Browse > Article
http://dx.doi.org/10.9758/cpn.2018.16.4.361

Comparative Efficacy and Safety of Long-acting Injectable and Oral Second-generation Antipsychotics for the Treatment of Schizophrenia: A Systematic Review and Meta-analysis  

Park, Seon-Cheol (Department of Psychiatry, Haeundae Paik Hospital, Inje University College of Medicine Busan)
Choi, Mi Young (National Evidence-based Healthcare Collaborating Agency)
Choi, Jina (National Evidence-based Healthcare Collaborating Agency)
Park, Eunjung (National Evidence-based Healthcare Collaborating Agency)
Tchoe, Ha Jin (National Evidence-based Healthcare Collaborating Agency)
Suh, Jae Kyung (National Evidence-based Healthcare Collaborating Agency)
Kim, Young Hoon (Department of Psychiatry, Gongju National Hospital)
Won, Seung Hee (Department of Psychiatry, School of Medicine, Kyungpook National University)
Chung, Young-Chul (Department of Psychiatry, Chonbuk National University Hospital)
Bae, Kyung-Yeol (Department of Psychiatry, Chonnam National University Medical School)
Lee, Sang-Kyu (Department of Psychiatry, Hallym University Chuncheon Sacred Hospital, Hallym University College of Medicine)
Park, Chan Mi (National Evidence-based Healthcare Collaborating Agency)
Lee, Seung-Hwan (Department of Psychiatry, Inje University Ilsan Paik Hospital)
Publication Information
Clinical Psychopharmacology and Neuroscience / v.16, no.4, 2018 , pp. 361-375 More about this Journal
Abstract
We aimed to compare the efficacy and safety of long-acting injectable (LAI) and oral second-generation antipsychotics (SGAs) in treating schizophrenia by performing a systematic review and meta-analysis. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library, as well as five Korean databases, were systemically searched to identify studies published from 2000 to 16 April 2015, which compared the efficacy and safety of LAI and oral SGAs. Using data from randomized controlled trials (RCTs), meta-analyses were conducted. In addition, the GRADE (the Grading of Recommendations, Assessment, Development and Evaluation) approach was applied to explicitly assess the quality of the evidence. A total of 30 studies including 17 RCTs and 13 observational studies were selected. The group treated with LAI SGAs was characterized by significantly lower relapse rates, longer times to relapse and fewer hospital days, but also by a higher occurrence of extrapyramidal syndrome and prolactin-related symptoms than that in the group treated with oral SGAs. Our findings demonstrate that there is moderate to high level of evidence suggesting that in the treatment of schizophrenia, LAI SGAs have higher efficacy and are associated with higher rates of extrapyramidal syndrome and prolactin-related symptoms. Additionally, the use of LAI SGAs should be combined with appropriate measures to reduce dopamine $D_2$ antagonism-related symptoms.
Keywords
Efficacy; Long-acting injectable; Safety; Schizophrenia; Second-generation antipsychotics;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Barrio P, Batalla A, Castellvi P, Hidalgo D, Garcia M, Ortiz A, et al. Effectiveness of long-acting injectable risperidone versus oral antipsychotics in the treatment of recent-onset schizophrenia: a case-control study. Int Clin Psychopharmacol 2013;28:164-170.
2 Beauclair L, Chue P, McCormick J, Camacho F, Lam A, Luong D. Impact of risperidone long-acting injectable on hospitalisation and medication use in Canadian patients with schizophrenia. J Med Econ 2007;10:427-442.   DOI
3 Buckley PF, Schooler NR, Goff DC, Hsiao J, Kopelowicz A, Lauriello J, et al ; PROACTIVE Study. Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study. Schizophr Bull 2015;41:449-459.   DOI
4 Chue P, Eerdekens M, Augustyns I, Lachaux B, Molcan P, Eriksson L, et al. Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets. Eur Neuropsychopharmacol 2005;15:111-117.   DOI
5 de Arce Cordon R, Eding E, Marques-Teixeira J, Milanova V, Rancans E, Schreiner A. Descriptive analyses of the aripiprazole arm in the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE). Eur Arch Psychiatry Clin Neurosci 2012;262:139-149.   DOI
6 Detke HC, Weiden PJ, Llorca PM, Choukour M, Watson SB, Brunner E, et al. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia. J Clin Psychopharmacol 2014;34:426-434.   DOI
7 Fe Bravo-Ortiz M, Gutierrez-Casares JR, Rodriguez-Morales A, Garcia MA, Hidalgo-Borrajo R. Influence of type of treatment on the well-being of Spanish patients with schizophrenia and their caregivers. Int J Psychiatry Clin Pract 2011;15:286-295.   DOI
8 Olfson M, Mechanic D, Hansell S, Boyer CA, Walkup J, Weiden PJ. Predicting medication noncompliance after hospital discharge among patients with schizophrenia. Psychiatr Serv 2000;51:216-222.   DOI
9 Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. Oral versus depot antipsychotic drugs for schizophrenia--a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res 2011;127:83-92.   DOI
10 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.   DOI
11 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.   DOI
12 Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull 2014;40:192-213.   DOI
13 Manchanda R, Chue P, Malla A, Tibbo P, Roy MA, Williams R, et al. Long-acting injectable antipsychotics: evidence of effectiveness and use. Can J Psychiatry 2013;58(5 Suppl 1):5S-13S.
14 Kishi T, Matsunaga S, Iwata N. Mortality risk associated with long-acting injectable antipsychotics: a systematic review and meta-analyses of randomized controlled trials. Schizophr Bull 2016;42:1438-1445.   DOI
15 Peng X, Ascher-Svanum H, Faries D, Conley RR, Schuh KJ. Decline in hospitalization risk and health care cost after initiation of depot antipsychotics in the treatment of schizophrenia. Clinicoecon Outcomes Res 2011;3:9-14.
16 Martin CR, Allan R. Factor structure of the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4). Psychol Health Med 2007;12:126-134.   DOI
17 Heinrichs DW, Hanlon TE, Carpenter WT Jr. The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome. Schizophr Bull 1984;10:388-398.   DOI
18 Lambert T, Olivares JM, Peuskens J, DeSouza C, Kozma CM, Otten P, et al. Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium. Ann Gen Psychiatry 2011;10:10.   DOI
19 Tiihonen J, Wahlbeck K, Lonnqvist J, Klaukka T, Ioannidis JP, Volavka J, et al. 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 2006;333:224.   DOI
20 Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011;168:603-609.   DOI
21 Grimaldi-Bensouda L, Rouillon F, Astruc B, Rossignol M, Benichou J, Falissard B, et al ; CGS Study Group. Does longacting 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.   DOI
22 Keks NA, Ingham M, Khan A, Karcher K. Long-acting injectable risperidone v. olanzapine tablets for schizophrenia or schizoaffective disorder. Randomised, controlled, open-label study. Br J Psychiatry 2007;191:131-139.   DOI
23 Gaebel W, Schreiner A, Bergmans P, de Arce R, Rouillon F, Cordes J, et al. 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 2010;35:2367-2377.   DOI
24 Huang SS, Lin CH, Loh el-W, Yang HY, Chan CH, Lan TH. Antipsychotic formulation and one-year rehospitalization of schizophrenia patients: a population-based cohort study. Psychiatr Serv 2013;64:1259-1262.   DOI
25 Ishigooka J, Nakamura J, Fujii Y, Iwata N, Kishimoto T, Iyo M, et al ; ALPHA Study Group. Efficacy and safety of aripiprazole once-monthly in Asian patients with schizophrenia: a multicenter, randomized, double-blind, non-inferiority study versus oral aripiprazole. Schizophr Res 2015;161:421-428.   DOI
26 Kim B, Lee SH, Choi TK, Suh S, Kim YW, Lee E, et al. Effectiveness of risperidone long-acting injection in first-episode schizophrenia: in naturalistic setting. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1231-1235.   DOI
27 Lang K, Meyers JL, Korn JR, Lee S, Sikirica M, Crivera C, et al. Medication adherence and hospitalization among patients with schizophrenia treated with antipsychotics. Psychiatr Serv 2010;61:1239-1247.   DOI
28 Ostuzzi G, Bighelli I, So R, Furukawa TA, Barbui C. Does formulation matter? A systematic review and meta-analysis of oral versus long-acting antipsychotic studies. Schizophr Res 2017;183:10-21.   DOI
29 Correll CU, Kishimoto T, Kane JM. Randomized controlled trials in schizophrenia: opportunities, limitations, and trial design alternatives. Dialogues Clin Neurosci 2011;13:155-172.
30 Misawa F, Kishimoto T, Hagi K, Kane JM, Correll CU. Safety and tolerability of long-acting injectable versus oral antipsychotics: A meta-analysis of randomized controlled studies comparing the same antipsychotics. Schizophr Res 2016;176:220-230.   DOI
31 Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther 1989;251:238-246.
32 Fischer-Barnicol D, Lanquillon S, Haen E, Zofel P, Koch HJ, Dose M, et al ; Working Group 'Drugs in Psychiatry'. Typical and atypical antipsychotics: the misleading dichotomy. Results from the Working Group 'Drugs in Psychiatry' (AGATE). Neuropsychobiology 2008;57:80-87.   DOI
33 Charych EI, Liu F, Moss SJ, Brandon NJ. GABA(A) receptors and their associated proteins: implications in the etiology and treatment of schizophrenia and related disorders. Neuropharmacology 2009;57:481-495.   DOI
34 Higgins JPT, Green SS. Cochrane handbook for systematic reviews of interventions. Chichester:Wiley-Blackwell;2008.
35 Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS; Scientific Advisory Board and the Executive Committee of the Grand Challenges on Global Mental Health. Grand challenges in global mental health. Nature 2011;475:27-30.   DOI
36 Munetz MR, Benjamin S. How to examine patients using the Abnormal Involuntary Movement Scale. Hosp Community Psychiatry 1988;39:1172-1177.
37 Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al ; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:1.   DOI
38 Kim SY, Park JE, Lee YJ, Seo HJ, Sheen SS, Hahn S, et al. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol 2013;66:408-414.   DOI
39 Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64:383-394.   DOI
40 Ascher-Svanum H, Novick D, Haro JM, Bertsch J, McDonnell D, Detke H. Predictors of psychiatric hospitalization during 6 months of maintenance treatment with olanzapine long-acting injection: post hoc analysis of a randomized, double-blind study. BMC Psychiatry 2013;13:224.   DOI
41 Bai YM, Chen TT, Wu B, Hung CH, Lin WK, Hu TM, et al. A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study. Pharmacopsychiatry 2006;39:135-141.   DOI
42 Huang X, Lin J, Demner-Fushman D. Evaluation of PICO as a knowledge representation for clinical questions. AMIA Annu Symp Proc 2006:359-363.
43 Grunder G, Hippius H, Carlsson A. The 'atypicality' of antipsychotics: a concept re-examined and re-defined. Nat Rev Drug Discov 2009;8:197-202.   DOI
44 Kim YS, Ahn YM, Jeong SH. Principle and practice of long-acting injectable antipsychotics. Seoul;Seoul National University Press;2010. p.40-41. Korean.
45 Fusar-Poli P, Kempton MJ, Rosenheck RA. Efficacy and safety of second-generation long-acting injections in schizophrenia: a meta-analysis of randomized-controlled trials. Int Clin Psychopharmacol 2013;28:57-66.   DOI
46 Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382-389.   DOI
47 Tandon R, Nasrallah HA, Keshavan MS. Schizophrenia, "just the facts" 5. Treatment and prevention. Past, present, and future. Schizophr Res 2010;122:1-23.   DOI
48 Guy W. ECDEU assessment manual for psychopharmacology, Revised 1976. Rockville:National Institute for Mental Health;1976.
49 Kay SR, Fiszbein A, Opler LA. The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261-276.   DOI
50 Spill B, Konoppa S, Kissling W, Maino K, Messer T, Heres S. Long-term observation of patients successfully switched to risperidone long-acting injectable: A retrospective, naturalistic 18-month mirror-image study of hospitalization rates and therapy costs. Int J Psychiatry Clin Pract 2010;14:53-62.   DOI
51 Suzuki H, Gen K. The influence of switching from oral risperidone to risperidone long-acting injection on the clinical symptoms and cognitive function in schizophrenia. Ther Adv Psychopharmacol 2012;2:23-29.   DOI
52 Suzuki H, Inoue Y, Gen K. A study of the efficacy and safety of switching from oral risperidone to risperidone long-acting injection in older patients with schizophrenia. Ther Adv Psychopharmacol 2012;2:227-234.   DOI
53 Weiden PJ, Schooler NR, Weedon JC, Elmouchtari A, Sunakawa A, Goldfinger SM. A randomized controlled trial of long-acting injectable risperidone vs continuation on oral atypical antipsychotics for first-episode schizophrenia patients: initial adherence outcome. J Clin Psychiatry 2009;70:1397-1406.   DOI
54 Rouillon F, Eriksson L, Burba B, Raboch J, Kaprinis G, Schreiner A. Functional recovery results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE). Acta Neuropsychiatr 2013;25:297-306.   DOI
55 Llorca PM, Kahn JP, Moreau-Mallet V, Bouhours P, The French StoRMi Investigators Group. Symptom control, functioning, and hospitalization status in French patients changed from oral atypical antipsychotics to risperidone long-acting injectable. Int J Psychiatry Clin Pract 2006;10:276-284.   DOI
56 Macfadden W, Ma YW, Thomas Haskins J, Bossie CA, Alphs L. A prospective study comparing the long-term effectiveness of injectable risperidone long-acting therapy and oral aripiprazole in patients with schizophrenia. Psychiatry (Edgmont) 2010;7:23-31.
57 McDonnell DP, Kryzhanovskaya LA, Zhao F, Detke HC, Feldman PD. 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.
58 Chouinard G, Margolese HC. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophr Res 2005;76:247-265.   DOI
59 Kishi T, Oya K, Iwata N. Long-acting injectable antipsychotics for the prevention of relapse in patients with recent-onset psychotic disorders: a systematic review and meta-analysis of randomized controlled trials. Psychiatry Res 2016;246:750-755.   DOI
60 Lafeuille MH, Dean J, Carter V, Duh MS, Fastenau J, Dirani R, et al. Systematic review of long-acting injectables versus oral atypical antipsychotics on hospitalization in schizophrenia. Curr Med Res Opin 2014;30:1643-1655.   DOI
61 Kim YK, Choi J, Park SC. A novel bio-psychosocial-behavioral treatment model in schizophrenia. Int J Mol Sci 2017;18:E734.   DOI
62 Karadag F, Sengul CB, Enli Y, Karakulah K, Alacam H, Kaptanoglu B, et al. Relationship between serum bilirubin levels and metabolic syndrome in patients with schizophrenia spectrum disorders. Clin Psychopharmacol Neurosci 2017;15:153-162.   DOI
63 Tripathi A, Kar SK, Shukla R. Cognitive deficits in schizophrenia: Understanding the biological correlates and remediation strategies. Clin Psychopharmacol Neurosci 2018;16:7-17.   DOI
64 Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 2005;162:441-449.   DOI
65 Weiden PJ, Schooler NR, Weedon JC, Elmouchtari A, Sunakawa-McMillan A. Maintenance treatment with long-acting injectable risperidone in first-episode schizophrenia: a randomized effectiveness study. J Clin Psychiatry 2012;73:1224-1233.   DOI
66 Willis M, Svensson M, Lothgren M, Eriksson B, Berntsson A, Persson U. The impact on schizophrenia-related hospital utilization and costs of switching to long-acting risperidone injections in Sweden. Eur J Health Econ 2010;11:585-594.   DOI
67 Wykes T, Rose D, Williams P, David AS. Working alliance and its relationship to outcomes in a randomized controlled trial (RCT) of antipsychotic medication. BMC Psychiatry 2013;13:28.   DOI
68 Smeraldi E, Cavallaro R, Folnegovic-Smalc V, Bidzan L, Emin Ceylan M, Schreiner A. Long-term remission in schizophrenia and schizoaffective disorder: results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE). Ther Adv Psychopharmacol 2013;3:191-199.   DOI
69 Schmauss M, Sacchetti E, Kahn JP, Medori R. Efficacy and safety of risperidone long-acting injectable in stable psychotic patients previously treated with oral risperidone. Int Clin Psychopharmacol 2007;22:85-92.   DOI
70 Schmauss M, Diekamp B, Gerwe M, Schreiner A, Ibach B. Does oral antipsychotic pre-treatment influence outcome of a switch to long-acting injectable risperidone in patients with schizophrenia? Pharmacopsychiatry 2010;43:73-80.   DOI
71 Fleischhacker WW, Sanchez R, Perry PP, Jin N, Peters-Strickland T, Johnson BR, et al. Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, noninferiority study. Br J Psychiatry 2014;205:135-144.   DOI
72 Corrigan PW, Liberman RP, Engel JD. From noncompliance to collaboration in the treatment of schizophrenia. Hosp Community Psychiatry 1990;41:1203-1211.
73 Novick D, Haro JM, Suarez D, Perez V, Dittmann RW, Haddad PM. Predictors and clinical consequences of non-adherence with antipsychotic medication in the outpatient treatment of schizophrenia. Psychiatry Res 2010;176:109-113.   DOI