 1983; 67:378–388.

45. Gardos G, Cole JO, Rapkin RM, LaBrie RA, Baquelod E, Moore P, et al. Anticholinergic challenge and neuroleptic withdrawal. Changes in dyskinesia and symptom measures. Arch Gen Psychiatry. 1984; 41:1030–1035.

46. Palmstierna T, Wistedt B. Tardive psychosis: does it exist? Psychopharmacology (Berl). 1988; 94:144–145.

47. Dold M, Fugger G, Aigner M, Lanzenberger R, Kasper S. Dose escalation of antipsychotic drugs in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Res. 2015; 166:187–193.

48. Tiihonen J, Tanskanen A, Taipale H. 20-Year Nationwide Follow-Up Study on Discontinuation of Antipsychotic Treatment in First-Episode Schizophrenia. Am J Psychiatry. 2018; 175:765–773.

49. Kahn RS. On the Continued Benefit of Antipsychotics After the First Episode of Schizophrenia. Am J Psychiatry. 2018; 175:712–713.

50. Mace S, Dzahini O, Cornelius V, Anthony D, Stewart R, Taylor D. Antipsychotic use and unexpected death: a hospital-based case-control study. Acta Psychiatr Scand. 2015; 132:479–488.

51. Vita A, De Peri L, Deste G, Barlati S, Sacchetti E. The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter? A Meta-analysis and Meta-regression of Longitudinal Magnetic Resonance Imaging Studies. Biol Psychiatry. 2015; 78:403–412.

52. Catts SV, O’Toole BI. The treatment of schizophrenia: Can we raise the standard of care? Aust N Z J Psychiatry. 2016; 50:1128–1138.

53. Lugg W. Antipsychotic-induced supersensitivity - A reappraisal. Aust N Z J Psychiatry. 2022; 56:437–444.

54. Fountoulakis KN, Moeller HJ, Kasper S, Tamminga C, Yamawaki S, Kahn R, et al. The report of the joint WPA/CINP workgroup on the use and usefulness of antipsychotic medication in the treatment of schizophrenia. CNS Spectr. 2020; 1–25.

55. Hojlund M, Kemp AF, Haddad PM, Neill JC, Correll CU. Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials. Lancet Psychiatry. 2021; 8:471–486.

56. Sudo A, Takeuchi H. Breakthrough psychotic symptoms on antipsychotic maintenance medication (BAMM). Jpn J Clin Psychopharmacol. 2022; 25:1011–1018.

57. Rubio JM, Schoretsanitis G, John M, Tiihonen J, Taipale H, Guinart D, et al. Psychosis relapse during treatment with long-acting injectable antipsychotics in individuals with schizophrenia-spectrum disorders: an individual participant data meta-analysis. Lancet Psychiatry. 2020; 7:749–761.

58. Citrome L. A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder. Neuropsychiatr Dis Treat. 2006; 2:427.

59. Kimura H, Kanahara N, Iyo M. Rationale and neurobiological effects of treatment with antipsychotics in patients with chronic schizophrenia considering dopamine supersensitivity. Behav Brain Res. 2021; 403:113126.

60. Kanahara N, Kimura H, Oda Y, Ito F, Iyo M. Recent Discussions on Dopamine Supersensitivity Psychosis: Eight Points to Consider When Diagnosing Treatment-Resistant Schizophrenia. Curr Neuropharmacol. 2021; 19:2214–2226.

61. Eum S, Schneiderhan ME, Brown JT, Lee AM, Bishop JR. Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report. BMC Psychiatry. 2017; 17:238.

62. Schoretsanitis G, Kane JM, Correll CU, Rubio JM. Predictors of Lack of Relapse After Random Discontinuation of Oral and Long-acting Injectable Antipsychotics in Clinically Stabilized Patients with Schizophrenia: A Re-analysis of Individual Participant Data. Schizophr Bull. 2022; 48:296–306.

63. Takeuchi H, Siu C, Remington G, Fervaha G, Zipursky RB, Foussias G, et al. Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia. Neuropsychopharmacology. 2019; 44:1036–1042.

64. Kane JM, McEvoy JP, Correll CU, Llorca PM. Controversies Surrounding the Use of Long-Acting Injectable Antipsychotic Medications for the Treatment of Patients with Schizophrenia. CNS Drugs. 2021; 35:1189–1205.

65. Barnes TR, Drake R, Paton C, Cooper SJ, Deakin B, Ferrier IN, et al. Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2020; 34:3–78.

66. Correll CU, Martin A, Patel C, Benson C, Goulding R, Kern-Sliwa J, et al. Systematic literature review of schizophrenia clinical practice guidelines on acute and maintenance management with antipsychotics. Schizophrenia (Heidelb). 2022; 8:5.

67. Kishimoto T, Hagi K, Kurokawa S, Kane JM, Correll CU. 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; 8:387–404.

68. Kane JM, Schooler NR, Marcy P, Correll CU, Achtyes ED, Gibbons RD, et al. Effect of Long-Acting Injectable Antipsychotics vs Usual Care on Time to First Hospitalization in Early-Phase Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2020; 77:1217–1224.

69. Tiihonen J, Mittendorfer-Rutz E, Majak M, Mehtala J, Hoti F, Jedenius E, et al. Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29823 Patients With Schizophrenia. JAMA Psychiatry. 2017; 74:686–693.

70. Lee NY, Kim SH, Cho SJ, Chung YC, Jung IK, Kim CY, et al. A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea. Int Clin Psychopharmacol. 2014; 29:279–287.

71. Samara MT, Dold M, Gianatsi M, Nikolakopoulou A, Helfer B, Salanti G, et al. Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis. JAMA Psychiatry. 2016; 73:199–210.

72. Yun JY, Lee JS, Kang SH, Nam B, Lee SJ, Lee SH, et al. Korean Treatment Guideline on Pharmacotherapy of Co-existing Symptoms and Antipsychotics-related Side Effects in Patients with Schizophrenia. Korean J Schizophr Res. 2019; 22:21–33.

73. Kogure M, Kanahara N, Kimura M, Hanaoka S, Hirano H, Iyo M. Long-Term Treatment With Long-Acting Injectable Antipsychotic in Schizophrenia Patients With and Without Dopamine Supersensitivity Psychosis: A 6-Year Retrospective Comparative Study. J Clin Psychopharmacol. 2022; 42:357–364.

74. Samaha AN, Reckless GE, Seeman P, Diwan M, Nobrega JN, Ka- pur S. Less is more: antipsychotic drug effects are greater with transient rather than continuous delivery. Biol Psychiatry. 2008; 64:145–152.

75. Kimura H, Kanahara N, Sasaki T, Komatsu N, Ishige M, Muneoka K, et al. Risperidone long-acting injectable in the treatment of treatment-resistant schizophrenia with dopamine supersensitivity psychosis: Results of a 2-year prospective study, including an additional 1-year follow-up. J Psychopharmacol. 2016; 30:795–802.

76. Amato D, Canneva F, Cumming P, Maschauer S, Groos D, Dahlmanns JK, et al. A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter. Mol Psychiatry. 2020; 25:2101–2118.

77. Uchida H, Mamo DC, Kapur S, Labelle A, Shammi C, Mannaert EJ, et al. Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia. J Clin Psychiatry. 2008; 69:1281–1286.

78. Servonnet A, Uchida H, Samaha AN. Continuous versus extended antipsychotic dosing in schizophrenia: Less is more. Behav Brain Res. 2021; 401:113076.

79. Sasaki H, Hashimoto K, Inada T, Fukui S, Iyo M. Suppression of oro-facial movements by rolipram, a cAMP phosphodiesterase inhibitor, in rats chronically treated with haloperidol. Eur J Pharmacol. 1995; 282:71–76.

80. Misawa F, Fujii Y, Takeuchi H. Tardive Dyskinesia and Long-Acting Injectable Antipsychotics: Analyses Based on a Spontaneous Reporting System Database in Japan. J Clin Psychiatry. 2022; 83.

81. Yang KC, Liao YT, Yang YK, Lin SK, Liang CS, Bai YM. Evidence-Based Expert Consensus Regarding Long-Acting Injectable Antipsychotics for Schizophrenia from the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN). CNS Drugs. 2021; 35:893–905.

82. Correll CU, Sliwa JK, Najarian DM, Saklad SR. Practical considerations for managing breakthrough psychosis and symptomatic worsening in patients with schizophrenia on long-acting injectable antipsychotics. CNS Spectr. 2019; 24:354–370.

83. Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018; 51:e1.

84. de Leon J. A Critical Commentary on the 2017 AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology. Pharmacopsychiatry. 2018; 51:63–68.

85. Baldelli S, Clementi E, Cattaneo D. Can We Rely on AGNP Therapeutic Targets Also For LAI Antipsychotics? Pharmacopsychiatry. 2018; 51:270–271.

86. Schoretsanitis G, Spina E, Hiemke C, de Leon J. A systematic review and combined analysis of therapeutic drug monitoring studies for long-acting risperidone. Expert Rev Clin Pharmacol. 2017; 10:965–981.

87. Baldelli S, Cheli S, Montrasio C, Cattaneo D, Clementi E. Therapeutic drug monitoring and pharmacogenetics of antipsychotics and antidepressants in real life settings: A 5-year single centre experience. World J Biol Psychiatry. 2021; 22:34–45.

88. Mauri MC, Maffini M, Di Pace C, Reggiori A, Paletta S, Moliterno D, et al. “Long-acting” olanzapine in maintenance therapy of schizophrenia: A study with plasma levels. Int J Psychiatry Clin Pract. 2015; 19:99–105.

89. Hyza M, Silhan P, Ceskova E, Skront T, Kacirova I, Urinovska R, et al. Plasma Levels of Long-Acting Injectable Antipsychotics in Outpatient Care: A Retrospective Analysis. Neuropsychiatr Dis Treat. 2021; 17:1069–1075.

90. D’Anna G, Rotella F, Santarelli G, Scannerini S, Fanelli A, Ricca V, et al. Therapeutic Drug Monitoring of Long-Acting Injectable Antipsychotics as a Predictor of Relapse in Schizophrenia Spectrum Disorders: A 1-Year Pilot Study. Ther Drug Monit. 2022; 44:805–810.

91. Waggershauser M, Steinert T. Breakthrough psychosis under antipsychotic maintenance treatment and social stress. Psychol Med. 2019; 49:2808–2809.

92. Correll CU, Rubio JM, Inczedy-Farkas G, Birnbaum ML, Kane JM, Leucht S. Efficacy of 42 Pharmacologic Cotreatment Strategies Added to Antipsychotic Monotherapy in Schizophrenia: Systematic Overview and Quality Appraisal of the Meta-analytic Evidence. JAMA Psychiatry. 2017; 74:675–684.

93. Galling B, Roldan A, Hagi K, Rietschel L, Walyzada F, Zheng W, et al. Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta-analysis and meta-regression analysis. World Psychiatry. 2017; 16:77–89.

94. Correll CU, Rummel-Kluge C, Corves C, Kane JM, Leucht S. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull. 2009; 35:443–457.

95. Dong M, Zeng LN, Zhang Q, Yang SY, Chen LY, Najoan E, et al. Prescription of antipsychotic and concomitant medications for adult Asian schizophrenia patients: Findings of the 2016 Research on Asian Psychotropic Prescription Patterns (REAP) survey. Asian J Psychiatr. 2019; 45:74–80.

96. Grover S, Sahoo S, Mehra A. Perceptions of Psychiatrists Toward the Use of Long-Acting Injectable Antipsychotics: An Online Survey Study From India. J Clin Psychopharmacol. 2019; 39:611–619.

97. Evernden C, Giang I, Anderson M. The use of concurrent long-acting injectable antipsychotic therapy with paliperidone palmitate and aripiprazole monohydrate in a patient with schizophrenia. Ment Health Clin. 2021; 11:305–310.

98. Schottle D, Janetzky W, Luedecke D, Beck E, Correll CU, Wiedemann K. Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study. BMC Psychiatry. 2018; 18:365.

99. Haddad PM, Brain C, Scott J. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies. Patient Relat Outcome Meas. 2014; 5:43–62.