The role of long-acting injectable antipsychotics in schizophrenia: A critical appraisal

Therapeutic Advances in Psychopharmacology

Volumn 4, Issue 5, 2014, Pages 198-219

  Brissos, Sofia ^a   Veguilla, Miguel Ruiz ^b   Taylor, David ^c   Balanzá Martinez, Vicent ^d  

^a Lisbon's Psychiatric Hospitalar Centre   (Portugal)

^b HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^c SOUTH LONDON AND MAUDSLEY NHS FOUNDATION TRUST   (United Kingdom)

^d UNIVERSITY OF VALENCIA   (Spain)

Author keywords

adherence; atypical; clinical trial; depot; history; long acting injections; pharmacology; treatment; typical

Indexed keywords

ARIPIPRAZOLE; FLUPENTIXOL DECANOATE; FLUPHENAZINE DECANOATE; FLUPHENAZINE ENANTHATE; HALOPERIDOL DECANOATE; NEUROLEPTIC AGENT; OLANZAPINE; PALIPERIDONE; PERPHENAZINE DECANOATE; RISPERIDONE; ZUCLOPENTHIXOL DECANOATE;

COST EFFECTIVENESS ANALYSIS; DRUG COST; DRUG HALF LIFE; DYSTONIA; HUMAN; MAXIMUM PLASMA CONCENTRATION; MEDICATION COMPLIANCE; NEUROLEPTIC MALIGNANT SYNDROME; NONHUMAN; PATIENT ATTITUDE; PATIENT COMPLIANCE; PHYSICIAN ATTITUDE; PRACTICE GUIDELINE; PSYCHIATRIST; PSYCHOPHARMACOTHERAPY; REVIEW; SCHIZOPHRENIA; TARDIVE DYSKINESIA;

EID: 84997859186     PISSN: 20451253     EISSN: 20451261     Source Type: Journal    
DOI: 10.1177/2045125314540297     Document Type: Review

References (196)

1. Achilla E. McCrone P. (2013) The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations. Appl Health Econ Health Policy 11: 95–106
2. Adams C. Fenton M. Quairashi S. David A. (2001) Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. Br J Psychiatry 179: 290–299.
3. Agarwal N. Port J. Bazzocchi M. Renshaw P. (2010) Update on the use of MR for assessment and diagnosis of psychiatric diseases. Radiology 255: 23–41.
4. Agid O. Foussias G. Remington G. (2010) Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention. Expert Opin Pharmacother 11: 2301–2317.
5. Almond S. Knapp M. Francois C. Toumi M. Brugha T. (2004) Relapse in schizophrenia: costs, clinical outcomes and quality of life. Br J Psychiatry 184: 346–351.
6. Altamura A. Aguglia E. Bassi M. Bogetto F. Cappellari L. De Giorgi S. et al. (2012) Rethinking the role of long-acting atypical antipsychotics in the community setting. Int Clin Psychopharmacol 27: 336–349.
7. Alvarez-Jiménez M. González-Blanch C. Crespo-Facorro B. Hetrick S. Rodríguez-Sánchez J. Pérez-Iglesias R. et al. (2008) Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematic critical reappraisal. CNS Drugs 22: 547–562.
8. Andreasen N. Carpenter W. Jr. Kane J. Lasser R. Marder S. Weinburger D. (2005) Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 162: 441–449.
9. Bai Y. Ting Chen T. Chen J. Chang W. Wu B. Hung C. et al. (2007) Equivalent switching dose from oral risperidone to risperidone long-acting injection: a 48-week randomized, prospective, single-blind pharmacokinetic study. J Clin Psychiatry 68: 1218–1225.
10. Bartzokis G. Lu P. Amar P. Raven E. Detore N. Altshuler L. et al. (2011) Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res 132: 35–41.
11. Bartzokis G. Lu P. Raven E. Amar C. Detore N. Couvrette A. et al. (2012) Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia. Schizophr Res 140: 122–128.
12. Birchwood M. Todd P. Jackson C. (1998) Early intervention in psychosis. The critical period hypothesis. Br J Psychiatry Suppl 172: 53–59.
13. Boonstra G. Burger H. Grobbee D. Kahn R. (2011) Antipsychotic prophylaxis is needed sfter remission from a first episode psychotic episode in schizophrenia patients: results from an aborted randomised trial. Int J Psychiatry Clin Pract 15: 128–134.
14. Brissos S. Dias V. Balanzá-Martinez V. Carita A. Figueira M. (2011) Symptomatic remission in schizophrenia patients: relationship with social functioning, quality of life, and neurocognitive performance. Schizophr Res 129: 133–136.
15. Brugger S. Davis J. Leucht S. Stone J. (2011) Proton magnetic resonance spectroscopy and illness stage in schizophrenia–a systematic review and meta-analysis. Biol Psychiatry 69: 495–503.
16. Canadian Psychiatric Association (2005) Clinical practice guidelines. Treatment of schizophrenia. Can J Psychiatry 50(13 Suppl. 1): 7–57.
17. Caroli F. Raymondet P. Izard I. Plas J. Gall B. Delgado A. (2011) Opinions of French patients with schizophrenia regarding injectable medication. Patient Prefer Adherence 5: 165–171.
18. Chatterjee A. Chakos M. Koreen A. Geisler S. Sheitman B. Woerner M. et al. (1995) Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never-medicated schizophrenic patients. Am J Psychiatry 152: 1724–1729.
19. Chen E. Hui C. Lam M. Chiu C. Law C. Chung D. et al. (2010) Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: random controlled trial. BMJ 19: c4024.
20. Chouinard G. Jones B. (1980) Neuroleptic–induced supersensitivity psychosis: clinical and pharmacologic characteristics. Am J Psychiatry 137: 16–21.
21. Chue P. Eerdekens M. Augustyns I. Lachaux B. Molcan P. Eriksson L. et al. (2005a) Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets. Eur Neuropsychopharmacol 15: 111–117.
22. Chue P. Heeg B. Buskens E. van Hout B. (2005b) Modelling the impact of compliance on the costs and effects of long-acting risperidone in Canada. Pharmacoeconomics 23(Suppl. 1): 62–74.
23. Coldham E. Addington J. Addington D. (2002) Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand 106: 286–290.
24. Conley R. Kelly D. Love R. McMahon R. (2003) Rehospitalization risk with second-generation and depot antipsychotics. Ann Clin Psychiatry 15: 23–31.
25. Correll C. Kishimoto T. Kane J. (2011) Randomized controlled trials in schizophrenia: opportunities, limitations, and trial design alternatives. Dialogues Clin Neurosci 13: 155–172.
26. Covell N. McEvoy J. Schooler N. Stroup T. Jackson C. Rojas I.; Schizophrenia Trials Network et al. (2012) Effectiveness of switching from long-acting injectable fluphenazine or haloperidol decanoate to long-acting injectable risperidone microspheres: an open-label, randomized controlled trial. J Clin Psychiatry 73: 669–675.
27. Covell N. Jackson C. Evans A. Essock S. (2002) Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles. Schizophr Bull 28: 17–29.
28. Crow T. MacMillan J. Johnson A. Johnstone E. (1986) A randomised controlled trial of prophylactic neuroleptic treatment. Br J Psychiatry 148: 120–127.
29. Currier G. Walsh P. (2013) Safety and efficacy review of inhaled loxapine for treatment of agitation. Clin Schizophr Relat Psychoses 7: 25–32.
30. Curry S. Whelpton R. de Schepper P. Vranckx S. Schiff A. (1979) Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man. Br J Clin Pharmacol 7: 325–331.
31. Davis J. (2010) The use of depot medications in the treatment of schizophrenia. Am J Psychiatry 167: 125–126.
32. Davis J. Matalon L. Watanabe M. Blake L. Matalon L. (1994) Depot antipsychotic drugs. Place in therapy. Drugs 47: 741–773.
33. De la Gándara J. San Molina L. Rubio G. Rodriguez-Morales A Hidalgo Borrajo R. Burón J. (2009) Experience with injectable long-acting risperidone in long-term therapy after an acute episode of schizophrenia: the SPHERE Study. Expert Rev Neurother 9: 1463–1474.
34. De Risio A. Lang A. (2014) History and therapeutic rationale of long acting antipsychotics. Curr Clin Pharmacol 9: 39–52.
35. Dencker S. (1984) The risk/benefit ratio of depot neuroleptics: a Scandinavian perspective. J Clin Psychiatry 45: 22–27.
36. Denham J. Adamson L. (1971) The contribution of fluphenazine enanthate and decanoate in the prevention of readmission of schizophrenic patients. Acta Psychiatr Scand 47: 420–430.
37. Devito R. Brink L. Sloan C. Jolliff F. (1978) Fluphenazine decanoate vs oral antipsychotics: a comparison of their effectiveness in the treatment of schizophrenia as measured by a reduction in hospital readmissions. J Clin Psychiatry 39: 26–34.
38. Dilla T. Ciudad A. Alvarez M. (2013) Systematic review of the economic aspects of nonadherence to antipsychotic medication in patients with schizophrenia. Patient Prefer Adherence 7: 275–284.
39. Eerdenkens M. Hove I. Remmerie B. Mannaert E. (2004) Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia. Schizophr Res 70: 91–100.
40. Ekerholm M. Firus Waltersson S. Fagerberg T. Söderman E. Terenius L. Agartz I. et al. (2012) Neurocognitive function in long-term treated schizophrenia: a five-year follow-up study. Psychiatry Res 200: 144–152.
41. Emsley R. Chiliza B. Asmal L. Mashile M. Fusar-Poli P. (2013) Long-acting injectable antipsychotics in early psychosis: a literature review. Early Interv Psychiatry 7: 247–254.
42. Emsley R. Oosthuizen P. Koen L. Niehaus D. Martinez G. (2012) Symptom recurrence following intermittent treatment in first-episode schizophrenia successfully treated for 2 years: a 3-year open-label clinical study. J Clin Psychiatry 73: e541–e547.
43. Emsley R. Oosthuizen P. Koen L. Niehaus D. Medori R. Rabinowitz J. (2008a) Remission in patients with first-episode schizophrenia receiving assured antipsychotic medication: a study with risperidone long-acting injection. Int Clin Psychopharmacol 23: 325–331.
44. Emsley R. Oosthuizen P. Koen L. Niehaus D. Medori R. Rabinowitz J. (2008b) Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies. Clin Ther 30: 2378–2386.
45. Fleischhacker W. Eerdekens M. Karcher K. Remington G. Llorca P. Chrzanowski W. et al. (2003) Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry 64: 1250–1257.
46. Francey S. Nelson B. Thompson A. Parker A. Kerr M. Macneil C. et al. (2010) Who needs antipsychotic medication in the earliest stages of psychosis? A reconsideration of benefits, risks, neurobiology and ethics in the era of early intervention. Schizophr Res 119: 1–10.
47. Fusar-Poli P. Kempton M. Rosenheck R. (2013) Efficacy and safety of second-generation long-acting injections in schizophrenia: a meta-analysis of randomized-controlled trials. Int Clin Psychopharmacol 28: 57–66.
48. Gaebel W. Jänner M. Frommann N. Pietzcker A. Köpcke W. Linden M. et al. (2002) First vs multiple episode schizophrenia: two-year outcome of intermittent and maintenance medication strategies. Schizophr Res 53: 145–159.
49. Gaebel W. Riesbeck M. Wölwer W. Klimke A. Eickhoff M. von Wilmsdorff M. et al. (2011) Relapse prevention in first episode schizophrenia- maintenance ves intermittent drug treatment with prodrome –based early intervention: results of randomized controlles trial within the German research network on schizophrenia. J Clin Psychiatry 72: 205–218.
50. Gaebel W. Schreiner A. Bergmans P de Arce R. Rouillon F. Cordes J. et al. (2010) Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable vs quetiapine: results of a long-term, open-label, randomized clinical trial. Neuropsychopharmacology 35: 2367–2377.
51. Gassó P. Mas S. Molina O. Bernardo M. Lafuente A. Parellada E. (2012) Neurotoxic/neuroprotective activity of haloperidol, risperidone and paliperidone in neuroblastoma cells. Prog Neuropsychopharmacol Biol Psychiatry 36: 71–77.
52. Geerts P. Martinez G. Schreiner A. (2013) Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses. BMC Psychiatry 13: 58.
53. Gefvert O. Eriksson B. Persson P. Helldin L. Björner A. Mannaert E. et al. (2005) Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia. Int J Neuropsychopharmacol 8: 27–36.
54. Gerlach J. (1995) Depot neuroleptics in relapse prevention: advantages and disadvantages. Int Clin Psychopharmacol 9(Suppl. 5): 17–20.
55. Gilday E. Nasrallah H. (2012) Clinical pharmacology of paliperidone palmitate a parenteral long-acting formulation for the treatment of schizophrenia. Rev Recent Clin Trials 7: 2–9.
56. Gilmer T. Dolder C. Lacro J. Folsom D. Lindamer L. Garcia P. et al. (2004) Adherence to treatment with antipsychotic medication and healthcare costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry 161: 692–699.
57. Gitlin M. Nuechterlein K. Subotnik K. Ventura J. Mintz J. Fogelson D. et al. (2001) Clinical outcome following neuroleptic discontinuation in patients with remitted recent –onset schizophrenia. Am J Psychiatry 158: 1835–1842.
58. Glazer W. (1984) Depot fluphenazine: risk/benefit ratio. J Clin Psychiatry 45: 28–35.
59. Glazer W. (2007) Who receives long-acting antipsychotic medications? Psychiatr Services 58: 437.
60. Glazer W. Kane J. (1992) Depot neuroleptic therapy: an underutilized treatment option. J Clin Psychiatry 53: 426–433.
61. Gottfries C. Green L (1974). Flupenthixol decanoate in treatment of out-patients. Acta Psychiatr Scand 255: 15–24.
62. Grimaldi-Bensouda L. Rouillon F. Astruc B. Rossignol M. Benichou J. Falissard B.; CGS Study Group et al. (2012) Does long-acting injectable risperidone make a difference to the real-life treatment of schizophrenia? Results of the Cohort for the General study of Schizophrenia (CGS). Schizophr Res 134: 187–194.
63. Haddad P. Taylor M. Niaz O. (2009) First-generation antipsychotic long-acting injections v. oral antipsychotics in schizophrenia: systematic review of Randomized controlled trials and observational studies. Br J Psychiatry 95: S20–S28.
64. Haro J. Novick D. Suarez D. Alonso J. Lépine J. Ratcliffe M.; SOHO Study Group (2006) Remission and relapse in outpatient care of schizophrenia: three-year results from the Schizophrenia Outpatient Health Outcomes study. J Clin Psychopharmacol 26: 571–578.
65. Haro J. Suarez D. Novick D. Brown J. Usall J. Naber D.; SOHO Study Group (2007) Three-year antipsychotic effectiveness in the outpatient care of schizophrenia: observational versus randomized studies results. Eur Neuropsychopharmacol 17: 235–244.
66. Haycox A. (2005) Pharmacoeconomics of long-acting risperidone: results and validity of cost-effectiveness models. Pharmacoeconomics 23(Suppl. 1): 3–16.
67. Heres S. Hamann J. Kissling W. Leucht S. (2006) Attitudes of psychiatrists toward antipsychotic depot medication. J Clin Psychiatry 67: 1948–1953.
68. Heres S. Hamann J. Mendel R. Wickelmaier F. Pajonk F. Leucht S. et al. (2008) Identifying the profile of optimal candidates for antipsychotic depot therapy A cluster analysis. Prog Neuropsychopharmacol Biol Psychiatry 32: 1987–1993.
69. Heres S. Schmitz F. Leucht S. Pajonk F. (2007) The attitude of patients towards antipsychotic depot treatment. Int Clin Psychopharmacol 22: 275–282.
70. Ho B. Andreasen N. Ziebell S. Pierson R. Magnotta V. (2011) Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry 68: 128–137.
71. Hogarty G. Schooler N. Ulrich R. Mussare F. Ferro P. Herron E (1979) Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride. Arch Gen Psychiatry 36: 1283–1294.
72. Hogarty G. Ulrich R. (1977) Temporal effects of drug and placebo in delaying relapse in schizophrenia outpatients. Arch Gen Psychiatry 34: 297–301.
73. Hogarty G. Ulrich R. (1998) The limitations of antipsychotic medication on schizophrenia relapse and adjustments and the contribution of psychosocial treatment. J Psychiatr Res 32: 243–250.
74. Humberstone V. Wheeler A. Lambert T. (2004) An audit of outpatient antipsychotic usage in the three health sectors of Auckland, New Zealand. Aust N Z J Psychiatry 38: 240–245.
75. Jaeger M. Rossler W. (2010) Attitudes towards long-acting depot antipsychotics: a survey of patients, relatives and psychiatrists. Psychiatry Res 175: 58–62.
76. Jann M. Ereshefsky L. Saklad S. (1985) Clinical pharmacokinetics of the depot antipsychotics. Clin Pharmacokinet 10: 315–333.
77. Johnson D. (2009) Historical perspective on antipsychotic long-acting injections. Br J Psychiatry 195: S7–S12.
78. Johnson D. Pasterski G. Ludlow J. Street K. Taylor R. (1983) The discontinuance of maintenance neuroleptic therapy in chronic schizophrenic patients: drug and social consequences. Acta Psychiatr Scand 67: 339–352.
79. J⊘rgensen A. (1980) Pharmacokinetic studies in volunteers of intravenous and oral cis (Z)-flupentixol and intramuscular cis (Z)-flupentixol decanoate in Viscoleo. Eur J Clin Pharmacol 18: 355–360.
80. Kane J. Aguglia E. Altamura A. Ayuso Gutierrez J. Brunello N. Fleischhacker W. (1998) Guidelines for depot antipsychotic treatment in schizophrenia. European Neuropsychopharmacology Consensus Conference in Siena, Italy. Eur Neuropsychopharmacol 8: 55–66
81. Kane J. Detke H. Naber D. Sethuraman G. Lin D. Bergstrom R. et al. (2010) Olanzapine long-acting injection: a 24-week, randomized, double-blind trial of maintenance treatment in patients with schizophrenia. Am J Psychiatry 167: 181–189.
82. Kane J. Eerdekens M. Lindenmayer J. Keith S. Lesem M. Karcher K. (2003) Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry 160: 1125–1132.
83. Kane J. Garcia-Ribera C. (2009) Clinical guideline recommendations for antipsychotic long-acting injections. Br J Psychiatry Suppl 52: 63–67.
84. Kane J. Honigfeld G. Singer J. Meltzer H. (1988) Clozapine for treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45: 789–796.
85. Kane J. Kishimoto T. Correll C. (2013a) Assessing the comparative effectiveness of long-acting injectable versus oral antipsychotic medications in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry. J Clin Epidemiol 66(8 Suppl.): S37–S41.
86. Kane J. Rifkin A. Quitkin F. Nayak D. Ramos-Lorenzi J. (1982) Fluphenazine vs placebo in patients with remitted, acute first episode schizophrenia. Arch Gen Psychiatry 39: 70–73.
87. Kane J. Sanchez R. Zhao J. Duca A. Johnson B. McQuade R. et al. (2013b) Hospitalization rates in patients switched from oral antipsychotics to aripiprazole once-monthly for the management of schizophrenia. J Med Econ 16: 917–925.
88. Kaplan G. Casoy J. Zummo J. (2013) Impact of long-acting injectable antipsychotics on medication adherence and clinical, functional, and economic outcomes of schizophrenia. Patient Prefer Adherence 13: 1171–1180.
89. Keefe R. Seidman L. Christensen B. Hamer R. Sharma T. Sitskoorn M. et al. (2004) Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. Am J Psychiatry 161: 985–995.
90. Keers R. Ullrich S Destavola B. Coid J. (2014) Association of violence with emergence of persecutory delusions in untreated schizophrenia. Am J Psychiatry 171: 332–339.
91. Keith S. (2009) Use of long-acting risperidone in psychiatric disorders: focus on efficacy, safety and cost-effectiveness. Expert Rev Neurother 9: 9–31.
92. Kelly D. Conley R. Carpenter W. (2005) First-episode schizophrenia: a focus on pharmacological treatment and safety considerations. Drugs 65: 1113–1138.
93. Kim B. Lee S. Choi T. Suh S. Kim Y. Lee E. et al. (2008) Effectiveness of risperidone long-acting injection in first-episode schizophrenia: in naturalistic setting. Prog Neuropsychopharmacol Biol Psychiatry 32: 1231–1235.
94. Kim S. Lee Y. Jang J. Yoo T. Kim J. Shin I. et al. (2013) Comparison of attitudes toward long-acting injectable antipsychotics among psychiatrists and patients. Int Clin Psychopharmacol 28: 80–86.
95. Kim S. Solari H. Weiden P. Bishop J. (2012) Paliperidone palmitate injection for the acute and maintenance treatment of schizophrenia in adults. Patient Prefer Adherence 6: 533–545.
96. Kirschner M. Theodoridou A. Fusar-Pol I. Kaiser S. Jäger M. (2013) Patients’ and clinicians’ attitude towards long-acting depot antipsychotics in subjects with a first episode of psychosis. Ther Adv Psychopharmacol 3: 89–99.
97. Kirson N. Weiden P. Yermakov S. Huang W. Samuelson T. Offord S. et al. (2013) Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry 74: 568–575.
98. Kishimoto T. Robenzadeh A. Leucht C. Leucht S. Watanabe K. Mimura M. et al. (2014) Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull 40: 192–213.
99. Kissling W. (1991) Guidelines for neuroleptic relapse prevention in schizophrenia. In: Kissling W. (ed.), Guidelines for Neuroleptic Relapse Prevention in Schizophrenia. Berlin: Springer Verlag, pp. 1–6.
100. Kissling W. Moller H. Walter K. Wittmann B. Krueger R. Trenk D. (1985) Double-blind comparison of haloperidol decanoate and fluphenazine decanoate effectiveness, side-effects, dosage and serum levels during a six months’ treatment for relapse prevention. Pharmacopsychiatry 18: 240–245.
101. Knapp M. Mangalore R. Simon J. (2004) The global costs of schizophrenia. Schizophr Bull 30: 279–293.
102. Knox E. Stimmel G. (2004) Clinical review of a long-acting, injectable formulation of risperidone. Clin Ther 26: 1994–2002.
103. Knudsen P. (1985) Chemotherapy with neuroleptics: clinical and pharmacokinetic aspects with a particular view to depot preparations. Acta Psychiatr Scand 72(Suppl. 322): 51–75.
104. Koola M. Wehring H. Kelly D. (2012) The Potential Role of Long-acting Injectable Antipsychotics in People with Schizophrenia and Comorbid Substance Use. J Dual Diagn 8: 50–61.
105. Lafeuille M.H. Laliberté-Auger F. Lefebvre P. Frois C. Fastenau J. Duh M.S. (2013) Impact of atypical long-acting injectable versus oral antipsychotics on rehospitalization rates and emergency room visits among relapsed schizophrenia patients: a retrospective database analysis. BMC Psychiatry 13: 221.
106. Lai Y. Huang M. Chen C. Tsai C. Pan C. Chiu C. (2009) Pharmacokinetics and efficacy of a direct switch from conventional depot to risperidone long-acting injection in Chinese patients with schizophrenic and schizoaffective disorders. Psychiatry Clin Neurosci 63: 440–448.
107. Larsen N. Hansen L. (1989) Prediction of the optimal perphenazine decanoate dose based on blood samples drawn within the first three weeks. Ther Drug Monit 11: 642–646.
108. Lasser R. Bossie C. Gharabawi G. Turner M. (2004) Patients with schizophrenia previously stabilized on conventional depot antipsychotics experience significant clinical improvements following treatment with long-acting risperidone. Eur Psychiatry 19: 219–225.
109. Lehman A. Lieberman J. Dixon L. McGlashan T. Miller A. Perkins D.; American Psychiatric Association; Steering Committee on Practice Guidelines et al. (2004) Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 161(2 Suppl.): 1–56.
110. Leucht S. Heres S. (2006) Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry 67: 3–8.
111. Leucht C. Heres S. Kane J. Kissling W. Davis J. Leucht S. (2011) Oral versus depot antipsychotic drugs for schizophrenia—A critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res 127: 83–92.
112. Lin J. Wong B. Offord S. Mirski D. (2013) Healthcare cost reductions associated with the use of LAI formulations of antipsychotic medications versus oral among patients with schizophrenia. J Behav Health Serv Res 40: 355–366.
113. Lindenmayer J. Liu-Seifert H. Kulkarni P. Kinon B. Stauffer V. Edwards S. et al. (2009) Medication nonadherence and treatment outcome in patients with schizophrenia or schizoaffective disorder with suboptimal prior response. J Clin Psychiatry 70: 990–996.
114. Llorca P. Abbar M. Courtet P Guillaume S. Lancrenon S. Samalin L. (2013) Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness. BMC Psychiatry 13: article 340.
115. MacFadden W. Ma Y. Thomas Haskins J. Bossie C. Alphs L. (2010) A prospective study comparing the long-term effectiveness of injectable risperidone long-acting therapy and oral aripiprazole in patients with schizophrenia. Psychiatry 7: 23–31.
116. March J. Silva S. Compton S. Shapiro M. Califf R. Krishnan R. (2005) The case for practical clinical trials in psychiatry. Am J Psychiatry 162: 836–846.
117. Marchiaro L. Rocca P. LeNoci F. Longo P. Montemagni C. Rigazzi C. et al. (2005) Naturalistic, retrospective comparison between second-generation antipsychotics and depot neuroleptics in patients affected by schizophrenia. J Clin Psychiatry 66: 1423–1431
118. Marder S. Hubbard J. Van Putten T. Midha K. (1989) Pharmacokinetics of long-acting injectable neuroleptic drugs: clinical implications. Psychopharmacology 98: 433–439.
119. Marder S. Van Putten T. Mintz J. McKenzie J. Lebell M. Faltico G. et al. (1984) Costs and benefits of two doses of fluphenazine. Arch Gen Psychiatry 41: 1025–1029.
120. Marinis T. Saleem P. Glue P. Arnoldussen W. Teijeiro R. Lex A. et al. (2007) Switching to long-acting injectable risperidone is beneficial with regard to clinical outcomes, regardless of previous conventional medication in patients with schizophrenia. Pharmacopsychiatry 40: 257–263.
121. Marriot P. Hiep A. (1976) A mirror image outpatient study at a depot phenothiazine clinic. Aust N Z J Psychiatry 10: 163.
122. McCreadie R. Wiles D. Grant S. Crokett G. Mahmood Z. Livingston M. et al. (1989) The Scottish first episode schizophrenia study. VII. Two year follow-up. Acta Psychiatr Scand 80: 597–602.
123. McEvoy J. (2006) Risks versus benefits of different types of long-acting injectable antipsychotics. J Clin Psychiatry 67(Suppl. 5): 15–18.
124. McGorry P. Killackey E. Yung A. (2007) Early intervention in psychotic disorders: detection and treatment of the first episode and the critical early stages. Med J Aust 187: S8–S10.
125. Meyer J. Stahl S. (2009) The metabolic syndrome and schizophrenia. Acta Psychiatr Scand 119: 4–14.
126. Mihajlović G. Jovanović-Mihajlović N. Radmanović B. Radonjić K. Djukić-Dejanović S. Janković S. et al. (2011) Quality of life of schizophrenic patients treated with haloperidol depot and injection preparation of long-lasting risperidone. Srp Arh Celok Lek 139: 36–40.
127. Moncrieff J. (2006) Does antipsychotic withdrawl provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal–related relapse. Acta Psychiatr Scand 114: 3–13.
128. Moore D. Kelly D. Sherr J. Love R. Conley R. (1998) Rehospitalization rates for depot antipsychotics and pharmacoeconomic implications: comparison with risperidone. Am J Health Syst Pharm 55(Suppl. 4): 17–19.
129. Moore T. Buchanan R. Buckley P. Chiles J. Conley R. Crismon M. et al. (2007) The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry 68: 1751–1762.
130. Morken G. Widen J. Grawe R. (2008) Non-adherence to antipsychotic medication, relapse and rehospitalisation in recent-onset schizophrenia. BMC Psychiatry 8: article 32.
131. Muirhead D. Harvey C. Ingram G. (2006) Effectiveness of community treatment orders for treatment of schizophrenia with oral or depot antipsychotic medication: clinical outcomes. Aust N Z J Psychiatry 40: 596–605.
132. Nahata T. Saini T. (2009) Formulation optimization of long-acting depot injection of aripiprazole by using D-optimal mixture design. PDA J Pharm Sci Technol 63: 113–122.
133. NICE (2009) Schizophrenia: Core Interventions in the Treatment and Management of Schizophrenia in Primary and Secondary Care (update). NICE Clinical Guidelines No. 82. London: National Institute for Health and Care Excellence.
134. Niaz O. Haddad P. (2010) Injectable long-acting antipsychotics (LAI). In: Mortimer A. McKenna P. (eds), The Year in Schizophrenia, 2010. Oxford: Atlas Medical Publishing, pp. 33–54.
135. Nickl-Jockschat T. Schneider F. Pagel A. Laird A. Fox P. Eickhoff S. (2011) Progressive pathology is functionally linked to the domains of language and emotion: meta-analysis of brain structure changes in schizophrenia patients. Eur Arch Psychiatry Clin Neurosci 261: S166–S171.
136. Novakovic V. Adel T. Peselow E. Lindenmayer J. (2013) Long-acting injectable antipsychotics and the development of postinjection delirium/sedation syndrome (PDSS). Clin Neuropharmacol 36: 59–62.
137. Offord S Wong B. Mirski D. Baker R. Lin J. (2013) Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral. J Med Econ 16: 231–239.
138. Oh P. Lanctôt K. Mittman N. Iskedjian M. Einarson T. (2001) Cost-utility of risperidone compared with standard conventional antipsychotics in chronic schizophrenia. J Med Econ 4: 137–156.
139. Olfson M. Mechanic D. Hansell S. Boyer C. Walkup J. (1999) Prediction of homelessness within three months of discharge among inpatients with schizophrenia. Psychiatr Serv 50: 667–673.
140. Olivares J. Pinal B. Cinos C. (2011) Comparison of long-acting antipsychotic injection and oral antipsychotics in schizophrenia. Neuropsychiatry 1: 275–289.
141. Olivares J. Rodriguez-Morales A. Diels J. Povey M. Jacobs A. Zhao Z.; e-STAR Spanish Study Group et al. (2009) Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR). Eur Psychiatry 24: 287–296.
142. Pandarakalam J. (2003) The long-acting depot antipsychotic drugs. Hosp Med 64: 603–608.
143. Parellada E. Velligan D. Emsley R. Kissling W. (2012) Long-acting injectable antipsychotics in first-episode schizophrenia. Schizophr Res Treatment 2012: 318535.
144. Patel M. David A. (2005) Why aren't depot antipsychotics prescribed more often and what can be done about it? Adv Psychiatr Treatment 11: 203–213.
145. Patel M. De Zoysa N. Bernadt M. David A. (2009) Depot and oral antipsychotics: patient preferences and attitudes are not the same thing. J Psychopharmacol 23: 789–796.
146. Patel M. Haddad P. Chaudhry I. McLoughlin S. Husain N. David A. (2010) Psychiatrists’ use, knowledge and attitudes to first and second generation antipsychotic long-acting injections: comparison over five years. J Psychopharmacol 24: 1473–1482.
147. Patel M. Nikolaou V. David A. (2003) Eliciting psychiatrists’ beliefs about side effects of typical and atypical antipsychotic drugs. Int J Psychiatry Clin Pract 7: 117–120.
148. Perkins D. (2002) Predictors of noncompliance in patients with schizophrenia. J Clin Psychiatry 63: 1121–1128.
149. Peusken J. Mertens C. Kusters J. et al. (2010a) Long acting risperidone in the treatment of schizophrenia: data from a 24-month Belgian electronic schizophrenia adherence registry (eSTAR): an observational study. Acta Psychiatr Belg 110: 34–46.
150. Peuskens J. Olivares J. Pecenak J. Tuma I. Bij de Weg H. Eriksson L. et al. (2010b) Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries. Curr Med Res Opin 26: 501–509.
151. Potkin S. Bera R. Zubek D. Lau G. (2013) Patient and prescriber perspectives on long-acting injectable (LAI) antipsychotics and analysis of in-office discussion regarding LAI treatment for schizophrenia. BMC Psychiatry 13: article 261.
152. Poulsen J. Olesen O. Larsen N. (1994) Fluctuation of serum zuclopenthixol concentrations in patients treated with zuclopenthixol decanoate in viscoleo. Ther Drug Monit 16: 155–159.
153. Rabin C. Liang Y Ehrlichman R. Budhian A. Metzger K. Majewski-Tiedeken C. et al. (2008) In vitro and in vivo demonstration of risperidone implants in mice. Schizophr Res 98: 66–78.
154. Ravasio R. Sanfilippo L. De Paoli G. Cerra C. Fratino P. Della Giovanna M. (2009) Analisi di costo-efficacia dello switch da un antipsicotico orale a risperidone a rilascio prolungato nel trattamento dei pazienti affetti da schizofrenia. Giorn Ital Health Technol Ass 2: 1–8.
155. Reichhart T. Kissling W. (2013) Societal costs of nonadherence in schizophrenia: homicide/suicide. M&B 1: 19–22.
156. Remington G. Adams M. (1995) Depot neuroleptic therapy: clinical considerations. Can J Psychiatry 40: S5–S11.
157. Reyntijens A. Heykants J. Woestenborghs R. Gelders Y. Aerts T. (1982) Pharmacokinetics of haloperidol decanoate. Int Pharmacopsychiatry 17: 238–246.
158. Rifkin A. Quitkin F. Rabiner C. (1977) Fluphenazine decanoate, fluphenazine hydrochloride given orally and placebo in remitted schizophrenia: relapse rate over one year. Arch Gen Psychiatry 34: 43–47.
159. Robinson D. Woerner M. Napolitano B. Patel R. Sevy S. Gunfez-Bruce H. et al. (2006) Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes. Am J Psychiatry 163: 2096–2102.
160. Rocca P. Sandei L. Bava I. Frieri T. (2013) Risperidone long-acting injection in the treatment of first episode schizophrenia. Curr Psychopharmacol 2: 29–36.
161. Rosaria D. Alice B. (2010) Profile of olanzapine long-acting injection for the maintenance treatment of adult patients with schizophrenia. Neuropsychiatr Dis Treat 6: 573–581.
162. Rothbard A. Kuno E. Foley K. (2003) Trends in the rate and type of antipsychotic medications prescribed to persons with schizophrenia. Schizophr Bull 29: 531–540.
163. Samalin L. Charpeaud T. Blanc O. Heres S. Llorca P. (2013) Clinicians’ attitudes toward the use of long-acting injectable antipsychotics. J Nerv Ment Dis 201: 553–559.
164. Schooler N. (2003) Relapse and rehospitalization: comparing oral and depot antipsychotics. J Clin Psychiatry 64: 14–17.
165. Schooler N. Levine J. Severe J. Brauzer B. DiMascio A. Klerman G. et al. (1980) Prevention of relapse in schizophrenia: an evaluation of fluphenazine decanoate. Arch Gen Psychiatry 37: 16–24.
166. Stahl S. (2001) Does evidence from clinical trials in psychopharmacology apply in clinical practice? J Clin Psychiatry 62: 6–7.
167. Stip E. Abdel-Baki A. Bloom D. Grignon S. Roy M. (2011) An expert opinion from the Association des médecins psychiatres du Québec. Can J Psychiatry 56: 367–376.
168. Strassnig M. Miewald J. Keshavan M. Ganguli R. (2007) Weight gain in newly diagnosed first-episode psychosis patients and healthy comparisons: one-year analysis. Schizophr Res 93: 90–98.
169. Suzuki H. Gen K. (2012) The influence of switching from haloperidol decanoate depot to risperidone long-acting injection on the clinical symptoms and cognitive function in schizophrenia. Hum Psychopharmacol 27: 470–475.
170. Svedberg B. Backenroth-Ohsako G. Lützén K. (2003) On the path to recovery: patients’ experiences of treatment with long-acting injections of antipsychotic medication. Int J Ment Health Nurs 12: 110–18.
171. Swartz M. Swanson J. Wagner H. Burns B. Hiday V. (2001) Effects of involuntary outpatient commitment and depot antipsychotics on treatment adherence in persons with severe mental illness. J Nerv Ment Dis 189: 583–592.
172. Taylor D. (2005) Establishing a dose-response relationship for haloperidol decanoate. Psychiatrist 29: 104–107.
173. Taylor D. (2009) Psychopharmacology and adverse effects of antipsychotic long-acting injections: a review. Br J Psychiatry 195: S13–S19.
174. Taylor M. Ng K. (2013) Should long-acting (depot) antipsychotics be used in early schizophrenia? A systematic review. Aust N Z J Psychiatry 47: 624–630.
175. Thyssen A. Rusch S. Herben V. Quiroz J. Mannaert E. (2010) Risperidone long-acting injection: pharmacokinetics following administration in deltoid versus gluteal muscle in schizophrenic patients. J Clin Pharmacol 50: 1011–1021.
176. Tiihonen J. Haukka J. Taylor M. Haddad P. Patel M. Korhonen P. (2011) A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 168: 603–609.
177. Tiihonen J. Wahlbeck K. Lönnqvist J. Klaukka T. Ioannidis J. Volavka J. et al. (2006) Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ 333: 224.
178. Trudeau M. Bruneau M. Stip E. Grünberg F. Boivin M. (1999) [Categorical refusal of treatment by psychiatric patients: balance, survey and prospects]. Can J Psychiatry 44: 583–588.
179. Turner M. Eerdekens E. Jacko M. Eerdekens M. (2004) Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics. Int Clin Psychopharmacol 19: 241–249.
180. Valenstein M. Copeland L. Blow F. McCarthy J. Zeber J. Gillon L. et al. (2002) Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission. Med Care 40: 630–639.
181. Vaughan K. McConaghy N. Wolf C. Myhr C. Black T. (2000) Community treatment orders: relationship to clinical care, medication compliance, behavioural disturbance and readmission. Aust N Z J Psychiatry 34: 801–808.
182. Velligan D.I. Weiden P.J. Sajatovic M. Scott J. Carpenter D. Ross R., Expert Consensus Panel on Adherence Problems in Serious and Persistent Mental Illness et al. (2009) The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry 70: 1–46
183. Velligan D. Weiden P. Sajatovic M. Scott J. Carpenter D. Ross R. et al. (2010) Strategies for addressing adherence problems in patients with serious and persistent mental illness: recommendations from the expert consensus guidelines. J Psychiatr Pract 16: 306–324.
184. Verghese C. DeLeon J. Nair C. Simpson G. (1996) Clozapine withdrawal effects and receptor profiles of typical and atypical neuroleptics. Biol Psychiatry 39: 135–138.
185. Viala A. Cornic F. Vacheron M. (2012) Treatment adherence with early prescription of long-acting injectable antipsychotics in recent-onset schizophrenia. Schizophr Res Treatment 2012: 368687.
186. Viala A. Hou N. Ba B. Durand A. Dufour H. D’Agostino N. et al. (1984) Blood and plasma kinetics of cis(Z)-clopenthixol and fluphenazine in psychiatric patients after intramuscular injection of their decanoic esters. Psychopharmacology 83: 147–150.
187. Viguera A. Baldessarini R. Hegarty J. van Kammen D. Tohen M. (1997) Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Arch Gen Psychiatry 54: 49–55.
188. Waddell L. Taylor M. (2009) Attitudes of patients and mental health staff to antipsychotic long-acting injections: systematic review. Br J Psychiatry Suppl 195: s43–s50.
189. Walburn J. Gray R. Gournay K. Quraishi S. David A. (2001) Systematic review of patient and nurse attitudes to depot antipsychotic medication. Br J Psychiatry 179: 300–307.
190. Wang L. Wang A. Zhao X. Liu X. Wang D. Sun F. et al. (2012) Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism. Int J Pharm 427: 284–292.
191. Weiden P. (2007) Understanding and addressing adherence issues in schizophrenia: from theory to practice. J Clin Psychiatry 68: 14–19.
192. Wu E. Birnbaum H. Shi L. Ball D. Kessler R. Moulis M. et al. (2005) The economic burden of schizophrenia in the United States in 2002. J Clin Psychiatry 66: 1122–1129.
193. Wunderink L. Nienhuis F. Sytema S. Slooff C. Knegtering R. Wiersma D. (2007) Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry 68: 654–661.
194. Young C. Taylor D. (2006) Health resource utilization associated with switching to risperidone long-acting injection. Acta Psychiatr Scand 114: 14–20.
195. Zhornitsky S. Stip E. (2012) Oral versus Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia and Special Populations at Risk for Treatment Nonadherence: A Systematic Review. Schizophr Res Treatment 2012: 1–12.
196. Zhu B. Ascher-Svanum H. Shi L. Faries D. Montgomery W. Marder S. (2008) Time to discontinuation of depot and oral first-generation antipsychotics in the usual care of schizophrenia. Psychiatr Serv 59: 315–317.