Clinical Pharmacokinetics

, Volume 57, Issue 12, pp 1493–1528 | Cite as

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

  • Massimo Carlo MauriEmail author
  • Silvia Paletta
  • Chiara Di Pace
  • Alessandra Reggiori
  • Giovanna Cirnigliaro
  • Isabel Valli
  • Alfredo Carlo Altamura
Review Article


Therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding side effects by maintaining long-term exposure to minimally effective blood concentrations. The rationale for using therapeutic drug monitoring in relation to second-generation antipsychotics is still being discussed at least with regard to the real clinical utility, but there is evidence that it can improve efficacy, especially when patients do not respond or develop side effects using therapeutic doses. Furthermore, drug plasma concentration determinations can be of some utility in medico-legal problems. This review concentrates on the clinical pharmacokinetic data related to clozapine, risperidone, paliperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole, sertindole, asenapine, iloperidone, lurasidone, brexpiprazole and cariprazine and briefly considers the main aspects of their pharmacodynamics. Optimal plasma concentration ranges are proposed for clozapine, risperidone, paliperidone and olanzapine because the studies of quetiapine, amisulpride, asenapine, iloperidone and lurasidone provide only limited information and there is no direct evidence concerning ziprasidone, aripiprazole, sertindole, brexpiprazole and cariprazine: the few reported investigations need to be confirmed and extended.


Compliance with Ethical Standards


No external funding was used in the preparation of this article.

Conflict of interest

Massimo Carlo Mauri, Silvia Paletta, Chiara Di Pace, Alessandra Reggiori, Giovanna Cirnigliaro, Isabel Valli and Alfredo Carlo Altamura have no conflicts of interest that are directly relevant to the contents of this article.


  1. 1.
    Brodie BB. Displacement of one drug by another from carrier or receptor sites. Proc R Soc Med. 1965;58:946–55.PubMedPubMedCentralGoogle Scholar
  2. 2.
    McCutcheon R, Beck K, D’Ambrosio E, Donocik J, Gobjila C, Jauhar S, Kaar S, Pillinger T, Reis Marques T, Rogdaki M, Howes OD. Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia. Acta Psychiatr Scand. 2018;137(1):39–46.PubMedGoogle Scholar
  3. 3.
    Buur-Rasmussen B, Brosen K. Cytochrome P450 and therapeutic drug monitoring with respect to clozapine. Eur Neuropsychopharmacol. 1999;9:453–9.PubMedGoogle Scholar
  4. 4.
    Prior TI, Chue PS, Tibbo P, Baker GB. Drug metabolism and atypical antipsychotics. Eur Neuropsychopharmacol. 1999;9:301–9.PubMedGoogle Scholar
  5. 5.
    Mauri MC, Volonteri L, Dell’Osso B, Regispani F, Papa P, Baldi ML, Bareggi SR. Predictors of clinical outcome in schizophrenic patients responding to clozapine. J Clin Psychopharmacol. 2003;23(6):660–4.PubMedGoogle Scholar
  6. 6.
    Steen NE, Aas M, Simonsen C, Dieset I, Tesli M, Nerhus M, Gardsjord E, Mørch R, Agartz I, Melle I, Ueland T, Spigset O, Andreassen OA. Serum levels of second-generation antipsychotics are associated with cognitive function in psychotic disorders. World J Biol Psychiatry. 2017;18(6):471–82.PubMedGoogle Scholar
  7. 7.
    Preskorn SH. Therapeutic drug monitoring (TDM) in psychiatry (part I): why studies attempting to correlate drug concentration and antidepressant response don’t work. J Psychiatr Pract. 2014;20(2):133–7.PubMedGoogle Scholar
  8. 8.
    Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, Eckermann G, Egberts K, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 2018;51(1–02):9–62.PubMedGoogle Scholar
  9. 9.
    Meltzer HY, Bastani B, Ramirez L, Matsubara S. Clozapine: new research on efficacy and mechanism of action. Eur Arch Psychiatry Neurol Sci. 1989;238:332–9.PubMedGoogle Scholar
  10. 10.
    Meltzer HY. The mechanism of action of clozapine in relation to its clinical advantages. In: Meltzer HY, editor. Novel antipsychotic drugs. New York: Raven Press Ltd; 1992. p. 1–13.Google Scholar
  11. 11.
    Perry PJ, Miller DD, Arndt SV, Cadoret RJ. Clozapine and norclozapine plasma concentrations and clinical response treatment-refractory schizophrenic patients. Am J Psychiatry. 1991;148:231–5.PubMedGoogle Scholar
  12. 12.
    Hasegawa M, Gutierrez-Esteinou R, Way L, Meltzer HY. Relationship between clinical efficacy and clozapine concentration in plasma in schizophrenia: effect of smocking. J Clin Psychopharmacol. 1993;13:383–90.PubMedGoogle Scholar
  13. 13.
    Potkin SG, Bera R, Gulasekaram B, Costa J, Hayes S, Jin Y, Richmond G, Carreon D, Sitanggan K, Gerber B, Telford J, Plon L, Plon H, Park L, Chang YJ, Oldroyd J, Cooper T. Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia. J Clin Psychiatry. 1994;55:133–6.PubMedGoogle Scholar
  14. 14.
    Kronig MH, Munne RA, Szymansky S, Safferman AZ, Pollack S, Cooper T, Kane JM, Lieberman JA. Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients. Am J Psychiatry. 1995;152:179–82.PubMedGoogle Scholar
  15. 15.
    Mauri MC, Volonteri LS, Fiorentini A, Invernizzi G, Bareggi SR. Clinical outcome and plasma levels of clozapine and norclozapine in drug-resistant schizophrenic patients. Schizophr Res. 2004;66:197–8.PubMedGoogle Scholar
  16. 16.
    Freeman DJ, Oyewumi LK. Will routine therapeutic drug monitoring have a place in clozapine therapy? Clin Pharmacokinet. 1997;32:95–100.Google Scholar
  17. 17.
    Khan AY, Preskorn SH. Examining concentration-dependence toxicity of clozapine: role of therapeutic drug monitoring. J Psychiat Pract. 2005;11:289–301.Google Scholar
  18. 18.
    Ackenheil VM, Brau H, Burkhart A, Franke A, Pacha W. Antipsychotic efficacy in relation to plasma levels of clozapine. Arzneimttelforschung. 1976;26:1156–8.Google Scholar
  19. 19.
    Thorup M, Fog R. Clozapine tretment of schizophrenic patients: plasma concentration and coagulation factors. Acta Psychiatr Scand. 1977;66:123–6.Google Scholar
  20. 20.
    Brau VH, Burkhart A, Pacha W, Ackenheil VM. Relationships between effects and plasma levels of clozapine. Arzneimttelforschung. 1978;28:1300.Google Scholar
  21. 21.
    Bell R, Mc Laren A, Galanos J, Copolov D. The clinical use of plasma clozapine levels. Aust N Z J Psychiatry. 1998;32:567–74.PubMedGoogle Scholar
  22. 22.
    Volpicelli SA, Centorrino F, Puopolo PR, Kando J, Frankenburg FR, Baldessarrini RJ, Flood JG. Determination of clozapine, norclozapine and clozapine-N-oxide in serum by liquid chromatography. Clin Chem. 1993;39:1656–9.PubMedGoogle Scholar
  23. 23.
    Palego L, Biondi L, Giannaccini G, Sarno N, Elmi S, Ciapparelli A, Cassano GB, Lucacchini A, Martini C, Dell’Osso L. Clozapine, norclozapine plasma levels, their sum and ratio in 50 psychotic patients. Influence of patient-related veriables. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:473–80.PubMedGoogle Scholar
  24. 24.
    Overall JE, Gorham DR. The brief psychiatric rating scale. Psychol Rep. 1962;10:799–812.Google Scholar
  25. 25.
    Llorca PM, Lancon C, Disdier B, Farisse J, Sapin C, Auquier P. Effectiveness of clozapine in neuroleptic-resistent schizophrenia: clinical response and plasma concentrations. J Psychiatry Neurosci. 2002;27:30–7.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Kay SR, Fiszbein A, Opler LA. the positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76.PubMedGoogle Scholar
  27. 27.
    Guy W. ECDEU Assessment manual for psychopharmacology. DHEW Publication; 1976. pp. 76–388.Google Scholar
  28. 28.
    Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with clorpromazine. Arch Gen Psychiatry. 1988;45:789–96.PubMedGoogle Scholar
  29. 29.
    Jann MW, Grimsley SR, Gray EC, Chang WH. Pharmacokinetics and pharmacodynamics of clozapine. Clin Pharmacokinetic. 1993;24:161–76.Google Scholar
  30. 30.
    Choc MG, Lehr RG, Hsuan F, Honigfeld G, Smith HT, Borison R, Volavka J. Multiple-dose pharmacokinetics of clozapine in patients. Pharm Res. 1987;4:402–5.PubMedGoogle Scholar
  31. 31.
    Choc MG, Hsuan F, Honigfeld G, Robinson WT, Ereshefsky L, Crismon ML, Saklad SR, Hirschowitz J, Wagner R. Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients. Pharm Res. 1990;7:347–51.PubMedGoogle Scholar
  32. 32.
    Fabrazzo M, La Pia S, Monteleone P, Esposito G, Pinto A, De Simone L, Bencivenga R, Maj M. Is the time corse of clozapine response correlated to the time course of clozapine plasma levels? A one-year prospective study in drug-resistant patients with schizophrenia. Neuropsychopharmacology. 2002;27:1050–5.PubMedGoogle Scholar
  33. 33.
    Miller DD, Fleming F, Holman TL, Perry P. Plasma clozapine concentrations as a predictor of clinical response: a follow-up study. J Clin Psychiatry. 1994;55:117–21.PubMedGoogle Scholar
  34. 34.
    Schulte P. What is an adequate trial with clozapine? Therapeutic drug monitoring and time to response in treatment-refractory schizophrenia. Clin Pharmacokinet. 2003;42:607–18.PubMedGoogle Scholar
  35. 35.
    Eap CB, Bender S, Jaquenoud SE, Cucchia G, Jonzier-Perey M, Baumann P, Allorge D, Broly F. Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. J Clin Psychopharmacol. 2004;24:214–9.PubMedGoogle Scholar
  36. 36.
    Akamine Y, Sugawara-Kikuchi Y, Uno T, Shimizu T, Miura M. Quantification of the steady-state plasma concentrations of clozapine and N-desmethylclozapine in Japanese patients with schizophrenia using a novel HPLC method and the effects of CYPs and ABC transporters polymorphisms. Ann Clin Biochem. 2017;54(6):677–85.PubMedGoogle Scholar
  37. 37.
    Tóth K, Csukly G, Sirok D, Belic A, Kiss Á, Háfra E, Déri M, Menus Á, Bitter I, Monostory K. Potential role of patients’ CYP3A-status in clozapine pharmacokinetics. Int J Neuropsychopharmacol. 2017;20(7):529–37.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Wohkittel C, Gerlach M, Taurines R, Wewetzer C, Unterecker S, Burger R, Schreck D, Mehler-Wex C, Romanos M, Egberts K. Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice. J Neural Transm (Vienna). 2016;123(8):1021–31.PubMedGoogle Scholar
  39. 39.
    Nordstrom AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G. D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: A PET study of schizophrenic patients. Am J Psychiatry. 1995;152:1444–9.PubMedGoogle Scholar
  40. 40.
    Seeman P, Van Tool HHM. Deriving the therapeutic concentrations for clozapine and haloperidol: the apparent dissociation constant of a neuroleptic at the D2 or D4 receptor varies with the affinity of the competing radioligand. Eur J Pharmacol Mol Pharmacol. 1995;291:59–66.Google Scholar
  41. 41.
    Zhao AL, Zhao JP, Zhang YH, Xue ZM, Chen JD, Chen XG. Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine. Int J Neurosci. 2005;115:1539–47.PubMedGoogle Scholar
  42. 42.
    Molins C, Carceller-Sindreu M, Navarro H, Carmona C, Piñeiro M, Martínez E, Álvarez E, Portella MJ. Plasma ratio of clozapine to N-desmethylclozapine can predict cognitive performance in treatment-resistant psychotic patients. Psychiatry Res. 2017;258:153–7.PubMedGoogle Scholar
  43. 43.
    Rabinowitz J, Davidson M. Risperidone versus haloperidol in long-term hospitalized chronic patients in a double blind randomized trial: a post hoc analysis. Schizophr Res. 2001;50:89–93.PubMedGoogle Scholar
  44. 44.
    Emsley RA, Risperidone Working Group. Risperidone in the treatment of first-episode psychotic patients: a double-blind multicenter study. Schizophr Bull. 1999;25:721–9.PubMedGoogle Scholar
  45. 45.
    Peuskens J, Risperidone Study Group. Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Br J Psychiatry. 1995;166:712–26.PubMedGoogle Scholar
  46. 46.
    Jansen PAJ, Niemegeers CJE, Awouters F. Schellekens KHL, Megens AAHP, Meert TF. Pharmacology of risperidone (R 64 766), a new antipsychotics with serotonin-s2 and dopamine-D2 antagonistic properties. J Pharmacol Exp Ther. 1988;244:685–93.Google Scholar
  47. 47.
    Leysen JE, Gommeren W, Eens A, de Courcelles DDC, Stoof JC, Jansen PAJ. Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther. 1998;247:661–70.Google Scholar
  48. 48.
    Ereshefsky L, Lacombe S. Pharmacological profile of risperidone. Can J Psychiatry. 1993;38(Suppl. 3):80–8.Google Scholar
  49. 49.
    Mannens G, Huang ML, Meuldermans W, Hendrickx J, Woestenborghs R, Meibach R, Heykants J. Absorption, metabolism, and excretion of risperidone in humans. Drug Metab Disp. 1993;21:1134–41.Google Scholar
  50. 50.
    Baldessarini RJ. In: Goodman LS, Gilman A. The pharmacological basis of therapeutics. 9th ed. McGraw-Hill; 1996. pp. 399–430.Google Scholar
  51. 51.
    Schoretsanitis G, Stegmann B, Hiemke C, Gründer G, Schruers KR, Walther S, Lammertz SE, Haen E, Paulzen M. Pharmacokinetic patterns of risperidone-associated adverse drug reactions. Eur J Clin Pharmacol. 2016;72(9):1091–8.PubMedGoogle Scholar
  52. 52.
    Paulzen M, Haen E, Stegmann B, Unterecker S, Hiemke C, Gründer G, Schoretsanitis G. Clinical response in a risperidone-mediated naturalistic sample: patients’ characteristics and dose-dependent pharmacokinetic patterns. Eur Arch Psychiatry Clin Neurosci. 2016;267(4):325–33.PubMedGoogle Scholar
  53. 53.
    Huang ML, Van Peer A, Woestenborghs R, De Coster R, Heykants J, Jansen AA, Zylicz Z, Visscher HW, Jonkman JH. Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin Pharmacol Ther. 1993;54:257–68.PubMedGoogle Scholar
  54. 54.
    Vandenberghe F, Guidi M, Choong E, von Gunten A, Conus P, Csajka C, Eap CB. Genetics-based population pharmacokinetics and pharmacodynamics of risperidone in a psychiatric cohort. Clin Pharmacokinet. 2015;54(12):1259–72.PubMedGoogle Scholar
  55. 55.
    Aravagiri M, Marder SR, Wirshing D, Wirshing WC. Plasma concentrations of risperidone and its 9-hydroxy metabolite and their relationship to dose in schizophrenic patients: simultaneous determination by a high performance liquid chromatography with electrochemical detection. Pharmacopsychiatry. 1998;31:102–9.PubMedGoogle Scholar
  56. 56.
    Aravagiri M, Marder SR, Nuechterlein KH, Gitlin MJ. Intra- and interindividual variations in steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients treated chronically with various doses of risperidone. Ther Drug Monit. 2003;25:657–64.PubMedGoogle Scholar
  57. 57.
    Grant S, Fitton A. Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs. 1994;48:253–73.PubMedGoogle Scholar
  58. 58.
    Heykants J, Hunag ML, Mannens G, Meuldermans W, Snoeck E, Van Beijstetveldt L, Van Peer A, Woestenborghs R. The pharmacokinetics of risperidone in humans: a summary. J Clin Psychiatry. 1994;55(Suppl.):13–7.Google Scholar
  59. 59.
    Spina E, Avenoso A, Facciola G, Salemi M, Scordo MG, Ancione M, Madia AG, Perucca E. Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia. Psychopharmacology. 2001;153:238–43.PubMedGoogle Scholar
  60. 60.
    Olesen OV, Licht RW, Thomsen E, Bruun T, Viftrup JE, Linnet K. Serum concentrations and side effects in psychiatric patients during risperidone therapy. Ther Drug Monit. 1998;20:380–4.PubMedGoogle Scholar
  61. 61.
    Riedel M, Schwarz MJ, Strassing M, Spellmann A, Muller-Arends A, Weber K, Zach J, Muller N, Moller HJ. Risperidone plasma levels, clinical response and side-effects. Eur Arch Psychiatry Clin Neurosci. 2005;255:261–8.PubMedGoogle Scholar
  62. 62.
    Mauri MC, Laini V, Boscati L, Rudelli R, Salvi V, Orlandi R, Papa P. Long term treatment of chronic schizophrenia with risperidone: a study with plasma levels. Eur Psychiatry. 2001;16:57–63.PubMedGoogle Scholar
  63. 63.
    Chen PS, Yang YK, Su SF, Liao YC, Chang JW, Yeh TL. Correlation between scores on continuous performance test and plasma concentration for schizophrenic patients on risperidone. Psychiatry Clin Neurosci. 2004;58:168–72.PubMedGoogle Scholar
  64. 64.
    Kelleher JP, Centorrino F, Albert MJ, Baldessarini RJ. Advances in atypical antipsychotics for the treatment of schizophrenia: new formulations and new agents. CNS Drugs. 2002;16:249–61.PubMedGoogle Scholar
  65. 65.
    Kane JM, Eerdekens M, Lindenmayer JP, Keith SJ, Lesem M, Karcher K. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry. 2003;160:1125–32.PubMedGoogle Scholar
  66. 66.
    Chue P, Eerdekens M, Augustyns I, Lachaux B, Molcan P, Eriksson L, Pretorius H, David AS. Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets. Eur Neuropsychopharmacol. 2005;15:111–7.PubMedGoogle Scholar
  67. 67.
    Mannaert E, Vermeulen A, Remmerie B, Bouhours P, Levron JC. Pharmacokinetic profile of long-acting injectable risperidone at steady-state: comparison with oral administration. Encephale. 2005;31:609–15.PubMedGoogle Scholar
  68. 68.
    Mauri MC, Paletta S, Maffini M, Colasanti A, Dragogna F, Di Pace C, Altamura AC. Clinical pharmacology of atypical antipsychotics: an update. EXCLI J. 2014;13:1163–91.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Eerdekens M, Van Hove I, Remmerie B, Mannaert E. Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia. Schizophr Res. 2004;70:91–100.PubMedGoogle Scholar
  70. 70.
    Nesvag R, Hendset M, Refsum H, Tanum L. Serum concentrations of risperidone and 9-OH risperidone following intramuscular injection of long-acting risperidone compared with oral risperidone medication. Acta Psychiatr Scand. 2006;114:21–6.PubMedGoogle Scholar
  71. 71.
    Castberg I, Spigset O. Serum concentrations of risperidone and 9-hydroxyrisperidone after administration of the long-acting injectable form of risperidone: evidence from a routine therapeutic drug monitoring service. Ther Drug Monit. 2005;27:103–6.PubMedGoogle Scholar
  72. 72.
    Gefvert O, Eriksson B, Persson P, Helldin L, Bjorner A, Mannaert E, Remmerie B, Eerdekens M, Nyberg S. Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia. Int J Neuropsychopharmacol. 2005;8:27–36.PubMedGoogle Scholar
  73. 73.
    Korell J, Green B, Remmerie B, Vermeulen A. Determination of plasma concentration reference ranges for risperidone and paliperidone. CPT Pharmacomet Syst Pharmacol. 2017;6(9):589–95.Google Scholar
  74. 74.
    Odou P, Levron JC, Luyckx M, Brunet C, Robert H. Risperidone drug monitoring. Clin Drug Invest. 2000;19:283–92.Google Scholar
  75. 75.
    Marder SR, Meibach R. Risperidone in the treatment of schizophrenia. Am J Psychiatry. 1994;151:825–35.PubMedGoogle Scholar
  76. 76.
    Darby JK, Pasta DJ, Elfand L, Dabiri L, Clark L, Herbert J. Risperidone dose and blood level variability: accumulation effects and interindividual and intraindividual variability in the nonresponder patient in the clinical practice setting. J Clin Psychopharmacol. 1997;17:478–84.PubMedGoogle Scholar
  77. 77.
    Whitney Z, Boyda HN, Procyshyn RM, Elbe D, Black T, Eslami A, Barr AM. Therapeutic drug levels of second generation antipsychotics in youth: a systematic review. J Child Adolesc Psychopharmacol. 2015;25:234–45.PubMedGoogle Scholar
  78. 78.
    Dos Santos-Júnior A, Tamascia ML, Lorenzetti R, Della Torre OH, Paes LA, Fontana TS, Ferreira-Neto AP, Henriques TB, Hyslop S, de Mello MP, Celeri EH, Dalgalarrondo P, Guerra-Júnior G. Serum concentration of risperidone and adverse effects in children and adolescents. J Child Adolesc Psychopharmacol. 2017;27(2):211–2.PubMedGoogle Scholar
  79. 79.
    Corena-McLeod M. Comparative pharmacology of risperidone and paliperidone. Drugs R D. 2015;15(2):163–74.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Mauri MC, Reggiori A, Paletta S, Di Pace C, Altamura AC. Paliperidone for the treatment of schizophrenia and schizoaffective disorders: a drug safety evaluation. Exp Opin Drug Saf. 2017;16(3):365–79.Google Scholar
  81. 81.
    Macaluso M, Oliver H, Sohail Z. Pharmacokinetic drug evaluation of paliperidone in the treatment of schizoaffective disorder. Expert Opin Drug Metab Toxicol. 2017;13(8):871–9.PubMedGoogle Scholar
  82. 82.
    Arakawa R, Ito H, Takano A, Takahashi H, Morimoto T, Sassa T, Ohta K, Kato M, Okubo Y, Suhara T. Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology. 2008;197(2):229–35.PubMedGoogle Scholar
  83. 83.
    Conley R, Gupta SK, Sathyan G. Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form. Curr Med Res Opin. 2006;22(10):1879–92.PubMedGoogle Scholar
  84. 84.
    Citrome L. Oral paliperidone extended-release: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability. Expert Opin Drug Metab Toxicol. 2012;8(7):873–88.PubMedGoogle Scholar
  85. 85.
    Fowler JA, Bettinger TL, Argo TR. Paliperidone extended-release tablets for the acute and maintenance treatment of schizophrenia. Clin Ther. 2008;30(2):231–48.PubMedGoogle Scholar
  86. 86.
    Janicak PG, Winans EA. Paliperidone ER: a review of the clinical trial data. Neuropsychiat Dis Treat. 2007;3(6):869–83.Google Scholar
  87. 87.
    Spina E, Crupi R. Safety and efficacy of paliperidone extended-release in acute and maintenance treatment of schizophrenia. J Cent Nerv Sys Dis. 2011;3:27–41.Google Scholar
  88. 88.
    Tianmei S, Liang S, Yi L, Yun’Ai S, Chunmei G, Hongyan Z. Single-dose pharmacokinetics of paliperidone extended-release tablets in healthy Chinese subjects. Hum Psychopharmacol Clin Exp. 2010;25:404–9.Google Scholar
  89. 89.
    Nazirizadeh Y, Vogel F, Bader W, Haen E, Pfuhlmann B, Gründer G, Paulzen M, Schwarz M, Zernig G, Hiemke C. Serum concentrations of paliperidone versus risperidone and clinical effects. Eur J Clin Pharmacol. 2010;66:797–803.PubMedGoogle Scholar
  90. 90.
    Janssen Pharmaceuticals, Inc. Invega® Sustenna® (paliperidone palmitate). Full prescribing information. Titusville (NJ): Janssen Pharmaceuticals, Inc.; 2015.Google Scholar
  91. 91.
    Carter NJ. Extended-release intramuscular paliperidone palmitate:a review of its use in the treatment of schizophrenia. Drugs. 2012;72(8):1137–60.PubMedGoogle Scholar
  92. 92.
    Hoy SM, Scott LJ, Keating GM. Intramuscular paliperidone palmitate. CNS Drugs. 2010;24(3):227–44.PubMedGoogle Scholar
  93. 93.
    Kramer M, Litman R, Hough D, Lane R, Lim P, Liu Y, Eerdekens M. Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia: results of a randomized, double-blind, placebo-controlled efficacy and safety study. Int J Neuropsychopharmacol. 2010;13:635–47.PubMedGoogle Scholar
  94. 94.
    Di Pace C, Paletta S, Reggiori A, Maffini M, Chirico M, Mauri MC, Altamura AC. Paliperidone “long-acting” and plasma levels along 1 year of maintenance therapy in schizophrania and schizoaffective disorders. Eur Neuropsychopharmacol. 2015;25(Suppl. 2):525.Google Scholar
  95. 95.
    Berwaerts J, Liu Y, Gopal S, Nuamah I, Xu H, Savitz A, Coppola D, Alain Schotte A, Remmerie B, Eng C, Maruta N, Hough DW. 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.PubMedGoogle Scholar
  96. 96.
    Ravenstijn P, Remmerie B, Eng C, Savitz A, Samtani MN, Nuamah I, Chang CT, De Meulder M, Hough D, Gopal S. Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: a phase-1, single-dose, randomized, open-label study. J Clin Pharmacol. 2015;20(20):1–10.Google Scholar
  97. 97.
    McCormack PL, Wiseman LR. Olanzapine: a review of its use in the management of bipolar disorder. Drugs. 2004;64:2709–26.PubMedGoogle Scholar
  98. 98.
    Lieberman JA, Tollefson G, Tohen M, Green AI, Gur RE, Kahn R, McEvoy J, Perkins D, Sharma T, Zipurski R, Wei H, Hamer RM. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry. 2003;160:1396–404.PubMedGoogle Scholar
  99. 99.
    Lambert M, Haro JM, Novick D, Edgell ET, Kennedy L, Ratcliffe M, Naber D. Olanzapine vs other antipsychotics in actual out-patient settings: six months tolerability results from the European Schizophrenia Out-patient Health Outcomes study. Acta Psychiatr Scand. 2005;111:232–43.PubMedGoogle Scholar
  100. 100.
    Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dosoky A, Indran S. Olanzapine for schizophrenia. Cochrane Database Syst Rev. 2005;18:CD001359.Google Scholar
  101. 101.
    Bymaster F, Perry KW, Nelson DL, Wong DT, Rasmussen K, Moore NA, Calligaro DO. Olanzapine: a basic science update. Br J Psychiatry. 1999;37:36–40.Google Scholar
  102. 102.
    Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM. Olanzapine: pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999;37:177–93.PubMedGoogle Scholar
  103. 103.
    Kassahun K, Mattiuz E, Nyhart E Jr, Obermeyer B, Gillespie T, Murphy A, Goodwin RM, Tupper D, Callaghan JT, Lemberger L. Disposition and biotransformation of the antipsychotic agent olanzapine in humans. Drug Metab Dispos. 1997;25:81–93.PubMedGoogle Scholar
  104. 104.
    Lu ML, Wu YX, Chen CH, Kuo PT, Chen YH, Lin CH, Wu TH. Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor clinical efficacy in patients with schizophrenia. PLoS One. 2016;11(2):e0148539.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Kelly DL, Conley RR, Tamminga CA. Differential olanzapine plasma concentrations by sex in a fixed-dose study. Schizophr Res. 1999;40:101–4.PubMedGoogle Scholar
  106. 106.
    Dusci LJ, Peter Hackett L, Fellows LM, Ilett KF. Determination of olanzapine in plasma by high-performance liquid chromatography using ultraviolet absorbance detection. J Chromatogr B Anal Technol Biomed Life Sci. 2002;773:191–7.Google Scholar
  107. 107.
    Perry PJ, Lund BC, Sanger T, Beasley C. Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial. J Clin Psychopharmacol. 2001;21:14–20.PubMedGoogle Scholar
  108. 108.
    Gex-Fabry M, Balant-Gorgia AE, Balant LP. Therapeutic drug monitoring of olanzapine: the combined effect of age, gender, smoking, and comedication. Ther Drug Monit. 2003;25:46–53.PubMedGoogle Scholar
  109. 109.
    Bergemann N, Frick A, Parzer P, Kopitz J. Olanzapine plasma concentration, average daily dose, and interaction with co-medication in schizophrenic patients. Pharmacopsychiatry. 2004;37:63–8.PubMedGoogle Scholar
  110. 110.
    Mauri MC, Steinhilber CPC, Marino R, Invernizzi E, Fiorentini A, Cerveri G, Baldi ML, Barale F. Clinical outcome and olanzapine plasma levels in acute schizophrenia. Eur Psychiatry. 2005;20:55–60.PubMedGoogle Scholar
  111. 111.
    Aravagiri M, Ames D, Wirshing WC, Marder SR. Plasma level monitoring of olanzapine in patients with schizophrenia: determination by high-performance liquid chromatography with electrochemical detection. Ther Drug Monit. 1997;19:307–13.PubMedGoogle Scholar
  112. 112.
    Olesen OV, Linnet K. Olanzapine serum concentrations in psychiatric patients given standard doses: the influence of comedication. Ther Drug Monit. 1999;21:87–90.PubMedGoogle Scholar
  113. 113.
    Lane HY, Guo SC, Hwang TJ, Chen YS, Cheng JJ, Lee YC, Hong CJ, Hwu HG, Chang WH. Effects of olanzapine plasma concentrations on depressive symptoms in schizophrenia: a pilot study. J Clin Psychopharmacol. 2002;22:530–2.PubMedGoogle Scholar
  114. 114.
    Skogh E, Reis M, Dahl ML, Lundmark J, Bengtsson F. Therapeutic drug monitoring data on olanzapine and its N-demethyl metabolite in the naturalistic clinical setting. Ther Drug Monit. 2002;24:518–26.PubMedGoogle Scholar
  115. 115.
    Fellows L, Ahmad F, Castle DJ, Dusci LJ, Bulsara MK, Ilett KF. Investigation of target plasma concentration–effect relationships for olanzapine in schizophrenia. Ther Drug Monit. 2003;25:682–9.PubMedGoogle Scholar
  116. 116.
    Wright P, Lindborg SR, Birkett M, Meehan K, Jones B, Alaka K, Ferchland-Howe I, Pickard A, Taylor CC, Roth J, Battaglia J, Bitter I, Chouinard G, Morris PL, Breier A. Intramuscular olanzapine and intramuscular haloperidol in acute schizophrenia: antipsychotic efficacy and extrapyramidal safety during the first 24 hours of treatment. Can J Psychiatry. 2003;48:716–21.PubMedGoogle Scholar
  117. 117.
    Lindborg SR, Beasley CM, Alaka K, Taylor CC. Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients. Psychiatry Res. 2003;119(1–2):113–23.PubMedGoogle Scholar
  118. 118.
    Breier A, Meehan K, Birkett M, David S, Ferchland I, Sutton V, Taylor CC, Palmer R, Dossenbach M, Kiesler G, Brook S, Wright P. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry. 2002;59:441–8.PubMedGoogle Scholar
  119. 119.
    Di Lorenzo R, Brogli A. Profile of Olanzapine long-acting injection for the maintenance treatment of adult patients with schizophrenia. Neuropsychiat Dis Treat. 2010;6:573–81.Google Scholar
  120. 120.
    Lindenmayer JP. Long-acting injectable antipsychotics: focus on olanzapine pamoate. Neuropsychiat Dis Treat. 2010;6:261–7.Google Scholar
  121. 121.
    Luedecke D, Schöttle D, Karow A, Lambert M, Naber D. Post-Injection delirium/sedation syndrome in patients treated with olanzapine pamoate: mechanism, incidence, and management. CNS Drugs. 2015;29:41–6.PubMedGoogle Scholar
  122. 122.
    Perry PJ, Sanger T, Beasley C. Olanzapine plasma concentrations and clinical response in acutely ill schizophrenic patients. J Clin Psychopharmacol. 1997;17:472–7.PubMedGoogle Scholar
  123. 123.
    Kapur S, Zipursky RB, Remington G, Jones C, DaSilva J, Wilson AA, Houle S. 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry. 1998;155:921–8.PubMedGoogle Scholar
  124. 124.
    Attarbaschi T, Sacher J, Geiss-Granadia T, Klein N, Mossaheb N, Lanzenberger R, Asenbaum S, Dudczak R, Kasper S, Tauscher J. Striatal D2 receptor occupancy in bipolar patients treated with olanzapine. Eur Neuropsychopharmacol. 2007;17:102–7.PubMedGoogle Scholar
  125. 125.
    Mauri MC, Maffini M, Di Pace C, Reggiori A, Paletta S, Moliterno D, Rovera C, Altamura AC. “Long-acting” olanzapine in maintenance therapy of schizophrenia: a study with plasma levels. Int J Psychiatry Clin Pract. 2015;19:99–105.PubMedGoogle Scholar
  126. 126.
    McDonnell DP, Landry J, Detke HC. Long-term safety and efficacy of olanzapine long-acting injection in patients with schizophrenia or schizoaffective disorder: a 6-year, multinational, single-arm, open-label study. Int Clin Psychopharmacol. 2014;29:322–31.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Bergstrom R, Callaghan J, Cerimele J, Kurtz D, Hatcher B. Population pharmacokinetics and plasma concentrations of olanzapine. In: Tran P, Bymaster F, Tye N, Herra J, Breier A, Tollefson G, editors. Olanzapine (Zyprexa): a novel antipsychotic. Philadelphia (PA): Lippincott, Williams, and Wilkins; 2000. p. 232–52.Google Scholar
  128. 128.
    Perry PJ, Lund BC, Sanger T, Beasley C. Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial. J Clin Psychopharmacol. 2001;21:14–20.PubMedGoogle Scholar
  129. 129.
    Citrome L, Stauffer VL, Chen L, Kinon BJ, Kurtz DL, Jacobson JG, Bergstrom RF. Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/day in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol. 2009;29(3):278–83.PubMedGoogle Scholar
  130. 130.
    Arvanitis LA, Miller BG. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo: the Seroquel Trial 13 Study Group. Biol Psychiatry. 1997;42:233–46.PubMedGoogle Scholar
  131. 131.
    Peuskens J, Link CG. A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia. Acta Psychiatr Scand. 1997;96:265–73.PubMedGoogle Scholar
  132. 132.
    Small JG, Hirsch SRM, Arvanitis LA, Miller BG, Link CG. Quetiapine in patients with schizophrenia: a high- and low-dose double blind comparison with placebo. Arch Gen Psychol. 1997;54:549–57.Google Scholar
  133. 133.
    DeVane CL, Nemeroff CB. Clinical pharmacokinetics of quetiapine: an atypical antipsychotic. Clin Pharmacokinet. 2001;40:509–22.PubMedGoogle Scholar
  134. 134.
    Mauri MC, Fiorentini A, Volonteri LS, Beraldo S, Dell’Osso B, Valli I, Pirola R, Bareggi SR. Quetiapine in acute psychosis and personality disorders during hospitalization: assessment of a therapeutic range. Eur Neuropsychopharmacol. 2004;14(Suppl. 3):283–4.Google Scholar
  135. 135.
    Davis PC, Wong J, Gevfert O. Analysis and pharmacokinetics of quetiapine and two metabolites in human plasma using reversed-phase HPLC with ultraviolet and electrochemical detection. J Pharm Biomed Analysis. 1999;20:271–82.Google Scholar
  136. 136.
    Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P. A positron emission tomography study of quetiapine in schizophrenia. Arch Gen Psychiatry. 2000;57:553–9.PubMedGoogle Scholar
  137. 137.
    Caccia S. Biotransformation of post-clozapine antipsychotics: pharmacological implications. Clin Pharmacokinet. 2000;38:393–414.PubMedGoogle Scholar
  138. 138.
    Grimm SW, Stams KR, Bui K. In vitro prediction of potential metabolic drug interaction for Seroquel. Schizophr Res. 1997;24:198.Google Scholar
  139. 139.
    Gunasekara NS, Spencer CM. Quetiapine. A review of its use in schizophrenia. CNS Drugs. 1998;9:325–40.PubMedGoogle Scholar
  140. 140.
    Grimm SW, Richtand NM, Winter HR, Stams KR, Reel SB. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. Br J Pharmacol. 2006;61:58–69.Google Scholar
  141. 141.
    Thyrum PT, Fabre LF, Wong YWJ. Multiple dose pharmacokinetics of ICI 204,636 in schizophrenic men and women. Psychopharmacol Bull. 1996;32:525.Google Scholar
  142. 142.
    Sotaniemi EA, Arranto AJ, Pelkonen O, Pasanen M. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther. 1997;61:331–9.PubMedGoogle Scholar
  143. 143.
    Gefvert O, Bergstrom M, Langstrom B, Lundberg T, Lindstrom L, Yates R. Time course of central nervous dopamine D2 and 5HT2 receptor blockade and plasma drug concentration after discontinuation of quetiapine (Seroquel) in patients with schizophrenia. Psychopharmacology. 1998;135:119–26.PubMedGoogle Scholar
  144. 144.
    Fabre JR, Arvanitis L, Pultz J, Jones VM, Malick JB, Slotnick VB. ICI 204,636, a novel atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. Clin Ther. 1995;17:366–78.PubMedGoogle Scholar
  145. 145.
    Gefvert O, Lundberg T, Wieselgren I, Bergstrom M, Langstrom B, Wiesel F, Lindstrom L. D2 and 5HT2a receptor occupancy of different doses of quetiapine in schizophrenia: a PET study. Eur Neuropsychopharmacol. 2001;11:105–10.PubMedGoogle Scholar
  146. 146.
    Carriere P, Bonhomme D, Lemperiere T. Amisulpride has a superior risk/benefit profile to haloperidol in schizophrenia: results of a multicentre, double-blind study. Amisulpride Study Group. Eur Psychiatry. 2000;15:321–9.PubMedGoogle Scholar
  147. 147.
    Perrault G, Depoortere R, Morel E, Sanger DJ, Scatton B. Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity. J Pharmacol Exp Ther. 1997;280:73–82.PubMedGoogle Scholar
  148. 148.
    Schoemaker H, Claustre Y, Fage D, Rouquier L, Chergui K, Curet O, Oblin A, Gonon F, Carter C, Benavides J, Scatton B. Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther. 1997;280(1):83–97.PubMedGoogle Scholar
  149. 149.
    Kopecek M, Bares M, Svarc J, Dockery C, Horacek J. Hyperprolactinemia after low dose of amisulpride. Neuro Endocrinol Lett. 2004;25:419–22.PubMedGoogle Scholar
  150. 150.
    Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G. A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum Psychopharmacol. 2002;17:1–13.PubMedGoogle Scholar
  151. 151.
    Dufour A, Desanti C. Pharmacokinetics and metabolism of amisulpride. Ann Psychiatry. 1988;3:298–305.Google Scholar
  152. 152.
    Bergemann N, Kopitz J, Kress KR, Frick A. Plasma amisulpride levels in schizophrenia or schizoaffective disorder. Eur Neuropsychopharmacol. 2004;14:245–50.PubMedGoogle Scholar
  153. 153.
    Caley CF, Cooper CK. Ziprasidone: the fifth atypical antipsychotic. Ann Pharmacother. 2002;36:839–51.PubMedGoogle Scholar
  154. 154.
    Gunasekara NS, Spencer CM, Keating GM. Spotlight on ziprasidone in schizophrenia and schizoaffective disorder. CNS Drugs. 2002;16:645–52.PubMedGoogle Scholar
  155. 155.
    Schmidt AW, Lebel. LA, Howard HR Jr, Zorn SH. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile Eur J Pharmacol. 2001;425(3):197–201PubMedGoogle Scholar
  156. 156.
    Miceli JJ, Wilner KD, Hansen RA, Johnson AC, Apseloff G, Gerber N. Single- and multiple-dose pharmacokinetics of ziprasidone under non-fasting conditions in healthy male volunteers. Br J Clin Pharmacol. 2000;49(Suppl. 1):5S–13S.PubMedPubMedCentralGoogle Scholar
  157. 157.
    Wilner KD, Tensfeldt TG, Baris B, Smolarek TA, Turncliff RZ, Colburn WA. Single- and multiple-dose pharmacokinetics of ziprasidone in healthy young and elderly volunteers. Br J Clin Pharmacol. 2000;49(Suppl. 1):15S–20S.PubMedPubMedCentralGoogle Scholar
  158. 158.
    Stimmel GL, Gutierrez MA, Lee V. Ziprasidone: an atypical antipsychotic drug for the treatment of schizophrenia. Clin Ther. 2002;24:21–37.PubMedGoogle Scholar
  159. 159.
    Beedham C, Miceli JJ, Obach RS. Ziprasidone metabolism, aldehyde oxidase, and clinical implications. J Clin Psychopharmacol. 2003;23:229–32.PubMedGoogle Scholar
  160. 160.
    Prakash C, Kamel A, Gummerus J. Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions. Drug Metab Disp. 1997;25:863–72.Google Scholar
  161. 161.
    Wilner KD, Demattos SB, Anziano RJ, Apseloff G, Gerber N. Ziprasidone and the activity of cytochrome P450 2D6 in healthy extensive metabolizers. Br J Clin Pharmacol. 2000;49(Suppl. 1):43S–7S.PubMedPubMedCentralGoogle Scholar
  162. 162.
    Preskorn SH. Pharmacokinetics and therapeutics of acute intramuscular ziprasidone. Clin Pharmacokinet. 2005;44:1117–33.PubMedGoogle Scholar
  163. 163.
    Miceli JJ, Wilner KD, Swan SK, Tensfeldt TG. Pharmacokinetics, safety, and tolerability of intramuscular ziprasidone in healthy volunteers. J Clin Pharmacol. 2005;45(6):620–30.PubMedGoogle Scholar
  164. 164.
    Mamo D, Kapur S, Shammi CM, Papatheodorou G, Mann S, Therrien F, Remington G. A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone. Am J Psychiatry. 2004;161:818–25.PubMedGoogle Scholar
  165. 165.
    Suckow RF, Fein M, Correll CU, Coope TB. Determination of plasma ziprasidone using liquid chromatography with fluorescence detection. J Chromatogr B Anal Technol Biomed Life Sci. 2004;799:201–8.Google Scholar
  166. 166.
    Daniel DG, Zimbroff DL, Potkin SG, Reeves KR, Harrigan EP, Lakshminarayanan M. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group. Neuropsychopharmacology. 1999;20:491–505.PubMedGoogle Scholar
  167. 167.
    Goff DC, Posever T, Herz L, Simmons J, Kletti N, Lapierre K, Wilner K, Law CG, Ko GN. An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol. 1998;18:296–304.PubMedGoogle Scholar
  168. 168.
    Mailman RB, Murthy V. Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? Curr Pharm Des. 2010;16(5):488–501.PubMedPubMedCentralGoogle Scholar
  169. 169.
    Winans E. Aripiprazole. Am J Health Syst Pharm. 2003;60:2437–45.PubMedGoogle Scholar
  170. 170.
    Yokoi F, Grunder G, Biziere K, Stephane M, Dogan AS, Dannals RF, Ravert H, Suri A, Bramer S, Wong DF. Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C] raclopride. Neuropsychopharmacol. 2002;27:248–59.Google Scholar
  171. 171.
    McGavin JK, Goa KL. Aripiprazole. CNS Drugs. 2002;16:779–88.PubMedGoogle Scholar
  172. 172.
    Citrome L, Josiassen R, Bark N, Salazar DE, Mallikaarjun S. Pharmacokinetics of aripiprazole and concomitant lithium and valproate. J Clin Pharmacol. 2005;45:89–93.PubMedGoogle Scholar
  173. 173.
    DeLeon A, Patel NC, Crismon ML. Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability. Clin Ther. 2004;26:649–66.PubMedGoogle Scholar
  174. 174.
    Shirley M, Perry CM. Aripiprazole: a review of its use as maintenance treatment for adult patients with schizophrenia. Drugs. 2014;74:1097–110.PubMedGoogle Scholar
  175. 175.
    Mallikaarjun S, Salazar DE, Bramer SL. Pharmacokinetics, tolerability, and safety of aripiprazole following multiple oral dosing in normal healthy volunteers. J Clin Pharmacol. 2004;44:179–87.PubMedGoogle Scholar
  176. 176.
    Kirschbaum KM, Müller MJ, Malevani J, Mobascher A, Burchardt C, Piel M, Hiemke C. Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects. World J Biol Psychiatry. 2008;9(3):212–8.PubMedGoogle Scholar
  177. 177.
    Mallikaarjun S, Kane JM, Bricmont P, Robert McQuade R, William Carson W, Sanchez R, Forbes RA, Fleischhacker WW. Pharmacokinetics, tolerability and safety of aripiprazole once-monthly in adult schizophrenia: an open-label, parallel-arm, multiple-dose study. Schizophr Res. 2013;150(1):281–8.PubMedGoogle Scholar
  178. 178.
    Potkin SG, Raoufinia A, Mallikaarjun S, Bricmont P, Peters-Strickland T, Kasper W, Baker RA, Eramo A, Sanchez R, McQuade R. Safety and tolerability of once monthly aripiprazole treatment initiation in adults with schizophrenia stabilized on selected atypical oral antipsychotics other than aripiprazole. Curr Med Res Opin. 2013;29(10):1241–51.PubMedGoogle Scholar
  179. 179.
    Otsuka Pharmaceutical Europe Ltd. Abilify Maintena® EU (aripiprazole). Full prescribing information. Wexham: Otsuka Pharmaceutical Europe Ltd; 2016.Google Scholar
  180. 180.
    Otsuka Pharmaceutical Co., Ltd. Abilify Maintena® US (aripiprazole). Full prescribing information. Tokyo: Otsuka Pharmaceutical Co. Ltd; 2016.Google Scholar
  181. 181.
    Raoufinia A, Peters-Strickland T, Nylander A-G, Baker RA, Eramo A, Jin N, Bricmont P, Repella J, McQuade RD, Hertel P, Larsen F. Aripiprazole once-monthly 400 mg: comparison of pharmacokinetics, tolerability, and safety of deltoid versus gluteal administration. Int J Neuropsychopharmacol. 2017;20(4):295–304.PubMedPubMedCentralGoogle Scholar
  182. 182.
    Sanchez C, Arnt J, Dragsted N. Neurochemical and in vivo pharmacological profile of sertindole, a limbic selective neuroleptic compound. Drug Dev Res. 1992;22:239–50.Google Scholar
  183. 183.
    Hyttel J, Nielsen JB, Nowak G. The acute effect of sertindole on brain 5HT2, D2 and α1 receptors (ex vivo radioreceptor binding studies). J Neural Transm Gen Sect. 1992;89:61–9.PubMedGoogle Scholar
  184. 184.
    Perquin L, Steinert T. A review of the efficacy, tolerability and safety of sertindole in clinical trials. CNS Drugs. 2004;18(Suppl. 2):19–30.PubMedGoogle Scholar
  185. 185.
    Van Kammen DP, Mc Envoy JP, Targum SD, Kardatzke D, Sebree TB. A randomized, controlled, dose ranging trial of sertindole in patients with schizophrenia. Psychopharmacology. 1996;124:168–75.PubMedGoogle Scholar
  186. 186.
    Kasper S, Tauscher J, Küfferle B, Barnas C, Heβelmann B, Asenbaum S, Podreka I, Brücke T. Sertindole and dopamine D2 receptor occupancy in comparison to risperidone, clozapine and haloperidol: a 123I-IBZM SPECT study. Psychopharmacology. 1998;136:367–73.PubMedGoogle Scholar
  187. 187.
    Wilton LV, Heeley EL, Pickering RM, Shakir SA. Comparative study of mortality rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine. J Psychopharmacol. 2001;15:120–6.PubMedGoogle Scholar
  188. 188.
    Wong SL, Linnen P, Mack R, Granneman GR. Effect of food, antiacid, and dosage form on the pharmacokinetics and relative bioavailability of sertindole in healthy volunteers. Biopharm Drug Dispos. 1997;18:533–41.PubMedGoogle Scholar
  189. 189.
    Wong SL, Granneman GR. Modeling of sertindole pharmacokinetic disposition in healthy volunteers in short term dose-escalation studies. J Pharm Sci. 1998;87:1629–31.PubMedGoogle Scholar
  190. 190.
    Wong SL, Locke C, Staser J, Granneman GR. Lack of multiple dosing effects of sertindole on the pharmacokinetics of alprazolam in healthy volunteers. Psychopharmacology. 1998;135:236–41.PubMedGoogle Scholar
  191. 191.
    Sakamoto K, Nakamura Y, Aikoh S, Baba T, Perregaard J, Pedersen H, Moltzen EK, Mulford DJ, Yamaguchi T. Metabolism of sertindole: identification of the metabolites in the rat and dog, and species comparison of liver microsomal metabolism. Xenobiotica. 1995;25:1327–43.PubMedGoogle Scholar
  192. 192.
    Wong SL, Menacherry S, Mulford D, Schmitz PJ, Locke C, Granneman GR. Pharmacokinetics of sertindole and dehydrosertindole in volunteers with normal or impaired renal function. Eur J Pharmacol. 1997;52:223–7.Google Scholar
  193. 193.
    Drici MD, Wang WX, Liu XK, Woosley RL, Flockhart DA. Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. J Clin Psychopharmacol. 1998;18:477–81.PubMedGoogle Scholar
  194. 194.
    Zimbroff DL, Kane JM, Tamminga CA, Daniel DG, Mack RJ, Wozniak PJ, Sebree TB, Wallin BA, Kashkin KB. Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia. Am J Psychiatry. 1997;154:782.PubMedGoogle Scholar
  195. 195.
    Canal-Raffin M, Déridet E, Titier K, Frakra E, Molimard M, Moore N. Simplified ultraviolet liquid chromatographic method for determination of sertindole, dehydrosertindole and norsertindole, in human plasma. J Chromatogr B. 2005;814:61–7.Google Scholar
  196. 196.
    Shiraga T, Kaneko H, Iwasaki K, Tozuka Z, Suzuki A, Hata T. Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, anantipsychotic drug, in human liver microsomes. Xenobiotica. 1999;29:217–29.PubMedGoogle Scholar
  197. 197.
    Leysen JE, Janssen PM, Schotte A, Luyten WH, Megens AA. Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: role of 5HT2 receptors. Psychopharmacology. 1993;112(1 Suppl.):S40–54.PubMedGoogle Scholar
  198. 198.
    Prakash A, Lamb HM. Zotepine: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of schizophrenia. CNS Drugs. 1998;9(2):153–75.Google Scholar
  199. 199.
    Tatsumi M, Jansen K, Blakely RD, Richelson E. Pharmacological profile of neuroleptics at human monoamine transporters. Eur J Pharmacol. 1999;368:277–83.PubMedGoogle Scholar
  200. 200.
    Fleischhacker WW, Barnas C, Stuppäck CH, Unterweger B, Miller C, Hinterhuber H. Zotepine vs. haloperidol in paranoid schizophrenia: a double-blind trial. Psychopharmacol Bull. 1989;25:97–100.PubMedGoogle Scholar
  201. 201.
    Kondo T, Otani K, Mihara K, Tanaka O, Kaneko S, Fukushima Y. A study of the therapeutic spectrum of a fixed dose of zotepine and its relationship with serum concentrations of the drug. Hum Psychopharmacol. 1993;8:133–9.Google Scholar
  202. 202.
    Amann B, Sterr A, Mergl R, Dittmann S, Seemuller F, Dobmeier M, Orth M, Schaefer M, Grunze H. Zotepine loading in acute and severely manic patients: a pilot study. Bipolar Disord. 2005;7:471–6.PubMedGoogle Scholar
  203. 203.
    Shobo M, Kondo Y, Yamada H, Mihara T, Yamamoto N, Katsuoka M, Harada K, Ni K, Matsuoka N. Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake. J Pharmacol Exp Ther. 2010;333(3):772–81.PubMedGoogle Scholar
  204. 204.
    Ohki M, Morokawa Y, Yanagida H, Utagawa I, Morishima Y, Gen K, Sanaka T, Watanabe H, Ohta T, Kamimira M, et al. An evaluation of antiserotonine and antidopamine activities of zotepine and its metabolites. Int Clin Psychopharmacol. 1999;14:47.Google Scholar
  205. 205.
    Heal DJ, Needham PL. Comparison of the pharmacological profiles of zotepine and norzotepine. Eur Neuropsychopharmacol. 1996;6:105.Google Scholar
  206. 206.
    Saletu B, Grünberger J, Anderer P, Chwatal K. Relation between blood levels and average quantitative EEG and psychometrically assessed pharmacodynamic changes following zotepine [in German]. Fortschr Neurol Psychiatr. 1991;59(Suppl. 1):45–55.PubMedGoogle Scholar
  207. 207.
    Tanaka O, Kondo T, Otani K, Yasui N, Tokinaga N, Kaneko S. Single oral dose kinetics of zotepine and its relationship to prolactin response and side effects. Ther Drug Monit. 1998;20(1):117–9.PubMedGoogle Scholar
  208. 208.
    Kondo T, Otani K, Ishida M, Tanaka O, Kaneko S, Fukushima Y. Adverse effects of zotepine and their relationship to serum concentrations of the drug and prolactin. Ther Drug Monit. 1994;16(2):120–4.PubMedGoogle Scholar
  209. 209.
    Ishida M. Therapeutic and adverse effects of zotepine and their relationships with serum kinetics of the drug [in Japanese]. Yakubutsu Seishin Kodo. 1993;13(3):97–105.PubMedGoogle Scholar
  210. 210.
    Otani K, Kondo T, Kaneko S, Ishida M, Fukushima Y. Correlation between prolactin response and therapeutic effects of zotepine in schizophrenic patients. Int Clin Psychopharmacol. 1994;9(4):287–9.PubMedGoogle Scholar
  211. 211.
    Green B. Zotepine: a clinical review. Expert Opin Drug Metab Toxicol. 2009;5(2):181–6.PubMedGoogle Scholar
  212. 212.
    Szegedi A, Verweij P, van Duijnhoven W, Mackle M, Cazorla P, Fennema H. Meta analyses of the efficacy of asenapine for acute schizophrenia: comparisons with placebo and other antipsychotics. J Clin Psychiatry. 2012;73(12):1533–40.PubMedGoogle Scholar
  213. 213.
    Bobo WV. Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013;6(1):61–91.PubMedGoogle Scholar
  214. 214.
    Peeters P, Bockbrader H, Spaans E, Dogterom P, Lasseter K, Marbury T, Gibson GL, de Greef R. Asenapine pharmacokinetics in hepatic and renal impairment. Clin Pharmacokinet. 2011;50(7):471–81.PubMedGoogle Scholar
  215. 215.
    Reddy AVB, Venugopal N, Madhavi G. Simultaneous determination of asenapine and valproic acid in human plasma using LC-MS/MS: application of the method to support pharmacokinetic study. J Pharm Analysis. 2013;3(6):394–401.Google Scholar
  216. 216.
    Saphris product information. 2015. Available from: (Accessed).
  217. 217.
    Citrome L. Asenapine review, part I: chemistry, receptor affinity profile, pharmacokinetics and metabolism. Expert Opin Drug Metab Toxicol. 2014;10(6):893–903.PubMedGoogle Scholar
  218. 218.
    Stahl SM, Cucchiaro J, Simonelli D, Hsu J, Pikalov A, Loebel A. Effectiveness of lurasidone for patients with schizophrenia following 6 weeks of acute treatment with lurasidone, olanzapine, or placebo: a 6-month, open-label, extension study. J Clin Psychiatry. 2013;74:507–15.PubMedGoogle Scholar
  219. 219.
    Harvey PD, Siu CO, Ogasa M, Loebel A. Effect of lurasidone dose on cognition in patients with schizophrenia: post hoc analysis of a long-term, double-blind continuation study. Schizoph Res. 2015;166:334–8.Google Scholar
  220. 220.
    Luoni A, Macchi F, Papp M, Molteni R, Riva MA. Lurasidone exerts antidepressant properties in the chronic mild stress model through the regulation of synaptic and neuroplastic mechanisms in the rat prefrontal cortex. Int J Neuropsychopharmacol. 2015;18(4):1–12.Google Scholar
  221. 221.
    Citrome L. Lurasidone in schizophrenia: new information about dosage and place in therapy. Adv Ther. 2012;29(10):815–25.PubMedGoogle Scholar
  222. 222.
    Murai T, Nakako T, Ikeda K, Ikejiri M, Ishiyama T, Taiga M. Lack of dopamine D4 receptor affinity contributes to the procognitive effect of lurasidone. Behav Brain Res. 2014;261:26–30.PubMedGoogle Scholar
  223. 223.
    Citrome L. A Review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: an evidence-based medicine approach. CNS Drugs. 2013;27:879–911.PubMedGoogle Scholar
  224. 224.
    Caccia S, Pasina L, Nobili A. Critical appraisal of lurasidone in the management of schizophrenia. Neuropsych Dis Treat. 2012;8:155–68.Google Scholar
  225. 225.
    Arif SA, Mitchell MM. Iloperidone: a new drug for the treatment of schizophrenia. Am J Health Syst Pharm. 2011;68(4):301–8.PubMedGoogle Scholar
  226. 226.
    Rado JT, Janicak PG. Long-term efficacy and safety of iloperidone: an update. Neuropsychiat Dis Treat. 2014;10:409–15.Google Scholar
  227. 227.
    Cutler AJ, Kalali AH, Mattingly GW, Kunovac J, Meng X. Long-term safety and tolerability of iloperidone: results from a 25-week, open-label extension trial. CNS Spectr. 2013;18(1):43–54.PubMedGoogle Scholar
  228. 228.
    Shayegan DK, Stahl SM. Atypical antipsychotics: matching receptor profile to individual patient’s clinical profile. CNS Spectr. 2014;9(10 Suppl. 11):6–14.Google Scholar
  229. 229.
    Jia M, Li J, He X, Mingzhou Liu M, Zhou Y, Fan Y, Li W. Simultaneous determination of iloperidone and its two active metabolites in human plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study. J Chromatogr B. 2013;928:52–7.Google Scholar
  230. 230.
    Citrome L. Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion. Expert Opin Drug Metab Toxicol. 2010;6(12):1551–64.PubMedGoogle Scholar
  231. 231.
    Weiden PJ, Manning R, Wolfgang CD, Ryan JM, Mancione L, Han G, Ahmed S, Mayo MG. A randomized trial of iloperidone for prevention of relapse in schizophrenia: the REPRIEVE Study. CNS Drugs. 2016;30:735–47.PubMedPubMedCentralGoogle Scholar
  232. 232.
    Durgam S, Cutler AJ, Lu K, Migliore R, Ruth A, Laszlovszky I, Németh G, Meltzer HY. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind placebo- and active- controlled trial. J Clin Psychiatry. 2015;76(12):1574–82.Google Scholar
  233. 233.
    Seneca N, Finnema SJ, Laszlovszky I, Kiss B, Horváth A, Pásztor G, Kapás M, Gyertyán I, Farkas S, Innis RB, Halldin C, Gulyás B. Occupancy of dopamine D2 and D3 and serotonin 5-HT1A receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography. Psychopharmacology. 2011;218(3):579–87.PubMedPubMedCentralGoogle Scholar
  234. 234.
    Caccia S, Invernizzi RW, Nobili A, Pasina L. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia. Ther Clin Risk Manag. 2013;9:319–28.PubMedPubMedCentralGoogle Scholar
  235. 235.
    Citrome L. Cariprazine: chemistry, pharmacodynamics, pharmacokinetics, and metabolism, clinical efficacy, safety, and tolerability. Expert Opin Drug Metab Toxicol. 2013;9(2):193–206.PubMedGoogle Scholar
  236. 236.
    Citrome L. Cariprazine in schizophrenia: clinical efficacy, tolerability, and place in therapy. Adv Ther. 2013;30(2):114–26.PubMedGoogle Scholar
  237. 237.
    Citrome L. Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy. Adv Ther. 2013;30(2):102–13.PubMedGoogle Scholar
  238. 238.
    Stahl SM. Mechanism of action of cariprazine. CNS Spectr. 2016;21(2):123–7.PubMedGoogle Scholar
  239. 239.
    Gyertyán I, Kiss B, Sághy K, Laszy J, Szabó G, Szabados T, Gémesi LI, Pásztor G, Zájer-Balázs M, Kapás M, Csongor EÁ, Domány G, Tihanyi K, Szombathelyi Z. Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents. Neurochem Int. 2011;59:925–35.PubMedGoogle Scholar
  240. 240.
    Blier P, Ward NM. Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry. 2003;53(3):193–203.PubMedGoogle Scholar
  241. 241.
    Ohno Y. Therapeutic role of 5-HT1A receptors in the treatment of schizophrenia and Parkinson’s disease. CNS Neurosci Ther. 2011;17:58–65.PubMedGoogle Scholar
  242. 242.
    Nakamura T, Kubota T, Iwakaji A, Imada M, Kapás M, Morio Y. Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment). Drug Des Dev Ther. 2016;10:327–38.Google Scholar
  243. 243.
    Actavis. Cariprazine. Full prescribing information. Actavis; 2015.Google Scholar
  244. 244.
    Maeda K, Sugino H, Akazawa H, Amada N, Shimada J, Futamura T, Yamashita H, Ito N, McQuade RD, Mørk A, Pehrson AL, Hentzer M, Nielsen V, Bundgaard C, Arnt J, Stensbøl TB, Kikuchi T. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014;350(3):589–604.PubMedGoogle Scholar
  245. 245.
    Correll CU, Skuban A, Ouyang J, Hobart M, Pfister S, McQuade RD, Nyilas M, Carson WH, Sanchez R, Eriksson H. Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia: a 6-week randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2015;172:870–80.PubMedGoogle Scholar
  246. 246.
    Citrome L, Stensbøl TB, Maeda K. The preclinical profile of brexpiprazole: what is its clinical relevance for the treatment of psychiatric disorders? Expert Rev Neurother. 2015;15(10):1219–29.PubMedGoogle Scholar
  247. 247.
    McKeage K. Adjunctive brexpiprazole: a review in major depressive disorder. CNS Drugs. 2016;30(2):91–9.PubMedGoogle Scholar
  248. 248.
    Frankel Joshua S, Schwartz Thomas L. Brexpiprazole and cariprazine: distinguishing two new atypical antipsychotics from the original dopamine stabilizer aripiprazole. Ther Adv Psychopharmacol. 2017;7(1):29–41.PubMedGoogle Scholar
  249. 249.
    Das S, Barnwal P, Winston AB, Mondal S, Saha I. Brexpiprazole: so far so good. Ther Adv Psychopharmacol. 2016;6(1):39–54.PubMedPubMedCentralGoogle Scholar
  250. 250.
    Ishigooka J, Iwashita S, Higashi K, Liew EL, Tadori Y. Pharmacokinetics and safety of brexpiprazole following multiple-dose administration to Japanese patients with schizophrenia. J Clin Pharmacol. 2018;58(1):74–80.PubMedGoogle Scholar
  251. 251.
    Liu HC, Chang WH, Wei FC, Lin SK, Lin SK, Jann MW. Monitoring of plasma clozapine levels and its metabolites in refractory schizophrenic patients. Ther Drug Monit. 1996;18:200–7.PubMedGoogle Scholar
  252. 252.
    Mauri MC, Volonteri LS, Dell’Osso B, Regispani F, Papa P, Baldi M, Bareggi SR. Predictors of clinical outcome in schizophrenic patients responding to clozapine. J Clin Psychopharmacol. 2003;23:1–5.Google Scholar
  253. 253.
    Dettling M, Sachse C, Brockmoller J, Schley J, Muller-Oerlinghausen B, Pickersgill I, Rolfs A, Schaub RT, Schmider J. Long-term therapeutic drug monitoring of clozapine and metabolites in psychiatric in- and outpatients. Psychopharmacology. 2000;152:80–6.PubMedGoogle Scholar
  254. 254.
    Spina E, Avenoso A, Facciolà G, Scordo MG, Ancione M, Madia AG, Ventimiglia M, Perucca E. Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics. Psychopharmacology. 2000;148:83–9.PubMedGoogle Scholar
  255. 255.
    Van der Zwaag C, McGee M, McEnvoy JP, Freudenreich O, Wilson WH, Copper TB. Response of patients with treatment-refractory schizophrenia to clozapine within three serum level ranges. Am J Psychiatry. 1996;153:1579–84.Google Scholar
  256. 256.
    Centorrino F, Baldessarrini RJ, Kando JC, Frankenburg FR, Volpicelli SA, Flood JC. Clozapine and metabolites: concentrations in serum and clinical findings durino treatment of cronically psychotic patients. J Clin Psychopharmacol. 1994;14:119–25.PubMedGoogle Scholar
  257. 257.
    Olesen OV, Thomsen K, Jensen PN, Wulff CH, Rasmussen NA, Refshammer C, Soresen J, Bysted M, Christensen J, Rosenberg R. Clozapine serum levels and side effects during steady state treatment of schizophrenic patients: a cross-sectional study. Psychopharmacology. 1995;117:371–8.PubMedGoogle Scholar
  258. 258.
    Yoshimura R, Ueda N, Nakamura J. Possible relationship between combined plasma concentrations of risperidone plus 9-hydroxyrisperidone and extrapyramidal symptoms. Neuropsychobiology. 2001;44:129–33.PubMedGoogle Scholar
  259. 259.
    Anderson C, True J, Ereshefsky L, Miller A. Risperidone clinical efficacy: role of the metabolite 9-OH-risperidone. Psychopharmacol Bull. 1994;30(1):88.Google Scholar
  260. 260.
    Bondolfi G, Dufour H, Patris M, May JP, Billeter U, Eap CB, Baumann P. Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. Am J Psychiatry. 1998;155:499–504.PubMedGoogle Scholar
  261. 261.
    Lee HS, Tan CH, Khoo YM, Chee KT, Wong KE, Chong SA, Mahendran R, Yap JL, Low BL, Choo CH, Chan A. Serum concentrations and clinical effects of Risperidone in schizophrenic patients in Singapore: a preliminary report. Br J Clin Pharmacol. 1999;47:460–1.PubMedGoogle Scholar
  262. 262.
    Horvitz-Lennon M, Mattke S, Predmore Z, Howes OD. The role of antipsychotic plasma levels in the treatment of schizophrenia. Am J Psychiatry. 2017;174(5):421–6.PubMedGoogle Scholar
  263. 263.
    Patteet L, Morrens M, Maudens KE, Niemegeers P, Sabbe B, Neels H. Therapeutic drug monitoring of common antipsychotics. Ther Drug Monit. 2012;34:629–51.PubMedGoogle Scholar
  264. 264.
    Grundmann M, Kacirova I, Urinovska R. Therapeutic drug monitoring of atypical antipsychotic drugs. Acta Pharm. 2014;64:387–401.PubMedGoogle Scholar
  265. 265.
    Wang L, Yu L, Zhang AP, Fang C, Du J, Gu NF, Qin SY, Feng GY, Li XW, Xing QH, He L. Serum prolactin levels, plasma risperidone levels, polymorphism of cytochrome P450 2D6 and clinical response in patients with schizophrenia. J Psychopharmacol. 2007;21(8):837–42.PubMedGoogle Scholar
  266. 266.
    Lostia AM, Mazzarini L, Pacchiarotti I, Lionetto L, De Rossi P, Sanna L, Sani G, Kotzalidis GD, Girardi P, Simmaco M, Tatarelli R. Serum levels of risperidone and its metabolite, 9-hydroxyrisperidone: correlation between drug concentration and clinical response. Ther Drug Monit. 2009;31(4):475–81.PubMedGoogle Scholar
  267. 267.
    Yasui-Furukori N, Saito M, Nakagami T, Furukori H, Suzuki A, Kondo T, Kaneko S. Clinical response to risperidone in relation to plasma drug concentrations in acutely exacerbated schizophrenic patients. J Psychopharmacol. 2010;24(7):987–94.PubMedGoogle Scholar
  268. 268.
    Lu ML, Chen CH, Kuo PT, Lin CH, Wu TH. Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor metabolic parameters in patients with schizophrenia. Schizophr Res. 2018;193:139–45.PubMedGoogle Scholar
  269. 269.
    Aichhorn W, Marksteiner I, Walch T, Zernig G, Saria A, Kemmler G. Influence of age, gender, body weight and valproate comedication on quetiapine plasma concentrations. lnt Clin Psychopharmacol. 2006;21(2):81–5.PubMedGoogle Scholar
  270. 270.
    Dragicevic A, Muller MJ, Sachse J, Härtter S, Hiemke C. Therapeutic drug monitoring (TDM) of quetiapine. Lecture presented at the Symposium of the AGNP. Munich; 2003.Google Scholar
  271. 271.
    Dragicevic A, Sachse J, Härtter S, Hiemke C, Muller MJ. Serum concentrations of quetiapine and clinical effects. International Meeting on Pharmacovigilance in Psychiatry. Therapeutic Drug Monitoring and Pharmacogenetics of Psychotropic Drugs. Lausanne; 2005.Google Scholar
  272. 272.
    Dragicevic A, Trotzauer D, Hiemke C, Muller MJ. Gender and age effects on quetiapine serum concentrations in patients with schizophrenia or schizoaffective disorders. Lecture presented at the 24th Symposium of the AGNP. Munich; 2005.Google Scholar
  273. 273.
    Mauri MC, Volonteri LS, Fiorentini A, Pirola R, Bareggi SR. Two weeks’ quetiapine treatment for schizophrenia, drug-induced psychosis and borderline personality disorder: a naturalistic study with drug plasma levels. Expert Opin Pharmacother. 2007;8(14):2207–13.PubMedGoogle Scholar
  274. 274.
    Gerlach M, Hünnerkopf R, Rothenhöfer S, Libal G, Burger R, Clement HW, Fegert JM, Wewetzer Ch, Mehler-Wex C. Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders. Pharmacopsychiatry. 2007;40(2):72–6.PubMedGoogle Scholar
  275. 275.
    Hasselstrøm I, Linnet K. Quetiapine serum concentrations in psychiatric patients: the influence of comedication. Ther Drug Monit. 2004;26(5):486–9.PubMedGoogle Scholar
  276. 276.
    Albantakis L, Egberts K, Burger R, Kulpok C, Mehler-Wex C, Taurines R, Unterecker S, Wewetzer C, Romanos M, Gerlach M. Relationship between daily dose, serum concentration, and clinical response to quetiapine in children and adolescents with psychotic and mood disorders. Pharmacopsychiatry. 2017;50(6):248–55.PubMedGoogle Scholar
  277. 277.
    Sparshatt A, Taylor D, Patel MX, Kapur S. A systematic review of aripiprazole dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry. 2010;71(11):1447–56.PubMedGoogle Scholar
  278. 278.
    Lin SK, Chen CK, Liu YL. Aripiprazole and dehydroaripiprazole plasma concentrations and clinical responses in patientswith schizophrenia. J Clin Psychopharmacol. 2011;31(6):758–62.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Massimo Carlo Mauri
    • 1
    Email author
  • Silvia Paletta
    • 1
  • Chiara Di Pace
    • 1
  • Alessandra Reggiori
    • 1
  • Giovanna Cirnigliaro
    • 1
  • Isabel Valli
    • 2
  • Alfredo Carlo Altamura
    • 1
  1. 1.Clinical Psychopharmacology Unit, Department of Neuroscience and Mental Health, Clinical PsychiatryFondazione IRCCS Ca’ GrandaMilanItaly
  2. 2.Department of Psychosis StudiesKing’s College LondonLondonUK

Personalised recommendations