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Antipsychotics

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Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents

Abstract

Antipsychotic medications have been used for the treatment of patients with schizophrenia, schizoaffective, bipolar disorders, and other psychotic conditions. Antipsychotics administration can occur by various routes that includes oral, sublingual, intramuscular, and inhalation. Long-acting depot antipsychotics offer the clinician an additional option for chronic disease management. Most antipsychotics are metabolized by the hepatic CYP enzymes except ziprasidone and paliperidone. Antipsychotics are either substrates or inhibitors of P-glycoprotein. A “therapeutic” plasma concentration range has been recommended for antipsychotics except for asenapine, iloperidone, and lurasidone due to their recent entrance into clinical practice. Each antipsychotic agent possesses a different pharmacodynamic profile with receptor binding that accounts for their varying therapeutic effects regarding daily doses and their different adverse event characteristics. The antipsychotic doses are at the lower therapeutic range that achieves a dopamine receptor subtype 2 (D2) blockade of 65–85 % as measured by the PET technology. Yet, routine daily practice exceeds these low doses based upon the patient’s clinical response and tolerability indicating the limitations of linking pharmacokinetic and pharmacodynamic models with complex psychiatric diseases such as schizophrenia. Other pharmacodynamic effects include QT/QTc prolongation, prolactin changes, anticholinergic, sedation, and cardiovascular actions. Population pharmacokinetic analysis has been extended to antipsychotics, yielding some interesting findings regarding pharmacokinetic and pharmacodynamic models.

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References

  1. Perel JM, Jann MW (2006) Antipsychotics. In: Burton ME, Shaw LM, Schentag JJ, Evans WE (eds). Applied pharmacokinetics and pharmacodynamics – principles of therapeutic drug monitoring, 4th ed. Philadelphia, Lippincott Williams and Wilkins. pp 813–838

    Google Scholar 

  2. Jorgensen A (1986) Metabolism and pharmacokinetics of antipsychotics. In: Bridges JW, Chasseaud LF (eds) Progress in drug metabolism, vol 9. Taylor, and Francis, London, pp 111–174

    Google Scholar 

  3. Moons T, de Roo M, Clees S, Dom G (2011) Relationship between P-glycoprotein and second generation antipsychotics. Pharmacogenomics 12:1193–1211

    Article  CAS  PubMed  Google Scholar 

  4. Mauri MC, Volonteri LS, Colasanti A, Fiorentino A, De Gaspari IF, Bareggi SR (2007) Clinical pharmacokinetics of atypical antipsychotics. Clin Pharmacokinet 46:359–388

    Article  CAS  PubMed  Google Scholar 

  5. Sheehan JJ, Sliwa JK, Amatniek JC, Grinspan A, Canuso CM (2010) Atypical antipsychotic metabolism and excretion. Curr Drug Metab 11:516–525

    Article  CAS  PubMed  Google Scholar 

  6. Bartlett JA, Maarschalk KV (2012) Understanding the oral mucosal absorption and resulting clinical pharmacokinetics of asenapine. AAPS PharmSciTech 13:1110–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Weber J, McCormack PL (2009) Asenapine. CNS Drugs 23:781–792

    Article  CAS  PubMed  Google Scholar 

  8. Figueroa C, Brecher M, Hamer-Maansson JE, Winter H (2009) Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release. Prog Neuropsychopharmacol Biol Psychiatry 33:199–204

    Article  CAS  PubMed  Google Scholar 

  9. Yang LP, Polsker GL (2007) Paliperidone extended release. CNS Drugs 21:417–425

    Article  CAS  PubMed  Google Scholar 

  10. Citrome L (2009) Using oral ziprasidone effectively: the food effect and dose–response. Adv Ther 26:739–748

    Article  CAS  PubMed  Google Scholar 

  11. DeVane CL, Nemeroff CB (2001) Clinical pharmacokinetics of quetiapine. Clin Pharmacokinet 40:509–522

    Article  CAS  PubMed  Google Scholar 

  12. Preskorn S, Ereshefsky L, Chiu YY, Poola N, Loebel A (2013) Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open-label, crossover studies. Hum Psychopharmacol Clin Exp 28:495–505

    Article  CAS  Google Scholar 

  13. Cohen LJ (1994) Risperidone. Pharmacotherapy 14:253–265

    CAS  PubMed  Google Scholar 

  14. Spyker DA, Munzar P, Cassella JV (2010) Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers. J Clin Pharmacol 50:169–179

    Article  CAS  PubMed  Google Scholar 

  15. Simpson GM, Cooper TM, Lee JH, Young M (1978) Clinical and plasma level characteristics of intramuscular and oral loxapine. Psychopharmacol 56:225–227

    Article  CAS  Google Scholar 

  16. Milton GV, Jann MW (1995) Emergency treatment of psychotic symptoms. Clin Pharmacokinet 28:494–504

    Article  CAS  PubMed  Google Scholar 

  17. Forsman A, Ohman R (1976) Pharmacokinetics of haloperidol in man. Curr Ther Res 20:319–336

    CAS  PubMed  Google Scholar 

  18. Magliozzi JR, Hollister LF (1985) Elimination half-life and bioavailability of haloperidol in schizophrenic patients. J Clin Psychiatry 46:220–221

    Google Scholar 

  19. Froemming JS, Lam YWF, Jann MW et al (1989) Pharmacokinetics of haloperidol. Clin Pharmacokinet 17:396–423

    Article  CAS  PubMed  Google Scholar 

  20. Preskorn SH (2005) Pharmacokinetics and therapeutics of acute intramuscular ziprasidone. Clin Pharmacokinet 44:1117–1133

    Article  CAS  PubMed  Google Scholar 

  21. Bergstrom R, Mitchell M, Jewell H et al (1999) Examination of the safety, tolerability, and pharmacokinetics of intramuscular (IM) olanzapine compared to oral olanzapine in healthy subjects. Schziophr Res 36:305–306

    Article  Google Scholar 

  22. Boulton DW, Kolia G, Mallikaarjun S et al (2008) Pharmacokinetics and tolerability of intramuscular, oral, and intravenous aripiprazole in healthy subjects and in patients with schizophrenia. Br J Clin Pharmacol 47:475–485

    Article  CAS  Google Scholar 

  23. Jann MW, Ereshefsky L, Saklad SR (1985) Clinical pharmacokinetics of the depot antipsychotics. Clin Pharmacokinet 10:315–333

    Article  CAS  PubMed  Google Scholar 

  24. Meyer JM (2013) Understanding depot antipsychotics: an illustrated guide to kinetics. CNS Spectr 18:58–68

    Article  PubMed  Google Scholar 

  25. Eerdekens M, Van Hove I, Remmerie B, Mannaert M (2004) Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia. Schizophr Res 70:91–100

    Article  PubMed  Google Scholar 

  26. Mallikaarjun S, Kane JM, Bricmont P et al (2013) Pharmacokinetics, tolerability and safety of aripiprazole once-monthly in adult schizophrenia: an open-label, parallel-arm, multiple-dose study. Schizophr Res 150:281–288

    Article  PubMed  Google Scholar 

  27. Spanarello S, La Ferla T (2013) The pharmacokinetics of long-acting antipsychotic medications. Curr Clin Pharmacol 8:1–8

    Google Scholar 

  28. Deberdt R, Elens P, Berghmans W et al (1980) Intramuscular haloperidol decanoate for neuroleptic maintenance therapy, efficacy, dosage schedule, and plasma levels. Acta Psychiatrica Scand 62:356–363

    Article  CAS  Google Scholar 

  29. Wei FC, Jann MW, Lin HN, Paio-Chien C, Chang WH (1996) A practical loading dose method for converting schizophrenia patients from oral to depot haloperidol therapy. J Clin Psychiatry 57:298–302

    CAS  PubMed  Google Scholar 

  30. Ereshefsky L, Toney G, Saklad SR, Anderson C, Seidel D (1993) A loading-dose strategy for converting from oral to depot haloperidol. Hosp Community Psychiatry 44:1155–1161

    CAS  PubMed  Google Scholar 

  31. Hough D, Lindenmayer JP, Gopal S et al (2009) Safety and tolerability of deltoid and gluteal injections of paliperidone palmitate in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 33:1022–1031

    Article  CAS  PubMed  Google Scholar 

  32. Callaghan JT, Bergstrom R, Ptak LR et al (1999) Olanzapine. Clin Pharmacokinet 37:177–193

    Article  CAS  PubMed  Google Scholar 

  33. Rowell FJ, Hui SM, Fairburn AF et al (1980) The effect of age and thioridazine on the in-vitro binding of fluphenazine to normal human serum. Br J Clin Pharmacol 9:432–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rowell FJ, Hui SM, Fairburn AF et al (1981) Total and free serum haloperidol levels in schizophrenic patients and the effect of age, thioridazine and fatty acid on haloperidol serum protein binding in vitro. Br J Clin Pharmacol 11:377–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. DeVane CL (2002) Clinical significance of drug binding, protein binding, and binding displacement of interactions. Psychopharm Bull 36:5–21

    Google Scholar 

  36. Benet LZ, Hooper BA (2002) Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther 71:115–121

    Article  CAS  PubMed  Google Scholar 

  37. Cheng YF, Lundberg T, Bondesson U et al (1988) Clinical pharmacokinetics of clozapine in schizophrenic patients. Eur J Clin Pharmacol 34:445–449

    Article  CAS  PubMed  Google Scholar 

  38. Boulton DW, DeVane CL, Listion HL, Markowitz JS (2002) In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci 71:163–169

    Article  CAS  PubMed  Google Scholar 

  39. Nyberg G, Axelsson R, Martensson E (1981) Cerebrospinal fluid concentrations of thioridazine and its many metabolites in psychiatric patients. Eur J Clin Pharmacol 19:139–148

    Article  CAS  PubMed  Google Scholar 

  40. Wiles DH, Gelder MG (1980) Plasma fluphenazine levels by radioimmunoassay in schizophrenic patients treated with depot fluphenazine. Adv Biochem Psychopharmacol 24:599–602

    CAS  PubMed  Google Scholar 

  41. Skogh E, Sjodin I, Josefsson M, Dahl ML (2011) High correlation between serum and cerebrospinal fluid olanzapine concentrations in patients with schizophrenia or schizoaffective disorder medicating with oral olanzapine as the only antipsychotic drug. J Clin Psychopharmacol 31:4–9

    Article  CAS  PubMed  Google Scholar 

  42. Hall SD, Thummel KE, Watkins PB et al (1999) Molecular and physical mechanisms of first-pass extraction. Drug Metab Dispos 27:161–166

    CAS  PubMed  Google Scholar 

  43. Linnet K, Ejsing TB (2008) A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur Neuropsychopharmacol 18:157–169

    Article  CAS  PubMed  Google Scholar 

  44. Gonzalez-Vacarezza N, Dorado P, Penas-Lledo EM, Farinas H, Estevez-Carrizo FE, Llerena A (2013) MDR-1 genotypes and quetiapine pharmacokinetics in health volunteers. Drug Metabol Drug Interact 28:163–166

    Article  CAS  PubMed  Google Scholar 

  45. Consoli G, Lastella M, Ciapparelli A et al (2009) ABCB1 polymorphisms are associated with clozapine plasma levels in psychotic patients. Pharmacogenomics 10:1267–1276

    Article  CAS  PubMed  Google Scholar 

  46. Jaquenoud Sirot E, Knezevic B, Morena GP et al (2009) ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine. J Clin Psychopharmacol 29:319–326

    Article  CAS  PubMed  Google Scholar 

  47. Yasui-Furukori N, Mihara K, Takahata T et al (2004) Effects of various factors on steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone: lack of impact of MDR-1 genotypes. Br J Clin Pharmacol 57:569–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Suzuki Y, Tsuneyama N, Fukui N et al (2013) Impact of the ABCB1 gene polymorphism on plasma 9-hydroxyrisperidone and active moiety levels in Japanese patients with schizophrenia. J Clin Psychopharmacol 33:411–414

    Article  CAS  PubMed  Google Scholar 

  49. Jann MW, Lam YQF, Chang WH (1990) Reversible metabolism of haloperidol and reduced haloperidol in Chinese schizophrenic patients. Psychopharmacol 101:107–111

    Article  CAS  Google Scholar 

  50. Jann MW, Grimsely SR, Gray EC, Chang WH (1993) Pharmacokinetics and pharmacodynamics of clozapine. Clin Pharmacokinet 24:161–176

    Article  CAS  PubMed  Google Scholar 

  51. Sweet RA, Pollock BG, Mulsant BH et al (2000) Pharmacologic profile of perphenazine’s metabolites. J Clin Psychopharmacol 20:181–187

    Article  CAS  PubMed  Google Scholar 

  52. Arif SA, Mitchell MM (2011) Iloperidone: a new drug for the treatment of schizophrenia. Am Health Syst Pharm 68:301–308

    Article  CAS  Google Scholar 

  53. Citrome L (2011) Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic. Int J Clin Pract 65:189–210

    Article  CAS  PubMed  Google Scholar 

  54. Nyberg S, Jucaite A, Takano A et al (2013) Norepinephrine transporter occupancy in the human brain after oral quetiapine XR. Int J Neuropsychopharmacol 16:2235–2244

    Article  CAS  PubMed  Google Scholar 

  55. Dolder C, Nelson M, Deyo Z (2008) Paliperidone for schizophrenia. Am J Health Syst Pharm 65:403–413

    Article  CAS  PubMed  Google Scholar 

  56. Stip E, Zhornitsky S, Moteshafi H et al (2011) Ziprasidone for psychotic disorders: a meta-analysis and systematic review of the relationship between pharmacokinetics, pharmacodynamics, and clinical profile. Clin Ther 33:1853–1867

    Article  CAS  PubMed  Google Scholar 

  57. Gitlin MJ, Midha KK, Fogelson D, Nuechtterlin K (1988) Persistence of fluphenazine in plasma after decanoate withdrawal. J Clin Psychopharmacol 8:53–56

    Article  CAS  PubMed  Google Scholar 

  58. Chang WH, Lin SK, Juang DJ et al (1993) Prolonged haloperidol and reduced haloperidol plasma concentrations after decanoate withdrawal. Schizophr Res 9:35–40

    Article  CAS  PubMed  Google Scholar 

  59. Glue P, Banfield C (1996) Psychiatry, psychopharmacology, and P450’s. Hum Psychopharmacol 11:97–114

    Article  CAS  Google Scholar 

  60. Otani K, Aoshima T (2000) Pharmacogenetics of classical and atypical antipsychotic drugs. Ther Drug Monit 22:118–121

    Article  CAS  PubMed  Google Scholar 

  61. Ravyn D, Ravyn V, Lowney R, Nasrallah HA (2013) CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr Res 149:1–14

    Article  PubMed  Google Scholar 

  62. Liston HL, Markowitz JS, DeVane CL (2001) Drug glucuronidation in clinical pharmacology. J Clin Psychopharmacol 21:500–515

    Article  CAS  PubMed  Google Scholar 

  63. Soderberg MM, Dahl ML (2013) Pharmacogenetics of olanzapine metabolism. Pharmacogenomics 14:1319–1336

    Article  PubMed  CAS  Google Scholar 

  64. Zhou SF (2009) Polymorphism of human cytochrome P450 2D6 and its clinical significance. Part II. Clin Pharmacokinet 48:761–804

    Article  CAS  PubMed  Google Scholar 

  65. Dahl ML, Llerena A, Bondesson U et al (1994) Disposition of clozapine in man: lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms. Br J Clin Pharmacol 37:71–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Olesen OV, Linnet K (2000) Identification of the human cytochrome P450 isoforms mediating in vitro N-dealkylation of perphenazine. Br J Clin Pharmacol 50:563–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Dahl-Puustinen ML, Liden A, Alm C et al (1989) Disposition of perphenazine is related to polymorphic debrisoquine hydroxylation in human beings. Clin Pharmacol Ther 46:78–81

    Article  CAS  PubMed  Google Scholar 

  68. Linnet K, Wilborg O (1996) Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. Clin Pharmacol Ther 60:41–47

    Article  CAS  PubMed  Google Scholar 

  69. Jerling M, Dahl ML, Aberg-Wistedt A et al (1996) The CYP2D6 genotype predicts the oral clearance of neuroleptic agents perphenazine and zuclopenthixol. Clin Pharmacol Ther 59:423–428

    Article  CAS  PubMed  Google Scholar 

  70. Berecz R, de la Rubia A, Dorado P et al (2003) Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype. Eur J Clin Pharmacol 59:45–50

    CAS  PubMed  Google Scholar 

  71. Von Bahr C, Movin G, Nordin C et al (1991) Plasma levels of thioridazine and metabolites are influenced by the debrisoquine hydroxylation phenotype. Clin Pharmacol Ther 49:234–240

    Article  Google Scholar 

  72. Dorado P, Penas-Lledo EM, de la Rubia A, Llerena A (2009) Relevance of CYP2D6 – 1584C > G polymorphism for thioridazine: mesoridazine plasma concentration ratio in psychiatric patients. Pharmacogenomics 10:1083–1089

    Article  CAS  PubMed  Google Scholar 

  73. Gershon S, Sakalis G, Bowers PA (1981) Mesoridazine – a pharmacodynamics and pharmacokinetic profile. J Clin Psychiatry 42:463–469

    CAS  PubMed  Google Scholar 

  74. Gottschalk LA, Dinovo E, Bierner R (1975) Plasma levels of mesoridazine and its metabolites and clinical response in acute schizophrenia after a single intramuscular drug dose. Psychopharmacol Bull 11:33–34

    CAS  PubMed  Google Scholar 

  75. Llerena A, Berecz R, de la Rubia A et al (2001) Effect of thioridazine dosage on debrisoquine hydroxylation phenotype in psychiatric patients with different CYP2D6 genotypes. Ther Drug Monit 23:616–620

    Article  CAS  PubMed  Google Scholar 

  76. Luo JP, Vasishtha SC, Hawes EM et al (2011) In vitro identification of the human cytochrome p450 enzymes involved in the oxidative metabolism of loxapine. Biopharm Drug Dispos 32:398–407

    Article  CAS  PubMed  Google Scholar 

  77. Cohen BM, Harris PQ, Altesman RI, Cole J (1982) Amoxapine: neuroleptic as well as antidepressant. Am J Psychiatry 139:1165–1167

    Article  CAS  PubMed  Google Scholar 

  78. Reed A, Huie K, Perloff ES, Cassella JV, Takahashi LH (2012) Loxapine p-glycoprotein interactions in vitro. Drug Metab Lett 6:26–32

    Article  CAS  PubMed  Google Scholar 

  79. Llerena A, Alm C, Dahl ML et al (1992) Haloperidol disposition is dependent on debrisoquine hydroxylation phenotype. Ther Drug Monit 14:92–97

    Article  CAS  PubMed  Google Scholar 

  80. Lane HY, Hu OYP, Jann MW et al (1997) Dextromethorphan phenotyping and haloperidol disposition in schizophrenic patients. Psychiatry Res 69:105–111

    Article  CAS  PubMed  Google Scholar 

  81. Ohnuma T, Shibata N, Matsubara Y, Arai H (2003) Haloperidol plasma concentration in Japanese psychiatric subjects with gene duplication of CYP2D6. Br J Clin Pharmacol 56:315–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Panagiotidis G, Arthur HW, Kindh JD, Dahl ML, Sjoqvist F (2007) Depot haloperidol treatment in outpatients with schizophrenia on monotherapy: impact of CYP2D6 polymorphism on pharmacokinetics and treatment outcome. Ther Drug Monit 29:417–422

    Article  CAS  PubMed  Google Scholar 

  83. Llerena A, ed la Rubia A, Berecz R, Dorado P (2004) Relationship between haloperidol plasma concentration, debrisoquine metabolic ration, CYP2D6 and CYP2C9 genotypes in psychiatric patients. Pharmacopsychiatry 37:69–73

    Article  CAS  PubMed  Google Scholar 

  84. Hendset M, Molden E, Refsum H, Hermann M (2009) Impact of CYP2D6 genotype on steady-state serum concentrations of risperidone and 9-hydroxyrisperidone in patients using long-acting injectable risperidone. J Clin Psychopharmacol 29:537–541

    Article  CAS  PubMed  Google Scholar 

  85. Hendset H, Molden E, Kanpe M, Hermann M (2014) Serum concentrations of risperidone and aripiprazole in subgroups encoding CYP2D6 intermediate metabolizer phenotype. Ther Drug Monit 36:80–85

    CAS  PubMed  Google Scholar 

  86. Llerena A, Berecz R, Penas-Lledo E, Suveges A, Farinas H (2013) Pharmacogenetics of clinical response to risperidone. Pharmacogenomics 14:177–194

    Article  CAS  PubMed  Google Scholar 

  87. Croxtall JD (2012) Aripiprazole: a review of its use in the management of schizophrenia in adults. CNS Drugs 26:155–183

    Article  CAS  PubMed  Google Scholar 

  88. Kubo M, Koue T, Maune H, Fukuda T, Azuma J (2007) Pharmacokinetics of aripiprazole, a new antipsychotic, following oral dosing in healthy adult Japanese volunteers: influence of CYP2D6 polymorphism. Drug Metab Pharmacokinet 22:358–366

    Article  CAS  PubMed  Google Scholar 

  89. Suzuki T, Mihara K, Nakamura A et al (2011) Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia. Ther Drug Monit 33:21–24

    Article  CAS  PubMed  Google Scholar 

  90. Suzuki T, Mihara K, Nakamura A et al (2014) Effects of genetic polymorphism of CYP2D6, CYP3A5, and ABCB1 on the steady-state plasma concentrations of aripiprazole and its active metabolite dehydroaripiprazole, in Japanese patients with schizophrenia. Ther Drug Monit 36(5):651–655

    Article  CAS  PubMed  Google Scholar 

  91. Haag S, Spigset O, Lakso HA et al (2001) Olanzapine disposition in humans is unrelated to CYP1A2 and CYP2D6 phenotypes. Eur J Clin Pharmacol 57:493–497

    Article  Google Scholar 

  92. Shirley KL, Hon YY, Penzak SR et al (2003) Correlation of cytochrome P450 (CYP) 1A2 activity with olanzapine disposition in healthy volunteers. Neuropsychopharmacol. TBD 28:961–966

    Google Scholar 

  93. Perera V, Gross AS, Polasek TM et al (2013) Considering CYP1A2 phenotype and genotype for optimizing the dose of olanzapine in the management of schizophrenia. Expert Opin Drug Metab Toxicol 9:1115–1137

    CAS  PubMed  Google Scholar 

  94. Bertilsson L, Carillo JA, Dahl ML et al (1994) Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br J Clin Pharmacol 37:471–473

    Article  Google Scholar 

  95. Jann MW, Ludden TM, Ereshefsky L, Saklad SR, Richards AL (1985) Preliminary analysis of haloperidol population kinetics in schizophrenics. Clin Pharmacol Ther 37:203

    Google Scholar 

  96. Yukawa E, Hokazono T, Funakoshi A et al (2000) Epidemiologic investigation of the relative clearance of haloperidol by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients. J Clin Psychopharmacol 20:685–690

    Article  CAS  PubMed  Google Scholar 

  97. Uchida H, Mamo DC, Pollock BG et al (2012) Predicting plasma concentrating of risperidone associated with dosage change: a population pharmacokinetic study. Ther Drug Monit 34:182–187

    Article  CAS  PubMed  Google Scholar 

  98. Botts S, Diaz FJ, Santoro V et al (2008) Estimating the effects of co-medications on plasma olanzapine concentrations by using a mixed model. Prog Neuropsychopharmacol Biol Psychiatry 32:1453–1458

    Article  CAS  PubMed  Google Scholar 

  99. Kim JR, Seo HB, Cho JY et al (2008) Population pharmacokinetic modelling of aripiprazole and its active metabolite dehydroaripiprazole in psychiatric patients. Br J Clin Pharmacol 66:802–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ng W, Uchida H, Ismail Z et al (2009) Clozapine exposure and the impact of smoking and gender: a population pharmacokinetic study. Ther Drug Monit 31:360–366

    Article  CAS  PubMed  Google Scholar 

  101. Vermeulen A, Piotrovsky V, Ludwig EA (2007) Population pharmacokinetics of risperidone and 9-hydroxyrisperidone in patients with acute episodes associated with bipolar I disorder. J Pharmacokinet Pharmacodyn 34:183–206

    Article  CAS  PubMed  Google Scholar 

  102. Samtani M, Vermeulen A, Stuyckens K (2009) Population pharmacokinetics of intramuscular paliperidone palmitate in patients with schizophrenia. Clin Pharmacokinet 48:585–600

    Article  CAS  PubMed  Google Scholar 

  103. Gopal S, Gassmann-Mayer C, Palumbo J, Samtani MN, Shiwach R, Alphs L (2010) Practical guidance for dosing and switching paliperidone palmitate treatment in patients with schizophrenia. Curr Med Res Opin 26:377–387

    Article  CAS  PubMed  Google Scholar 

  104. Baumann P, Hiemke C, Ulrich S et al (2004) The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 37:243–265

    Article  CAS  PubMed  Google Scholar 

  105. Nazirizadeh Y, Vogel F, Bader W et al (2010) Serum concentrations of paliperidone versus risperidone and clinical effects. Eur J Clin Pharmacol 66:797–803

    Article  CAS  PubMed  Google Scholar 

  106. Sparshatt A, Taylor D, Patel MX, Kapur S (2010) A systematic review of aripiprazole – dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry 71:1447–1456

    Article  CAS  PubMed  Google Scholar 

  107. Lopez LV, Kane JM (2013) Plasma levels of second-generation antipsychotics and clinical response in acute psychosis: a review of the literature. Schizophr Res 147:368–374

    Article  PubMed  Google Scholar 

  108. Best-Shaw L, Gudbrandsen M, Nagar J, Rose D, David AS, Patel MX (2014) Psychiatrists’ perspectives on antipsychotic dose and the role of plasma concentration therapeutic drug monitoring. Ther Drug Monit 36(4):486–493

    Article  CAS  PubMed  Google Scholar 

  109. Dysken MW, Javaid JL, Chang SS et al (1981) Fluphenazine pharmacokinetics and therapeutic response. Psychopharmacol 73:205–210

    Article  CAS  Google Scholar 

  110. Mavroidis ML, Kanter DR, Hirschowitz J et al (1984) Fluphenazine plasma levels and clinical response. J Clin Psychiatry 45:370–373

    CAS  PubMed  Google Scholar 

  111. Van Putten T, Avavagri M, Marder SR et al (1991) Plasma fluphenazine levels and newly admitted schizophrenic patients. Psychopharmacol Bull 27:91–96

    PubMed  Google Scholar 

  112. Koreen AR, Lieberman J, Alvir J et al (1994) Relationship of plasma fluphenazine levels to treatment response and extrapyramidal side effects in first-episode schizophrenic patients. Am J Psychiatry 151:35–39

    Article  CAS  PubMed  Google Scholar 

  113. Levinson D, Simpson G, Lo ES et al (1995) Fluphenazine plasma levels, dosage, efficacy, and side effects. Am J Psychiatry 152:756–771

    Google Scholar 

  114. Van Putten T, Marder SR, Wirshing WC et al (1991) Neuroleptic plasma levels. Psychopharmacol Bull 17:197–216

    Google Scholar 

  115. Jann MW, Chang WH, Lam YWF et al (1992) Comparative analysis of haloperidol and reduced haloperidol in different ethnic populations. Prog Neuropsychopharmacol Biol Psychiatry 16:193–202

    Article  CAS  PubMed  Google Scholar 

  116. Jann MW, Chang WH, Davis CM et al (1989) Haloperidol and reduced haloperidol plasma levels in Chinese and non-Chinese psychiatric patients. Psychiatry Res 30:45–52

    Article  CAS  PubMed  Google Scholar 

  117. Conley R, An Nguyen J, Tamminga C (1991) Haloperidol kinetics and clinical response. Schizophr Res 4:287 (Abstract)

    Article  Google Scholar 

  118. Lane HY, Lin HY, OYP H et al (1997) Blood levels of reduced haloperidol versus clinical effects and extrapyramidal side effects of haloperidol. Prog Neuropsychopharmacol Biol Psychiatry 21:299–311

    Article  CAS  PubMed  Google Scholar 

  119. Crowley JJ, Ashraf-Khorassani M, Castagnoli N, Sullivan PF (2013) Brain levels of the neurotoxic pyridinium metabolite HPP+ and extrapyramidal symptoms in haloperidol-treated mice. Neurotoxic 39:153–157

    Article  CAS  Google Scholar 

  120. Hansen LB, Larsen NE, Vastergard P (1981) Plasma levels of perphenazine (Trilafon) related to development of extrapyramidal side effects. Psychopharmacol 74:306–309

    Article  CAS  Google Scholar 

  121. Hansen LB, Larsen NE, Gulmann N (1982) Dose-dependent response relationship of perphenazine in the treatment of acute psychoses. Psychopharmacol 78:112–115

    Article  CAS  Google Scholar 

  122. Axelsson R, Martensson E (1983) Clinical effects related to the serum concentrations of thioridazine and its metabolites. In: Gram LF et al (eds) Clinical pharmacology in psychiatry. McMillan, London, pp 165–174

    Chapter  Google Scholar 

  123. Vtial-Herne J, Gerbino L, Kay SR et al (1986) Mesoridazine and thioridazine: clinical effects and blood levels in refractory schizophrenics. J Clin Psychiatry 47:375–379

    Google Scholar 

  124. Molden E, Lunde H, Lunder N et al (2006) Pharmacokinetic variability of aripiprazole and the active metabolite dehydroaripiprazole in psychiatric patients. Ther Drug Monit 28:744–749

    Article  CAS  PubMed  Google Scholar 

  125. Lin SK, Chen CK, Liu YL (2011) Aripiprazole and dehydroaripiprazole plasma concentrations and clinical responses in patients with schizophrenia. J Clin Psychopharmacol 31:758–762

    Article  CAS  PubMed  Google Scholar 

  126. Perry PJ, Miller DD, Arndt SV et al (1991) Clozapine and norclozapine plasma concentrations and clinical response in treatment-refractory schizophrenics. Am J Psychiatry 48:231–235

    Google Scholar 

  127. Perry PJ (2000) Therapeutic monitoring of atypical antipsychotics: is it of potential clinical value? CNS Drugs 13:167–171

    Article  CAS  Google Scholar 

  128. Liu HC, Chang WH, Wei FC et al (1996) Monitoring of plasma clozapine levels and its metabolites in refractory schizophrenics. Ther Drug Monit 18:200–207

    Article  CAS  PubMed  Google Scholar 

  129. Perry PJ, Sanger T, Beasley C (1997) Olanzapine plasma concentrations and clinical response in acutely ill schizophrenic patients. J Clin Psychopharmacol 17:472–477

    Article  CAS  PubMed  Google Scholar 

  130. Perry PJ, Lund BC, Sanger T, Beasley C (2001) Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial. J Clin Psychopharmacol 21:14–20

    Article  CAS  PubMed  Google Scholar 

  131. Citrome L, Stauffer VL, Chen L et al (2009) Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia. J Clin Psychopharmacol 29:278–283

    Article  CAS  PubMed  Google Scholar 

  132. Skogh E, Reis M, Dahl ML, Lundmark J, Bengtsson F (2002) Therapeutic drug monitoring data on olanzapine and its N-desmethyl metabolite in the naturalistic clinical setting. Ther Drug Monit 24:518–526

    Article  CAS  PubMed  Google Scholar 

  133. Bishara D, Olofinjana O, Sparshatt A, Kapur S, Taylor D, Patel MX (2013) Olanzapine: a systematic review and meta-regression of the relationships between dose, plasma concentration, receptor occupancy and response. J Clin Psychopharmacol 33:329–335

    Article  CAS  PubMed  Google Scholar 

  134. Sparshatt A, Talyor D, Patel MX, Kapur S (2011) Relationship between daily dose, plasma concentrations, dopamine receptor occupancy, and clinical response to quetiapine: a review. J Clin Psychiatry 72:1108–1123

    Article  CAS  PubMed  Google Scholar 

  135. Gerlach M, Hunnerkopf R, Rothenhofer S et al (2007) Therapeutic drug monitoring of quetiapine and adolescents with psychotic disorders. Pharmacopsychiatry 40:72–76

    Article  CAS  PubMed  Google Scholar 

  136. Bowskill SV, Handley SA, Fsher DS, Flanagan RJ, Patel MX (2012) Risperidone and total 9-hydroxyrisperidone in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 2002–2010. Ther Drug Monit 34:349–355

    Article  CAS  PubMed  Google Scholar 

  137. Seto K, Dumontet J, Enson MHH (2011) Risperidone in schizophrenia: is there a role for therapeutic drug monitoring? Ther Drug Monit 33:275–283

    Article  CAS  PubMed  Google Scholar 

  138. Mauri MC, Colasanti A, Rossattini M et al (2007) Ziprasidone outcome and tolerability: a practical clinical trial with plasma drug levels. Pharmacopsychiatry 40:89–92

    Article  CAS  PubMed  Google Scholar 

  139. Vogel F, Gansmuller R, Leiblein T et al (2009) The use of ziprasidone in clinical practice: analysis of pharmacokinetic and pharmacodynamics aspects from the data of a drug monitoring survey. Eur Psychiatry 24:143–148

    Article  PubMed  Google Scholar 

  140. Van Strien AM, van den Tweel AVW, van den Heuvel ML, di Biase M, van den Brule AJC, van Marum RJ (2014) Correlation of haloperidol concentration in blood and cerebrospinal fluid. J Clin Psychopharmacol 34:516–517

    Article  PubMed  Google Scholar 

  141. Richelson E (1999) Receptor pharmacology of neuroleptics: relation to clinical effects. J Clin Psychiatry 60(suppl 10):5–14

    CAS  PubMed  Google Scholar 

  142. Richelson E, Sounder T (2000) Binding of antipsychotic drugs to human brain receptors – focus on newer generation compounds. Life Sci 68:29–39

    Article  CAS  PubMed  Google Scholar 

  143. Richelson E (2010) New antipsychotic drugs: how do their receptor-binding profiles compare? J Clin Psychiatry 71:1243–1244

    Article  PubMed  Google Scholar 

  144. Crismon ML, Argo TR, Buckley PF (2014) Chapter 50: Schizophrenia. In: DiPiro JT, Talbert RL, Yee GC et al (eds) Pharmacotherapy – a pathophysiologic approach, 9th edn. McGraw Hill, New York, pp 1019–1045

    Google Scholar 

  145. Kroeze WK, Hufeisen SJ, Popadak BA et al (2003) H1 histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacol 28:519–526

    Article  CAS  Google Scholar 

  146. Farde L, Wiessel FA, Halldin C, Sedvall G (1988) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 45:71–76

    Article  CAS  PubMed  Google Scholar 

  147. Andree B, Halldin C, Vries MZ, Farde L (1997) Central 5Ht2A and D2 dopamine receptor occupancy after sublingual administration of ORG 5222 in healthy men. Psychopharmacol 131:339–345

    Article  CAS  Google Scholar 

  148. Wong DF, Kuwabara H, Brasic JB et al (2013) Determination of dopamine D2 receptor occupancy by lurasidone using positron emission tomography in healthy male subjects. Psychopharmacol 229:245–252

    Article  CAS  Google Scholar 

  149. Nyberg S, Eriksson B, Oxenstierna G, Halldin C, Farde L (1999) Suggested minimal effective doses of risperidone based on PET-measured D2 and 5HT2A receptor occupancy in schizophrenic patients. Am J Psychiatry 156:869–875

    Article  CAS  PubMed  Google Scholar 

  150. Kapur S, Remington G, Zipursky RB, Wilson AA, Houle S (1995) The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: A PET study. Life Sci 57:L103–L107

    Article  Google Scholar 

  151. Varnas K, Varrone A, Farde L (2013) Modeling of PET data in CNS drug discovery and development. J Pharmacokinet Pharmacodyn 40:267–279

    Article  PubMed  CAS  Google Scholar 

  152. Barrett JS, McGuire J, Vezina H, Spitsin S, Douglas SD (2013) PET measurement of receptor occupancy as a tool to guide dose selection in neuropharmacology: are we asking the right questions? J Clin Psychopharmacol 33:725–728

    Article  PubMed  Google Scholar 

  153. Uchida H, Takeuchi H, Graff-Guerro A et al (2011) Dopamine D2 receptor occupancy and clinical effects. J Clin Psychopharmacol 31:497–502

    Article  CAS  PubMed  Google Scholar 

  154. Kapur S, Zipursky R, Remington G, Jones C, McKay G, Houle S (1997) PET evidence that loxapine is an equipotent blocker of 5HT2 and D2 receptors: implications for the therapeutics in schizophrenia. Am J Psychiatry 154:1525–1529

    Article  CAS  PubMed  Google Scholar 

  155. Arakawa R, Ito H, Takano A et al (2008) Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacol 197:229–235

    Article  CAS  Google Scholar 

  156. Tauscher-Wisiewski S, Kapur S, Tauscher T et al (2002) Quetiapine: an effective antipsychotics in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade. J Clin Psychiatry 63:992–997

    Article  Google Scholar 

  157. Mamo D, Kapur S, Shammi CM et al (2004) 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 161:818–825

    Article  PubMed  Google Scholar 

  158. Uchida H, Suzuki T (2014) Dose and dosing frequency of long-acting injectable antipsychotics. J Clin Psychopharmacol. [Epub ahead]

    Google Scholar 

  159. Uchida H, Takeuchi H, Graff-Guerrero A et al (2011) Predicting dopamine D2 receptor occupancy from plasma levels of antipsychotic drugs a systematic review of pooled analysis. J Clin Psychopharmacol 31:318–325

    Google Scholar 

  160. Moriguchi S, Bies RR, Remington G et al (2013) Estimated dopamine D2 receptor occupancy and remission in schizophrenia: analysis of the CATIE data. J Clin Psychopharmacol 33:682–685

    Article  CAS  PubMed  Google Scholar 

  161. Arranz MJ, Rivera M, Munro JC (2011) Pharmacogenetics of response to antipsychotics in patients with schizophrenia. CNS Drugs 25:933–969

    Article  CAS  PubMed  Google Scholar 

  162. Brennan MD (2014) Pharmacogenetics of second-generation antipsychotics. Pharmacogenomics 15:869–884

    Article  CAS  PubMed  Google Scholar 

  163. Zhang JP, Malhostra AK (2013) Pharmacogenetics of antipsychotics: recent progress and methodological issues. Expert Opin Drug Metab Toxicol 9:183–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Gasso P, Papagianni K, Mas S et al (2013) Relationship between CYP2D6 genotype and haloperidol pharmacokinetics and extrapyramidal symptoms in healthy volunteers. Pharmacogenomic 14:1551–1563

    Article  CAS  Google Scholar 

  165. Zivkovic M, Mihaljevic-Peles A, Bozina M et al (2013) The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse events in male schizophrenic patients treated with haloperidol. J Clin Psychopharmacol 33:593–599

    Article  CAS  PubMed  Google Scholar 

  166. Rajkumar AP, Poonkuzhali B, Kuruvilla A, Jacob M, Jacob KS (2013) Clinical predictors of serum clozapine levels in patients with treatment-resistant schizophrenia. Int Clin Psychopharmacol 28:50–56

    Article  PubMed  Google Scholar 

  167. Remington G, Agid O, Foussias G, Ferguson L, McDonald K, Powell V (2013) Clozapine and therapeutic drug monitoring: is there sufficient evidence for an upper threshold? Psychopharmacol 225:505–518

    Article  CAS  Google Scholar 

  168. Coppola D, Liu Y, Gopal S et al (2012) A one-year prospective study of the safety, tolerability and pharmacokinetics of the highest available dose of paliperidone palmitate in patients with schizophrenia. BMC Psychiatry 12:26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Cabaleiro T, Lopez-Rodriguez RL, Ochoa D, Roman M, NovLBOS J, Abad-Santos F (2013) Polymorphisms influencing olanzapine metabolism and adverse effects in healthy subjects. Hum Psychopharmacol Clin Exp 28:205–214

    Article  CAS  Google Scholar 

  170. Mas S, Gasso P, Alvarez S et al (2012) Intuitive pharmacogenetics: spontaneous risperidone dosage is related to CYP2D6, CYP3A5, and ABCB1 genotypes. Pharmacogenomics J 12:255–259

    Article  CAS  PubMed  Google Scholar 

  171. Cartwright AL, Wilby KJ, Corrgian S, Enson MHH (2013) Pharmacogenetics of risperidone: a systematic review of the clinical effects of CYP2D6 polymorphisms. Ann Pharmacther 47:350–360

    Article  CAS  Google Scholar 

  172. Almoguera B, Riveiro-Alvarez R, Lopez-Castroman J et al (2013) CYP2D6 poor metabolizer status might be associated with better response to risperidone treatment. Pharmacogenet Genomics 23:627–630. V

    Article  CAS  PubMed  Google Scholar 

  173. Choong E, Polari A, Kamdem RH et al (2013) Pharmacogenetic study on risperidone long-acting injection: influence of cytochrome P450 2D6 and pregnane X receptor on risperidone exposure and drug-induced side-effects. J Clin Psychopharmacol 33:289–298

    Article  CAS  PubMed  Google Scholar 

  174. Buckley NA, Sanders P (2000) Cardiovascular adverse effects of antipsychotic drugs. Drug Safe 23:215–228

    Article  CAS  Google Scholar 

  175. Hatta K, Takahashi T, Nakamura H et al (2001) The association between intravenous haloperidol and prolonged QT interval. J Clin Psychopharmacol 21:257–261

    Article  CAS  PubMed  Google Scholar 

  176. Tisdale JE, Rasty S, Padhi ID et al (2001) The effect of intravenous haloperidol on QT interval dispersion in critically ill patients: comparison with QT interval prolongation and assessment of risk of Torsades de Pointes. J Clin Pharmacol 41:1310–1318

    Article  CAS  PubMed  Google Scholar 

  177. Glassman AH, Bigger JT (2001) Antipsychotic drugs: prolonged QTc interval, Torsades de Pointes, and sudden death. Am J Psychiatry 158:1774–1782

    Article  CAS  PubMed  Google Scholar 

  178. Spyker DA, Voloshko P, Heyman ER, Cassella JV (2014) Loxapine delivered as a thermally generated aerosol does not prolong QTc in a through QT/QTc study in healthy subjects. J Clin Pharmacol 54:665–674

    Article  CAS  PubMed  Google Scholar 

  179. Potkin SG, Preskorn S, Hochfeld M, Meng X (2013) A thorough QTc study of 3 doses of iloperidone including metabolic inhibition via CYP2D6 and/or CYP3A4 and a comparison to quetiapine and ziprasidone. J Clin Psychopharmacol 33:3–10

    Article  CAS  PubMed  Google Scholar 

  180. Desai M, Tanus-Santos JE, Li L et al (2003) Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6. Pharmacogenomics J 3:105–113

    Article  CAS  PubMed  Google Scholar 

  181. Suzuki Y, Tsuneyama N, Kukui N et al (2014) Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia. Pharmacogenomics J 4:1–5

    Google Scholar 

  182. Peuskens J, Pani L, Detraux J, De Hert M (2014) The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs 28:421–453

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Cameron ME, Lawrence JM, Olrich JG (1972) Thioridazine (Mellaril retinopathy). Br J Opthal 56:131–134

    Article  CAS  Google Scholar 

  184. Hamilton JD (1985) Thioridazine retinopathy within the upper dosage limit. Psychosomatics 26:823–824

    Article  CAS  PubMed  Google Scholar 

  185. Hadden PW, Tay-Kearney MLT, Barry CJ, Constable IJ (2003) Thioridazine retinopathy. Clin Exp Opthal 31:533–534

    Article  Google Scholar 

  186. Borodoker N, Del Priore LV, Caevallo CA, Yannuzzi LA (2002) Retinopathy as a result of long-term use of thioridazine. Arch Opthal 120:994–995

    Article  Google Scholar 

  187. Holford NHG, Sheiner LB (1982) Kinetics of pharmacologic response. Pharmacol Ther 16:143–166

    Article  CAS  PubMed  Google Scholar 

  188. Sheiner LB, Rosenberg B, Marathe VV (1977) Estimation of population characteristics of pharmacokinetic parameters from routine clinical data. J Pharmacokinet Biopharm 5:445–479

    Article  CAS  PubMed  Google Scholar 

  189. Grasela TH, Sheiner LB, Rambeck HE et al (1983) Steady-state pharmacokinetics of phenytoin from routinely collected patient data. Clin Pharmacokinet 8:355–364

    Article  CAS  PubMed  Google Scholar 

  190. Diaz FJ, Santoro V, Spina E et al (2008) Estimating the size of the effects of co-medications on plasma clozapine concentrations using a model that controls for clozapine doses and confounding variables. Pharmacopsychiatry 41:81–91

    Article  CAS  PubMed  Google Scholar 

  191. Sherwin CMT, Saldana SN, Bies RR, Aman MG, Vinks AA (2013) Population pharmacokinetic modeling of risperidone and 9-hydroxyrisperidone to estimate CYP2D6 subpopulations in children and adolescents. Ther Drug Monit 34:535–544

    Article  CAS  Google Scholar 

  192. Olsen CK, Brennum LT, Kreilgaard M (2008) Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics. Eur J Pharmacol 584:318–327

    Article  CAS  PubMed  Google Scholar 

  193. Pilla Reddy V, Kozielska M, Johnson M et al (2012) Modeling and simulation of the positive and negative syndrome scale (PANSS) time course and dropout hazard in placebo arms of schizophrenia clinical trials. Clin Pharmacokinet 51:261–275

    Article  PubMed  Google Scholar 

  194. Pilla Reddy V, Petersson KJ, Suleiman AA, Vereulen A, Proost JH, Friberg LE (2012) Pharmacokinetic-pharmacodynamic modeling of severity levels of extrapyramidal side effects with Markov elements. Clin Pharmacol Ther 1:e1. doi:10.1038/psp.2012.9

    CAS  Google Scholar 

  195. Pilla Reddy V, Kozielska M, Suleiman AA et al (2013) Pharmacokinetic-pharmacodynamic modeling of antipsychotic drugs in patients with schizophrenia: Part II: the use of subscales of the PANSS score. Schizophr Res 146:153–161

    Article  PubMed  Google Scholar 

  196. Pilla Reddy V, Kozielska M, Johnson M et al (2013) Population pharmacokinetic-pharmacodynamic modeling of haloperidol in patients with schizophrenia using positive and negative syndrome rating scale. J Clin Psychopharmacol 33:731–739

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Pharmacotherapy, University of North Texas System College of Pharmacy (UNTSCP) and University of North Texas Health Science Center (UNTHSC), Fort Worth, TX, USA

    Michael W. Jann PharmD

  2. Department of Pharmacy Practice, College of Pharmacy, Mercer University, Atlanta, GA, USA

    W. Klugh Kennedy PharmD

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    Michael W. Jann

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    Scott R. Penzak

  3. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm., FORT WORTH, Texas, USA

    Lawrence J. Cohen

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Jann, M.W., Kennedy, W.K. (2016). Antipsychotics. In: Jann, M., Penzak, S., Cohen, L. (eds) Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents. Adis, Cham. https://doi.org/10.1007/978-3-319-27883-4_7

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