Skip to main content

Advertisement

Log in

Long-Acting Injections in Schizophrenia: a 3-Year Update on Randomized Controlled Trials Published January 2016–March 2019

  • Schizophrenia and Other Psychiatric Disorders (AK Pandurangi, Section Editor)
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This study was conducted in order to review randomized controlled trial (RCT) data published January 2016–March 2019 on long-acting injectable antipsychotics (LAIs) for schizophrenia.

Recent Findings

Thirty-one RCTs (primary studies = 7; post hoc analyses = 24; n = 4738) compared LAIs vs. placebo (studies = 11, n = 1875), LAIs vs. oral antipsychotics (OAPs) (studies = 7, n = 658), and LAI vs. LAI (studies = 13, n = 2205). LAIs included two new formulations, aripiprazole lauroxil nanocrystal dispersion and subcutaneously injectable risperidone Perseris, as well as aripiprazole lauroxil, aripiprazole once-monthly, paliperidone once-monthly, paliperidone 3-monthly, and risperidone-LAI. Regarding prevention of relapse and hospitalization, LAIs consistently outperformed placebo, being partly superior to OAPs, without relevant LAI–LAI differences. LAIs were comparable to OAPs regarding all-cause discontinuation, functioning, quality of life, and tolerability, being associated with higher patient satisfaction and service engagement. Recent meta-analyses yielded mixed results, but never favoring OAPs over LAIs.

Summary

In RCTs, LAIs are superior to placebo, but only in some aspects, superior to OAPs. Comparative effectiveness of LAIs vs. OAPs requires further study, ideally in generalizable/real-world samples.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, et al. Schizophrenia. Nat Rev Dis Primer. 2015;12(1):15067.

    Google Scholar 

  2. Kane JM, Correll CU. Pharmacologic treatment of schizophrenia. Dialogues Clin Neurosci. 2010;12(3):345–57.

    PubMed  PubMed Central  Google Scholar 

  3. Garay RP, Citrome L, Samalin L, Liu C-C, Thomsen MS, Correll CU, et al. Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder: an appraisal of phase III clinical trials of schizophrenia-targeted therapies as found in US and EU clinical trial registries. Expert Opin Pharmacother. 2016;17(7):921–36.

    CAS  PubMed  Google Scholar 

  4. Insel TR. Rethinking schizophrenia. Nature. 2010;468(7321):187–93.

    CAS  PubMed  Google Scholar 

  5. Carpenter WT, Koenig JI. The evolution of drug development in schizophrenia. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2008;33(9):2061–79.

    CAS  Google Scholar 

  6. • Krogmann A, Peters L, von Hardenberg L, Bödeker K, Nöhles VB, Correll CU. Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities. CNS Spectrum. 2019;24(S1):38–69. https://doi.org/10.1017/S109285291900124 in press. Up-to to-date summary of positive, negative, failed and ongoing phase 2 and phase 3 studies of different pharmacological entities targeting various symptom domains in patients with schizophrenia.

    Article  Google Scholar 

  7. Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. 2014;16(4):505–24.

    PubMed  PubMed Central  Google Scholar 

  8. Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry Off J World Psychiatr Assoc WPA. 2013 Oct;12(3):216–26.

    Google Scholar 

  9. • Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry Off J World Psychiatr Assoc WPA. 2018;17(2):149–60. State-of-the-art review evaluating the evidence for and against the long-term maintenance treatment in patients with schizophrenia.

    Google Scholar 

  10. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet Lond Engl. 2012;379(9831):2063–71.

    CAS  Google Scholar 

  11. • Kishimoto T, Hagi K, Nitta M, Kane JM, Correll CU. Long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta-analysis of direct head-to-head comparisons. World Psychiatry Off J World Psychiatr Assoc WPA. 2019;18(2):208–24. Meta-analysis evaluating the comparative efficacy, safety and effectiveness of oral second-generation antipsychotics relative to each other in long-term maintenance head-to-head studies.

    Google Scholar 

  12. Kishimoto T, Agarwal V, Kishi T, Leucht S, Kane JM, Correll CU. Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics. Mol Psychiatry. 2013;18(1):53–66.

    CAS  PubMed  Google Scholar 

  13. •• Correll CU, Citrome L, Haddad PM, Lauriello J, Olfson M, Calloway SM, et al. The use of long-acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1–24. State-of-the-art review evaluating the evidence of long-acting injectable antipsychotics in the management of schizophrenia.

    PubMed  Google Scholar 

  14. Kane JM, Kishimoto T, Correll CU. Assessing the comparative effectiveness of long-acting injectable vs. oral antipsychotic medications in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry. J Clin Epidemiol. 2013;66(8 Suppl):S37–41.

    PubMed  PubMed Central  Google Scholar 

  15. 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(1):192–213.

    PubMed  Google Scholar 

  16. 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(10):957–65.

    PubMed  Google Scholar 

  17. • Kishimoto T, Hagi K, Nitta M, Leucht S, Olfson M, Kane JM, et al. Effectiveness of long-acting injectable vs oral antipsychotics in patients with schizophrenia: a meta-analysis of prospective and retrospective cohort studies. Schizophr Bull. 2018;44(3):603–19. Meta-analysis of cohort studies evaluating the evidence of the relative effectiveness of long-acting injectable antipsychotics versus oral antipsychotics for treatment persistence and hospitalization in the management of schizophrenia.

    PubMed  Google Scholar 

  18. Park S-C, Choi MY, Choi J, Park E, Tchoe HJ, Suh JK, et al. Comparative efficacy and safety of long-acting injectable and oral second-generation antipsychotics for the treatment of schizophrenia: a systematic review and meta-analysis. Clin Psychopharmacol Neurosci Off Sci J Korean Coll Neuropsychopharmacol. 2018;16(4):361–75.

    CAS  Google Scholar 

  19. • Leucht S, Leucht C, Huhn M, Chaimani A, Mavridis D, Helfer B, et al. Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, Bayesian meta-analysis, and meta-regression of efficacy predictors. Am J Psychiatry. 2017;174(10):927–42. State-of-the-art meta-analysis of the evidence of acute efficacy of oral antipsychotics in the treatment of schizophrenia.

    PubMed  Google Scholar 

  20. • 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;246:750–5. Small meta-analysis of randomized controlled trials comparing efficacy and effectiveness of long-acting injectable antipsychotics with oral antipsychotics in patients with recent-onset psychotic disorders.

    CAS  PubMed  Google Scholar 

  21. • 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(2–3):220–30. Meta-analysis of randomized controlled trials comparing the safety and tolerability of t long-acting injectable antipsychotics with the same oral antipsychotics in patients with schizophrenia.

    PubMed  Google Scholar 

  22. Indivior. FDA approves PERSERIS (risperidone) for extended-release injectable suspension for the treatment of schizophrenia in adults. Press Release [Internet]. 2018 Jul 27; Available from: Available from: http://indivior.com/wp- content/uploads/2018/07/PERSERIS-Press-Release-FINAL.pdf

  23. • Citrome L. Sustained-release risperidone via subcutaneous injection: a systematic review of RBP-7000 (PERSERIS TM ) for the treatment of schizophrenia. Clin Schizophr Relat Psychoses. 2018;12(3):130–41. Up-to-date summary of the available data for the first subcutaneously injectable long-acting injectable antipsychotic.

    PubMed  Google Scholar 

  24. Alkermes, Inc. Data on file (Clinical Study Report ALK9072-B102). Walth MA. 2017.

  25. 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.

    PubMed  Google Scholar 

  26. 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(6):1438–45.

    PubMed  PubMed Central  Google Scholar 

  27. Hard ML, Wehr AY, Du Y, Weiden PJ, Walling D, von Moltke L. Pharmacokinetic evaluation of a 1-day treatment initiation option for starting long-acting aripiprazole lauroxil for schizophrenia. J Clin Psychopharmacol. 2018;38(5):435–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. • Nasser AF, Henderson DC, Fava M, Fudala PJ, Twumasi-Ankrah P, Kouassi A, 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(2):130–40. First phase 3 trial comparing a subcutaneously injectable long-acting injectable antipsychotic with placebo, leading to FDA approval.

    CAS  PubMed  Google Scholar 

  29. Ivaturi V, Gopalakrishnan M, Gobburu JVS, Zhang W, Liu Y, Heidbreder C, et al. Exposure-response analysis after subcutaneous administration of RBP-7000, a once-a-month long-acting Atrigel formulation of risperidone: E-R analysis of RBP-7000, a long acting risperidone formulation. Br J Clin Pharmacol. 2017;83(7):1476–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ismail Z, Peters-Strickland T, Miguelez M, Baker RA, Hertel P, Eramo A, et al. Aripiprazole once-monthly in the treatment of acute psychotic episodes in schizophrenia: post hoc analysis of positive and negative syndrome scale Marder factor scores. J Clin Psychopharmacol. 2017;37(3):347–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kane JM, Peters-Strickland T, Baker RA, Hertel P, Eramo A, Jin N, 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 Nov 24;75(11):1254–60.

    PubMed  Google Scholar 

  32. Citrome L, Risinger R, Cutler AJ, Du Y, Zummo J, Nasrallah HA, 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. 2018;23(4):284–90.

    PubMed  Google Scholar 

  33. Meltzer HY, Risinger R, Nasrallah HA, Du Y, Zummo J, Corey L, et al. A randomized, double-blind, placebo-controlled trial of aripiprazole lauroxil in acute exacerbation of schizophrenia. J Clin Psychiatry. 2015;76(08):1085–90.

    PubMed  Google Scholar 

  34. Potkin SG, Risinger R, Du Y, Zummo J, Bose A, Silverman B, et al. Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation. Schizophr Res. 2017;190:115–20.

    PubMed  Google Scholar 

  35. Emsley R, Nuamah I, Gopal S, Hough D, Fleischhacker WW. Relapse after antipsychotic discontinuation in schizophrenia as a withdrawal phenomenon vs illness recurrence: a post hoc analysis of a randomized placebo-controlled study. J Clin Psychiatry. 2018;19:79(4).

    Google Scholar 

  36. 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;2–3(116):107–17.

    Google Scholar 

  37. Bell Lynum KS, Turkoz I, Kim E. Paliperidone palmitate once-every-3-months in adults with early illness schizophrenia. Early Interv Psychiatry. 2019;13(3):667–72.

    PubMed  Google Scholar 

  38. Berwaerts J, Liu Y, Gopal S, Nuamah I, Xu H, Savitz A, 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(8):830–9.

    PubMed  Google Scholar 

  39. Alphs L, Mao L, Lynn Starr H, Benson C. A pragmatic analysis comparing once-monthly paliperidone palmitate versus daily oral antipsychotic treatment in patients with schizophrenia. Schizophr Res. 2016;170(2–3):259–64.

    PubMed  Google Scholar 

  40. Alphs L, Bossie C, Mao L, Lee E, Starr HL. Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent-onset versus more chronic schizophrenia and a history of criminal justice system involvement: paliperidone LAI in recent schizophrenia. Early Interv Psychiatry. 2018;12(1):55–65.

    PubMed  Google Scholar 

  41. Lynn Starr H, Bermak J, Mao L, Rodriguez S, Alphs L. Comparison of long-acting and oral antipsychotic treatment effects in patients with schizophrenia, comorbid substance abuse, and a history of recent incarceration: an exploratory analysis of the PRIDE study. Schizophr Res. 2018;194:39–46.

    CAS  PubMed  Google Scholar 

  42. Alphs L, Mao L, Rodriguez SC, Hulihan J, Starr HL. Design and rationale of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study: a novel comparative trial of once-monthly paliperidone palmitate versus daily oral antipsychotic treatment for delaying time to treatment failure in persons with schizophrenia. J Clin Psychiatry. 2014;75(12):1388–93.

    PubMed  Google Scholar 

  43. Kim E, Correll CU, Mao L, Starr HL, Alphs L. Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia. CNS Spectr. 2016;21(6):466–77.

    PubMed  Google Scholar 

  44. Malla A, Chue P, Jordan G, Stip E, Koczerginski D, Milliken H, et al. An exploratory, open-label, randomized trial comparing risperidone long-acting injectable with oral antipsychotic medication in the treatment of early psychosis. Clin Schizophr Relat Psychoses. 2016;9(4):198–208.

    PubMed  Google Scholar 

  45. Huang M, Yu L, Pan F, Lu S, Hu S, Hu J, et al. A randomized, 13-week study assessing the efficacy and metabolic effects of paliperidone palmitate injection and olanzapine in first-episode schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:122–30.

    CAS  PubMed  Google Scholar 

  46. Bozzatello P, Bellino S, Mancini I, Sandei L, Zanalda E, Rocca P. Effects on satisfaction and service engagement of paliperidone palmitate compared with oral paliperidone in patients with schizophrenia: an open label randomized controlled trial. Clin Drug Investig. 2019;39(2):169–78.

    CAS  PubMed  Google Scholar 

  47. Stroup TS, Bareis NA, Rosenheck RA, Swartz MS, McEvoy JP. Heterogeneity of treatment effects of long-acting injectable antipsychotic medications. J Clin Psychiatry. 2018;27:80(1).

    Google Scholar 

  48. McEvoy JP, Byerly M, Hamer RM, Dominik R, Swartz MS, Rosenheck RA, et al. Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial. JAMA. 2014 May 21;311(19):1978–87.

    PubMed  PubMed Central  Google Scholar 

  49. Savitz AJ, Xu H, Gopal S, Nuamah I, Ravenstijn P, Janik A, 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(7):pyw018.

    PubMed  PubMed Central  Google Scholar 

  50. • Savitz AJ, Xu H, Gopal S, Nuamah I, Hough D, Mathews M. Paliperidone palmitate 3-month treatment results in symptomatic remission in patients with schizophrenia: a randomized, multicenter, double-blind, and noninferiority study. Int Clin Psychopharmacol. 2017;32(6):329–36. Large active-controlled randomized trial demonstrating similar efficacy with paliperidone once-monthly vs. paliperidone three-monthly.

    PubMed  Google Scholar 

  51. Mathews M, Pei H, Savitz A, Nuamah I, Hough D, Alphs L, et al. Paliperidone palmitate 3-monthly versus 1-monthly injectable in patients with schizophrenia with or without prior exposure to oral risperidone or paliperidone: a post hoc, subgroup analysis. Clin Drug Investig. 2018;38(8):695–702.

    CAS  PubMed  Google Scholar 

  52. Savitz AJ, Xu H, Gopal S, Nuamah I, Ravenstijn P, Hough D, et al. Efficacy and safety of paliperidone palmitate 3-month versus 1-month formulation in patients with schizophrenia: comparison between European and non-European population. Neuropsychiatr Dis Treat. 2019;15:587–602.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Isitt JJ, Nadipelli VR, Kouassi A, Fava M, Heidbreder C. 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(1–3):126–31.

    PubMed  Google Scholar 

  54. Correll CU, Stanford AD, Claxton A, Du Y, Weiden PJ. Social and functional outcomes with two doses of aripiprazole lauroxil vs placebo in patients with schizophrenia: a post-hoc analysis of a 12-week phase 3 efficacy study. Psychiatry Res. 2019;274:176–81.

    CAS  PubMed  Google Scholar 

  55. Fu D-J, Turkoz I, Walling D, Lindenmayer J-P, Schooler NR, Alphs L. Paliperidone palmitate once-monthly maintains improvement in functioning domains of the Personal and Social Performance scale compared with placebo in subjects with schizoaffective disorder. Schizophr Res. 2018;192:185–93.

    PubMed  Google Scholar 

  56. Fu D-J, Turkoz I, Simonson RB, Walling DP, Schooler NR, Lindenmayer J-P, 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(03):253–62.

    PubMed  Google Scholar 

  57. Potkin SG, Loze J-Y, Forray C, Baker RA, Sapin C, Peters-Strickland T, et al. Relationship between response to aripiprazole once-monthly and paliperidone palmitate on work readiness and functioning in schizophrenia: a post-hoc analysis of the QUALIFY study. Savill M, editor. PLOS ONE. 2017;12(8):e0183475.

    PubMed  PubMed Central  Google Scholar 

  58. Potkin SG, Loze JY, Forray C, Baker RA, Sapin C, Peters-Strickland T, et al. Multidimensional assessment of functional outcomes in schizophrenia: results From QUALIFY, a head-to-head trial of aripiprazole once-monthly and paliperidone palmitate. Int J Neuropsychopharmacol. 2017;20(1):40–9.

    PubMed  Google Scholar 

  59. Naber D, Hansen K, Forray C, Baker RA, Sapin C, Beillat M, 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(1–2):498–504.

    PubMed  Google Scholar 

  60. Koshikawa Y, Takekita Y, Kato M, Sakai S, Onohara A, Sunada N, et al. The comparative effects of risperidone long-acting injection and paliperidone palmitate on social functioning in schizophrenia: a 6-month, open-label, randomized controlled pilot trial. Neuropsychobiology. 2016;73(1):35–42.

    CAS  PubMed  Google Scholar 

  61. Takekita Y, Koshikawa Y, Fabbri C, Sakai S, Sunada N, Onohara A, et al. Cognitive function and risperidone long-acting injection vs. paliperidone palmitate in schizophrenia: a 6-month, open-label, randomized, pilot trial. BMC Psychiatry. 2016;16(1):172.

    PubMed  PubMed Central  Google Scholar 

  62. Potkin SG, Loze J-Y, Forray C, Baker RA, Sapin C, Peters-Strickland T, et al. Multidimensional assessment of functional outcomes in schizophrenia: results From QUALIFY, a head-to-head trial of aripiprazole once-monthly and paliperidone palmitate. Int J Neuropsychopharmacol. 2016:pyw093.

  63. Nasrallah HA, Newcomer JW, Risinger R, Du Y, Zummo J, Bose A, et al. Effect of aripiprazole lauroxil on metabolic and endocrine profiles and related safety considerations among patients with acute schizophrenia. J Clin Psychiatry. 2016;77(11):1519–25.

    PubMed  Google Scholar 

  64. Kern Sliwa J, Savitz A, Nuamah I, Mathews M, Gopal S, Elefant E, et al. An assessment of injection site reaction and injection site pain of 1-month and 3-month long-acting injectable formulations of paliperidone palmitate. Perspect Psychiatr Care. 2018;54(4):530–8.

    PubMed  Google Scholar 

  65. Mathews M, Nuamah I, Savitz AJ, Hough DW, Najarian D, Kim E, et al. Time to onset and time to resolution of extrapyramidal symptoms in patients with exacerbated schizophrenia treated with 3-monthly vs once-monthly paliperidone palmitate. Neuropsychiatr Dis Treat. 2018;14:2807–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Potkin SG, Loze J-Y, Forray C, Baker RA, Sapin C, Peters-Strickland T, et al. Reduced sexual dysfunction with aripiprazole once-monthly versus paliperidone palmitate: results from QUALIFY. Int Clin Psychopharmacol. 2017;32(3):147–54.

    PubMed  PubMed Central  Google Scholar 

  67. • Kane JM, Schooler NR, Marcy P, Achtyes ED, Correll CU, Robinson DG. Patients with early-phase schizophrenia will accept treatment with sustained-release medication (long-acting injectable antipsychotics): results from the recruitment phase of the PRELAPSE trial. J Clin Psychiatry. 2019;80(3). Preliminary results of the cluster-randomized PRELAPSE trial showing that >75% of first-episode and early-phase patients within 5 years of the onset of schizophrenia will receive at least one long-acting injectable antipsychotic treatment within 3 months of service engagement when adequately training the entire treatment team.

  68. Haddad PM, Kishimoto T, Correll CU, Kane JM. Ambiguous findings concerning potential advantages of depot antipsychotics: in search of clinical relevance. Curr Opin Psychiatry. 2015;28(3):216.

    PubMed  Google Scholar 

  69. •• Tiihonen J, Tanskanen A, Taipale H. 20-Year nationwide follow-up study on discontinuation of antipsychotic treatment in first-episode schizophrenia. Am J Psychiatry. 2018;175(8):765–73. Nationwide database study showing that in real-world settings and including all patients in a country diagnosed with schizophrenia, long-acting injectable antipsychotics rank among the most efficacious treatments for the prevention of hospitalization.

    PubMed  Google Scholar 

  70. •• Taipale H, Mittendorfer-Rutz E, Alexanderson K, Majak M, Mehtälä J, Hoti F, et al. Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia. Schizophr Res. 2018;197:274–80. Nationwide database study showing that in real-world settings and including all patients in a country diagnosed with schizophrenia, long-acting injectable antipsychotics reduce all-cause mortality by >30% compared to clinicians' choice oral antipsychotics.

    PubMed  Google Scholar 

  71. Vermeulen JM, van Rooijen G, van de Kerkhof MPJ, Sutterland AL, Correll CU, de Haan L. Clozapine and long-term mortality risk in patients with schizophrenia: a systematic review and meta-analysis of studies lasting 1.1-12.5 years. Schizophr Bull. 2019;45(2):315–29.

    PubMed  Google Scholar 

  72. Carbon M, Kane JM, Leucht S, Correll CU. Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis. World Psychiatry. 2018;17(3):330–40.

    PubMed  PubMed Central  Google Scholar 

  73. Correll CU, Joffe BI, Rosen LM, Sullivan TB, Joffe RT. Cardiovascular and cerebrovascular risk factors and events associated with second-generation antipsychotic compared to antidepressant use in a non-elderly adult sample: results from a claims-based inception cohort study. World Psychiatry Off J World Psychiatr Assoc WPA. 2015;14(1):56–63.

    Google Scholar 

  74. Vancampfort D, Correll CU, Galling B, Probst M, Hert MD, Ward PB, et al. Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis. World Psychiatry. 2016;15(2):166–74.

    PubMed  PubMed Central  Google Scholar 

  75. Correll CU, Solmi M, Veronese N, Bortolato B, Rosson S, Santonastaso P, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry. 2017;16(2):163–80.

    PubMed  PubMed Central  Google Scholar 

  76. Citrome L. New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia. Expert Rev Neurother. 2013;13(7):767–83.

    CAS  PubMed  Google Scholar 

  77. Sajatovic M, Ross R, Legacy SN, Correll CU, Kane JM, DiBiasi F, et al. Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics – —expert consensus survey part 1. Neuropsychiatr Dis Treat. 2018;14:1463–74.

    PubMed  PubMed Central  Google Scholar 

  78. Sajatovic M, Ross R, Legacy SN, Byerly M, Kane JM, DiBiasi F, et al. Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder – —expert consensus survey part 2. Neuropsychiatr Dis Treat. 2018 Jun;14:1475–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. • Correll CU, Sliwa JK, Najarian DM, Saklad SR. Practical considerations for managing breakthrough psychosis and symptomatic worsening in patients with schizophrenia on long-acting injectable antipsychotics. CNS Spectr. 2018:1–17. Practical review regarding the clinical evaluation and management of patients with (breakthrough) psychosis while being treated with a long-acting injectable antipsychotic.

  80. Heres S, Hamann J, Kissling W, Leucht S. Attitudes of psychiatrists toward antipsychotic depot medication. J Clin Psychiatry. 2006;67(12):1948–53.

    PubMed  Google Scholar 

  81. Correll C. Addressing barriers to using long-acting injectable antipsychotics and appropriately monitoring antipsychotic adverse effects. J Clin Psychiatry. 2013;74(8):e16.

    Google Scholar 

  82. Correll CU, Lauriello J. Long-acting injectable antipsychotics: where do they fit in the treatment plan? J Clin Psychiatry. 2018;79(1).

    PubMed  Google Scholar 

  83. • Weiden PJ, Kim E, Bermak J, Turkoz I, Gopal S, Berwaerts J. Does half-life matter after antipsychotic discontinuation?: a relapse comparison in schizophrenia with 3 different formulations of paliperidone. J Clin Psychiatry. 2017;78(7):e813–20. Indirect comparison of the median time to (impending) relapse in patients allocated double blindly to switch to placebo after open-label stabilization on either oral paliperidone, once-monthly injectable paliperidone or three-monthly injectable paliperidone, demonstrating significantly increased delays with the long-acting injectable formulations, and especially with the formulation with the longest injection interval.

    Google Scholar 

  84. McEvoy JP, Risinger R, Mykhnyak S, Du Y, Liu C-C, Stanford AD, et al. Durability of therapeutic response with long-term aripiprazole lauroxil treatment following successful resolution of an acute episode of schizophrenia. J Clin Psychiatry. 2017;78(8):1103–9.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christoph U. Correll.

Ethics declarations

Conflict of Interest

Luisa Peters, Amanda Krogmann, Laura von Hardenberg, Katja Bödeker, and Viktor B. Nöhles each declare no potential conflicts of interest. Christoph U. Correll has been a consultant and/or advisor to or has received honoraria from: Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen, and Otsuka. He served on a Data Safety Monitoring Board for Boehringer-Ingelheim, Lundbeck, Rovi, Supernus, and Teva. He received royalties from UpToDate and grant support from Janssen and Takeda. He is also a shareholder of LB Pharma.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Schizophrenia and Other Psychiatric Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peters, L., Krogmann, A., von Hardenberg, L. et al. Long-Acting Injections in Schizophrenia: a 3-Year Update on Randomized Controlled Trials Published January 2016–March 2019. Curr Psychiatry Rep 21, 124 (2019). https://doi.org/10.1007/s11920-019-1114-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11920-019-1114-0

Keywords

Navigation