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References 1. Kane JM, Honigfeld G, Singer J, Meltzer H. Clozapine in treatment-resistant schizophrenics. Psychopharmacol Bull 1988;24:62–67. 2. Melzer HY. Defining treatment refractoriness in schizophrenia. Schizophr Bull 1990;16:563–565 3. Meltzer HY. Dimensions of outcome with clozapine. Br J Psychiatry Suppl. 1992; (17):46-53 4. Sommer IE, Begemann MJH, Temmerman A, Leucht S. Pharmacological Augmentation Strategies for Schizophrenia Patients With Insufficient Response to Clozapine: A Quantitative Literature Review. Schizophr. Bull. 38(5), 1003–1011 (2012) 5

References 1. N. Y. Hasan, M. A. Elkawy, B. E. Elzeany and N. E. Wagieh, Stability indicating methods for the determination of clozapine, J. Pharm. Biomed. Anal. 30 (2002) 35-47; DOI: 10.1016/S0731-7085(02) 00125-5. 2. M. Ackenheil, Clozapine pharmacokinetic investigations and biochemical effects in man, Psychopharmacology 99 (1989) 32-37; DOI: 10.1007/bf00442556. 3. A. A. Ambike, K. Mahadik and A. Paradkar, Spray-dried amorphous solid dispersions of simvastatin, a low Tg drug: in vitro and in vivo evaluations, Pharm. Res. 22 (2005) 990-998; DOI: 10.1007/ s11095

). The atypical antipsychotic, clozapine, was first developed in 1961 and introduced in Europe in 1970 ( De Fazio et al. 2015 ). It marked a major advancement in psychiatry due to its effective management of negative symptoms in schizophrenia, in addition to reducing suicidality without the increased burden of extra-pyramidal side effects. Clozapine has been shown to be superior in efficacy with 50–60% of patients with previous treatment resistant schizophrenia responding to the medication ( Lally et al. 2015 ). As a result of clozapine’s broad and concerning side

SI, Rao JS. Effects of chronic clozapine administration on markers of arachidonic acid cascade and synaptic integrity in rat brain. Psychopharmacology (Berl) 222, 663–674, 2012. Kiss A, Majercikova Z. Repeated asenapine treatment does not participate in the mild stress induced FosB/ΔFosB expression in the rat hypothalamic paraventricular nucleus neurons. Neuropeptides 61, 57–65, 2017. Kontkanen O, Lakso M, Wong G, Castren E. Chronic antipsychotic drug treatment induces long-lasting expression of fos and jun family genes and activator protein 1 complex in the rat

the clinic? Psychiatr Clin North Am 2007; 30: 125-38. 5. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharmaco - kinet 2009; 48: 761-804. 6. Wall CA, Croarkin PE, Swintak C, Koplin BA. Psychiatric pharmacogenomics in pediatric psychopharmacology. Child Adolesc Psychiatr Clin N Am 2012; 21: 773-88. 7. Kohlrausch FB. Pharmacogenetics in schizophrenia: a review of clozapine studies. Rev Bras Psiquiatr 2013; 35: 305-17. 8. Castle DJ, Buckley PF, eds. Schizophrenia. Oxford: Oxford University Press, 2012. 9. Hasan A

jako metoda postępowania u chorych na schizofrenię ze słabą odpowiedzią na klozapinę. 6. Sobów T. Klozapina: między skutecznością a bezpieczeń-stwem. Psychiatria i Psychologia Kliniczna , 2015, 15.2: 57-60. 7. Aamani M., Kalyan K., Somasundara B. “A Study on Efficacy of CLOZAPINE in TreatmentResistantSchizophrenia.” International Journal of ScientificResearch, 2016, 4.6. 8. Meder J., Tyszkowska M., Jarema M., Araszkiewicz A., Szafrański T. Leki przeciwpsychotyczne w praktyce lekarza psychiatry. Le-czenie pacjentów z rozpoznaniem schizofrenii lekoopornej. Psy

. Bunevicius R, Steibliene V, Prange AJ. Thyroid axis function after in-patient treatment of acute psychosis with anti-psychotics: a naturalistic study. BMC Psychiatry 14, 279, 2014. Chang JS, Ha KS, Young LK, Sik KY, Min AY. The effects of long-term clozapine add-on therapy on the rehospitalization rate and the mood polarity patterns in bipolar disorders. J Clin Psychiatry 67, 461–467, 2006. Chen ML, Tsai FM, Lee MC, Lin YY. Antipsychotic drugs induce cell cytoskeleton reorganization in glial and neuronal cells via Rho/Cdc42 signal pathway. Prog Neuropsychopharmacol Biol

the antipsychotic drug mosapramine on the expression of Fos protein in the rat brain: comparison with haloperidol, clozapine and risperidone. Life Sci 67, 2865–2872, 2000. Hallbeck M. Dynorphin mRNA-expressing neurons in the rat paraventricular hypothalamic nucleus project to the spinal cord. Neurosci Lett 285, 161–164 2000. Hallbeck M, Larhammar D, Blomqvist A. Neuropeptide expression in rat paraventricular hypothalamic neurons that project to the spinal cord. J Comp Neurol 433, 222–238, 2001. He M, Deng C, Huang X. The role of hypothalamic H1 receptor antagonism

References S. Miyamoto, G. E. Duncan, C. E. Marx and J. A. Lieberman, Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs, Mol. Psychiatry   10 (2005) 79-104; DOI: 10.1038/sj.mp.4001556. S. Natesan, G. E. Reckless, K. B. Barlow, J. N. Nobrega and S. Kapur, Amisulpride the ‘atypical’ atypical antipsychotic-comparison to haloperidol, risperidone and clozapine, Schizophr. Res.   105 (2008) 224-235; DOI: 10.1016/j.schres.2008.07.005. V. Bigliani, R. S. Mulligan, P. D. Acton, D. Visvikis, P. J. Ellm, C

antagonist in patients with schizophrenia and hyponatremia. Biol Psychiatry. 2008:4(12):1097-1100. 62. Takagi S, Watanabe Y, Imaoka T, Sakata M, Watanabe M. Treatment of psychogenic polydipsia with acetazolamide: a report of 5 cases. Clin Neuropharmacol. 2011;34(1):5-7 63. Spears NM, Leadbetter RA, Shutty MS Jr. Clozapine treatment in polydipsia and intermittent hyponatremia. J Clin Psychiatry. 1996;57(3):123-8. 64. Canuso CM, Goldman, MB. Clozapine restores water balance in schizophrenic patients with polydipsia-hyponatremia syndrome. J Neuropsychiatry Clin Neurosci.1999