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Kombinacije antipsihotika

  Doc.dr.sc. Marina Šagud, dr. med., specijalist psihijatar
  prof. dr. sc. Alma Mihaljević Peleš, dr.med, specijalist psihijatar

  22.08.2011.

Začuđuje nesrazmjer između malog broja studija kombinacije dva antipsihotika (uglavnom otvorenih, na malom broju bolesnika) i vrlo čestog propisivanja ovakvih kombinacija u kliničkoj praksi. Kombinirana terapija stabilizatora raspoloženja i antipsihotika nove generacije vrlo se često primjenjuje u kliničkoj praksi. Prednost je kraće vrijeme do postizanja poboljšanja, veći postotak poboljšanja, ali i mogućost primjene nižih doza nego svakog lijeka zasebno.

Kombinacije antipsihotika
U svakodnevnoj praksi često se primjenjuje kombinacija dva antipsihotika.

U idealnom slučaku, terapija shizofrenije je monoterapija antipsihotikom. Sukladno, npr. algoritmu skupine Texas, takva je kombinacija indicirana nakon dovoljno duge terapije s najprije jednim antipsihotikom II generacije, te zatim drugim antipsihotikom, ili I ili II generacije, te potom monoterapije klozapinom. U tom se slučaju indicirana kombinirana terapija klozapina s jednim od antipsihotika I ili II generacije (Argo i sur, 2008). Medicina zasnovana na dokazima temelji se u stvari na randomiziranim kliničkim studijama (Correll, 2010), koje uključuju pažljivo odabrane bolesnike, uz primjenu lijeka u strogo kontroliranim uvjetima, te se njihovi rezultati ne mogu u potpunosti generalizirati na cjelokupnu populaciju koju vidimo svakodnevno. Međutim, u svakodnevnoj praksi često se primjenjuje kombinacija dva antipsihotika. Prema norveškoj studiji, 35.6% shizofrenih bolesnika dobivalo je kombinaciju antipsihotika (Kroken i sur, 2009), a prema španjolskoj čak 55.5% (Lerma-Carrillo i sur, 2008). U kliničkoj praksi najčešće su kombinacije klozapina ili olanzapina, koji su relativno slabiji blokatori D2 receptora, a imaju učinak na brojne druge receptorske sustave, s antipsihoticima koji su snažni ali i selektivni D2 blokatori (Goodwin i sur, 2009), poput sulpirida ili amisulprida (Zink i sur, 2010), ali i haloperidola i flufenazina. Jedna studija je mjerila okupiranost D2 receptora u strijatumu u osoba liječenih kombinacijom klozapina u dozi od 225 do 500 mg/dan, i haloperidola u dozi od 4 mg/dan (Kapur i sur, 2001). Nakon dodavanja haloperidola, okupiranost D2 receptora je porasla sa 55% na 79% (Kapur i sur, 2001). Začuđuje nesrazmjer između malog broja studija kombinacije dva antipsihotika (uglavnom otvorenih, na malom broju bolesnika) i vrlo čestog propisivanja ovakvih kombinacija u kliničkoj praksi. Opisano je da u kliničkoj praksi, čak oko 60% bolesnika koji dobivaju klozapin dobiva istodobno još jedan antipsihotik (za pregled molim vidjeti Honer i sur, 2009.

Dakle, unatoč raširenoj kliničkoj praksi, istraživanja o kombinaciji antipsihotika je malo (Goodwin i sur, 2009). Pokušaj analize učinkovitosti kombinacije klozapina s drugim antipsihoticima završio je bez zaključka, jer su studije male i metodološki različite (Cipriani i sur, 2009).

Kombinirana terapija stabilizatora raspoloženja i antipsihotika nove generacije vrlo se često primjenjuje u kliničkoj praksi. Prednost je kraće vrijeme do postizanja poboljšanja, veći postotak poboljšanja, ali i mogućost primjene nižih doza nego svakog lijeka zasebno.

Koje kombinacije antipsihotika se ne preporučuju?

Ne preporučuju se kombinacije:

1) Karbamazepina s olanzapinom ili klozapinom (povećana vjerojatnost agranulocitoze), a dodatno karbamazepin nekoliko puta snizuje koncentracije ovih lijekova te strvara potrebu za puno višim dozama olanzapina, odnosno, klozapina.

2) Risperidona i paroksetina jer paroksetin može značajno povisiti koncentraciju risperidona.

3) Risperidona i karbamazepina jer karbamazepin putem indukcije CYP 3A4 snizuje za oko 50% koncentraciju i risperidona i njegovog glavnog metabilita 9-OH-risperidona.

4) Antipsihotika međusobno, zbog prije svega farmakodinamskih interakcija. Zajedničkim antagonističkim učinkom na D2 receptore može doći do teških ekstrapiramidnih nuspojava. Iznimka su kombinacije antipsihotika koji se slabije vežu na D2 receptor-klozapina, kvetipina i olanzapina, s antipsihoticima koji se čvrsto vežu za D2 receptor i pri tome ne djeluju na druge receptore (D2 selektivni antipsihotici): haloperidolom, flufenazinom, sulpiridom i amisulpridom.

Učinkovitost antipsihotika

Učinkovitost antipsihotika ne ovisi samo o njegovom mehanizmu djelovanja, odnosno, o farmakokinetskim osobinama. Ne postoji antipsihotik koji je „čarobna pilula" i koji će rješiti sve probleme bolesnika. Antipsihotici su neophodni u liječenju jer omogućuju kontrolu psihotičnih simptoma, čime „stvaraju podlogu" za daljnje poboljšanje simptoma. Međutim, liječenje shizofrenije predstavlja mnogo više od primjene antipsihotika. Liječenje psihoze ovisi o mnogo čimbenika, koji su prikazani u tablici.

*Oboljeli od shizofrenije imaju povećanu ekspresiju P glikoproteina u temporalnom korteksu, amigdalima i bazalnim ganglijima, što znači da lijekovi slabije prolaze u mozak. Isto teoretski može biti jedan od razloga za potrebu za višim dozama antipsihotika u kroničnih shizofrenih bolesnika, odnosno, za terapijsku rezistenciju (De Klerk i sur, 2010).

Zaključak

Idealan antipsihotik trebao bi smanjiti dopaminsku hiperaktivnost u mezolimbičkom sustavu, odnosno, strijatumu, kompenzirati dopaminsku hipokativnost u frontanom korteksu, a biti bez utjecaja na razinu dopamina u regijama mozga odgovornim za nastanak EPS i hiperprolaktinemije, ne uzrokovati porast apetita niti tjelesne težine, niti pretjeranu sedaciju. Idealan antipsihotik ne postoji.

Rješenje je, uz dobro poznavanje osobina antipsihotika, individualni pristup bolesniku. Iako neprekidno raste naša količina znanja o farmakogenetici, slikovnim metodama prikaza, te odnosu koncentracije antipsihotika i kliničkog učinka, ove metode za sada nisu dio kliničke rutine.

Međutim, poznavanje farmakodinamike i farmakokinetike svakog pojedinog antipsihotika koji imamo na raspolaganju, omogućuje nam odabir lijeka i doziranja prema osobinama bolesnika, vodećim simptomima psihotičnog poremećaja, kao i drugih obilježja koja utječu na liječenje.

Literatura

1. Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL (2009) Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo. 205(1):119-28
2. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laurelle M (2000). Increased baselina occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 97 (14): 8104-8109
3. Agid O, Mamo D, Ginovart N, Vitcu I, Wilson AA, Zipursky RB, Kapur S. Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response--a double-blind PET study in schizophrenia. Neuropsychopharmacology. 2007 Jun;32(6):1209-15
4. Alexopolus GS, Weiden PJ, Preskorn SH, Fahnestock PA, Carpenter D, Ross R, Docherty JP (2009) A roadmap to key pharmacological principles in using antipsychotics in the treatment of older patients. J Cin Psychiatry 70 (1): 131-138
5. Arakawa R, Okumura M, Hiroshi I, Takano A, Takahashi H, Takano H, Maeda J, Okubo Y, Suhara T (2010) Positron emission tomography measurement of dopamine D2 receptor occupancy in pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. J Clin Psychiatry
6. Argo TR, Crismon ML, Miller AL, Moore TA, Bendele SD, Suehs B (2008) Texas medical algorithm project procedural manual. Schizophrenia clinicians manual: 1-62
7. Assié MB, Dominguez H, Consul-Denjean N, Newman-Tancredi A. In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles. Naunyn Schmiedebergs Arch Pharmacol. 2006;373(6):441-50
8. Attarbaschi T, Sacher J, Geiss-Granadia T, Klein N, Mossaheb N, Lanzenberger R, Asenbaum S, Dudczak R, Kasper S, Tauscher J (2007) Striatal D2 receptor occupancy in bipolar patients treated with olanzapine. Eur Neuropsychopharmacol 17: 102-107
9. Brouwers EE, Söhne M, Kuipers S, van Gorp EC, Schellens JH, Koks CH, Beijnen JH, Huitema AD (2009) Ciprofloxacin strongly inhibits clozapine metabolism: two case reports. Clin Drug Investig 29(1):59-63
10. Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, et al (2002) Aripiprazole, a novel antipsychotic, is a high-affnity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther; 302:381-389
11. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT (1996) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 14 (2): 87-96
12. Catafau AM, Penengo MM, Nucci G, Bullich S, Corripio I, Parellada E, García-Ribera C, Gomeni R, Merlo-Pich E; Barcelona Clinical Imaging in Psychiatry Group. Pharmacokinetics and time-course of D(2) receptor occupancy induced by atypical antipsychotics in stabilized schizophrenic patients. J Psychopharmacol. 2008 Nov;22(8):882-94
13. Chang WH, Juang DJ, Lin SK, Huang JD, Lam YF, Jann MW, Chien CP (2004) Disposition of haloperidol and reduced haloperidol plasma levels after single dose haloperidole decanoate administration. Human Psychopharmacol Clin Experim 10 (1): 47-51
14. Cipriani A, Boso M, Barbui C (2009) Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia. Cochrane Database Syst Rev (3)
15. Correll CU (2010) From receptor pharmacology to improved outcomes: individualising the selection, dosing and switching of antipsychotics. Eur Psychiatry, in press
16. De Haan L, Lavalaye J, Van Bruggen M, Van Nimwegen L, Booij J, Van Amelsvoort T, Linszen D (2004) Subjective experience and dopamine D2 receptor occupancy in patients treated with antipsychotics: clinical implications. Can J Psychiatry 40: 290-296
17. De Haan L, Lavalaye J, Booij J, Linszen D (2005) Confort, self-confidence, safety and dopamine D2 receptor occupancy by antipsychotics. Am J Psychiatry 162 (8): 1544-1545
18. De Hert M, Hudyana H, Dockx L, Bernagie C, Sweers K, Tack J, Leucht S, Peuskens J (2010) Second-generation antipsychotics and constipation: a review of the literature. Eur Psychiatry, in press
19. De Klerk OL, Willemsen ATM, Bosker FJ, Bartels AL, Hendrikse NH, Den Boer JA, Dierckx RA (2010) Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia: a study with 11C verapamil as a probe for P-glycoprotein function. Psychiatry Res: Neuroimaging 183: 151-156
20. De Leon J, Armstrong SC, Cozza KL (2005) Med drug-drug interactions update. The dosing of atypical antipsychotics. Psychosomatics 46: 262-273
21. De Leon J, Sandson NB, K. L. Cozza KL (2008) A Preliminary Attempt to Personalize Risperidone Dosing Using Drug-Drug Interactions and Genetics: Part I. Psychosomatics 49(3): 258 - 270
22. Desai M, Tanus-Santos JE, Li L, Gorski JC, Arefayene M, Liu Y, Desta Z, Flockhart DA (2003) Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6. Pharmacogenomics J3(2):105-13.
23. Dysken MW, Javaid JI, Chang SS, Schaffer C, Shahid A, Davis JM (1981) Fluphenazine pharmacokinetics and therapeutic response. Psychopharmacology 73 (3): 205-210
24. Farde L, Wiesel FA, Nordström AL, Sedvall G (1989) D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology; 99 Suppl:S28-31
25. Figueroa C, Brecher M, Hamer-Maansson JE, Winter H. Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(2):199-204
26. Frankle WG, Laruelle M (2002) Neuroreceptor imaging in psychiatric disorders. Ann Nucl Med;16(7):437-46
27. Frankle WG, Gil R, Hackett E, Mawlawi O, Zea-Ponce Y, Zhu Z, Kochan LD, Cangiano C, Slifstein M, Gorman JM, Laruelle M, Abi-Dargham A. Occupancy of dopamine D2 receptors by the atypical antipsychotic drugs risperidone and olanzapine: theoretical implications. Psychopharmacology (Berl). 2004 Oct;175(4):473-80.
28. Gefvert O, Bergström M, Långström B, Lundberg T, Lindström L, Yates R (1998) Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel) in patients with schizophrenia. Psychopharmacology 135 (2): 119-126
29. Goodwin G, Fleischhacker W, Arango C, Baumann P, Davidson M, de Hert M, Falkai P, Kapur S, Leucht S, Licht R, Naber D, O'Keane V, Papakostas G, Vieta E, Zohar J (2009) Advantages and disadvantages of combination treatment with antipsychotics ECNP Consensus Meeting, March 2008, Nice. Eur Neuropsychopharmacol 19(7):520-532
30. Harasko-van der Meer C, Brücke T, Wenger S, Fischer P, Deecke L, Podreka I (1993) Two cases of long term dopamine D2 receptor blockade after depot neuroleptics. J Neural Transm Gen Sect 94(3):217-21
31. Hasselstrøm J, Linnet K (2006) In vitro studies on quetiapine metabolism using the substrate depletion approach with focus on drug-drug interactions. Drug Metabol Drug Interact. 2006;21(3-4):187-211
32. Howes OD, Egerton A, Allan V, McGuire P, Stokes P, Kapur S (2009). Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: Insights from PET and SPECT imaging. Current Pharmaceutical Design 15: in press
33. Ito H, Takano H, Takahashi H, Arakawa R, Miyoshi M, Kodaka F, Okumura M, Otsuka T, Suhara T. Effects of the antipsychotic risperidone on dopamine synthesis in human brain measured by positron emission tomography with L-[beta-11C]DOPA: a stabilizing effect for dopaminergic neurotransmission? J Neurosci. 2009; 29(43):13730-4
34. Jann MW, Ereshewsky L, Saklad SR (1985) Clinical pharmacokinetics of the depot antipsychotics. Clin Pharmacokinet 10 (4)-315-333
35. Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity. Neuropsychopharmacology. 2008 Sep;33(10):2303-12
36. Jia F, Mobarakeh JI, Dai H, Kato M, Xu A, Okuda T, Sakurai E, Okamura N, Takahashi K, Yanai K. Blocking histamine H(1) improves learning and mnemonic dysfunction in mice with social isolation plus repeated methamphetamine injection. J Pharmacol Sci. 2008 Jun;107(2):167-74
37. Kane JM i Sharif ZA (2008) Atypical antipsychotics: sedation versus efficacy. J Clin Psychiatry 69 (Suppl 1): 18-31
38. Kane JM i Correll CU (2010) Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry 71 (9): 1115-1123
39. Kapur S, Zipursky R, Roy P, Jones C, Remington G, Reed K, Houle S. The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study. Psychopharmacology (Berl). 1997 May;131(2):148-52
40. Kapur S, Zipursky R, Jones C, Remington G, Houle S (2000) Relationship between dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 157:514-520
41. Kapur S, Roy P, Daskalakis J, Remington G, Zipursky R. Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. Am J Psychiatry. 2001;158(2):311-4.
42. Kasper S, Tauscher J, Küfferle B, Barnas C, Hesselmann B, Asenbaum S, Podreka I, Brücke T (1998) Sertindole and dopamine D2 receptor occupancy in comparison to risperidone, clozapine and haloperidol - a 123I-IBZM SPECT study. Psychopharmacology 136(4):367-73
43. Kessler RM, Ansari MS, Riccardi P, Li R, Jayathilake K, Dawant B, Meltzer HY. Occupancy of striatal and extrastriatal dopamine D2 receptors by clozapine and quetiapine. Neuropsychopharmacology. 2006 Sep;31(9):1991-2001
44. Kornhuber J, Schultz A, Wiltfang J, Meineke I, Gleiter CH, Zöchling R, Boissl KW, Leblhuber F, Rieder P (1999) Persistence of haloperidol in human brain tissue. Am J Psychiatry 156: 885-890
45. Kroken RA, Johnsen E, Ruud T, Wentzel-Larsen T, Jørgensen HA (2009) Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry 9:24
46. Kuroki T, Meltzer HY, Ichikawa J (1999) Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol Exp Ther 288(2):774-781
47. Laurelle M, Abu-Dargham A (1999)Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J Psychopharmacol 13 (4): 358-374
48. Lerma-Carrillo I, de Pablo Brühlmann S, del Pozo ML, Pascual-Pinazo F, Molina JD, Baca-García E (2008) Antipsychotic polypharmacy in patients with schizophrenia in a brief hospitalization unit. Clin Neuropharmacol 31(6):319-332
49. Lindenmayer JP (2010) Long-acting antipsychotics: focus on olanzapine pamoate. Neuropsychiatric disease and treatment 6: 261-267
50. Mamo DC, Uchida H, Vitcu I, Barsoum P, Gendron A, Goldstein J, Kapur S (2008) Quetiapine extended-release versus immediate-release formulation: a positron emission tomography study. J Clin Psychiatry;69(1):81-6
51. Mamo D, Kapur S, Keshavan M, Laruelle M, Taylor CC, Kothare PA, Barsoum P, McDonnell D(2008A) D2 receptor occupancy of olanzapine pamoate depot using positron emission tomography: an open-label study in patients with schizophrenia. Neuropsychopharmacology;33(2):298-304
52. Martinot JL, Paillère-Martinot ML, Poirier MF, Dao-Castellana MH, Loc'h C, Mazière B(1996) In vivo characteristics of dopamine D2 receptor occupancy by amisulpride in schizophrenia. Psychopharmacology;124(1-2):154-8
53. McIntyre RS, Soczynska JK, Mancini D, Woldeyohannes HO, Konarski JZ, Kennedy SH. Comparing features of bipolar disorder to major depressive disorder in a tertiary mood disorders clinic. Ann Clin Psychiatry. 2007 Oct-Dec;19(4):313-7
54. Medori R, Mannaert E, Gründer G (2006) Plasma antipsychotic concentration and receptor occupancy, with special focus on risperidone long-acting injectable. Eur Neuropsychopharmacol 16 (4): 233-240
55. Mehta MA, Montgomery AJ, Kitamura Y, Grasby PM (2008) Dopamine D2 receptor occupancy levels of acute sulpiride challenges that produce working memory and learning impairments in healthy volunteers. Psychopharmacology (Berl).;196(1):157-65
56. Miller R (2009) Mechanisms of action of antipsychotic drugs of different classes, refractoriness to therapeutic effects of classical neuroleptics, and individual variations in sensitivity to their actions: part II. Current Neuropharmacol 7: 315-330
57. Miller R (2009 A) Mechanisms of Action of Antipsychotic Drugs of Different Classes, Refractoriness to Therapeutic Effects of Classical Neuroleptics, and Individual Variation in Sensitivity to their Actions: PART I. Curr Neuropharmacol. 7(4):302-14.
58. Mørk A, Witten LM, Arnt J (2009) Effect of sertindole on extracellular dopamine, acetylcholine, and glutamate in the medial prefrontal cortex of conscious rats: a comparison with risperidone and exploration of mechanisms involved. Psychopharmacology 206(1):39-49
59. Perez-Costas E, Guidetti P, Melendez-Ferro M, Kelley JJ, Roberts RC. Neuroleptics and animal models: feasibility of oral treatment monitored by plasma levels and receptor occupancy assays. J Neural Transm. 2008 May;115(5):745-53
60. Product information Solian: date of most recent amendment: 23.02.2009., Solian PI MKT60777v5.0: 1-13
61. Prescribing information: Ziprasidon (Geodon), revised: November, 2009, LAB-0273-16.0
62. Remington G, Mamo D, Labelle A, Reiss J, Shammi C, Mannaert E, Mann S, Kapur S. A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone. Am J Psychiatry. 2006 Mar;163(3):396-401
63. Samaha AN, Seeman P, Stewart J, Rajabi H, Kapur S. "Breakthrough" dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. J Neurosci. 2007 Mar 14;27(11):2979-86
64. Seeman P (2005) an update of fast-off dopamine D2 atypical antipsychotics. Am J Psychiatry 162: 1984-1985
65. Sellin AK, Shad M, Tamminga C (2008) Muscarinic agonists for the treatment of cognition of schizophrenia. CNS Spectr 13 (11): 985-996
66. Sheehan JJ, Sliwa JK, Amatniek JC, Grinspan A, Canuso CM (2010) Atypical antipsychotic metabolism and excretion. Curr Drug Metab 11: 516-525
67. Stahl S (2008) Selective histamine H1 antagonism: novel hypnotic and pharmacological actions challenge classical notions of antihistamines. Trends in psychopharmacology. CNS Spectr 13: 1-12
68. Swensson TH (2003) Alpha-adrenoreceptor modulation hypothesis of antipsychotic atipicallity. Progress Psychopharmacol Biol Psychiatry 27 (7): 1145-1158
69. Tauscher J, Küfferle B, Asenbaum S, Fischer P, Pezawas L, Barnas C, Tauscher-Wisniewski S, Brücke T, Kasper S (1999) In vivo 123I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol. Psychopharmacology;141(2):175-81
70. Tauscher J, Küfferle B, Asenbaum S, Tauscher-Wisniewski S, Kasper S (2002) Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. Psychopharmacology;162(1):42-9
71. Tauscher J, Hussain T, Agid O, Verhoeff NP, Wilson AA, Houle S, Remington G, Zipursky RB, Kapur S.(2004) Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics. Am J Psychiatry;161(9):1620-5
72. Tauscher J, Jones C, Remington G, Zipursky R, Kapur S (2007) Significant dissociation of brain and plasma kinetics with antipsychotics. Mol Psychiatry 7: 317-321
73. Vernaleken I, Janouschek H, Raptis M, Hellmann S, Veselinovic T, Bro öcheler A, Boy C, Cumming P, Hiemke C, Rösch F, Schäfer WM, Gründer G (2010) Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas. Int J Neuropsychopharmacol 13: 951-960
74. Wang J, Omori IM, Fenton M, Soares B (2010) Sulpiride augmentation for schizophrenia. Cochraine database system review 20 (1)
75. Zanger UM, Turpeinen M, Klein K, Schwab M (2008) Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem 392: 1093-1198
76. Zink M, Englisch S, Meyer-Lindenberg A (2010) Polypharmacy in schizophrenia. Curr Opp Psychiatry 23: In press
77. Wang Z, Kemp DE, Chan PK, Fang Y, Ganocy SJ, Calabrese JR, Gao K. Comparisons of the tolerability and sensitivity of quetiapine-XR in the acute treatment of schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and generalized anxiety disorder. Int J Neuropsychopharmacol. 2010; 1-12

Izvor: Poslijediplomski tečaj I. kategorije: Antipsihotici u kliničkoj praksi
Voditeljice:
prof. dr. sc. Alma Mihaljević - Peleš
dr.sc. Marina Šagud

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