Current Antipsychotics pp 267-298

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 212)

Delivery Systems and Dosing for Antipsychotics

Chapter

Abstract

Schizophrenia is a devastating illness, affecting approximately 1–2 % of the world population. Age of onset is generally between 20 and 30 years of age with a chronic, unremitting course for the duration of the patient’s life. Although schizophrenia is among the most severe and debilitating illnesses known to medicine, its treatment has remained virtually unchanged for over 50 years. This chapter covers several major concepts in experimental drug development and delivery: (1) the concept of “typical” vs. “atypical” classifications for antipsychotic drugs as it relates to dosing; (2) the development of depot formulations for improved medication adherence; and (3) several promising areas for future therapeutic advances related to the methods and duration of drug administration. These areas include sublingual, injectable, and implantable drug delivery strategies that have the potential to effect rapid and dramatic improvements in schizophrenia outcomes.

Keywords

Atypicality Adherence Depot formulation Chlorpromazine equivalents Dopamine hypothesis of schizophrenia Dosing equivalents of antipsychotics Release mechanisms Implants for long-term delivery Sublingual drug delivery Transdermal delivery systems 

References

  1. Adis R&D Profile (2005) Histrelin hydrogel implant – Valera: histrelin implant, LHRH-Hydrogel Implant, RL 0903, SPD 424. Drugs R&D 6(1):53–55Google Scholar
  2. Adams SG Jr, Howe JT (1993) Predicting medication compliance in a psychotic population. J Nerv Ment Dis 181:558–560PubMedGoogle Scholar
  3. Adams CE, Fenton MK, Quraishi S, David AS (2001) Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. Br J Psychiatry 179:290–299PubMedGoogle Scholar
  4. Agid O, Kapur S, Remington G (2008) Emerging drugs for schizophrenia. Expert Opin Emerg Drugs 13:479–495PubMedGoogle Scholar
  5. Amann LC, Gandall MJ, Halene TB, Ehrlichman RS, White SL, McCarren HS, Siegel SJ (2010) Mouse behavioral endophenotypes for schizophrenia. Brain Res Bull 83(3–4):147–161PubMedGoogle Scholar
  6. Ascher-Svanum H, Faries DE, Zhu B, Ernst FR, Swartz MS, Swanson JW (2006) Medication adherence and long-term functional outcomes in the treatment of schizophrenia in usual care. J Clin Psychiatry 67:453–460PubMedGoogle Scholar
  7. Barnes DE, Robinson B, Csernansky JG, Bellows EP (1990) Sensitization versus tolerance to haloperidol-induced catalepsy: multiple determinants. Pharmacol Biochem Behav 36:883–887PubMedGoogle Scholar
  8. Bergen J, Hunt G, Armitage P, Bashir M (1998) Six-month outcome following a relapse of schizophrenia. Aust N Z J Psychiatry 32:815–822PubMedGoogle Scholar
  9. Berkland C, King M, Cox A, Kim K, Pack DW (2002) Precise control of PLG microsphere size provides enhanced control of drug release rate. J Control Release 82:137–147PubMedGoogle Scholar
  10. Blanco D, Alonso MJ (1998) Protein encapsulation and release from poly(lactide-co-glycolide) microspheres: effect of the protein and polymer properties and of the co-encapsulation of surfactants. Eur J Pharm Biopharm 45:285–294PubMedGoogle Scholar
  11. Bloch Y, Mendlovic S, Strupinsky S, Altshuler A, Fennig S, Ratzoni G (2001) Injections of depot antipsychotic medications in patients suffering from schizophrenia: do they hurt? J Clin Psychiatry 62:855–859PubMedGoogle Scholar
  12. Blom JH, Hirdes WH, Schroder FH, de Jong FH, Kwekkeboom DJ, van’t Veen AJ, Sandow J, Krauss B (1989) Pharmacokinetics and endocrine effects of the LHR analogue buserelin after subcutaneous implantation of a slow release preparation in prostatic cancer patients. Urol Res 17:43–46PubMedGoogle Scholar
  13. Borgman RJ (1982) Bioavailability, dosage regimens, and new delivery systems. In: Craig CR, Stitzel RE (eds) Modern pharmacology. Little, Brown and Company, Boston, MA, pp 63–74Google Scholar
  14. Borison RL, Diamond B, Pathiraja A, Meibach RC (1994) Pharmacokinetics of risperidone in chronic schizophrenic patients. Psychopharmacol Bull 30:193–197PubMedGoogle Scholar
  15. Boyd KN, Mailman RB (2012) Dopamine receptor signaling and current and future antipsychotic drugs. In: Geyer M, Gross G (eds) Novel antischizophrenia treatments, vol 212, Handbook of Experimental Pharmacology. Springer, HeidelbergGoogle Scholar
  16. Carlsson A, Lindqvist M (1963) Effect of chlorpromazine or haloperidol on formation of 3methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenh) 20:140–144Google Scholar
  17. Casper ES, Regan JR (1993) Reasons for admission among six profile subgroups of recidivists of inpatient services. Can J Psychiatry 38:657–661PubMedGoogle Scholar
  18. Castle DJ, Pantelis C (2003) Comprehensive care for people with schizophrenia living in the community. Med J Aust 178(Suppl):S45–S46PubMedGoogle Scholar
  19. Chan AL, Chien YW, Jin Lin S (2008) Transdermal delivery of treatment for Alzheimer’s disease: development, clinical performance and future prospects. Drugs Aging 25:761–775PubMedGoogle Scholar
  20. Cheer SM, Wagstaff AJ (2004) Quetiapine. A review of its use in the management of schizophrenia. CNS Drugs 18:173–199PubMedGoogle Scholar
  21. Chwieduk CM, Keating GM (2010) Paliperidone extended release: a review of its use in the management of schizophrenia. Drugs 70:1295–1317PubMedGoogle Scholar
  22. Citrome L (2009) Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. Int J Clin Pract 63:1762–1784PubMedGoogle Scholar
  23. Conlon L, Fahy TJ, OToole R, Gilligan J, Prescott P (2002) Risperidone in chronic schizophrenia: a detailed audit, open switch study and two-year follow-up of patients on depot medication. Eur Psychiatry 17:459–465PubMedGoogle Scholar
  24. Coombes AG, Heckman JD (1992) Gel casting of resorbable polymers. 1. Processing and applications. Biomaterials 13:217–224PubMedGoogle Scholar
  25. Cramer JR, Rosenheck R (1998) Compliance with medication regimens for mental and physical disorders. Psychiatr Serv 49:196–201PubMedGoogle Scholar
  26. Csernansky JG, Bellows EP, Barnes DE, Lombrozo L (1990) Sensitization versus tolerance to the dopamine turnover-elevating effects of haloperidol: the effect of regular/intermittent dosing. Psychopharmacology (Berl) 101:519–524Google Scholar
  27. Dankert ME, Brensinger CM, Metzger KL, Li C, Koleva SG, Mesen A, Laprade B, Wiguna T, Han C, Farooq S, Severus WE, Gayares JG, Langosch JM, Lallart X, Tateno M, Mihai A, Nair SR, Belmaker R, Rybakowski J, Owe-Larsson B, Kane JM, Johnstone EC, MacIntyre DJ, Malhotra S, Gonzalez-Pinto A, Mosquera F, Babb SM, Habib pour E, Fatemi SS, Swanson C, Adler C, Young A, Hoeft F, Sivakumar K, Radoeva PD, Lallart EA, Bilker WB, Siegel SJ (2008) Attitudes of patients and family members towards implantable psychiatric medication. Schizophr Res 105:279–286PubMedGoogle Scholar
  28. Dankert ME, Brensinger CM, Ralph LN, Seward DA, Bilker WB, Siegel SJ (2010) Psychiatric health care provider attitudes towards implantable medication. Psychiatry Res 177:167–171PubMedGoogle Scholar
  29. David AS (1990) Insight and psychosis. Br J Psychiatry 156:798–808PubMedGoogle Scholar
  30. Delay J, Deniker P, Harl J, Grasset A (1952a) [N-dimethylamino-prophylchlorophenothiazine (4560 RP) therapy of confusional states]. Ann Med Psychol (Paris) 110:398–403Google Scholar
  31. Delay J, Deniker P, Harl JM (1952b) Therapeutic use in psychiatry of phenothiazine of central elective action (4560 RP). Ann Med Psychol (Paris) 110:112–117Google Scholar
  32. Dorta MJ, Santovena A, Llabres M, Farina JB (2002) Potential applications of PLGA film-implants in modulating in vitro drugs release. Int J Pharm 248:149–156PubMedGoogle Scholar
  33. Edlund U, Albertsson AC (2003) Polyesters based on diacid monomers. Adv Drug Deliv Rev 55:585–609PubMedGoogle Scholar
  34. Ereshefsky L, Mascarenas CA (2003) Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics. J Clin Psychiatry 64(Suppl 16):18–23PubMedGoogle Scholar
  35. Ereshefsky L, Watanabe MD, Tran-Johnson TK (1989) Clozapine: an atypical antipsychotic agent. Clin Pharm 8:691–709PubMedGoogle Scholar
  36. Ezrin-Waters C, Seeman P (1977) Tolerance of haloperidol catalepsy. Eur J Pharmacol 41:321–327PubMedGoogle Scholar
  37. Fenton WS (2000) Prevalence of spontaneous dyskinesia in schizophrenia. J Clin Psychiatry 61(Suppl 4):10–14PubMedGoogle Scholar
  38. Fenton WS, Wyatt RJ, McGlashan TH (1994) Risk factors for spontaneous dyskinesia in schizophrenia. Arch Gen Psychiatry 51:643–650PubMedGoogle Scholar
  39. Fenton WS, Blyler CR, Wyatt RJ, McGlashan TH (1997) Prevalence of spontaneous dyskinesia in schizophrenic and non-schizophrenic psychiatric patients. Br J Psychiatry 171:265–268PubMedGoogle Scholar
  40. Fleischhacker WW, McQuade RD, Marcus RN, Archibald D, Swanink R, Carson WH (2009) A double-blind, randomized comparative study of aripiprazole and olanzapine in patients with schizophrenia. Biol Psychiatry 65:510–517PubMedGoogle Scholar
  41. Foster J, Brewer C, Steele T (2003) Naltrexone implants can completely prevent early (1-month) relapse after opiate detoxification: a pilot study of two cohorts totalling 101 patients with a note on naltrexone blood levels. Addict Biol 8:211–217PubMedGoogle Scholar
  42. Fowler JE Jr, Gottesman JE, Reid CF, Andriole GL Jr, Soloway MS (2000) Safety and efficacy of an implantable leuprolide delivery system in patients with advanced prostate cancer. J Urol 164:730–734PubMedGoogle Scholar
  43. Geddes J, Freemantle N, Harrison P, Bebbington P (2000) Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ 321:1371–1376PubMedGoogle Scholar
  44. Gerrits M, de Greef R, Peeters P (2010) Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects. Biopharm Drug Dispos 31:351–357PubMedGoogle Scholar
  45. Gilmer TP, Dolder CR, Lacro JP, Folsom DP, Lindamer L, Garcia P, Jeste DV (2004) Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry 161:692–699PubMedGoogle Scholar
  46. Ginovart N, Kapur S (2012) Role of dopamine D2 receptors for antipsychotic activity. In: Geyer M, Gross G (eds) Novel antischizophrenia treatments, vol 212, Handbook of Experimental Pharmacology. Springer, Berlin, pp xxx–xxxGoogle Scholar
  47. Ginovart N, Wilson AA, Hussey D, Houle S, Kapur S (2009) D2-receptor upregulation is dependent upon temporal course of D2-occupancy: a longitudinal [11C]-raclopride PET study in cats. Neuropsychopharmacology 34:662–671PubMedGoogle Scholar
  48. Glazer WM (2000a) Expected incidence of tardive dyskinesia associated with atypical antipsychotics. J Clin Psychiatry 61(Suppl 4):21–26PubMedGoogle Scholar
  49. Glazer WM (2000b) Review of incidence studies of tardive dyskinesia associated with typical antipsychotics. J Clin Psychiatry 61(Suppl 4):15–20PubMedGoogle Scholar
  50. Gruen PH, Sachar EJ, Langer G, Altman N, Leifer M, Frantz A, Halpern FS (1978) Prolactin responses to neuroleptics in normal and schizophrenic subjects. Arch Gen Psychiatry 35:108–116PubMedGoogle Scholar
  51. Gründer G, Hippius H, Carlsson A (2009) The ‘atypicality’ of antipsychotics: a concept re-examined and re-defined. Nat Rev Drug Discov 8:197–202PubMedGoogle Scholar
  52. Huang X, Brazel CS (2001) On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release 73:121–136PubMedGoogle Scholar
  53. Hudson TJ, Owen RR, Thrush CR, Han X, Pyne JM, Thapa P, Sullivan G (2004) A pilot study of barriers to medication adherence in schizophrenia. J Clin Psychiatry 65:211–216PubMedGoogle Scholar
  54. Irani F, Dankert M, Brensinger C, Bilker WB, Nair SR, Kohler CG, Kanes SJ, Turetsky BI, Moberg PJ, Ragland JD, Gur RC, Gur RE, Siegel SJ (2004) Patient attitudes towards surgically implantable, long-term delivery of psychiatric medicine. Neuropsychopharmacology 29:960–968PubMedGoogle Scholar
  55. Jain RA (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490PubMedGoogle Scholar
  56. Johnson DA (1981) Long-term maintenance treatment in chronic schizophrenia. Some observations on outcome and duration. Acta Psychiatr Belg 81:161–172PubMedGoogle Scholar
  57. Johnson DA (1984) Observations on the use of long-acting depot neuroleptic injections in the maintenance therapy of schizophrenia. J Clin Psychiatry 45:13–21PubMedGoogle Scholar
  58. Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, Murray RM, Markwick A, Lewis SW (2006) Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 63:1079–1087PubMedGoogle Scholar
  59. Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45:789–796PubMedGoogle Scholar
  60. Kane JM, Aguglia E, Altamura AC, Ayuso Gutierrez JL, Brunello N, Fleischhacker WW, Gaebel W, Gerlach J, Guelfi JD, Kissling W, Lapierre YD, Lindstrom E, Mendlewicz J, Racagni G, Carulla LS, Schooler NR (1998) Guidelines for depot antipsychotic treatment in schizophrenia. European Neuropsychopharmacology Consensus Conference in Siena, Italy. Eur Neuropsychopharmacol 8:55–66PubMedGoogle Scholar
  61. Kane JM, Leucht S, Carpenter D, Docherty JP (2003) The expert consensus guideline series. Optimizing pharmacologic treatment of psychotic disorders Introduction: methods, commentary, and summary. J Clin Psychiatry 64(Suppl 12):5–19PubMedGoogle Scholar
  62. Kapur S, Seeman P (2001) Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry 158:360–369PubMedGoogle Scholar
  63. Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P (2000) A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry 57:553–559PubMedGoogle Scholar
  64. Kasper S (2006) Optimisation of long-term treatment in schizophrenia: treating the true spectrum of symptoms. Eur Neuropsychopharmacol 16(Suppl 3):S135–S141PubMedGoogle Scholar
  65. Keefe RS (2006) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Biol Psychiatry 59:965Google Scholar
  66. Keefe RS, Sweeney JA, Gu H, Hamer RM, Perkins DO, McEvoy JP, Lieberman JA (2007) Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry 164(7):1061–71PubMedGoogle Scholar
  67. Keith S (2006) Advances in psychotropic formulations. Prog Neuropsychopharmacol Biol Psychiatry 30:996–1008PubMedGoogle Scholar
  68. Keith SJ, Kane JM (2003) Partial compliance and patient consequences in schizophrenia: our patients can do better. J Clin Psychiatry 64:1308–1315PubMedGoogle Scholar
  69. Kinon BJ, Stauffer VL, McGuire HC, Kaiser CJ, Dickson RA, Kennedy JS (2003) The effects of antipsychotic drug treatment on prolactin concentrations in elderly patients. J Am Med Dir Assoc 4:189–194PubMedGoogle Scholar
  70. Kitchell JP, Wise DL (1985) Poly(lactic/glycolic acid) biodegradable drug-polymer matrix systems. Methods Enzymol 112:436–448PubMedGoogle Scholar
  71. Knox ED, Stimmel GL (2004) Clinical review of a long-acting, injectable formulation of risperidone. Clin Ther 26:1994–2002PubMedGoogle Scholar
  72. Kohler U, Schroder H, Augustin W, Sabel BA (1994) A new animal model of dopamine supersensitivity using s.c. implantation of haloperidol releasing polymers. Neurosci Lett 170:99–102PubMedGoogle Scholar
  73. Kulkarni RK, Pani KC, Neuman C, Leonard F (1966) Polylactic acid for surgical implants. Arch Surg 93:839–843PubMedGoogle Scholar
  74. Lambert T, Brennan A, Castle D, Kelly DL, Conley RR (2003) Perception of depot antipsychotics by mental health professionals. J Psychiatr Pract 9:252–260PubMedGoogle Scholar
  75. Langer G, Sachar EJ, Gruen PH, Halpern FS (1977) Human prolactin responses to neuroleptic drugs correlate with antischizophrenic potency. Nature 266:639–640PubMedGoogle Scholar
  76. Lauriello J, Lambert T, Andersen S, Lin D, Taylor CC, McDonnell D (2008) An 8-week, double-blind, randomized, placebo-controlled study of olanzapine long-acting injection in acutely ill patients with schizophrenia. J Clin Psychiatry 69:790–799PubMedGoogle Scholar
  77. Lemoine D, Preat V (1998) Polymeric nanoparticles as delivery system for influenza virus glycoproteins. J Control Release 54:15–27PubMedGoogle Scholar
  78. Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S (2011) Oral versus depot antipsychotic drugs for schizophrenia–a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res 127:83–92PubMedGoogle Scholar
  79. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223PubMedGoogle Scholar
  80. Lim ST, Forbes B, Berry DJ, Martin GP, Brown MB (2002) In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits. Int J Pharm 231:73–82PubMedGoogle Scholar
  81. Liu FI, Kuo JH, Sung KC, Hu OY (2003) Biodegradable polymeric microspheres for nalbuphine prodrug controlled delivery: in vitro characterization and in vivo pharmacokinetic studies. Int J Pharm 257:23–31PubMedGoogle Scholar
  82. Love RC (2002) Strategies for increasing treatment compliance: the role of long-acting antipsychotics. Am J Health Syst Pharm 59:S10–S15PubMedGoogle Scholar
  83. Marder SR (2003) Overview of partial compliance. J Clin Psychiatry 64(Suppl 16):3–9PubMedGoogle Scholar
  84. McEvoy J (2004) The relationship between insight into psychosis and compliance with medications. In: Amador XFD, Anthony S (eds) Insight and psychosis. Oxford University Press, OxfordGoogle Scholar
  85. McEvoy JP, Apperson LJ, Appelbaum PS, Ortlip P, Brecosky J, Hammill K, Geller JL, Roth L (1989a) Insight in schizophrenia. Its relationship to acute psychopathology. J Nerv Ment Dis 177:43–47PubMedGoogle Scholar
  86. McEvoy JP, Applebaum PS, Apperson LJ, Geller JL, Freter S (1989b) Why must some schizophrenic patients be involuntarily committed? The role of insight. Compr Psychiatry 30:13–17PubMedGoogle Scholar
  87. McEvoy JP, Freter S, Everett G, Geller JL, Appelbaum P, Apperson LJ, Roth L (1989c) Insight and the clinical outcome of schizophrenic patients. J Nerv Ment Dis 177:48–51PubMedGoogle Scholar
  88. Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25:233–255PubMedGoogle Scholar
  89. Menzin J, Boulanger L, Friedman M, Mackell J, Lloyd JR (2003) Treatment adherence associated with conventional and atypical antipsychotics in a large state Medicaid program. Psychiatr Serv 54:719–723PubMedGoogle Scholar
  90. Metzger KL, Shoemaker JM, Kahn JB, Maxwell CR, Liang Y, Tokarczyk J, Kanes SJ, Hans M, Lowman AM, Dan N, Winey KI, Swerdlow NR, Siegel SJ (2007) Pharmacokinetic and behavioral characterization of a long-term antipsychotic delivery system in rodents and rabbits. Psychopharmacology (Berl) 190:201–211Google Scholar
  91. Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM (2008) Nano/micro technologies for delivering macromolecular therapeutics using poly(D, L-lactide-co-glycolide) and its derivatives. J Control Release 125:193–209PubMedGoogle Scholar
  92. Nasrallah HA (2008) Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 13:27–35PubMedGoogle Scholar
  93. Nasrallah HA, Lasser R (2006) Improving patient outcomes in schizophrenia: achieving remission. J Psychopharmacol 20:57–61PubMedGoogle Scholar
  94. Nasrallah HA, Gopal S, Gassmann-Mayer C, Quiroz JA, Lim P, Eerdekens M, Yuen E, Hough D (2010) A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia. Neuropsychopharmacology 35:2072–2082PubMedGoogle Scholar
  95. Nordstrom AL, Farde L, Halldin C (1993) High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET. Psychopharmacology (Berl) 110:365–367Google Scholar
  96. Nordstrom AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G (1995) D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry 152:1444–1449PubMedGoogle Scholar
  97. Oh SH, Lee JY, Ghil SH, Lee SS, Yuk SH, Lee JH (2006) PCL microparticle-dispersed PLGA solution as a potential injectable urethral bulking agent. Biomaterials 27:1936–1944PubMedGoogle Scholar
  98. Okada H, Toguchi H (1995) Biodegradable microspheres in drug delivery. Crit Rev Ther Drug Carrier Syst 12:1–99PubMedGoogle Scholar
  99. Palmer BW, Jeste DV (2006) Relationship of individual cognitive abilities to specific components of decisional capacity among middle-aged and older patients with schizophrenia. Schizophr Bull 32:98–106PubMedGoogle Scholar
  100. Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nat Biotechnol 26:1261–1268PubMedGoogle Scholar
  101. Prausnitz MR, Mitragotri S, Langer R (2004) Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov 3:115–124PubMedGoogle Scholar
  102. Rabin CR, Siegel SJ (2010) Antipsychotic dosing and drug delivery. Curr Top Behav Neurosci 4:141–177PubMedGoogle Scholar
  103. Rabin C, Liang Y, Ehrlichman RS, Budhian A, Metzger KL, Majewski-Tiedeken C, Winey KI, Siegel SJ (2008) In vitro and in vivo demonstration of risperidone implants in mice. Schizophr Res 98:66–78PubMedGoogle Scholar
  104. Rafati H, Lavelle EC, Coombes AG, Stolnik S, Holland J, Davis SS (1997) The immune response to a model antigen associated with PLG microparticles prepared using different surfactants. Vaccine 15:1888–1897PubMedGoogle Scholar
  105. Rauser L, Savage JE, Meltzer HY, Roth BL (2001) Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor. J Pharmacol Exp Ther 299:83–89PubMedGoogle Scholar
  106. Rittmannsberger H, Pachinger T, Keppelmuller P, Wancata J (2004) Medication adherence among psychotic patients before admission to inpatient treatment. Psychiatr Serv 55:174–179PubMedGoogle Scholar
  107. Sabel BA, Dominiak P, Hauser W, During MJ, Freese A (1990) Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats. J Pharmacol Exp Ther 255:914–922PubMedGoogle Scholar
  108. Samaha AN, Reckless GE, Seeman P, Diwan M, Nobrega JN, Kapur S (2008) Less is more: antipsychotic drug effects are greater with transient rather than continuous delivery. Biol Psychiatry 64:145–152PubMedGoogle Scholar
  109. Sedvall G (1980) Relationships among biochemical, clinical, and pharmacokinetic variables in neuroleptic-treated schizophrenic patients. Adv Biochem Psychopharmacol 24:521–528PubMedGoogle Scholar
  110. See RE, Ellison G (1990) Intermittent and continuous haloperidol regimens produce different types of oral dyskinesias in rats. Psychopharmacology (Berl) 100:404–412Google Scholar
  111. Seeman P, Lee T (1975) Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188:1217–1219PubMedGoogle Scholar
  112. Seeman P, Chau-Wong M, Tedesco J, Wong K (1975) Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc Natl Acad Sci USA 72:4376–4380PubMedGoogle Scholar
  113. Seeman P, Corbett R, Van Tol HH (1997) Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors. Neuropsychopharmacology 16:93–110, discussion 111–35PubMedGoogle Scholar
  114. Seemen P, Tallerico T (1998) Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry 3:123–134Google Scholar
  115. Sharma R, Saxena D, Dwivedi AK, Misra A (2001) Inhalable microparticles containing drug combinations to target alveolar macrophages for treatment of pulmonary tuberculosis. Pharm Res 18:1405–1410PubMedGoogle Scholar
  116. Sharon AC, Wise DL (1981) Development of drug delivery systems for use in treatment of narcotic addiction. NIDA Res Monogr 28:194–213PubMedGoogle Scholar
  117. Shen WW (1999) A history of antipsychotic drug development. Compr Psychiatry 40:407–414PubMedGoogle Scholar
  118. Siegel SJ (2005) Extended release drug delivery strategies in psychiatry: theory to practice. Psychiatry 2:22–31PubMedGoogle Scholar
  119. Siegel SJ, Ralph L (2009) Demystifying schizophrenia for the physician. Jones and Bartlett Publishers, Boston, MAGoogle Scholar
  120. Siegel SJ, Winey KI, Gur RE, Lenox RH, Bilker WB, Ikeda D, Gandhi N, Zhang WX (2002) Surgically implantable long-term antipsychotic delivery systems for the treatment of schizophrenia. Neuropsychopharmacology 26:817–823PubMedGoogle Scholar
  121. Siegel SJ, Irani F, Brensinger CM, Kohler CG, Bilker WB, Ragland JD, Kanes SJ, Gur RC, Gur RE (2006a) Prognostic variables at intake and long-term level of function in schizophrenia. Am J Psychiatry 163:433–441PubMedGoogle Scholar
  122. Siegel SJ, Kahn JB, Metzger K, Winey KI, Werner K, Dan N (2006b) Effect of drug type on the degradation rate of PLGA matrices. Eur J Pharm Biopharm 64:287–293PubMedGoogle Scholar
  123. Spiers ID, Eyles JE, Baillie LW, Williamson ED, Alpar HO (2000) Biodegradable microparticles with different release profiles: effect on the immune response after a single administration via intranasal and intramuscular routes. J Pharm Pharmacol 52:1195–1201PubMedGoogle Scholar
  124. Tandon R, Targum SD, Nasrallah HA, Ross R (2006) Strategies for maximizing clinical effectiveness in the treatment of schizophrenia. J Psychiatr Pract 12:348–363PubMedGoogle Scholar
  125. Tanner T, Marks R (2008) Delivering drugs by the transdermal route: review and comment. Skin Res Technol 14:249–260PubMedGoogle Scholar
  126. Torche AM, Le Corre P, Albina E, Jestin A, Le Verge R (2000) PLGA microspheres phagocytosis by pig alveolar macrophages: influence of poly(vinyl alcohol) concentration, nature of loaded-protein and copolymer nature. J Drug Target 7:343–354PubMedGoogle Scholar
  127. Trichard C, Paillere-Martinot ML, Attar-Levy D, Recassens C, Monnet F, Martinot JL (1998) Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients. Am J Psychiatry 155:505–508PubMedGoogle Scholar
  128. Turner MS, Stewart DW (2006) Review of the evidence for the long-term efficacy of atypical antipsychotic agents in the treatment of patients with schizophrenia and related psychoses. J Psychopharmacol 20:20–37PubMedGoogle Scholar
  129. Valenstein M, Copeland LA, Owen R, Blow FC, Visnic S (2001) Adherence assessments and the use of depot antipsychotics in patients with schizophrenia. J Clin Psychiatry 62:545–551PubMedGoogle Scholar
  130. Valenstein M, Blow FC, Copeland LA, McCarthy JF, Zeber JE, Gillon L, Bingham CR, Stavenger T (2004) Poor antipsychotic adherence among patients with schizophrenia: medication and patient factors. Schizophr Bull 30:255–264PubMedGoogle Scholar
  131. Vauquelin G, Bostoen S, Vanderheyden P, Seeman P (2012) Clozapine, atypical antipsychotics, and the benefits of fast-off D(2) dopamine receptor antagonism. Naunyn Schmiedebergs Arch Pharmacol 385:337–372PubMedGoogle Scholar
  132. Venkatraman S, Gale R (1998) Skin adhesives and skin adhesion. 1. Transdermal drug delivery systems. Biomaterials 19:1119–1136PubMedGoogle Scholar
  133. Viguera AC, Baldessarini RJ, Hegarty JD, van Kammen DP, Tohen M (1997) Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Arch Gen Psychiatry 54:49–55PubMedGoogle Scholar
  134. Wang CK, Wang WY, Meyer RF, Liang Y, Winey KI, Siegel SJ (2010) A rapid method for creating drug implants: translating laboratory based methods into a scalable manufacturing process. J Biomed Mater Res B Appl Biomater 93:562–572PubMedGoogle Scholar
  135. Weiden PJ, Olfson M (1995) Cost of relapse in schizophrenia. Schizophr Bull 21:419–429PubMedGoogle Scholar
  136. Witt C, Kissel T (2001) Morphological characterization of microspheres, films and implants prepared from poly(lactide-co-glycolide) and ABA triblock copolymers: is the erosion controlled by degradation, swelling or diffusion? Eur J Pharm Biopharm 51:171–181PubMedGoogle Scholar
  137. Witt C, Mader K, Kissel T (2000) The degradation, swelling and erosion properties of biodegradable implants prepared by extrusion or compression moulding of poly(lactide-co-glycolide) and ABA triblock copolymers. Biomaterials 21:931–938PubMedGoogle Scholar
  138. Zygmunt A, Olfson M, Boyer CA, Mechanic D (2002) Interventions to improve medication adherence in schizophrenia. Am J Psychiatry 159:1653–1664PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, School of MedicineColumbia UniversityNew YorkUSA
  2. 2.Translational Research Laboratories, Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA

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