モーズレイ処方ガイドライン第14版(The Maudsley PrescribingGuidelines inPsychiatry 14thEdition)menu open

小児・青年期の精神病

統合失調症は小児では稀であるが,青年期になるとその罹患率は急激に増加する。診断を下す前に詳細な発達および身体の評価を必要とする場合が多い1, 2。早発性統合失調症スペクトラム(EOSS)障害はしばしば慢性化し,多くの症例で抗精神病薬の長期投与が必要となる3

第一世代抗精神病薬(FGA)についてはいくつかRCTが行われており,その多くで高用量が使用され,いずれの試験でも錐体外路副作用(EPSE)と過鎮静が高頻度に認められた4。薬剤誘発性ジスキネジアも問題になることがあり5,比較的低用量の使用時でもこの問題は起こりうる6。小児・青年期の患者ではFGAの使用は避けるべきである。

EOSS障害における第二世代抗精神病薬(SGA)に関する無作為化比較試験が多数ある。オランザピン7-9,リスペリドン7, 8, 10, 11,アリピプラゾール12, 13,クエチアピン13, 14,パリペリドン15,アセナピン16,ziprasidone17,ルラシドン18はいずれも精神病の治療に有効であることが示されている。システマティック・レビューとネットワークメタ解析から,ziprasidone(有効性に劣る)およびアセナピン(有効性が不明)を除くほとんどのSGAの有効性は同程度であることが示唆されている19。ziprasidoneの心臓に対する安全性には懸念がある20, 21。それは,ziprasidoneがQT間隔延長を促すためである。アリピプラゾールは,青年期の患者ではQTに影響を及ぼさないようである22

小児・青年期の患者では,成人と比較して錐体外路症状,プロラクチン上昇,鎮静(アリピプラゾールでも生じる13),体重増加,代謝系への影響等,副作用のリスクが高い23

クロザピンは青年期における治療抵抗性の精神病に有効であるというエビデンスがあるが,この患者群では成人よりも好中球減少症やけいれん発作が起こりやすい可能性がある24-27。若年者の治療から得られたデータに基づき,クロザピンに移行する前にオランザピンを試すべきであろう28。それはオランザピンが効果を示す可能性があるためである。とはいえ,青年期においては,クロザピンはオランザピンより明らかに有効である25, 26

全般的に,小児・青年期の精神病の治療アルゴリズムは成人と同様である[統合失調症に関する章(Chapter 1)参照]。NICE29では,経口抗精神病薬と家族介入および個別のCBTとの併用を推奨している。開始用量は,成人用量の下限もしくはそれ以下とする。

小児・青年期の患者に抗精神病薬を処方する場合,常に統合失調症に関する章の指針に従って投与前パラメータを測定し,モニタリングを行う。小児・青年期の患者については,胴囲および臀囲,すべての運動障害の評価,栄養状態の評価,食事内容,身体活動レベルも測定する29

(加治 正喬)

参照文献
  1. Pina-Camacho L, et al. Autism spectrum disorder and schizophrenia: boundaries and uncertainties. Br J Psych Adv 2016; 22:316–324.
  2. Hayes D, et al. Dilemmas in the treatment of early-onset first-episode psychosis. Ther Adv Psychopharmacol 2018; 8:231–239.
  3. Kumra S, et al. Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull 2008; 34:60–71.
  4. Lee ES, et al. Psychopharmacologic treatment of schizophrenia in adolescents and children. Child Adolesc Psychiatr Clin N Am 2020; 29:183–210.
  5. Connor DF, et al. Neuroleptic-related dyskinesias in children and adolescents. J Clin Psychiatry 2001; 62:967–974.
  6. Campbell M, et al. Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 1997; 36:835–843.
  7. Sikich L, et al. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial. Neuropsychopharmacology 2004; 29:133–145.
  8. Sikich 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; 165:1420–1431.
  9. Kryzhanovskaya L, 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; 48:60–70.
  10. Haas M, et al. 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; 19:611–621.
  11. Haas M, et al. Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: double-blind study. Br J Psychiatry 2009; 194:158–164.
  12. Findling RL, et al. A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Am J Psychiatry 2008; 165:1432–1441.
  13. Pagsberg AK, 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; 4:605–618.
  14. Findling RL, et al. Efficacy and safety of quetiapine in adolescents with schizophrenia investigated in a 6-week, double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol 2012; 22:327–342.
  15. Singh J, et al. A randomized, double-blind study of paliperidone extended-release in treatment of acute schizophrenia in adolescents. Biol Psychiatry 2011; 70:1179–1187.
  16. Findling RL, 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; 25:384–396.
  17. 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; 23:531–544.
  18. Arango C, et al. Lurasidone compared to other atypical antipsychotic monotherapies for adolescent schizophrenia: a systematic literature review and network meta-analysis. Eur Child Adolesc Psychiatry 2020; 29:1195–1205.
  19. Pagsberg AK, et al. Acute antipsychotic treatment of children and adolescents with schizophrenia-spectrum disorders: a systematic review and network meta-analysis. J Am Acad Child Adolesc Psychiatry 2017; 56:191–202.
  20. Scahill L, et al. Sudden death in a patient with Tourette syndrome during a clinical trial of ziprasidone. J Psychopharmacol 2005; 19:205–206.
  21. Blair J, et al. Electrocardiographic changes in children and adolescents treated with ziprasidone: a prospective study. J Am Acad Child Adolesc Psychiatry 2005; 44:73–79.
  22. Jensen KG, 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 (Berl) 2018; 235:681–693.
  23. Correll CU Addressing adverse effects of antipsychotic treatment in young patients with schizophrenia. J Clin Psychiatry 2011; 72:e01.
  24. Kumra S, et al. Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison. Arch Gen Psychiatry 1996; 53:1090–1097.
  25. Shaw P, et al. Childhood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry 2006; 63:721–730.
  26. Kumra S, et al. Clozapine and “high-dose” olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biol Psychiatry 2008; 63:524–529.
  27. Schneider C, et al. Systematic review of the efficacy and tolerability of clozapine in the treatment of youth with early onset schizophrenia. Eur Psychiatry 2014; 29:1–10.
  28. Agid O, et al. An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis. J Clin Psychiatry 2011; 72:1439–1444.
  29. National Institute for Health and Care Excellence. Psychosis and schizophrenia in children and young people: recognition and management. Clinical Guidance 155 [CG155]. 2013 (last updated October 2016). https://www.nice.org.uk/guidance/cg155 .