Long-Acting Injectable Antipsychotics: Evidence of Effectiveness and Use

Johnson D.A.W. . Historical perspective on antipsychotic long-acting injections. Br J Psychiatry. 2009; 195(2): S7–S12.

Davis J.M. , Matalon L. , Watanabe M.D. . Depot antipsychotic drugs. Place in therapy. Drugs. 1994; 47: 741–773.

Lieberman J.A. , Stroup T.S. , McEvoy J.P. . Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005; 353(12): 1209–1223.

Blashko C. , Bowen R.C. , Enns M. . Canadian Consensus Group on SAD. Canadian consensus guidelines for the treatment of seasonal affective disorder. In: Levitt A.J. , Lam R.W. , editors. Vancouver (BC): Clinical & Academic Publishing; 1999. p 18.

Kane J.M. , Eerdekens M. , Lindenmayer J.P. . Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotics. Am J Psychiatry. 2003; 160: 1125–1132.

Chue P. , Eerdekens M. , Augustyns I. . Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets. Eur Neuropsychopharmacol. 2005; 15: 111–117.

Fleischhacker W.W. , Eerdekens M. , Karcher K. . 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. 2003; 64: 1250–1257.

Hosalli P. , Davis J.M. . Depot risperidone for schizophrenia. Cochrane Database Syst Rev. 2003; 4: CD004161.

Kramer M. , Litman R. , Hough D. . Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study. Int J Neuropsychopharmacol. 2010; 13(5): 635–647.

Nasrallah H.A. , Gopal S. , Gassmann-Mayer C. . A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia. Neuropsychopharmacology. 2010; 35(10): 2072–2082.

Gopal S. , Hough D.W. , Xu H. . Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose–response study. Int Clin Psychopharmacol. 2010; 25(5): 247–256.

Pandina G.J. , Lindenmayer J.P. , Lull J. . A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol. 2010; 30(3): 235–244.

Nussbaum A.M. , Stroup T.S. . Paliperidone palmitate for schizophrenia. Cochrane Database Syst Rev. 2012; 6: CD008296.

Leucht C. , Heres S. , Kane J.M. . Oral versus depot antipsychotic drugs for schizophrenia—a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res. 2011; 127(1-3): 83–92.

Kishimoto T. , Robenzadeh A. , Leucht C. . Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2013 Jan 2. Epub ahead of print. p 1–22.

Keith S. , Pani L. , Nick B. . Practical application of pharmacotherapy with long-acting risperidone for patients with schizophrenia. Psychiatr Serv. 2004; 55(9): 997–1005.

Louzã M.R. , Elkis H. , Ruschel S. . Long-acting injectable risperidone in partially adherent and nonadherent patients with schizophrenia. Neuropsychiatr Dis Treat. 2011; 7: 391–398.

Lasser R. , Bossie C. , Gharabawi G. . Remission in schizophrenia: results from a 1-year study of long-acting risperidone injection. Schizophr Res. 2005; 77(2-3): 215–227.

Lambert T. , Olivares J. , Peuskens J. . Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium. Ann Gen Psychiatry. 2011; 10: 10.

Moller H.J. , Llorca P.M. , Sacchetti E. . Efficacy and safety of direct transition to risperidone long-acting injectable in patients treated with various antipsychotic therapies. Int Clin Psychopharmacol. 2005; 20(3): 121–130.

Olivares J. , Rodriguez-Martinez A. , Burón J. . Cost-effectiveness analysis of switching antipsychotic medication to long-acting injectable risperidone in patients with schizophrenia: a 12- and 24-month follow-up from the e-STAR database in Spain. Appl Health Econ Health Policy. 2008; 6(1): 41–53.

Kissling W. , Heres S. , Lloyd K. . Direct transition to long-acting risperidone-analysis of long-term efficacy. J Psychopharmacol. 2005; 19: 15–21.

Llorca P.M. , Sacchetti E. , Lloyd K. . Long-term remission in schizophrenia and related psychoses with long-acting risperidone: results obtained in an open-label study with an observation period of 18 months. Int J Clin Pharmacol Ther. 2008; 46: 14–22.

Andreasen N. , Carpenter W. , Kane J. . Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005; 162: 441–449.

Cassidy C.M. , Norman R. , Manchanda R. . Testing definitions of symptom remission in first-episode psychosis for prediction of functional outcome at 2 years. Schizophr Bull. 2010; 36(5): 1001–1008.

Chue P. , Chue J. . The cost-effectiveness of risperidone long-acting injection in the treatment of schizophrenia. Expert Rev Pharmacoecon Outcomes Res. 2012; 12(3): 259–269.

de Arce Cordón R. , Eding E. , Marques-Teixeira J. . Descriptive analyses of the aripiprazole arm in the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE). Eur Arch Psychiatry Clin Neurosci. 2012; 262(2): 139–149.

Nasrallah H.A. , Duchesne I. , Mehnert A. . Health-related quality of life in patients with schizophrenia during treatment with long-acting, injectable risperidone. J Clin Psychiatry. 2004; 65(4): 531–536.

Lindenmayer J. , Khan A. , Eerdekens M. . Long-term safety and tolerability of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder. Eur Neuropsychopharmacol. 2007; 17(2): 138–144.

Cramer J. , Rosenheck R. . Compliance with medication regimens for mental and physical disorders. Psychiatr Serv. 1998; 49(2): 196–201.

Tattan T.M. , Creed F.H. . Negative symptoms of schizophrenia and compliance with medication. Schizophr Bull. 2001; 27(1): 149–155.

Pinikahana J. , Happell B. , Taylor M. . Exploring the complexity of compliance in schizophrenia. Issues Ment Health Nurs. 2002; 23(5): 513–528.

Leucht S. , Tardy M. , Komossa K. . Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012; 379(9831): 2063–2071.

Adams C. , Fenton M. , Quraishi S. . Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. Br J Psychiatry. 2001; 179(4): 290–299.

Gaebel W. , Schreiner A. , Bergmans P. . Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable vs quetiapine: results of a long-term, open-label, randomized clinical trial. Neuropsychopharmacol. 2010; 35(12): 2367–2377.

Hough D. , Gopal S. , Vijapurkar U. . Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2010; 116(2-3): 107–117.

Malla A. , Norman R. , Bechard-Evans L. . Factors influencing relapse during a 2-year follow-up of first-episode psychosis in a specialized early intervention service. Psychol Med. 2008; 38(11): 1585–1593.

Levy E. , Pawliuk N. , Joober R. . Medication-adherent first-episode psychosis patients also relapse: why? Can J Psychiatry. 2012; 57(2): 78–84.

Young J. , Spitz R. , Hillbrand M. . Medication adherence failure in schizophrenia: a forensic review of rates, reasons, treatments, and prospects. J Am Acad Psychiatry Law. 1999; 27(3): 426–444.

Rosenheck R.A. , Krystal J.H. , Lew R. . Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011; 364(9): 842–851.

Olivares J.M. , Rodriguez-Morales A. , Diels J. . 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. 2009; 24: 287–296.

Kozma C.M. , Slaton T. , Dirani R. . Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52–week open-label extension (OLE). Curr Med Res Opin. 2011; 27(8): 1603–1611.

Snaterse M. , Welch R. , Chue P. . Effectiveness and tolerability outcomes of a risperidone long-acting injection compared to conventional depot antipsychotics in a Canadian hospital. Presented at 44th American College of Neuropsychopharmacology Annual Meeting; 2005 Dec 11–15; Waikoloa (HI).

Beauclair L. , Chue P. , McCormick J. . Impact of risperidone long-acting injectable on hospitalization and medication use in Canadian patients with schizophrenia. J Med Econ. 2007; 10(4): 427–442.

Tiihonen J. , Haukka J. , Taylor M. . A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011; 168: 603–609.

Chue P. . Risperidone long-acting injection. In: Haddad P. , Lambert T. , Lauriello J. , editors. Antipsychotic long acting injections: their role in psychiatric practice. New York (NY): Oxford University Press; 2010.

Chue P. , Chue J. . A review of paliperidone palmitate. Expert Rev Neurother. 2012; 12(12): 1383–1397.

Bishara D. . Once-monthly paliperidone injection for the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2010; 6: 561–572.

Sedky K. , Nazir R. , Lindenmayer J.P. . Paliperidone palmitate: once-monthly treatment option for schizophrenia. Curr Psychiatry. 2010; 9(3): 48–49.

Chouinard N.H. , Bhanji M. , Light H.C. . Patient characteristics, symptom severity, and movement disorders in patients with schizophrenia and schizoaffective disorder. Biol Psychiatry. 2003; 53(Suppl):21S.

Csernansky J.G. , Schuchart E.K. . Relapse and rehospitalisation rates in patients with schizophrenia: effects of second generation antipsychotics. CNS Drugs. 2002; 16(7): 473–484.

Beasley C.M. , Dellva M.A. , Tamura R.N. . Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol. Br J Psychiatry. 1999; 174: 23–30.

Tollefson G.D. , Beasley C.M. Jr , Tran P.V. . Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. Am J Psychiatry. 1997; 154(4): 457–465.

Glazer W. . Expected incidence of tardive dyskinesia associated with atypical antipsychotics. J Clin Psychiatry. 2000; 61(Suppl 4):21–26.

Gharabawi G. , Bossie C. , Zhu Y. . An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: results from a long-term study. Schizophr Res. 2005; 77(2-3): 129–139.

Robinson D. , Woerner M.G. , Alvir J.M. . Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999; 56(3): 241–247.

Emsley R. , Rabinowitz J. , Medori R. ; Early Psychosis Global Working Group. Remission in early psychosis: rates, predictors, and clinical and functional outcome correlates. Schizophr Res. 2007; 89:129–139.

Emsley R. , Oosthuizen P. , Koen L. . Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies. Clin Ther. 2008; 30: 2378–2386.

Callaly T. , Trauer T. . Patterns of use of antipsychotic medication in a regional community mental health service. Australas Psychiatry. 2000; 8: 220–224.

Hanssens L. , De Hert M. , Wampers M. . Pharmacological treatment of ambulatory schizophrenia patients in Belgium. Clin Pract Epidemiol Ment Health. 2006; 2: 11.

Williams R. , Kopala L. , Malla A. . Medication decisions and clinical outcomes in the Canadian National Outcomes Measurement Study in Schizophrenia. Acta Psychiatr Scand Suppl. 2006; 113(430): 12–21.

Sim K. , Su A. , Ungvari G.S. . Depot antipsychotic use in schizophrenia: an East Asian perspective. Hum Psychopharmacol. 2004; 19(2): 103–109.

Xiang Y. , Weng Y. , Leung C. . Clinical and social determinants of use of depot antipsychotics for patients with schizophrenia in Hong Kong. Hong Kong J Psychiatry. 2006; 16(2): 71–75.

Humberstone V. , Wheeler A. , Lambert T. . An audit of outpatient antipsychotic usage in the three health sectors of Auckland, New Zealand. Aust N Z J Psychiatry. 2004; 38(4): 240–245.

Dencker S.J. , Axelsson R. . Optimizing the use of depot antipsychotics. CNS Drugs. 1996; 6(5); 367–381.

Foster K. , Meltzer H. , Gill B. . Adults with a psychotic disorder living in the community. OPCS surveys of psychiatric morbidity in Great Britain, report 8. London (GB): TSO (The Stationery Office); 1996.

West J.C. , Marcus S.C. , Wilk J. . Use of depot antipsychotic medications for medication nonadherence in schizophrenia. Schizophr Bull. 2008; 34(5): 995–1001.

Paton C. , Lelliott P. , Harrington M. . Patterns of antipsychotic and anticholinergic prescribing for hospital inpatients. J Psychopharmacol. 2003; 17(2): 223–229.

Valenstein M. , Copeland L.A. , Owen R. . Adherence assessments and the use of depot antipsychotics in patients with schizophrenia. J Clin Psychiatry. 2001; 62(7): 545–551.

Covell N. , Jackson C. , Evans A. . Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles. Schizophr Bull. 2002; 28(1): 17–29.

Shi L. , Ascher-Svanum H. , Zhu B. . Characteristics and use patterns of patients taking first-generation depot antipsychotics or oral antipsychotics for schizophrenia. Psychiatr Serv. 2007; 58(4): 482–488.

Lambert T.J. , Singh B.S. , Patel M.X. . Community treatment orders and antipsychotic long-acting injections. Br J Psychiatry. 2009; 52: S57–S62.

Tiihonen J. , Wahlbeck K. , Lonnqvist J. . Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalization due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ. 2006; 333: 224–227.

Tiihonen J. , Haukka J. , Taylor M. . A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011; 168: 603–609.

Grimaldi-Bensouda L. , Rouillon F. , Astruc B. . 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. 2012; 134: 187–194.

Haddad P.M. , Tiihonen J. , Haukka J. . The place of observational studies in assessing the effectiveness of depot antipsychotics. Schizophr Res. 2011; 131: 260–261.

Stip E. , Abdel-Baki A. , Bloom D. . Long-acting injectable antipsychotics: an expert opinon from the Association des medecins psychiatres du Quebec. Can J Psychiatry. 2011; 56(6): 367–376.

Chue P. . Long-acting risperidone injection: efficacy, safety and cost-effectiveness of the first long-acting atypical antipsychotic. Neuropsychiatr Dis Treat. 2007; 3(1): 1–27.