Long-acting injectable antipsychotics update: lengthening the dosing interval and expanding the diagnostic indications

References

• Otsuka Pharmaceutical Co., Ltd. Abilify Maintena (aripiprazole) extended-release injectable suspension. Product Label. 2017 Jul.
   Google Scholar
• Janssen Pharmaceuticals, Inc. Invega Sustenna (paliperidone palmitate) extended-release injectable suspension. Product Label. 2017 Jun.
   Google Scholar
• Janssen Pharmaceuticals, Inc. Invega Trinza (paliperidone palmitate) extended-release injectable suspension. Product Label. 2017 Feb.
   Google Scholar
• Alkermes, Inc. Aristada (aripiprazole lauroxil) extended-release injectable suspension. Product Label. 2017 Jun.
   Google Scholar
• Volavka J, Citrome L. Oral antipsychotics for the treatment of schizophrenia: heterogeneity in efficacy and tolerability should drive decision-making. Expert Opin Pharmacother. 2009;10:1917–1928.
   PubMed Web of Science ®Google Scholar
• Valenstein M, Ganoczy D, McCarthy JF, et al. Antipsychotic adherence over time among patients receiving treatment for schizophrenia: a retrospective review. J Clin Psychiatry. 2006;67:1542–1550.
   PubMed Web of Science ®Google Scholar
• Byerly MJ, Nakonezny PA, Lescouflair E. Antipsychotic medication adherence in schizophrenia. Psychiatr Clin North Am. 2007;30:437–452.
   PubMed Web of Science ®Google Scholar
• Lingam R, Scott J. Treatment non-adherence in affective disorders. Acta Psychiatr Scand. 2002;105:164–172.
   PubMed Web of Science ®Google Scholar
• Lacro JP, Dunn LB, Dolder CR, et al. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002;63:892–909.
   PubMed Web of Science ®Google Scholar
• 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 Web of Science ®Google Scholar
• Weiden P, Rapkin B, Zygmunt A, et al. Postdischarge medication compliance of inpatients converted from an oral to a depot neuroleptic regimen. Psychiatr Serv. 1995;46:1049–1054.
   PubMed Web of Science ®Google Scholar
• Stahl SM. Long-acting injectable antipsychotics: shall the last be first? CNS Spectr. 2014;19:3–5.
   PubMed Web of Science ®Google Scholar
• 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;74:686–693.
   PubMed Web of Science ®Google Scholar
• Citrome L. New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia. Expert Rev Neurother. 2013;13:767–783.
   PubMed Web of Science ®Google Scholar
• Taylor D. Psychopharmacology and adverse effects of antipsychotic long-acting injections: a review. Br J Psychiatry Suppl. 2009;52:S13–9.
   PubMedGoogle Scholar
• Harrison TS, Goa KL. Long-acting risperidone: a review of its use in schizophrenia. CNS Drugs. 2004;18:113–132.
   PubMed Web of Science ®Google Scholar
• Chue P. Risperidone long-acting injection. Expert Rev Neurother. 2003;3:435–446.
   PubMedGoogle Scholar
• Janssen Pharmaceuticals, Inc. Risperdal Consta (risperidone) long acting injection. Product Label. 2017 Feb.
   Google Scholar
• Kane JM, Eerdekens M, Lindenmayer JP, et al. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry. 2003;160:1125–1132.
   PubMed Web of Science ®Google Scholar
• Macfadden W, Alphs L, Jt H, et al. A randomized, double-blind, placebo-controlled study of maintenance treatment with adjunctive risperidone long-acting therapy in patients with bipolar I disorder who relapse frequently. Bipolar Disord. 2009;11:827–839.
   PubMed Web of Science ®Google Scholar
• Quiroz JA, Yatham LN, Palumbo JM, et al. Risperidone long-acting injectable monotherapy in the maintenance treatment of bipolar I disorder. Biol Psychiatry. 2010;68:156–162.
   PubMed Web of Science ®Google Scholar
• Vieta E, Montgomery S, Sulaiman AH, et al. A randomized, double-blind, placebo-controlled trial to assess prevention of mood episodes with risperidone long-acting injectable in patients with bipolar I disorder. Eur Neuropsychopharmacol. 2012;22:825–835.
   PubMed Web of Science ®Google Scholar
• Citrome L. Paliperidone palmitate - review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication. Int J Clin Pract. 2010;64:216–239.
   PubMed Web of Science ®Google Scholar
• Greenberg WM, Citrome L. Paliperidone palmitate for schizoaffective disorder: a review of the clinical evidence. Neurol Ther. 2015;4:81–91.
   PubMed Web of Science ®Google Scholar
• Eli Lilly and Co. Zyprexa Relprevv (olanzapine) extended-release injectable suspension. Product Label. 2017 Jan.
   Google Scholar
• Citrome L. Olanzapine pamoate: a stick in time? A review of the efficacy and safety profile of a new depot formulation of a second-generation antipsychotic. Int J Clin Pract. 2009;63:140–150.
   PubMed Web of Science ®Google Scholar
• Detke HC, McDonnell DP, Brunner E, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry. 2010;10:43.
   PubMed Web of Science ®Google Scholar
• McDonnell DP, Detke HC, Bergstrom RF, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry. 2010;10:45.
   PubMed Web of Science ®Google Scholar
• Chue P, Chue J. A review of olanzapine pamoate. Expert Opin Pharmacother. 2012;13:1661–1670.
   PubMed Web of Science ®Google Scholar
• Citrome L, Holt RI, Walker DJ, et al. Weight gain and changes in metabolic variables following olanzapine treatment in schizophrenia and bipolar disorder. Clin Drug Investig. 2011;31:455–482.
   PubMed Web of Science ®Google Scholar
• McDonnell DP, Kryzhanovskaya LA, Zhao F, et al. Comparison of metabolic changes in patients with schizophrenia during randomized treatment with intramuscular olanzapine long-acting injection versus oral olanzapine. Hum Psychopharmacol. 2011;26:422–433.
   PubMed Web of Science ®Google Scholar
• Naber D, Hansen K, Forray C, et al. Qualify: a randomized head-to-head study of aripiprazole once-monthly and paliperidone palmitate in the treatment of schizophrenia. Schizophr Res. 2015;168:498–504.
   PubMed Web of Science ®Google Scholar
• Citrome L. Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil. Expert Rev Clin Pharmacol. 2016;9:169–186.
   PubMed Web of Science ®Google Scholar
• Ravenstijn P, Remmerie B, Savitz A, et al. Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: A phase-1, single-dose, randomized, open-label study. J Clin Pharmacol. 2016;56:330–339.
   PubMed Web of Science ®Google Scholar
• Berwaerts J, Liu Y, Gopal S, et al. Efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo for relapse prevention of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2015;72:830–839.
   PubMed Web of Science ®Google Scholar
• Savitz AJ, Xu H, Gopal S, et al. Efficacy and safety of paliperidone palmitate 3-month formulation for patients with schizophrenia: a randomized, multicenter, double-blind, noninferiority study. Int J Neuropsychopharmacol. 2016;19:pyw018.
   PubMed Web of Science ®Google Scholar
• Hard ML, Mills RJ, Sadler BM, et al. Aripiprazole lauroxil: pharmacokinetic profile of this long-acting injectable antipsychotic in persons with schizophrenia. J Clin Psychopharmacol. 2017;37:289–295.
   PubMed Web of Science ®Google Scholar
• Meltzer HY, Risinger R, Nasrallah HA, et al. A randomized, double-blind, placebo-controlled trial of aripiprazole lauroxil in acute exacerbation of schizophrenia. J Clin Psychiatry. 2015;76:1085–1090.
   PubMed Web of Science ®Google Scholar
• Kane JM, Peters-Strickland T, Baker RA, et al. Aripiprazole once-monthly in the acute treatment of schizophrenia: findings from a 12-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014;75:1254–1260.
   PubMed Web of Science ®Google Scholar
• Citrome L, Risinger R, Cutler AJ, et al. Effect of aripiprazole lauroxil in patients with acute schizophrenia as assessed by the Positive and Negative Syndrome Scale-supportive analyses from a Phase 3 study. CNS Spectr. 2017 Jun 19:1–7. [Epub ahead of print]. DOI:10.1017/S1092852917000396.
   Google Scholar
• Hard ML, Mills RJ, Sadler BM, et al. Pharmacokinetic profile of a 2-month dose regimen of aripiprazole lauroxil: a Phase I study and a population pharmacokinetic model. CNS Drugs. 2017;31:617–624.
   PubMed Web of Science ®Google Scholar
• McEvoy JP, Risinger R, Mykhnyak S, et al. Durability of therapeutic response with long-term aripiprazole lauroxil treatment following successful resolution of an acute episode of schizophrenia. J Clin Psychiatry. Forthcoming.
   Google Scholar
• Fu DJ, Turkoz I, Simonson RB, et al. Paliperidone palmitate once-monthly reduces risk of relapse of psychotic, depressive, and manic symptoms and maintains functioning in a double-blind, randomized study of schizoaffective disorder. J Clin Psychiatry. 2015;76:253–262.
   PubMed Web of Science ®Google Scholar
• Citrome L, Ketter TA. When does a difference make a difference? Interpretation of number needed to treat, number needed to harm, and likelihood to be helped or harmed. Int J Clin Pract. 2013;67:407–411.
   PubMed Web of Science ®Google Scholar
• Calabrese JR, Sanchez R, Jin N, et al. Efficacy and safety of aripiprazole once-monthly in the maintenance treatment of bipolar I disorder: a double-blind, placebo-controlled, 52-week randomized withdrawal study. J Clin Psychiatry. 2017;78:324–331.
   PubMed Web of Science ®Google Scholar
• Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168:603–609.
   PubMed Web of Science ®Google Scholar
• Subotnik KL, Casaus LR, Ventura J, et al. Long-acting injectable risperidone for relapse prevention and control of breakthrough symptoms after a recent first episode of schizophrenia. A randomized clinical trial. JAMA Psychiatry. 2015;72:822–829.
   PubMed Web of Science ®Google Scholar
• Kishimoto T, Nitta M, Borenstein M, et al. 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.
   PubMed Web of Science ®Google Scholar
• Kirson NY, Weiden PJ, Yermakov S, et al. Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry. 2013;74:568–575.
   PubMed Web of Science ®Google Scholar
• Lindström L, Lindström E, Nilsson M, et al. Maintenance therapy with second generation antipsychotics for bipolar disorder - a systematic review and meta-analysis. J Affect Disord. 2017;213:138–150.
   PubMed Web of Science ®Google Scholar
• Jaeger M, Rossler W. Attitudes towards long-acting depot antipsychotics: a survey of patients, relatives and psychiatrists. Psychiatry Res. 2010;175:58–62.
   PubMed Web of Science ®Google Scholar
• Caroli F, Raymondet P, Izard I, et al. Opinions of French patients with schizophrenia regarding injectable medication. Patient Prefer Adherence. 2011;5:165–171.
   PubMed Web of Science ®Google Scholar
• Vinogradov S, Fisher M, Warm H, et al. The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia. Am J Psychiatry. 2009;166:1055–1062.
   PubMed Web of Science ®Google Scholar
• Kantrowitz JT, Citrome L. Schizoaffective disorder: a review of current research themes and pharmacological management. CNS Drugs. 2011;25:317–331.
   PubMed Web of Science ®Google Scholar
• Remington GJ, Adams ME. Depot neuroleptic therapy: clinical considerations. Can J Psychiatry. 1995;40(3 Suppl 1):S5–11.
   PubMed Web of Science ®Google Scholar
• Gomeni R, Heidbreder C, Fudala PJ, et al. A model-based approach to characterize the population pharmacokinetics and the relationship between the pharmacokinetic and safety profiles of RBP-7000, a new, long-acting, sustained-released formulation of risperidone. J Clin Pharmacol. 2013;53:1010–1019.
   PubMed Web of Science ®Google Scholar
• Laffont CM, Gomeni R, Zheng B, et al. Population pharmacokinetics and prediction of dopamine D2 receptor occupancy after multiple doses of RBP-7000, a new sustained-release formulation of risperidone, in schizophrenia patients on stable oral risperidone treatment. Clin Pharmacokinet. 2014;53:533–543.
   PubMed Web of Science ®Google Scholar
• Laffont CM, Gomeni R, Zheng B, et al. Population pharmacokinetic modeling and simulation to guide dose selection for RBP-7000, a new sustained-release formulation of risperidone. J Clin Pharmacol. 2015;55:93–103.
   PubMed Web of Science ®Google Scholar
• Nasser AF, Henderson DC, Fava M, et al. Efficacy, safety, and tolerability of RBP-7000 once-monthly risperidone for the treatment of acute schizophrenia: an 8-week, randomized, double-blind, placebo-controlled, multicenter Phase 3 study. J Clin Psychopharmacol. 2016;36:130–140.
   PubMed Web of Science ®Google Scholar
• Isitt JJ, Nadipelli VR, Kouassi A, et al. Health-related quality of life in acute schizophrenia patients treated with RBP-7000 once monthly risperidone: an 8-week, randomized, double-blind, placebo-controlled, multicenter phase 3 study. Schizophr Res. 2016;174:126–131.
   PubMed Web of Science ®Google Scholar
• Ivaturi V, Gopalakrishnan M, Jvs G, et al. Exposure-response analysis after subcutaneous administration of RBP-7000, a once-a-month long-acting Atrigel formulation of risperidone. Br J Clin Pharmacol. 2017;83:1476–1498.
   PubMed Web of Science ®Google Scholar
• Llaudó J, Anta L, Ayani I, et al. Phase I, open-label, randomized, parallel study to evaluate the pharmacokinetics, safety, and tolerability of one intramuscular injection of risperidone ISM at different dose strengths in patients with schizophrenia or schizoaffective disorder (PRISMA-1). Int Clin Psychopharmacol. 2016;31:323–331.
   PubMed Web of Science ®Google Scholar
• Michaelides C Braeburn Pharma Keeps Up with Competitors with Long-Acting Risperidone for Schizophrenia. 2017 May 16 [cited 2017 Jul 22]. Available from: http://www.biospace.com/News/braeburn-pharma-keeps-up-with-competitors-with/456642
   Google Scholar
• Braeburn Pharmaceuticals. Braeburn pharmaceuticals achieves primary endpoint in pivotal phase 2/3 study of BB0817, risperidone 6-month implant for treatment of schizophrenia. Phase 3 Safety Study Underway; NDA filing targeted for year-end 2017. 2017 Apr 26 [cited 2017 Jul 22]. Available from: https://braeburnpharmaceuticals.com/braeburn-achieves-primary-endpoint-study-implant-schizophrenia/
   Google Scholar
• Remenar JF. Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics. Mol Pharm. 2014;11:1739–1749.
   PubMed Web of Science ®Google Scholar
• Nahata T, Saini TR. D-optimal designing and optimization of long acting microsphere-based injectable formulation of aripiprazole. Drug Dev Ind Pharm. 2008;34:668–675.
   PubMed Web of Science ®Google Scholar
• Nahata T, Saini TR. Formulation optimization of long-acting depot injection of aripiprazole by using D-optimal mixture design. PDA J Pharm Sci Technol. 2009;63:113–122.
   PubMedGoogle Scholar
• Hiraoka S, Uchida S, Namiki N. Preparation and characterization of high-content aripiprazole-loaded core-shell structure microsphere for long-release injectable formulation. Chem Pharm Bull (Tokyo). 2014;62:654–660.
   PubMed Web of Science ®Google Scholar
• Nakashima A, Izumi T, Ohya K, et al. Design of highly dispersible PLGA microparticles in aqueous fluid for the development of long-acting release injectables. Chem Pharm Bull (Tokyo). 2017;65:157–165.
   PubMed Web of Science ®Google Scholar
• Nanaki S, Tseklima M, Terzopoulou Z, et al. Use of mesoporous cellular foam (MCF) in preparation of polymeric microspheres for long acting injectable release formulations of paliperidone antipsychotic drug. Eur J Pharm Biopharm. 2017;117:77–90.
   PubMed Web of Science ®Google Scholar
• Nahata T, Saini TR. Optimization of formulation variables for the development of long acting microsphere based depot injection of olanzapine. J Microencapsul. 2008;25:426–433.
   PubMed Web of Science ®Google Scholar
• Lachaine J, Lapierre ME, Abdalla N, et al. Impact of switching to long-acting injectable antipsychotics on health services use in the treatment of schizophrenia. Can J Psychiatry. 2015;60(3 Suppl 2):S40–7.
   PubMedGoogle Scholar
• Lin J, Wong B, Offord S, et al. Healthcare cost reductions associated with the use of LAI formulations of antipsychotic medications versus oral among patients with schizophrenia. J Behav Health Serv Res. 2013;40:355–366.
   PubMed Web of Science ®Google Scholar
• Achilla E, McCrone P. 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. 2013;11:95–106.
   PubMedGoogle Scholar