Abstract
Purpose
To conduct an overview to summarize the efficacy and safety of aripiprazole for the treatment of schizophrenia.
Methods
A literature search was performed in PubMed, the Cochrane Library, LILACS, and the Centre for Reviews and Dissemination, for articles published until March 31, 2017. We included systematic reviews with meta-analyses of randomized controlled trials assessing the efficacy, and/or the safety of aripiprazole, for patients with schizophrenia. Two authors independently performed the study selection, data extraction, and quality assessment. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the Risk of Bias in Systematic Review (ROBIS) tool were used to appraise the quality of evidence and the risk of bias in the reviews, respectively.
Results
Fourteen studies fulfilled the inclusion criteria. Aripiprazole showed efficacy similar to that of both typical and atypical antipsychotic drugs (except olanzapine and amisulpride). Aripiprazole caused significantly lower weight gain and alterations in glucose and cholesterol levels, as compared to clozapine, risperidone, and olanzapine. In addition, aripiprazole caused significantly fewer general extrapyramidal side effects, less use of antiparkinsonian drugs, and akathisia, compared with typical antipsychotic drugs and risperidone. The overall quality of evidence in the reviews ranged from “very low” to “moderate,” principally because of the risk of bias of original trials, inconsistency, and imprecision in the outcomes. According to the ROBIS tool, there are four reviews with “high” risk of bias and five with “unclear” risk of bias.
Conclusions
Aripiprazole exhibited efficacy similar to that of other antipsychotic drugs and a better safety profile than that of typical (i.e., less some extrapyramidal side effects) and atypical (i.e., less metabolic changes) antipsychotic drugs.
Similar content being viewed by others
References
American Psychiatric Association (APA) (2013) Diagnostic and statistical manual of mental disorders. 5th ed. 2. Mental disorders—classification. 3. Mental disorders—diagnosis
Simeone JC, Ward AJ, Rotella P, Collins J, Windisch R (2015) An evaluation of variation in published estimates of schizophrenia prevalence from 1990–2013: a systematic literature review. BMC Psychiatry 15:193
Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine H et al (2013) Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden Of Disease Study 2010. Lancet 382(9904):1575–1586
Harvey PD (2014) Disability in schizophrenia: contributing factors and validated assessments. J Clin Psychiatry 75(suppl 1):15–20
Saha S, Chant D, McGrath J (2007) A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 64(10):1123–1131
Seida JC, Schouten JR, Mousavi SS, Hamm M, Beaith A, Vandermeer B, et al. (2012) First- and second-generation antipsychotics for children and young adults. Comparative Effectiveness Review No. 39. (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290–2007-10021.) AHRQ Publication No. 11(12)-EHC077-EF. Rockville: Agency for Healthcare Research and Quality
Cook DJ, Mulrow CD, Haynes RB (1997) Systematic reviews: synthesis of best evidence for clinical decisions. Ann Intern Med 126(5):376–380
American Diabetes Association (ADA) (2004) Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 27:596–601
Divac N, Prostran M, Jakovcevski I, Cerovac N (2014) Review article second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int 2014:656370
Thomson D, Russell K, Becker L, Klassend T, Hartling L (2010) The evolution of a new publication type: steps and challenges of producing overviews of reviews. Res Synth Methods 1(3–4):198–211
Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276
Schünemann H, Brozek J, Guyatt G, Oxman A, editors (The GRADE Working Group) (2013) GRADE handbook for grading quality of evidence and strength of recommendations. Available from: http://www.guidelinedevelopment.org/handbook. Accessed May 12, 2017
Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JP (2014) Evaluating the quality of evidence from a network meta-analysis. PLoS One 9(7):e99682
Whiting P, Savović J, Higgins JP, Caldwell DM, Reeves BC, Shea B, Davies P, Kleijnen J, Churchill R, ROBIS group (2016) ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol 69:225–234
Bai Z, Wang G, Cai S, Ding X, Liu W, Huang D, Shen W, Zhang J, Chen K, Yang Y, Zhang L, Zhao X, Ouyang Q, Zhao J, Lu H, Hao W (2017) Efficacy, acceptability and tolerability of 8 atypical antipsychotics in Chinese patients with acute schizophrenia: a network meta-analysis. Schizophr Res 185:73–79
Belgamwar RB, El-Sayeh HG (2011) Aripiprazole versus placebo for schizophrenia. Cochrane Database Syst Rev (8):CD006622
Bhattacharjee J, El-Sayeh HG (2008) Aripiprazole versus typical antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev (3):CD006617
Khanna P, Komossa K, Rummel-Kluge C, Hunger H, Schwarz S, El-Sayeh HG, et al (2014) Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev (2):CD006569
Klemp M, Tvete IF, Skomedal T, Gaasemyr J, Natvig B, Aursnes I (2011) A review and Bayesian meta-analysis of clinical efficacy and adverse effects of 4 atypical neuroleptic drugs compared with haloperidol and placebo. J Clin Psychopharmacol 31(6):698–704
Kunitomi T, Hashiguchi M, Mochizuki M (2014) Indirect comparison analysis of efficacy and safety between olanzapine and aripiprazole for schizophrenia. Br J Clin Pharmacol 77(5):767–776
Leucht S, Komossa K, Rummel-Kluge C, Corves C, Hunger H, Schmid F et al (2009) A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry 166(2):152–163
Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373(9657):31–41
Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382(9896):951–962
Majer IM, Gaughran F, Sapin C, Beillat M, Treur AM (2015) Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials. J Mark Access Health Policy 3. doi https://doi.org/10.3402/jmahp.v3.27208
Moteshafi H, Stip E (2012) Comparing tolerability profile of quetiapine, risperidone, aripiprazole and ziprasidone in schizophrenia and affective disorders: a meta-analysis. Expert Opin Drug Saf 11(5):713–732
Oya K, Kishi T, Iwata N (2015) Efficacy and tolerability of aripiprazole once monthly for schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat 11:2299–2307
Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, Kissling W, Davis JM, Leucht S (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 123(2–3):225–233
Thomas JE, Caballero J, Harrington CA (2015) The incidence of akathisia in the treatment of schizophrenia with aripiprazole, asenapine and lurasidone: a meta-analysis. Curr Neuropharmacol 13(5):681–691
Hendrick V, Dasher R, Gitlin M, Parsi M (2017) Minimizing weight gain for patients taking antipsychotic medications: the potential role for early use of metformin. Ann Clin Psychiatry 29(2):120–124
Bushe C, Holt R (2004) Prevalence of diabetes and impaired glucose tolerance in patients with schizophrenia. Br J Psychiatry 184(suppl. 47):s67–s71
Ryan MC, Collins P, Thakore JH (2003) Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry 160(2):284–289
Nelson RH (2013) Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 40(1):195–211
Joy CB, Adams CE, Lawrie SM (2006) Haloperidol versus placebo for schizophrenia. Cochrane Database Syst Rev (4):CD003082
Holder SD, Edmunds AL, Morgan S (2017) Psychotic and bipolar disorders: antipsychotic drugs. FP Essent 455:23–29
Sheehan R, Horsfall L, Strydom A, Osborn D, Walters K, Hassiotis A (2017) Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study. BMJ Open 7(8):e017406
Nawal W, Komal W, Muhammad WS (2017) Bupropion-induced acute dystonia with dose escalation and use of Naranjo nomogram. Cureus 9(4):e1157
Karthik MS, Prabhu N (2014) Temporomandibular joint dislocation due to atypical antipsychotic-induced acute dystonia: a case report. Ther Adv Psychopharmacol 4(6):282–284
Blanchet PJ, Kivenko V (2016) Drug-induced parkinsonism: diagnosis and management. JPRLS 6:83–91
Klingberg S, Wölwer W, Engel C, Wittorf A, Herrlich J, Meisner C et al (2011) Negative symptoms of schizophrenia as primary target of cognitive behavioral therapy: results of the randomized clinical TONES study. Schizophr Bull 37(Suppl 2):S98–S110
Veerman SRT, Schulte PFJ, Haan L (2017) Treatment for negative symptoms in schizophrenia: a comprehensive review. Drugs 77(13):1423–1459
Bühn S, Mathes T, Prengel P, Wegewitz U, Ostermann T, Robens S, Pieper D (2017) The risk of bias in systematic reviews tool showed fair reliability and good construct validity. J Clin Epidemiol 91:121–128
Faggion CM Jr, Monje A, Wasiak J (2018) Appraisal of systematic reviews on the management of peri-implant diseases with two methodological tools. J Clin Periodontol 45:754–766. https://doi.org/10.1111/jcpe.12893
Shea BJ, Hamel C, Wells GA, Bouter LM, Kristjansson E, Grimshaw J, Henry DA, Boers M (2009) AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol 62(10):1013–1020
Burda BU, Holmer HK, Norris SL (2016) Limitations of A Measurement Tool to Assess Systematic Reviews (AMSTAR) and suggestions for improvement. Syst Rev 5:58
Faggion CM Jr (2015) Critical appraisal of AMSTAR: challenges, limitations, and potential solutions from the perspective of an assessor. BMC Med Res Methodol 15:63
Author information
Authors and Affiliations
Contributions
E.L.A.R. and P.M.A. planned the study. E.L.A.R. and T.M.L. performed the literature search and the qualitative analysis, supervised by P.M.A. E.L.A.R. wrote the first draft, and T.M.L., M.E.B.V., S.S., and P.M.A. reviewed the manuscript. All authors contributed to and have approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors have no potential conflicts of interest relevant to disclose. The research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Rights and permissions
About this article
Cite this article
Ribeiro, E.L.A., de Mendonça Lima, T., Vieira, M.E.B. et al. Efficacy and safety of aripiprazole for the treatment of schizophrenia: an overview of systematic reviews. Eur J Clin Pharmacol 74, 1215–1233 (2018). https://doi.org/10.1007/s00228-018-2498-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-018-2498-1