Purpose of Review
Schizophrenia is a leading cause of disease burden in youth and can significantly impair an adolescent’s peer and familial relationships and academic functioning. Therefore, safe and effective treatments are needed. This article reviews the pharmacological treatment of adolescents with schizophrenia, when possible, with a focus on the past five years of research.
There are relatively few randomized controlled trials (RCTs) and head-to-head trials informing selection of a medication in pediatric schizophrenia. However, recent literature focusing on the efficacy and tolerability of atypical antipsychotics has led to the Food and Drug Administration (FDA) approval of multiple agents, specifically risperidone, olanzapine, quetiapine, aripiprazole, paliperidone, and lurasidone, for the treatment of pediatric schizophrenia. Asenapine has also been studied in a large RCT within the past five years, but participants randomized to asenapine treatment did not do statistically significantly better than those assigned to receive placebo. Comparison RCTs on clozapine have indicated benefit in treatment-resistant pediatric schizophrenia, but at the cost of significant side effect burden. Common adverse events with atypical antipsychotics include weight gain, akathisia, hyperprolactinemia, and somnolence.
Atypical antipsychotics remain first-line treatment for children and adolescents with early onset schizophrenia. However, further study is required to develop more effective and better tolerated treatment options, and in addition to pharmacologic management, current guidelines recommend combination treatment with psychotherapy and psychoeducation.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Hollis C. Adult outcomes of child- and adolescent-onset schizophrenia: diagnostic stability and predictive validity. Am J Psychiatry. 2000;157(10):1652–9.
Rabinowitz J, Levine SZ, Hafner H. A population based elaboration of the role of age of onset on the course of schizophrenia. Schizophr Res. 2006;88(1–3):96–101.
Young CM, Findling RL. Pharmacologic treatment of adolescent and child schizophrenia. Expert Rev Neurother. 2004;4(1):53–60.
Bourgeois FT, et al. Pediatric versus adult drug trials for conditions with high pediatric disease burden. Pediatrics. 2012;130(2):285–92.
Association, A.P., Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition: DSM-5. Washington. DC: American Psychiatric Association; 2013.
Burd L, Kerbeshian J. A North Dakota prevalence study of schizophrenia presenting in childhood. J Am Acad Child Adolesc Psychiatry. 1987;26(3):347–50.
Loranger AW. Sex difference in age at onset of schizophrenia. Arch Gen Psychiatry. 1984;41(2):157–61.
Jarbin H, Ott Y, Von Knorring AL. Adult outcome of social function in adolescent-onset schizophrenia and affective psychosis. J Am Acad Child Adolesc Psychiatry. 2003;42(2):176–83.
McClellan, J., S. Stock, and A.A.o.C.a.A.P.C.o.Q. Issues, Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry, 2013. 52(9): p. 976–990.
Haas M, Eerdekens M, Kushner S, Singer J, Augustyns I, Quiroz J, et al. Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: double-blind study. Br J Psychiatry. 2009;194(2):158–64.This RCT indicates that risperidone dosing from 1.5mg-6mg daily leads to statistically significant improvement in the PANSS.
Haas M, Unis AS, Armenteros J, Copenhaver MD, Quiroz JA, Kushner SF. A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and safety of risperidone in adolescents with schizophrenia. J Child Adolesc Psychopharmacol. 2009;19(6):611–21.This RCT indicates that higher dose risperidone dosing (4-6mg) leads to more rapid improvement in symptoms compared with lower doses (1-3mg).
Kryzhanovskaya L, Schulz SC, McDougle C, Frazier J, Dittmann R, Robertson-Plouch C, et al. Olanzapine versus placebo in adolescents with schizophrenia: a 6-week, randomized, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009;48(1):60–70. This RCT suggests that olanzapine at a mean daily dose of 11.1mg leads to improvement in the BPRS-C when compared with placebo by 6-weeks.
Beasley CM Jr, et al. Olanzapine versus placebo: results of a double-blind, fixed-dose olanzapine trial. Psychopharmacology. 1996;124(1–2):159–67.
Stentebjerg-Olesen M, Ganocy SJ, Findling RL, Chang K, DelBello M, Kane JM, et al. Early response or nonresponse at week 2 and week 3 predict ultimate response or nonresponse in adolescents with schizophrenia treated with olanzapine: results from a 6-week randomized, placebo-controlled trial. Eur Child Adolesc Psychiatry. 2015;24(12):1485–96. This post-hoc analysis reviewed time to improvement, and found that 85.5% of improvement in patients on olanzapine occurs by the end of week three of treatment.
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(3):441–9.This article suggests that adolescents who have an early response to treatment, defined by 20% or more reduction in BPRS-C score by week two, have significantly better outcomes than those who do not.
Ross RG, et al. A 1-year open-label trial of olanzapine in school-age children with schizophrenia. J Child Adolesc Psychopharmacol. 2003;13(3):301–9.
Findling RL, McKenna K, Earley WR, Stankowski J, Pathak S. Efficacy and safety of quetiapine in adolescents with schizophrenia investigated in a 6-week, double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2012;22(5):327–42.This placebo-controlled RCT establishes that quetiapine is an effective treatment for psychosis in adolescents.
Findling RL, et al. Ziprasidone in adolescents with schizophrenia: results from a placebo-controlled efficacy and long-term open-extension study. J Child Adolesc Psychopharmacol. 2013;23(8):531–44.This placebo controlled RCT establishes that ziprasidone can be effective for treatment of psychosis in adolescents, but patients must follow dosing protocols without deviation.
Findling RL, Robb A, Nyilas M, Forbes RA, Jin N, Ivanova S, et al. A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Am J Psychiatry. 2008;165(11):1432–41.This placebo controlled RCT establishes the efficacy of aripiprazole for treatment of psychosis in adolescents.
Correll CU, Kohegyi E, Zhao C, Baker RA, McQuade R, Salzman PM, et al. Oral aripiprazole as maintenance treatment in adolescent schizophrenia: results from a 52-week, randomized, placebo-controlled withdrawal study. J Am Acad Child Adolesc Psychiatry. 2017;56(9):784–92.This recently published, placebo controlled RCT with a crossover design suggests that patients on aripiprazole experience a significantly longer time to exacerbation of psychotic symptoms when compared with placebo.
Matsumoto H, et al. Safety and efficacy from a 6-week double-blind study and a 52-week open-label extension of aripiprazole in adolescents with schizophrenia in Japan. Psychiatry Clin Neurosci. 2018;72(9):701–12.This recently published randomized control trial finds that by six weeks, there is statistically significant improvemnt in groups taking aripirazole doses between 2-30mg, with continued improvement during a 52-week open label extension.
Singh J, et al. A randomized, double-blind study of paliperidone extended-release in treatment of acute schizophrenia in adolescents. Biol Psychiatry. 2011;70(12):1179–87.This placebo controlled RCT suggests that paliperidone can be effective in reducing symptoms of schizophrenia when doses from 3mg-12mg are used.
Findling RL, Landbloom RP, Mackle M, Pallozzi W, Braat S, Hundt C, et al. Safety and efficacy from an 8 week double-blind trial and a 26 week open-label extension of asenapine in adolescents with schizophrenia. J Child Adolesc Psychopharmacol. 2015;25(5):384–96.This recently published placebo controlled RCT finds that asenapine does not separate from placebo when used to treat psychosis in adolescents at a total daily dose of 5mg-10mg.
Findling RL, Landbloom RL, Szegedi A, Koppenhaver J, Braat S, Zhu Q, et al. Asenapine for the acute treatment of pediatric manic or mixed episode of bipolar I disorder. J Am Acad Child Adolesc Psychiatry. 2015;54(12):1032–41.
Goldman R, Loebel A, Cucchiaro J, Deng L, Findling RL. Efficacy and safety of lurasidone in adolescents with schizophrenia: a 6-week, randomized placebo-controlled study. J Child Adolesc Psychopharmacol. 2017;27(6):516–25.This recently published placebo controlled RCT establishes that lurasidone is effective for treatment of psychosis in adolescents, at doses of 40mg-80mg.
Kumra S, Frazier JA, Jacobsen LK, McKenna K, Gordon CT, Lenane MC, et al. Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry. 1996;53(12):1090–7.
Shaw P, et al. Childhood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry. 2006;63(7):721–30.
Kumra S, Kranzler H, Gerbino-Rosen G, Kester HM, de Thomas C, Kafantaris V, et al. Clozapine and “high-dose” olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biol Psychiatry. 2008;63(5):524–9.
Sikich L, Frazier JA, McClellan J, Findling RL, Vitiello B, Ritz L, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry. 2008;165(11):1420–31.This RCT compares molindone, olanzapine, and risperidone and finds that by eight weeks of treatment, there is no statistically significant difference in response.
Findling RL, Johnson JL, McClellan J, Frazier JA, Vitiello B, Hamer RM, et al. Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study. J Am Acad Child Adolesc Psychiatry. 2010;49(6):583–94.
Pagsberg AK, Jeppesen P, Klauber DG, Jensen KG, Rudå D, Stentebjerg-Olesen M, et al. Quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis: the multicentre, double-blind, randomised tolerability and efficacy of antipsychotics (TEA) trial. Lancet Psychiatry. 2017;4(8):605–18.This recently published RCT compares responses to quetiapine ER and aripiprazole and finds no statistically significant difference at 12 weeks.
Jensen KG, Gärtner S, Correll CU, Rudå D, Klauber DG, Stentebjerg-Olesen M, et al. Change and dispersion of QT interval during treatment with quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis: results from the TEA trial. Psychopharmacology. 2018;235(3):681–93.
Savitz, A.J., et al., Efficacy and safety of paliperidone extended release in adolescents with schizophrenia: a randomized, double-blind study. J Am Acad Child Adolesc Psychiatry, 2015. 54(2): p. 126–137.e1.This recently published RCT compared paliperidone ER and aripirazole and found that both medications led to statistically and clinically significant improvement at days 56 and 182, and that neither medication was superior.
Conflict of Interest
Dr. Nadia Zaim declares that she has no conflict of interest.
Dr. Amanda Sun declares that she has no conflict of interest.
Dr. Findling is a consultant for Acadia, receives grants from and is a consultant for Aevi, receives grants from and is a consultant for Akili, receives grants from and is a consultant for Alcobra, receives grants from and is a consultant for Allergan, is a consultant for Amerex, has an honoraria from Am Acad CAP, receives royalties from American Psychiatric Press, is a consultant for Arbor, is a consultant for Bracket, has an honoraria from Daiichi-Sankyo, is a consultant for Epharma Solutions, receives grants from Forest, is a consultant for Genetech, is a consultant for Ironshore, is a consultant for KemPharm, is a consultant for Luminopia, receives grants from and is a consultant for Lundbeck, is a consultant for Merck, receives grants from and is a consultant for NIH, receives grants from and is a consultant for Neurim, is a consultant for Noven, is a consultant for Nuvelution, is a consultant for Otsuka, receives grants from PCORI, receives grants from Pfizer, is a consultant for Physicians Postgraduate Press, is a consultant for Purinix, is a consultant for Receptor Life Sciences, receives grants from and is a consultant for Roche, receives personal fees from Sage, receives grants and is a consultant for Shire, receives grants and is a consultant for Sunovion, receives grants and is a consultant for Supernus Pharmaceuticals, receives grants from Syneurx, is a consultant for Teva, is a consultant for Touchpoint, is a consultant for Tris, and receives grants from and is a consultant for Validus, outside the submitted work.
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.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Child and Adolescent Psychiatry
About this article
Cite this article
Zaim, N., Findling, R.L. & Sun, A. Antipsychotics for Treatment of Adolescent Onset Schizophrenia: a Review. Curr Treat Options Psych 7, 23–38 (2020). https://doi.org/10.1007/s40501-020-00198-9