Schizophrenia treatment critical review on the drugs and mechanisms of action of antipsychotics

Actas Espanolas de Psiquiatria

Volumn 37, Issue 6, 2009, Pages 330-342

  Tajima, K ^a   Fernandez H ^a   Lopez lbor J J ^a   Carrasco, J L ^a   Diaz Marsa M ^a  

^a HOSPITAL CLÍNICO SAN CARLOS   (Spain)

Author keywords

Antipsychotics; Dopamine partial agonist; Schizophrenia

Indexed keywords

NEUROLEPTIC AGENT;

FORECASTING; HUMAN; REVIEW; SCHIZOPHRENIA;

ANTIPSYCHOTIC AGENTS; FORECASTING; HUMANS; SCHIZOPHRENIA;

EID: 77649197551     PISSN: 11399287     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (118)

1. Miyamoto S, Lieberman JA, Fleischhacker WW, Aoba A, Marder SR. Antipsychotic drugs. In: A Tasman, J Kay, JA Lieberman (eds.). Psychiatry (2 ed.) (pp. 1928-64). Chichester: John Wiley and Sons, Ltd, 2003.
2. Miyamoto S, Stroup TS, Duncan GE, Aoba A, Lieberman JA. Acute pharmacologic treatment of schizophrenia. In: SR Hirsch, DR Weinberger (eds.). Schizophrenia (2 ed.) (pp. 442-73). Oxford: Blackwell Science, 2003.
3. Remington G. Understanding antipsychotic 'atypicality': a clinical and pharmacological moving target. J Psychiatry Neurosci 2003;28:275-284
4. Miyamoto S, Duncan GE, Goff DC, Lieberman JA. Therapeutics of schizophrenia. In: KL Davis, D Charney, JT Coyle, C Nemeroff (eds.). Neuropsychopharmacology: The Fifth Generation of Progress (pp. 775-807). Philadelphia: Lippincott Williams and WiIkins, 2002.
5. MiyamotoS,DuncanGE,MailmanRB,LiebermanJA. Developingnovelantipsychoticdrugs:strategiesandgoals. CurrOpinCPNSInvestDrugs2000;2:25-39.(Pubitemid30128608)
6. Kane JM. Schizophrenia. N Engl J Med 1996;334:34-41.
7. Lewis DA, Lieberman JA. Catching up on schizophrenia: natural history and neurobiology. Neuron 2000;28:325-334
8. SharifZA.Commontreatmentgoalsofantipsychotics:acutetreatment. JClinPsychiatry1998;59(Suppl.19):5-8.(Pubitemid29016144)
9. Schulz C, McGorry P. Traditional antipsychotic medications: contemporary clinical use. In: PF Buckley, JL Waddington (eds.). Schizophrenia and Mood Disorders: The New Drug Therapies in Clinical Practice. Woburn, MA: Butterworth-Heinemann, 2000.
10. Marder SR, Van Putten T. Antipsychotic medications. In: AF Schatzberg, CB Nemeroff (eds.). The American Psychiatric Press Textbook of Psychopharmacology (pp. 247-61). Washington, DC: American Psychiatric Press, lnc, 1995.
11. Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976;192:480-483
12. Seeman P, Lee T, Chau-Wong M, Wong K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976;261:717-719
13. Seeman P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1987;1:133-152
14. Miyamoto S, Mailman RB, Lieberman JA, Duncan GE. Blunted brain metabolic response to ketamine in mice lacking D1A dopamine receptors. Brain Res 2001;894:167-180 (Pubitemid 32218729)
15. Remington G, Kapur S. D2 and 5-HT2 receptor effects of antipsychotics: bridging basic and clinical findings using PET. J Clin Psychiatry 1999; 60(Suppl. 10): 15-19
16. Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry 1992;49:538-544
17. KapurS,RemingtonG,JonesC,WilsonA,DaSilvaJ,HouleS,etal. HighlevelsofdopamineD2receptoroccupancywithlowdosehaloperidoltreatment: aPETstudy.AmJPsychiatry1996;153:948-950(Pubitemid26225470)
18. Nordstrom AL, Farde L, Wiesel FA, Forslund K, Pauli S, Halldin C, et al. Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol Psychiatry 1993;33:227-235 (Pubitemid 23091497)
19. Kapur S, Zipursky R, Jones C, Remington G, Houle S. Relationship between dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 2000;157:514-520 (Pubitemid 30191189)
20. NybergS,FardeLNon- equipotentdosespartlyexplaindifferencesamongantipsychotics- implicationsofPETstudies.Psychopharmacology2000;148:22-23(Pubitemid30062468)
21. Kapur S, Zipursky R, Roy P, Jones C, Remington G, Reed K, et al. The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study. Psychopharmacology 1997;131:148-152 (Pubitemid 27261602)
22. Silvestri S, Seeman MV, Negrete JC, Houle S, Shammi CM, Remington GJ, et al. Increased dopamine D2 receptor binding alter long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology 2000;152:174-180 (Pubitemid 30776410)
23. SchoemakerH,ClaustreY,FageD,RouquierL,CherguiK,CuretO,etal. Neurochemicalcharacteristicsofamisulpride,anatypicaldopamineD2/ D3receptorantagonistwithbothpresynapticandlimbicselectivity. JPharmacolExpTher1997;280:83-97.(Pubitemid27171391)
24. Waddington J, Casey D. Comparative pharmacology of classical and novel (second-generation) antipsychotics. In: PF Buckley, JL Waddington (eds.). Schizophrenia and Mood Disorders: The New Drug Therapies in Clinical Practice (pp. 3-13). Woburn, MA: Butterworth-Heinemann, 2000.
25. Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D1, D2 and Serotonin2 pKi values. J Pharmacol Exp Ther 1989;251:238-246
26. Lieberman JA. Understanding the mechanism of action of atypical antipsychotic drugs: a review of compounds in use and development. BrJ Psychiatry 1993;163:7-18.
27. DuncanGE,ZornS,LiebermanJA. Mechanismsoftypicalandatypicalantipsychoticdrugactioninrelation- dopamineandNMDAreceptorhypofunctionhypothesesofschizophrenia. MolPsychiatry1999;4:418-428(Pubitemid29497729)
28. KapurS,ZipurskyRB,RemingtonG,JonesC,DaSilvaJ,WilsonAA,etal. 5-HT2andD2receptoroccupancyofolanzapineinschizophrenia:aPETinvestigation. AmJPsychiatry1998;155:921-928(Pubitemid28307604)
29. KapurS,ZipurskyRB,RemingtonG.Clinicalandtheoreticalimplicationsof5- HT2andD2receptoroccupancyofclozapine,risperidone,andolanzapineinschizophrenia. AmJPsychiatry1999;156:286-293(Pubitemid29077120)
30. KapurS,ZipurskyR,JonesC,ShammiCS,RemingtonG,SeemanP. Apositronemissiontomographystudyofquetiapineinschizophrenia: apreliminaryfindingofanantipsychoticeffectwithonlytransientlyhighdopamineD2rece ptoroccupancy.ArchGenPsychiatry2000;57:553-559(Pubitemid30349435)
31. Nordstrom AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G. D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry 1995;152:1444-1449
32. Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001 ;158:360-369
33. SeemanP,TallericoT. RapidreleaseofantipsychoticdrugsfromdopamineD2receptors: anexplanationforlowreceptoroccupancyandearlyclinicalrelapseuponwithdrawalofcloz apineorquetiapine.AmJPsychiatry1999;156:876-884(Pubitemid29260342)
34. Meltzer HY. Pre-clinical pharmacology of atypical antipsychotic drugs: a selective review. Br J Psychiatry 1996;29(Suppl.): 23-31.
35. Keltner NL, Johnson V. Biological perspectives. Aripiprazole: a third generation of antipsychotics begins? Perspect Psychiatr Care 2002;38:157-159
36. Ichikawa J, lshii H, Bonaccorso S, Fowler WL, O'Laughlin IA, Meltzer HY. 5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem 2001;76:1521-1531 (Pubitemid 32198256)
37. Li X-M, Perry KW, Wong DT, Bymaster FP. Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum. Psychopharmacology 1998;136:153-161 (Pubitemid 28137955)
38. Deutsch SI, Mastropaolo J, Schwartx BL, Rosse R, Morihisa JM. A 'glutamatergic hypothesis' of schizophrenia.Rationale for pharmacotherapy with glycine. Clin Neuropharmacol 1989;12:1-13.
39. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991;148:1301-1308
40. Giardino L, Bortolotti F, Orazzo C, Pozza M, Monteleone P, Calza L et al. Effect of chronic clozapine administration on MK801binding sites in the rat brain: a side-preference action in cortical areas. Brain Res 1997;762:216-218 (Pubitemid 27315952)
41. McCoy L, Cox C, Richfield EK. Antipsychotic drug regulation of AMPA receptor affinity states and GluR1, GluR2 splice variant expression. Synapse 1998;28:195-207.
42. Ossowska K, Pietraszek M, Wardas J, Nowak G, Wolfarth S. Chronic haloperidol and clozapine administration increases the number of cortical NMDA receptors in rats. Naunyn-Schmiedeberg'sArch Pharmacol 1999;359:280-287 (Pubitemid 29210958)
43. Spurney CF, Baca SM, Murray AM, Jaskiw GE, Kleinman JE, Hyde TM. Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats. Synapse 1999;34:266-276 (Pubitemid 29523133)
44. Tarazi Fl, Florijn WJ, Creese I. Regulation of ionotropic glutamate receptors following subchronic and chronic treatment with typical and atypical antipsychotics. Psychopharmacology 1996;128:371-379 (Pubitemid 26417679)
45. Tascedda F, Lovati E, Blom JM, Muzzioli P, Brunello N, Racagni G, et al. Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic seroquel (quetiapine fumarate). Neuropsychopharmacology 1999;21:211-217 (Pubitemid 29304582)
46. Kikuchi T, Tottori K, Uwahodo Y, Hirose T, Miwa T, Oshiro Y, et al. 7-(4-butyloxy)-3,4-dihydro-2(1H)-quino linone (OPC- 14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther 1995; 274:329-336
47. Lawler CP, Prioleau C, Lewis MM, Mak C, Jiang D, Schetz JA, et al. Interactions of the novel antipsychotic aripiprazole (OPC14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology 1999;20:612-627 (Pubitemid 29189265)
48. Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 2003;28:1400-1411 (Pubitemid 41070874)
49. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia. Practice Guidelines for the Treatment of Psychiatric Disorders (pp. 299-412). Washington, D.C.: American Psychiatric Association, 2000.
50. Spohn HE, Strauss ME. Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia. J Abnorm Psychol 1989;98:367-380
51. Meltzer HY. Long-term effects of neuroleptic drugs on the neuroendocrine system. Adv Biochem Psychopharmacol 1985;40:59-68.
52. Gaebel W. Towards the improvement of compliance: the significance of psycho-education and new antipsychotic drugs. Int Clin Psychopharmacol 1997;12(Suppl.1):S37-S42. (Pubitemid 27171187)
53. Leucht S, Pitschel-Walz G, Engel RR, Kissling W. Amisulpride, an unusual 'atypical' antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry 2002;159:180-190
54. Markowitz JS, Brown CS, Moore TR. Atypical antipsychotics Part I: pharmacology, pharmacokinetics, and efficacy. Ann Pharmacother 1999;33:73-85. (Pubitemid 29056560)
55. Remington G, Kapur S. Atypical antipsychotics: are some more atypical than others? Psychopharmacology 2000;148: 3-15.
56. Geddes J, Freemantle N, Harrison P, Bebbington P. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ 2000;321:1371-1376
57. Leucht S, Pitschel-Walz G, Abraham D, Kissling W. Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 1999;35:51-68.
58. Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry 2003; 60:553-564
59. BuchananRW,GoldJM.Negativesymptoms:diagnosis,treatmentandprognosis. IntClinPsychopharmacol1996;11(Suppl.2):3-11.(Pubitemid26194495)
60. Collaborative Working Group on Clinical Trial Evaluations. Assessing the effects of atypical antipsychotics on negative symptoms. Collaborative Working Group on Clinical Trial Evaluations. J Clin Psychiatry 1998;59(Suppl. 12):28-34.
61. Keefe RSE, Silva SG, Perkins DO, Lieberman JA. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 1999;25:201-222
62. Meltzer HY, McGurk SR. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 1999;25:233-255
63. Weiss E, Kemmler G, Fleischhacker WW. Improvement of cognitive dysfunction after treatment with second-generation antipsychotics. Arch Gen Psychiatry 2002;59:572-573
64. Harvey PD, Keefe RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 2001;158:176-184 (Pubitemid 32116511)
65. Carpenter WT, Gold JM. Another view of therapy for cognition in schizophrenia. Biol Psychiatry 2002;51: 969-971
66. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45: 789-796
67. Patel JK, Pinais DA, Breier A. Schizophrenia and other psychoses. In: A Tasman, J Kay, JA Lieberman (eds.). Psychiatry (2 ed.) (pp. 1131-206). Chichester: John Wiley and Sons, Ltd, 2003.
68. DevV,RaniwallaJ.Quetiapine: areviewofitssafetyinthemanagementofschizophrenia.DrugSaf2000;23:295-307. (Pubitemid30786326)
69. AllisonDB,MentoreJL,HeoM,ChandlerLP,CappelleriJC,InfanteMC,etal. Antipsychotic-inducedweightgain:acomprehensiveresearchsynthesis. AmJPsychiatry1999;156:1686-1696(Pubitemid29517559)
70. Kane JM, Carson WH, Saha AR, McQuade RD, Ingenito GG, Zimbroff DL, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002; 63:763-771
71. Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2003;60:681-690 (Pubitemid 36818630)
72. Goldman-Rakic PS, Muly III EC, Williams GV. D1 receptors in prefrontal cells and circuits. Brain Res Rev 2000;31:295-301.
73. Seeman P, Guan HC, Van ToI HH. Dopamine D4 receptors elevated in schizophrenia. Nature 1993;365:441-445
74. Lahti RA, Roberts RC, Cochrane EV, Primus RJ, Gallager DW, Conley RR, et al. Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: a NGD-94-1 study. Mol Psychiatry 1998;3:528-533
75. GurevichEV,BordelonY,ShapiroRM,ArnoldSE,GurRE,JoyceJN. MesolimbicdopamineD3receptorsanduseofantipsychoticsinpatientswithschizophrenia. Apostmortemstudy.ArchGenPsychiatry1997;54:225-232(Pubitemid27132051)
76. Abi-Saab WM, D'Souza DC, Madonick SH, Krystal JH. Targeting the glutamate system. In: A Breier, PV Tran, JM Herrera, GD Tollefson, FP Bymaster (eds.). Current Issues in the Psychopharmacology of Schizophrenia (pp. 304-32). Philadelphia: Lippincott Williams and Wilkins Healthcare, 2001.
77. Goff DC, Henderson DC, Evins AE, Amico E. A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia. Biol Psychiatry 1999;45:512-514 (Pubitemid 29130454)
78. McCullumsmith RE, Meador-Woodruff JH. Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology 2002;26:368-375
79. Goff D, Berman I, Posever T, Leahy L, Lynch G. A preliminary dose-escalation trial of CX 516 (ampakine) added to clozapine in schizophrenia. Schizophr Res 1999;36:280.
80. MoghaddamB,AdamsB,VermanA,DalyD. Activationofglutamatergicneurotransmissionbyketamine- anovelstepinthepathwayfromNMDAreceptorblockade- dopaminergicandcognitivedisruptionsassociatedwiththeprefrontalcortex. JNeurosci1997;17:2921-2927(Pubitemid27155025)
81. G. J. Marek. A mGlu2/3 receptor agonist for schizophrenia. Fuente: Actas Esp Psiquiatr 2008;36(Suppl. 1):37-39
82. Goff D, Berman I, Posever T, Leahy L, Lynch G. A preliminary dose-escalation trial of CX 516 (ampakine) added to clozapine in schizophrenia. Schizophr Res 1999;36:280.
83. Do KQ, Trabesinger AH, Kirsten-Kruger M, Lauer CJ, Dydak U, Hell D, et al. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci 2000;12:3721-3728 (Pubitemid 30796074)
84. Uhlen S, Muceniece R, Rangel N, Tiger G, Wikberg JE. Comparison of the binding activities of some drugs on alpha 2A, alpha 2B and alpha 2C-adrenoceptors and non-adrenergic imidazoline sites in the guinea pig. Pharmacol Toxicol 1995;76: 353-364
85. Friedman Jl, Adler DN, Temporini HD, Kemether E, Harvey PD, White L, et al. Guanfacine treatment of cognitive impairment in schizophrenia. Neuropsychopharmacology 2001;25:402-409 (Pubitemid 32777790)
86. Millan MJ, Gobert A, Newman-Tancredi A, Lejeune F, Cussac D, Rivet JM, et al. S18327 (1-ethyl]3-phenyl imidazolin-2-one), a novel, potential antipsychotic displaying marked antagonist properties at alpha(1)- and alpha(2)-adrenergic receptors: I. Receptorial, neurochemical, and electrophysiological profile. J Pharmacol Exp Ther 2000;292:38-53.
87. Liljequist R, Haapalinna A, Ahlander M, Li YH, Mannisto PT. Catechol O-methyltransferase inhibitor tolcapone has minor influence on performance in experimental memory models in rats. Behav Brain Res 1997;82:195-202. (Pubitemid 27045822)
88. Watkins P. COMT inhibitors and liver toxicity. Neurology 2000;55:S51-S2.
89. Rezvani AH, Levin ED. Cognitive effects of nicotine. Biol Psychiatry 2001;49:258-267
90. AdlerLE,OlincyA,WaldoM,HarrisJG,GriffithJ,StevensK,etal.Schizophrenia, sensorygating,andnicotinicreceptors.SchizophrBull1998;24:189-202. (Pubitemid28404980)
91. Schreiber R, Dalmus M, De Vry J. Effects of alpha 4/beta 2- and alpha 7-nicotine acetylcholine receptor agonists on prepulse inhibition of the acoustic startle response in rats and mice. Psychopharmacology 2002;159:248-257
92. Bontempi B, Whelan KT, Risbrough VB, Rao TS, Buccafusco JJ, Lloyd GK, et al. SIB-1553A, (?/-)-4-[[2-(1-methyl-2-pyrrol¡ dinyl) ethyl]thio]phenol hydrochloride, a subtype-selective Iigand for nicotinic acetylcholine receptors with putative cognitive-enhancing properties: effects on working and reference memory performances in aged rodents and nonhuman primates. J Pharmacol Exp Ther 2001 ;299:297-306.
93. MaelickeA. AllostericmodulationofnicotinicreceptorsasatreatmentstrategyforAlzheimer'sdisea se.DementGeriatrCognDisord2000;11(Suppl.1):11-18(Pubitemid30687516)
94. Bymaster FP, Felder C, Ahmed S, McKinzie D. Muscarinic receptors as a target for drugs treating schizophrenia. Curr Drug Target CNS Neurol Disord 2002;1:163-181
95. BodickNC,OffenWW,LeveyAl,CutlerNR,GauthierSG,SatlinA,etal. Effectsofxanomeline,aselectivemuscarinicreceptoragonist, oncognitivefunctionandbehavioralsymptomsinAlzheimerdisease.ArchNeurol1997;54: 465-473(Pubitemid27172867)
96. Perry KW, Bymaster FP, Shannon HE, Rasmussen K, DeLapp NW, Zhang W, et al. The muscarinic agonist xanomeline has antipsychotic-like activity in animals and in man. Schizophr Res 1999;36:117-118
97. Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 1987;2:1483-1486
98. Emrich HM, Leweke FM, Schneider U. Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system. Pharmacol Biochem Behav 1997;56:803-807 (Pubitemid 27189767)
99. Rein W, Arvanitis L Antipsychotic effect of four different Compounds results of the metatrial. Eur Neuropsychopharmacol 2003;13:S95.
100. Kinkead B, Nemeroff CB. Neurotensin: an endogenous antipsychotic. Curr Opin Pharmacol 2002;2:99-103.
101. Jungerman T, Rabinowitz D, Klein E. Deprenyl augmentation for treating negative symptoms of schizophrenia: a double-blind, controlled study. J Clin Psychopharmacol 1999;19: 522-525
102. Schmidt CJ, Chapin DS, McCarthy SA, Fujiwara RA, Harms JF, Shrikhande A, et al. The neurochemical and behavioral effects of papaverine in vivo suggest PDE10 inhibition is 'antipsychotic'. Schizophr Res 2003;60:114.
103. DeutschSI,RosseRB,SchwartzBL,Fay-McCarthyM,RosenbergPB,FearingK. Methyleneblueadjuvanttherapyofschizophrenia.ClinNeuropharmacol1997;20: 357-363(Pubitemid27329738)
104. TourneyG, ErbJLTemporalvariationsinandrogensandstresshormonesincontrolandschizophrenicsu bjects.BiolPsychiatry1979;14:395-404.(Pubitemid9171623)
105. Strauss EB, Sands DE, Robibson AM, Tindall WJ, Stevenson WAH. Use of dehydroisoandrosterone in psychiatric treatment: a preliminary survey. Br Med J 1952;2:64-66.
106. Sands DE. Further studies on endocrine treatment in adolescence and early adult life. J Ment Sci 1954;100:211-219
107. Strauss EB, Stevenson WAH. Use of dehydroisoandrosterone in psychiatrie practice. J Neurol Neurosurg Psychiatry 1955; 18:137-144
108. Straus RD, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry 2003;60:133-141 (Pubitemid 36173119)
109. Thome J, Foley P, Riederer P. Neurotrophic factors and the maldevelopmental hypothesis of schizophrenic psychoses. Review article. J Neural Transm 1998;105:85-100. (Pubitemid 28132598)
110. WeinbergerDR. Implicationsofnormalbraindevelopmentforthepathogenesisofschizophrenia. ArchGenPsychiatry1987;44:660-669(Pubitemid17099795)
111. Stahl SM. When neurotrophic factors get on your nerves: therapy for neurodegenerative disorders. J Clin Psychiatry 1998;59:277-278
112. Arranz MJ, Munro J, Birkett J, Bolonna A, Mancama D, Sodhi M, et al. Pharmacogenetic prediction of clozapine response. Lancet 2000;355:1615-1616
113. Shastry BS. Schizophrenia: a genetic perspective (review). Int J Mol Med 2002;9:207-212
114. Arranz MJ, Kerwin RW. Advances in the pharmacogenetic prediction of antipsychotic response. Toxicology 2003;192:33-35 (Pubitemid 37158019)
115. Catalán R, Segarra I, Eguiluz M, Rodriguez M, Sánchez M, Prieto M, et al. El tiempo de psicosis no tratada como factor predictivo y pronóstico en el curso de los primeros episodios psicóticos. Actas Esp Psiquiatr 2007;35(3).
116. Mc Glashan TH, Miller TJ, Woods SW. (2001). Pre-onset detection and intervention research in schizophrenia psychoses: current estimates of benefit and risk. Schizophr Bull 27(4):563-570
117. Sáiz Ruiz J, Bobes García J, Vallejo Ruiloba J, Giner Ubago J, Garcia-Portilla MP. Consenso sobre la salud fisica del paciente con esquizofrenia de las Sociedades Españolas de Psiquiatríe;a y de Psiquiatría Biológica. Actas Esp Psiquiatr 2008; 36(5):251-264
118. Sicras-Mainar A, Rejas-Gutiérrez J, Navarro-Artieda R, Blanca-Tamayo M. Impacto de Ia obesidad en Ia utilización de fármacos antipsicóticos en población adulta atendida en varios centros de atención primaria. Actas Esp Psiquiatr 2008;36(2):90-93