Zusammenfassung
Polypharmazie in der Behandlung der Schizophrenie ist – wie häufig auch in der Behandlung anderer psychischer Störungen – das Resultat einer Therapieresistenz. Bis zu 70% der schizophrenen Patienten erreichen keine Vollremission, mindestens 30% der Betroffenen sprechen auf zwei oder mehr Monotherapien mit modernen Antipsychotika nicht an.
Nach wie vor ist die Frage, ob eine Polypharmazie in der Behandlung der Schizophrenie Vorteile gegenüber einer Monotherapie hat, nicht eindeutig geklärt. Die klinische Praxis zeigt jedoch, dass entgegen wiederholt formulierter, plausibler Empfehlungen, z. B. in den Leitlinien von Fachgesellschaften, eine Monotherapie mit Antipsychotika zu verordnen, auch weiterhin häufig und regional sogar mit steigender Tendenz Kombinationstherapien durchgeführt werden. Obwohl bereits vor mehr als 10 Jahren das Fehlen kontrollierter Studien zur Polypharmazie und die daraus resultierende geringe wissenschaftliche Evidenz für eine weltweit in großem Umfang angewandte Praxis als „a dirty little secret“ kritisiert wurde, stellt Polypharmazie weiterhin eher die Regel als die Ausnahme dar und wird umso häufiger angewandt, je schwerer und je länger der Patient erkrankt ist.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Literatur
Addington D, Addington J, Patten S, Remington G, Moamai J, Labelle A, Beauclair L (2002) Double-blind, placebo-controlled comparison of the efficacy of sertraline as treatment for a major depressive episode in patients with remitted schizophrenia, J. Clin. Psychopharmacol., 22(1), 20–25
Adesanya A, Pantelis C (2000) Adjunctive risperidone treatment in patients with 'clozapine-resistant schizophrenia', Aust N Z J Psychiatry. 34(3), 533–4
Afshar H, Roohafza H, Mousavi G, Golchin S, Toghianifar N, Sadeghi M, Talaei M (2009) Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial, J. Psychopharmacol., 23(2), 157–162
Agelink MW, Kavuk I, Ak I (2004) Clozapine with amisulpride for refractory schizophrenia, Am. J. Psychiatry, 161(5), 924–925
Allen SA (2000) Effect of chlorpromazine and clozapine on plasma concentrations of haloperidol in a patient with schizophrenia, J. Clin. Pharmacol., 40(11), 1296–1297
Anghelescu I, Szegedi A, Schlegel S, Weigmann H, Hiemke C, Wetzel H (1998) Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial, Eur. Neuropsychopharmacol., 8(4), 315–320
Anil Yagcioglu AE, Kivircik Akdede BB, Turgut TI, Tumuklu M, Yazici MK, Alptekin K, Ertugrul A, Jayathilake K, Gogus A, Tunca Z, Meltzer HY (2005) A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety, J. Clin. Psychiatry, 66(1), 63–72
Arana GW, Ornsteen ML, Kanter F, Friedman HL, Greenblatt DJ, Shader RI (1986) The use of benzodiazepines for psychotic disorders: a literature review and preliminary clinical findings, Psychopharmacol. Bull., 22(1), 77–87
Arango C, Kirkpatrick B, Buchanan RW (2000) Fluoxetine as an adjunct to conventional antipsychotic treatment of schizophrenia patients with residual symptoms, J. Nerv. Ment. Dis., 188(1), 50–53
Arvanitis LA, Miller BG (1997) Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group, Biol. Psychiatry, 42(4), 233–246
Assion HJ, Reinbold H, Lemanski S, Basilowski M, Juckel G (2008) Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial, Pharmacopsychiatry, 41(1), 24–28
Atre-Vaidya N, Taylor MA (1989) Effectiveness of lithium in schizophrenia: do we really have an answer?, J. Clin. Psychiatry, 50(5), 170–173
Baandrup L, Gasse C, Jensen VD, Glenthoj BY, Nordentoft M, Lublin H, Fink-Jensen A, Lindhardt A, Mortensen PB (2010) Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study, J. Clin. Psychiatry, 71(2), 103–108
Bacher NM, Kaup BA (1996) Combining risperidone with standard neuroleptics for refractory schizophrenic patients, Am. J. Psychiatry, 153(1), 137
Barbui C, Accordini S, Nose M, Stroup S, Purgato M, Girlanda F, Esposito E, Veronese A, Tansella M, Cipriani A (2011) Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial, J. Clin. Psychopharmacol., 31(3), 266–273
Barnes, T. R. (2011) Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology, J. Psychopharmacol., 25(5), 567–620
Barnes, T. R, C. Paton (2011) Antipsychotic polypharmacy in schizophrenia: benefits and risks, CNS. Drugs, 25(5), 383–399
Baynes D, Mulholland C, Cooper SJ, Montgomery RC, MacFlynn G, Lynch G, Kelly C, King DJ (2000) Depressive symptoms in stable chronic schizophrenia: prevalence and relationship to psychopathology and treatment, Schizophr. Res., 45(1–2), 47–56
Beasley CM Jr., Tollefson G, Tran P, Satterlee W, Sanger T, Hamilton S (1996) Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial, Neuropsychopharmacology, 14(2), 111–123
Beelen AP1, Yeo KT, Lewis LD (2001) Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone, Hum Exp Toxicol. 20(4), 215–9
Behdani, F, P. Hebrani, A. A. Rezaei, E. Rafee (2011) Effect of topiramate augmentation in chronic schizophrenia: a placebo-controlled trial, Arch. Iran Med., 14(4), 270–275
Berk M, Gama CS, Sundram S, Hustig H, Koopowitz L, D'Souza R, Malloy H, Rowland C, Monkhouse A, Monkhouse A, Bole F, Sathiyamoorthy S, Piskulic D, Dodd S (2009) Mirtazapine add-on therapy in the treatment of schizophrenia with atypical antipsychotics: a double-blind, randomised, placebo-controlled clinical trial, Hum. Psychopharmacol., 24(3), 233–238
Berk M, Ichim C, Brook S (2001) Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study, Int. Clin. Psychopharmacol., 16(2), 87–92
Berry N, Pradhan S, Sagar R, Gupta SK (2003) Neuroleptic malignant syndrome in an adolescent receiving olanzapine-lithium combination therapy, Pharmacotherapy. 23(2), 255–9. Review
Berlant JL (1986) Neuroleptics and reserpine in refractory psychoses, J. Clin. Psychopharmacol., 6(3), 180–184
Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, Lindenmayer JP, Citrome L, McEvoy JK, Kunz M, Chakos M, Cooper TB, Horowitz TL, Lieberman JA (2002) Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder, Am. J Psychiatry, 159(6), 1018–1028
Bitter I, Dossenbach MR, Brook S, Feldman PD, Metcalfe S, Gagiano CA, Furedi J, Bartko G, Janka Z, Banki CM, Kovacs G, Breier A (2004) Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia, Prog. Neuropsychopharmacol Biol. Psychiatry, 28(1), 173–180
Blier P, Slater S, Measham T, Koch M, Wiviott G (1998) Lithium and clozapine-induced neutropenia/agranulocytosis, Int Clin Psychopharmacol. 13(3), 137–40
Bondolfi G, Dufour H, Patris M, May JP, Billeter U, Eap CB, Baumann P (1998) Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group, Am. J Psychiatry, 155(4), 499–504
Brunot A, Lachaux B, Sontag H, Casadebaig F, Philippe A, Rouillon F, Clery-Melin P, Hergueta T, Llorca PM, Moreaudefarges T, Guillon P, Lebrun T (2002) Pharmaco-epidemiological study on antipsychotic drug prescription in French Psychiatry: Patient characteristics, antipsychotic treatment, and care management for schizophrenia, Encephale, 28(2), 129–138
Buchanan RW, Kirkpatrick B, Bryant N, Ball P, Breier A (1996) Fluoxetine augmentation of clozapine treatment in patients with schizophrenia, Am. J. Psychiatry, 153(12), 1625–1627
Buchanan RW, Kreyenbuhl J, Kelly DL, Noel JM, Boggs DL, Fischer BA, Himelhoch S, Fang B, Peterson E, Aquino PR, Keller W (2010) The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements, Schizophr. Bull., 36(1), 71–93
Carlsson A, Waters N, Waters S, Carlsson ML (2000) Network interactions in schizophrenia – therapeutic implications, Brain Res. Brain Res. Rev., 31(2–3), 342–349
Casey DE, Daniel DG, Tamminga C, Kane JM, Tran-Johnson T, Wozniak P, bi-Saab W, Baker J, Redden L, Greco N, Saltarelli M (2009) Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia, Neuropsychopharmacology, 34(5), 1330–1338
Casey DE, Daniel DG, Wassef A, Tracy KA, Wozniak P, Sommerville KW (2003) Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia, Neuropsychopharmacology, 28(1), 182–192
Centorrino F, Goren JL, Hennen J, Salvatore P, Kelleher JP, Baldessarini RJ (2004) Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case-control study of risks versus benefits, Am. J. Psychiatry, 161(4), 700–706
Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B (2001) Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials, Am. J. Psychiatry, 158(4), 518–526
Chakos MH, Glick ID, Miller AL, Hamner MB, Miller DD, Patel JK, Tapp A, Keefe RS, Rosenheck RA (2006) Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial, Psychiatr. Serv., 57(8), 1094–1101
Chan J, Sweeting M (2007) Review: Combination therapy with non-clozapine atypical antipsychotic medication: a review of current evidence, J. Psychopharmacol., 21(6), 657–664
Chang JS, Ahn YM, Park, Lee KY, Kim SH, Kang UG, Kim YS (2008) Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial, J. Clin. Psychiatry, 69(5), 720–731
Chang, J. S., Lee NY, Ahn YM, Kim YS (2012) The sustained effects of aripiprazole-augmented clozapine treatment on the psychotic symptoms and metabolic profiles of patients with refractory schizophrenia, J. Clin. Psychopharmacol., 32(2), 282–284
Chen B, Cardasis W (1996) Delirium induced by lithium and risperidone combination, Am J Psychiatry. 153(9), 1233–4
Chong SA, Tan CH, Lee HS (1997) Atrial ectopics with clozapine-risperidone combination, J Clin Psychopharmacol. 17(2), 130¬–1
Chue P, Welch R, Snaterse M (2001) Combination risperidone and quetiapine therapy in refractory schizophrenia, Can. J. Psychiatry, 46(1), 86–87
Cipriani A., Accordini S, Nose M, Purgato M, Girlanda F, Tansella M, Barbui C (2013) Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia: a 12-month, randomized, naturalistic trial, J. Clin. Psychopharmacol., 33(4), 533–537
Citrome L, Jaffe A, Levine J, Allingham B (2002) Use of mood stabilizers among patients with schizophrenia, 1994–2001, Psychiatr. Serv., 53(10), 1212
Citrome L, Levine J, Allingham B (2000) Changes in use of valproate and other mood stabilizers for patients with schizophrenia from 1994 to 1998, Psychiatr. Serv., 51(5), 634–638
Clarke LA, Lindenmayer JP, Kaushik S (2006) Clozapine augmentation with aripiprazole for negative symptoms, J. Clin. Psychiatry, 67(4), 675–676
Conley RR, Kelly DL, Richardson CM, Tamminga CA, Carpenter WT Jr. (2003) The efficacy of high-dose olanzapine versus clozapine in treatment-resistant schizophrenia: a double-blind crossover study, J Clin. Psychopharmacol., 23(6), 668–671
Conley RR, Tamminga CA, Bartko JJ, Richardson C, Peszke M, Lingle J, Hegerty J, Love R, Gounaris C, Zaremba S (1998) Olanzapine compared with chlorpromazine in treatment-resistant schizophrenia, Am. J Psychiatry, 155(7), 914–920
Cook B, Hoogenboom G (2004) Combined use of amisulpride and clozapine for patients with treatment-resistant schizophrenia, Australas. Psychiatry, 12(1), 74–76
Cooke C, de Leon J (1999) Adding other antipsychotics to clozapine, J. Clin. Psychiatry, 60(10), 710
Correll CU, Rummel-Kluge C, Corves C, Kane JM, Leucht S (2009) Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials, Schizophr. Bull., 35(2), 443–457
Costello LE, Suppes T (1995) A clinically significant interaction between clozapine and valproate, J. Clin. Psychopharmacol., 15(2), 139–141
Covell NH, Jackson CT, Evans AC, Essock SM (2002) Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles, Schizophr. Bull., 28(1), 17–29
Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B (2000) Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation, Biol. Psychiatry, 48(5), 381–388
Cubala WJ, Wichowicz HM, Landowski J (2007) Refractory schizophrenia treated with clozapine combined with zuclopenthixol, Prog. Neuropsychopharmacol. Biol. Psychiatry, 31(3), 781–783
Davis KL, Kahn RS, Ko G, Davidson M (1991) Dopamine in schizophrenia: a review and reconceptualization, Am. J Psychiatry, 148(11), 1474–1486
De RA, Pancheri A, Simonetti G, Giannarelli D, Stefanutto L, Gentile B (2011) Add-on of aripiprazole improves outcome in clozapine-resistant schizophrenia, Prog. Neuropsychopharmacol. Biol. Psychiatry, 35(4), 1112–1116
de Groot IW, Heck AH, van Harten PN (2001) Addition of risperidone to clozapine therapy in chronically psychotic inpatients, J Clin Psychiatry. 62(2), 129–30
De Hert HM, van Winkel R, Wampers M, Kane J, van Os J, Peuskens J (2007) Remission criteria for schizophrenia: evaluation in a large naturalistic cohort, Schizophr. Res., 92(1–3), 68–73
de Lucena D, Fernandes BS, Berk M, Dodd S, Medeiros DW, Pedrini M, Kunz M, Gomes FA, Giglio LF, Lobato MI, Belmonte-de-Abreu PS, Gama CS (2009) Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine, J. Clin. Psychiatry, 70(10), 1416–1423
Delva NJ, Letemendia FJ (1982) Lithium treatment in schizophrenia and schizo-affective disorders, Br. J. Psychiatry, 141, 387–400
Dequardo JR, Roberts M (1996) Elevated clozapine levels after fluvoxamine initiation, Am. J Psychiatry, 153(6), 840–841
Dolder CR, Lacro JP, Dunn LB, Jeste DV (2002) Antipsychotic medication adherence: is there a difference between typical and atypical agents?, Am. J. Psychiatry, 159(1), 103–108
Donaldson SR, Gelenberg AJ, Baldessarini RJ (1983) The pharmacologic treatment of schizophrenia: a progress report, Schizophr. Bull., 9(4), 504–527
Duggal HS (2004) Aripirazole-olanzapine combination for treatment of schizophrenia, Can J Psychiatry. 49(2), 151
DuMortier G, Lochu A, Colen DM, Ghribi O, Roche-Rabreau D, DeGrassat K, Desce JM (1996) Elevated clozapine plasma concentrations after fluvoxamine initiation, Am. J Psychiatry, 153(5), 738–739
Durrenberger S, de Leon J (1999) Acute dystonic reaction to lithium and risperidone, J Neuropsychiatry Clin Neurosci, 11(4), 518–9
Dursun SM, Deakin JF (2001) Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study, J. Psychopharmacol., 15(4), 297–301
Dursun SM, Devarajan S (2000) Clozapine weight gain, plus topiramate weight loss, Can. J Psychiatry, 45(2), 198
Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ (2002) Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia, Am. J. Psychiatry, 159(9), 1596–1598
Ereshefsky L (1999) Pharmacologic and pharmacokinetic considerations in choosing an antipsychotic, J. Clin. Psychiatry, 60 Suppl 10, 20–30
Essock SM, Schooler NR, Stroup TS, McEvoy JP, Rojas I, Jackson C, Covell NH (2011) Effectiveness of switching from antipsychotic polypharmacy to monotherapy, Am. J. Psychiatry, 168(7), 702–708
Evins AE, Fitzgerald SM, Wine L, Rosselli R, Goff DC (2000) Placebo-controlled trial of glycine added to clozapine in schizophrenia, Am. J. Psychiatry, 157(5), 826–828
Fan X, Borba CP, Copeland P, Hayden D, Freudenreich O, Goff DC, Henderson DC (2013) Metabolic effects of adjunctive aripiprazole in clozapine-treated patients with schizophrenia, Acta Psychiatr Scand. 127(3), 217–26
Farber NB, Kim SH, Dikranian K, X. P. Jiang, C. Heinkel (2002) Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity, Mol. Psychiatry, 7(1), 32–43
Faries D, Scher-Svanum H, Zhu B, Correll C, Kane J (2005) Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics, BMC. Psychiatry, 5, 26
Fehr C. (2006) For: is monotherapy the gold standard of psychopharmacology?, Psychiatr. Prax., 33(5), 207–208
Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M (2001) A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia, Am. J. Psychiatry, 158(12), 2071–2074
Fleischhacker WW, Heikkinen ME, Olie JP, Landsberg W, Dewaele P, McQuade RD, Loze JY, Hennicken D, Kerselaers W (2010) Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial, Int. J. Neuropsychopharmacol., 13(8), 1115–1125
Fleischhacker WW, Uchida H (2012) Critical review of antipsychotic polypharmacy in the treatment of schizophrenia, Int. J. Neuropsychopharmacol., 1–11
Freedman R, Hall M, Adler LE, Leonard S (1995) Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia, Biol. Psychiatry, 38(1), 22–33
Freudenreich O, Goff DC (2002) Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current combinations, Acta Psychiatr. Scand., 106(5), 323–330
Freudenreich O, Henderson DC, Walsh JP, Culhane MA, Goff DC (2007) Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial, Schizophr. Res., 92(1–3), 90–94
Friedman J, Ault K, Powchik P (1997) Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine, Biol Psychiatry. 15;42(6): 522–352
Friedman JI, Adler DN, Howanitz E, Harvey PD, Brenner G, Temporini H, White L, Parrella M, Davis KL (2002) A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia, Biol. Psychiatry, 51(5), 349–357
Friedman JI, Lindenmayer JP, Alcantara, Bowler S, Parak M, White L, Iskander A, Parrella M, Adler DN, Tsopelas ND, Tsai WY, Novakovic V, Harvey PD, Davis KL, Kaushik S (2011) Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy, Neuropsychopharmacology, 36(6), 1289–1295
Fukuzako H, Fukuzako T, Hashiguchi T, Kodama S, Takigawa M, Fujimoto T (1999) Changes in levels of phosphorus metabolites in temporal lobes of drug-naive schizophrenic patients, Am. J Psychiatry, 156(8), 1205–1208
Gallego JA, Bonetti J, Zhang J, Kane JM, Correll CU (2012) Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009, Schizophr. Res., 138(1), 18–28
Ganguly R, Kotzan JA, Miller LS, Kennedy K, Martin BC (2004) Prevalence, trends, and factors associated with antipsychotic polypharmacy among Medicaid-eligible schizophrenia patients, 1998-2000, J. Clin. Psychiatry, 65(10), 1377–1388
Garcia G, Crismon ML, Dorson PG (1994) Seizures in two patients after the addition of lithium to a clozapine regimen, J Clin Psychopharmacol. 14(6), 426–8
Genc Y, Taner E, Candansayar S (2007) Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study, Adv. Ther., 24(1), 1–13
George S, Cowan C (2005) Effectiveness of amisulpride augmentation of clozapine in a non-responder to either drug alone: a case report, Acta Psychiatr. Scand., 111(2), 163
Gerson SL, Lieberman JA, Friedenberg WR, Lee D, Marx JJ Jr, Meltzer H (1991) Polypharmacy in fatal clozapine-associated agranulocytosis, Lancet, 338(8761), 262–263
Ghaemi SN (2002) Polypharmacy in Psychiatry, in Polypharmacy in Schizophrenia, edited by G. Oepen, pp. 101–132
Ghaleiha A, Noorbala AA, Farnaghi F, Hajiazim M, Akhondzadeh S (2010) A double-blind, randomized, and placebo-controlled trial of buspirone added to risperidone in patients with chronic schizophrenia, J. Clin. Psychopharmacol., 30(6), 678–682
Gilmer TP, Dolder CR, Folsom DP, Mastin W, Jeste DV (2007) Antipsychotic polypharmacy trends among Medicaid beneficiaries with schizophrenia in San Diego County, 1999–2004, Psychiatr. Serv., 58(7), 1007–1010
Glick ID, Bosch J, Casey DE (2009) A double-blind randomized trial of mood stabilizer augmentation using lamotrigine and valproate for patients with schizophrenia who are stabilized and partially responsive, J. Clin. Psychopharmacol., 29(3), 267–271
Glick ID, Pham D, Davis JM (2006) Concomitant medications may not improve outcome of antipsychotic monotherapy for stabilized patients with nonacute schizophrenia, J. Clin. Psychiatry, 67(8), 1261–1265
Godleski LS, Kerler R, Barber JW, Glick JL, Kellogg E, Vieweg WV, Yank GR (1989) Multiple versus single antipsychotic drug treatment in chronic psychosis, J. Nerv. Ment. Dis., 177(11), 686–689
Godleski LS, Sernyak MJ (1996) Agranulocytosis after addition of risperidone to clozapine treatment, Am J Psychiatry. 153(5), 735–6
Goff DC, Henderson DC, Evins AE, Amico E (1999a) A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia, Biol. Psychiatry, 45(4), 512–514
Goff DC, Keefe R, Citrome L, Davy K, Krystal JH, Large C, Thompson TR, Volavka J, Webster EL (2007) Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials, J. Clin. Psychopharmacol., 27(6), 582–589
Goff DC, Midha KK, Sarid-Segal O, Hubbard JW, Amico E (1995) A placebo-controlled trial of fluoxetine added to neuroleptic in patients with schizophrenia, Psychopharmacology (Berl), 117(4), 417–423
Goff DC, Tsai G, Levitt J, Amico E, Manoach D, Schoenfeld DA, Hayden DL, McCarley R, Coyle JT (1999b) A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia, Arch. Gen. Psychiatry, 56(1), 21–27
Goff DC, Tsai G, Manoach DS, Flood J, Darby DG, Coyle JT (1996) D-cycloserine added to clozapine for patients with schizophrenia, Am. J. Psychiatry, 153(12), 1628–1630
Gomberg RF (1999) Interaction between olanzapine and haloperidol, J Clin Psychopharmacol. 19(3), 272–3
Green MF, Kern RS, Braff DL, Mintz J (2000) Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the "right stuff"?, Schizophr. Bull., 26(1), 119–136
Grohmann R, Ruther E, Sassim N, Schmidt LG (1989) Adverse effects of clozapine, Psychopharmacology (Berl), 99 Suppl, S101–S104
Growe GA, Crayton JW, Klass DB, Evans H, Strizich M (1979) Lithium in chronic schizophrenia, Am. J. Psychiatry, 136(4A), 454–455
Gupta S, Sonnenberg SJ, Frank B (1998) Olanzapine augmentation of clozapine, Ann. Clin. Psychiatry, 10(3), 113–115
Häfner H (2004) Schizophrenie – von der Tradition zur Gegenwart, Neurotransmitter,(4), 64–68
Hahn MK, Remington G, Bois D, Cohn T (2010) Topiramate augmentation in clozapine-treated patients with schizophrenia: clinical and metabolic effects, J Clin Psychopharmacol. 30(6), 706–710
Haller E, Binder RL (1990) Clozapine and seizures, Am. J. Psychiatry, 147(8), 1069–1071
Harrow M, Yonan CA, Sands JR, Marengo J (1994) Depression in schizophrenia: are neuroleptics, akinesia, or anhedonia involved?, Schizophr. Bull., 20(2), 327–338
Harvey PD, Keefe RS (2001) Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment, Am. J Psychiatry, 158(2), 176–184
Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Thibaut F, Moller HJ (2012) World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance, World J. Biol. Psychiatry, 13(5), 318–378
Hashimoto Y, Uno J, Miwa T, Kurihara M, Tanifuji H, Tensho M (2012) Effects of antipsychotic polypharmacy on side-effects and concurrent use of medications in schizophrenic outpatients, Psychiatry Clin Neurosci. 66(5), 405–410. doi: 10.1111/j.1440-1819.2012.02376.x
Hedges DW, Jeppson KG (2002) New-onset seizure associated with quetiapine and olanzapine, Ann. Pharmacother., 36(3), 437–439
Henderson DC, Fan X, Copeland PM, Sharma B, Borba CP, Boxill R, Freudenreich O, Cather C, Evins AE, Goff DC (2009) Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients, J. Clin. Psychopharmacol., 29(2), 165–169
Henderson DC, Goff DC (1996) Risperidone as an adjunct to clozapine therapy in chronic schizophrenics, J Clin Psychiatry. 57(9), 395–7
Henderson DC, Goff DC, Connolly CE, Borba CP, Hayden D (2001) Risperidone added to clozapine: impact on serum prolactin levels, J Clin Psychiatry. 62(8): 605–8
Henderson DC, Kunkel L, Nguyen DD, Borba CP, Daley TB, Louie PM, Freudenreich O, Cather C, Evins AE, Goff DC (2006) An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia, Acta Psychiatr Scand. 113(2), 142–7
Heresco-Levy U, Ermilov M, Lichtenberg P, Bar G, Javitt DC (2004) High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia, Biol. Psychiatry, 55(2), 165–171
Hertling I, Philipp M, Dvorak A, Glaser T, Mast O, Beneke M, Ramskogler K, Saletu-Zyhlarz G, Walter H, Lesch OM (2003) Flupenthixol versus risperidone: subjective quality of life as an important factor for compliance in chronic schizophrenic patients, Neuropsychobiology, 47(1), 37–46
Hiemke C, Weigmann H, Hartter S, Dahmen N, Wetzel H, Muller H (1994) Elevated levels of clozapine in serum after addition of fluvoxamine, J Clin. Psychopharmacol., 14(4), 279–281
Honer WG, Thornton AE, Chen EY, Chan RC, Wong JO, Bergmann A, Falkai P, Pomarol-Clotet E, McKenna PJ, Stip E, Williams R, MacEwan, Wasan K, Procyshyn R (2006) Clozapine alone versus clozapine and risperidone with refractory schizophrenia, N. Engl. J Med., 354(5), 472–482
Horrobin DF (1998) The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental concept of schizophrenia, Schizophr. Res., 30(3), 193–208
Hovens JE, Dries PJ, Melman CT, Wapenaar RJ, Loonen AJ (2005) Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open-label study, J. Psychopharmacol., 19(1), 51–57
Huttunen MO, Tuhkanen H, Haavisto E, Nyholm R, Pitkanen M, Raitasuo V, Romanov M (1996) Low- and standard-dose depot haloperidol combined with targeted oral neuroleptics, Psychiatr. Serv., 47(1), 83–85
Ito C, Kubota Y, Sato M (1999) A prospective survey on drug choice for prescriptions for admitted patients with schizophrenia, Psychiatry Clin. Neurosci., 53 Suppl, S35–S40
Janssen B, Weinmann S, Berger M, Gaebel W (2004) Validation of polypharmacy process measures in inpatient schizophrenia care, Schizophr. Bull., 30(4), 1023–1033
Jarventausta K, Leinonen E (2000) Neuroleptic malignant syndrome during olanzapine and levomepromazine treatment, Acta Psychiatr. Scand., 102(3), 231–233
Jockers-Scherubl MC, Bauer A, Godemann F, Reischies FM, Selig F, Schlattmann P (2005) Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study, Int Clin. Psychopharmacol., 20(1), 27–31
Johnson DA (1988) The significance of depression in the prediction of relapse in chronic schizophrenia, Br. J. Psychiatry, 152, 320–323
Josiassen RC, Joseph A, Kohegyi E, Stokes S, Dadvand M, Paing WW, Shaughnessy RA (2005) Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial, Am. J. Psychiatry, 162(1), 130–136
Junghan U, Albers M, Woggon B (1993) Increased risk of hematological side-effects in psychiatric patients treated with clozapine and carbamazepine?, Pharmacopsychiatry, 26(6), 262
Kahn, R. S., W. W. Fleischhacker, H. Boter, M. Davidson, Y. Vergouwe, I. P. Keet, M. D. Gheorghe, J. K. Rybakowski, S. Galderisi, J. Libiger, M. Hummer, S. Dollfus, J. J. Lopez-Ibor, L. G. Hranov, W. Gaebel, J. Peuskens, N. Lindefors, A. Riecher-Rossler, D. E. Grobbee (2008) Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial, Lancet, 371(9618), 1085–1097
Kampf P, Agelink MW, Naber D (2005) Augmentation of clozapine with amisulpride: a promising therapeutic approach to refractory schizophrenic symptoms, Pharmacopsychiatry, 38(1), 39–40
Kando JC, Tohen M, Castillo J, Centorrino F (1994) Concurrent use of clozapine and valproate in affective and psychotic disorders, J. Clin. Psychiatry, 55(6), 255–257
Kane JM (1989) The current status of neuroleptic therapy, J. Clin. Psychiatry, 50(9), 322–328
Kane JM, Correll CU, Goff DC, Kirkpatrick B, Marder SR, Vester-Blokland E, Sun W, Carson WH, Pikalov A, Assuncao-Talbott S (2009) A multicenter, randomized, double-blind, placebo-controlled, 16-week study of adjunctive aripiprazole for schizophrenia or schizoaffective disorder inadequately treated with quetiapine or risperidone monotherapy, J. Clin. Psychiatry, 70(10), 1348–1357
Kapur S, Roy P, Daskalakis J, Remington G, Zipursky R (2001) Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine, Am. J. Psychiatry, 158(2), 311–314
Karow, A, D. Naber (2002) Subjective well-being and quality of life under atypical antipsychotic treatment, Psychopharmacology (Berl), 162(1), 3–10
Karunakaran K, Tungaraza TE, Harborne GC (2007) Is clozapine-aripiprazole combination a useful regime in the management of treatment-resistant schizophrenia?, J. Psychopharmacol., 21(4), 453–456
Kasckow JW, Mohamed S, Thallasinos A, Carroll B, Zisook S, Jeste DV (2001) Citalopram augmentation of antipsychotic treatment in older schizophrenia patients, Int. J. Geriatr. Psychiatry, 16(12), 1163–1167
Kaye NS (2003) Ziprasidone augmentation of clozapine in 11 patients, J. Clin. Psychiatry, 64(2), 215–216
Keks NA, Altson K, Hope J, Krapivensky N, Culhane C, Tanaghow A, Doherty P, Bootle A (1999) Use of antipsychosis and adjunctive medications by an inner urban community psychiatric service, Aust. N. Z. J. Psychiatry, 33(6), 896–901
Kennedy NB, Procyshyn RM (2000) Rational antipsychotic polypharmacy, Can. J. Clin. Pharmacol., 7(3), 155–159
Kilian R, Dietrich S, Toumi M, Angermeyer MC (2004) Quality of life in persons with schizophrenia in out-patient treatment with first- or second-generation antipsychotics, Acta Psychiatr. Scand., 110(2), 108–118
Kim, JH, Yim SJ, Nam JH (2006) A 12-week, randomized, open-label, parallel-group trial of topiramate in limiting weight gain during olanzapine treatment in patients with schizophrenia, Schizophr. Res., 82(1), 115–117
Kirli S, Caliskan M (1998) A comparative study of sertraline versus imipramine in postpsychotic depressive disorder of schizophrenia, Schizophr. Res., 33(1–2), 103–111
Kishimoto T, Agarwal V, Kishi T, Leucht S, Kane JM, Correll CU (2013) Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics, Mol. Psychiatry, 18(1), 53–66
Ko YH, Joe SH, Jung IK, Kim SH (2005) Topiramate as an adjuvant treatment with atypical antipsychotics in schizophrenic patients experiencing weight gain, Clin. Neuropharmacol., 28(4), 169–175
Kontaxakis VP, Havaki-Kontaxaki BJ, Stamouli SS, Christodoulou GN (2002) Toxic interaction between risperidone and clozapine: a case report, Prog Neuropsychopharmacol Biol Psychiatry.26(2), 407–409
Koponen HJ, Leinonen E, Lepola U (1996) Fluvoxamine increases the clozapine serum levels significantly, Eur Neuropsychopharmacol, 6(1), 69–71
Koreen AR, Lieberman JA, Kronig M, Cooper TB (1995) Cross-tapering clozapine and risperidone, Am J Psychiatry. 152(11), 1690
Kotler M, Strous RD, Reznik I, Shwartz S, Weizman A, Spivak B (2004) Sulpiride augmentation of olanzapine in the management of treatment-resistant chronic schizophrenia: evidence for improvement of mood symptomatology, Int Clin. Psychopharmacol., 19(1), 23–26
Kreinin A, Miodownik C, Sokolik S, Shestakova D, Libov I, Bergman J, Lerner V (2011) Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation, World J. Biol. Psychiatry, 12(8), 620–626
Kremer I, Vass A, Gorelik I, Bar G, Blanaru M, Javitt DC, Heresco-Levy U (2004) Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia, Biol. Psychiatry, 56(6), 441–446
Krivoy A, Malka L, Fischel T, Weizman A, Valevski A (2011) Predictors of clozapine discontinuation in patients with schizophrenia, Int. Clin. Psychopharmacol., 26(6), 311–315
Kuo FJ, Lane HY, Chang WH (1998) Extrapyramidal symptoms after addition of fluvoxamine to clozapine, J Clin. Psychopharmacol., 18(6), 483–484
Längle G, Steinert T, Weiser P, Schepp W, Jaeger S, Pfiffner C, Frasch K, Eschweiler GW, Messer T, Croissant D, Becker T, Kilian R (2012) Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment, Acta Psychiatr Scand. 125(5), 372–81
Lammers CH, Deuschle M, Weigmann H, Hartter S, Hiemke C, Heese C, Heuser I (1999) Coadministration of clozapine and fluvoxamine in psychotic patients – clinical experience, Pharmacopsychiatry, 32(2), 76–77
Lee MS, Han CS, You YW, Kim SH (1998a) Co-administration of sertraline and haloperidol, Psychiatry Clin. Neurosci., 52 Suppl, S193–S198
Lee MS, Kim YK, Lee SK, Suh KY (1998b) A double-blind study of adjunctive sertraline in haloperidol-stabilized patients with chronic schizophrenia, J. Clin. Psychopharmacol., 18(5), 399–403
Lejeune J, Larmo I, Chrzanowski W, Witte R, Karavatos A, Schreiner, Lex A, Medori R (2004) Oral risperidone plus oral lorazepam versus standard care with intramuscular conventional neuroleptics in the initial phase of treating individuals with acute psychosis, Int. Clin. Psychopharmacol., 19(5), 259–269
Lerner V, Bergman J, Borokhov A, Loewenthal U, Miodownik C (2005) Augmentation With Amisulpride for Schizophrenic Patients Nonresponsive to Antipsychotic Monotherapy, Clin. Neuropharmacol., 28(2), 66–71
Lerner V, Chudakova B, Kravets S, Polyakova I (2000) Combined use of risperidone and olanzapine in the treatment of patients with resistant schizophrenia: a preliminary case series report, Clin. Neuropharmacol., 23(5), 284–286
Lerner V, Libov I, Kotler M, Strous RD (2004) Combination of "atypical" antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder, Prog. Neuropsychopharmacol. Biol. Psychiatry, 28(1), 89–98
Leslie DL, Rosenheck RA (2001) Use of pharmacy data to assess quality of pharmacotherapy for schizophrenia in a national health care system: individual and facility predictors, Med. Care, 39(9), 923–933
Leucht S, Heres S, Kissling W, Davis JM (2011) Evidence-based pharmacotherapy of schizophrenia, Int. J. Neuropsychopharmacol., 14(2), 269–284
Leucht S, Kissling W, McGrath J (2004) Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials, J. Clin. Psychiatry, 65(2), 177–186
Leucht S, Kissling W, McGrath J (2007a) Lithium for schizophrenia, Cochrane. Database. Syst. Rev.,(3), CD003834
Leucht S, Kissling W, McGrath J, White P (2007b) Carbamazepine for schizophrenia, Cochrane. Database. Syst. Rev.,(3), CD001258
Leucht S, McGrath J, Kissling W (2003) Lithium for schizophrenia, Cochrane. Database. Syst. Rev.,(3), CD003834
Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM (2012) Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis, Lancet, 379(9831), 2063–2071
Levinson DF, Umapathy C, Musthaq M (1999) Treatment of schizoaffective disorder and schizophrenia with mood symptoms, Am. J. Psychiatry, 156(8), 1138–1148
Levy E, Margolese HC, Chouinard G (2002) Topiramate produced weight loss following olanzapine-induced weight gain in schizophrenia, J Clin. Psychiatry, 63(11), 1045
Lieberman JA, Papadakis K, Csernansky J, Litman R, Volavka J, Jia XD, Gage A (2009) A randomized, placebo-controlled study of memantine as adjunctive treatment in patients with schizophrenia, Neuropsychopharmacology, 34(5), 1322–1329
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(12), 1209–1223
Lim S, Bowers MB (2007) Augmentation of clozapine treatment with aripiprazole, J. Clin. Psychiatry, 68(5), 798–799
Linden M, Scheel T, Xaver EF (2004) Dosage finding and outcome in the treatment of schizophrenic inpatients with amisulpride. Results of a drug utilization observation study, Hum. Psychopharmacol., 19(2), 111–119
Lindenmayer JP, Iskander A, Park M, Apergi FS, Czobor P, Smith R, Allen D (1998) Clinical and neurocognitive effects of clozapine and risperidone in treatment-refractory schizophrenic patients: a prospective study, J Clin. Psychiatry, 59(10), 521–527
Lu ML, Lane HY, Lin SK, Chen KP, Chang WH (2004) Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances, J Clin. Psychiatry, 65(6), 766–771
Luchins DJ (1984) Fatal agranulocytosis in a chronic schizophrenic patient treated with carbamazepine, Am. J. Psychiatry, 141(5), 687–688
McCarthy RH, Terkelsen KG (1995) Risperidone augmentation of clozapine, Pharmacopsychiatry. 28(2), 61–3
Mahadik SP, Evans D, Lal H (2001) Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia, Prog. Neuropsychopharmacol. Biol. Psychiatry, 25(3), 463–493
Marder SR (1992) Risperidone: clinical development: north American results, Clin. Neuropharmacol., 15 Suppl 1 Pt A, 92A–93A
Marder SR, Glynn SM, Wirshing WC, Wirshing DA, Ross D, Widmark C, Mintz J, Liberman RP, Blair KE (2003) Maintenance treatment of schizophrenia with risperidone or haloperidol: 2-year outcomes, Am. J. Psychiatry, 160(8), 1405–1412
Masopust J, Tuma I, Libiger J (2008) Adjunctive aripiprazole decreased metabolic side effects of clozapine treatment, Neuro. Endocrinol. Lett., 29(4), 435–437
Meltzer HY, Kostakoglu A (2004) Combining Antipsychotics: Is there Evidence for Efficacy?, Psychiatric Times, XVII(9)
Meltzer HY (1992) Treatment of the neuroleptic-nonresponsive schizophrenic patient, Schizophr. Bull., 18(3), 515–542
Mitsonis CI, Dimopoulos NP, Mitropoulos PA, Kararizou EG, Katsa AN, Tsakiris FE, Katsanou MN (2007) Aripiprazole augmentation in the management of residual symptoms in clozapine-treated outpatients with chronic schizophrenia: An open-label pilot study, Prog. Neuropsychopharmacol. Biol. Psychiatry, 31(2), 373–377
Moore TA, Buchanan RW, Buckley PF, Chiles JA, Conley RR, Crismon ML, Essock SM, Finnerty M, Marder SR, Miller DD, McEvoy JP, Robinson DG, Schooler NR, Shon SP, Stroup TS, Miller AL (2007) The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update, J. Clin. Psychiatry, 68(11), 1751–1762
Morera AL1, Barreiro P, Cano-Muñoz JL (1999) Risperidone and clozapine combination for the treatment of refractory schizophrenia, Acta Psychiatr Scand. 99(4), 305–6; discussion 306¬–7
Muijen M, Silverstone T (1987) A comparative hospital survey of psychotropic drug prescribing, Br. J. Psychiatry, 150, 501–504
Mujica R, Weiden P (2001) Neuroleptic malignant syndrome after addition of haloperidol to atypical antipsychotic, Am. J. Psychiatry, 158(4), 650–651
Muller MJ, Wetzel H (1998) Dimensionality of depression in acute schizophrenia: a methodological study using the Bech-Rafaelsen Melancholia Scale (BRMES), J. Psychiatr. Res., 32(6), 369–378
Muller N, Riedel M, Scheppach C, Brandstatter B, Sokullu S, Krampe K, Ulmschneider M, Engel RR, Moller HJ, Schwarz MJ (2002) Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia, Am. J. Psychiatry, 159(6), 1029–1034
Muller T, Becker T, Fritze J (1988) Neuroleptic malignant syndrome after clozapine plus carbamazepine, Lancet, 2(8626–8627), 1500
Munro J, Matthiasson P, Osborne S, Travis M, Purcell S, Cobb AM, Launer M, Beer MD, Kerwin R (2004) Amisulpride augmentation of clozapine: an open non-randomized study in patients with schizophrenia partially responsive to clozapine, Acta Psychiatr. Scand., 110(4), 292–298
Muscatello MR, Bruno A, Pandolfo G, Mico U, Bellinghieri PM, Scimeca G, Cacciola M, Campolo D, Settineri S, Zoccali R (2011a) Topiramate augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study, J. Psychopharmacol., 25(5), 667–674
Muscatello MR, Bruno A, Pandolfo G, Mico U, Scimeca G, Di NF, Santoro V, Spina E, Zoccali RA (2011b) Effect of aripiprazole augmentation of clozapine in schizophrenia: a double-blind, placebo-controlled study, Schizophr. Res., 127(1–3), 93–99
Navarro V, Pons A, Romero A, Bernardo M (2001) Topiramate for clozapine-induced seizures, Am. J. Psychiatry, 158(6), 968–969
Oepen G (2002) Polypharmacy in Schizophrenia, in Polypharmacy in Psychiatry, edited by S. N. Ghaemi, Dekker
Olesen OV, Starup G, Linnet K (1996) Serious drug interaction between clozapine-Leponex and fluvoxamine-Fevarin, Ugeskr. Laeger, 158(48), 6931–6932
Owley T, Leventhal B, Cook EH Jr (2001) Risperidone-induced prolonged erections following the addition of lithium, J Child Adolesc Psychopharmacol, 11(4), 441–2
Patel JK, Salzman C, Green AI, Tsuang MT (1997) Chronic schizophrenia: response to clozapine, risperidone, and paroxetine, Am J Psychiatry. 154(4), 543–6
Paton C, Barnes TR, Cavanagh MR, Taylor D, Lelliott P (2008) High-dose and combination antipsychotic prescribing in acute adult wards in the UK: the challenges posed by p.r.n. prescribing, Br. J. Psychiatry, 192(6), 435–439
Paton C, Whittington C, Barnes TR (2007) Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis, J. Clin. Psychopharmacol., 27(2), 198–204
Peacock L, Gerlach J (1994) Clozapine treatment in Denmark: concomitant psychotropic medication and hematologic monitoring in a system with liberal usage practices, J. Clin. Psychiatry, 55(2), 44–49
Peet M, Brind J, Ramchand CN, Shah S, Vankar GK (2001) Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia, Schizophr. Res., 49(3), 243–251
Peterson GA, Byrd SL (1996) Diabetic ketoacidosis from clozapine and lithium cotreatment, Am J Psychiatry. 153(5), 737–8
Pettegrew JW, Keshavan MS, Panchalingam K, Strychor S, Kaplan DB, Tretta MG, Allen M (1991) Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy, Arch. Gen. Psychiatry, 48(6), 563–568
Peuskens J, Van Baelen B, De Smedt C, Lemmens P (2000) Effects of risperidone on affective symptoms in patients with schizophrenia, Int. Clin. Psychopharmacol., 15(6), 343–349
Pigato G, Toffanin T, Perini GI (2009) Is a high dosage aripiprazole-clozapine combination an effective strategy for treatment-resistant schizophrenic patients? A case report, Prog. Neuropsychopharmacol. Biol. Psychiatry, 33(1), 153–155
Potkin SG, Jin Y, Bunney BG, Costa J, Gulasekaram B (1999) Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia, Am. J. Psychiatry, 156(1), 145–147
Potkin SG, Thyrum PT, Alva G, Bera R, Yeh C, Arvanitis LA (2002) The safety and pharmacokinetics of quetiapine when coadministered with haloperidol, risperidone, or thioridazine, J. Clin. Psychopharmacol., 22(2), 121–130
Potter WZ, Ko GN, Zhang LD, Yan WW (1989) Clozapine in China: a review and preview of US/PRC collaboration, Psychopharmacology (Berl), 99 Suppl, S87–S91
Procyshyn RM, Honer WG, Wu TK, Ko RW, McIsaac SA, Young AH, Johnson JL, Barr AM (2010) Persistent antipsychotic polypharmacy and excessive dosing in the community psychiatric treatment setting: a review of medication profiles in 435 Canadian outpatients, J. Clin. Psychiatry, 71(5), 566–573
Procyshyn RM, Thompson B (2004) Patterns of antipsychotic utilization in a tertiary care psychiatric institution, Pharmacopsychiatry, 37(1), 12–17
Procyshyn RM, Tse G, Sin O, Flynn S (2002) Concomitant clozapine reduces smoking in patients treated with risperidone, Eur Neuropsychopharmacol. 12(1), 77–80
Raaska K, Raitasuo V, Neuvonen PJ (2002) Therapeutic drug monitoring data: risperidone does not increase serum clozapine concentration, Eur J Clin Pharmacol. 58(9), 587–591. Epub 2002 Nov 13
Raedler TJ, Jahn H, Arlt J, Kiefer F, Schick M, Naber D, Wiedemann K (2004) Adjunctive use of reboxetine in schizophrenia, Eur Psychiatry, 19(6), 366–369
Raju Kumar R Khanna S (2001) Clozapine-risperidone combination in treatment-resistant schizophrenia, Aust N Z J Psychiatry. 35(4), 543
Rajarethinam R, Gilani S, Tancer M, DeQuardo J (2003) Augmentation of clozapine partial responders with conventional antipsychotics, Schizophr. Res., 60(1), 97–98
Raskin S, Durst R, Katz G, Zislin J (2000) Olanzapine and sulpiride: a preliminary study of combination/augmentation in patients with treatment-resistant schizophrenia, J. Clin. Psychopharmacol., 20(5), 500–503
Rhoads E (2000) Polypharmacy of 2 atypical antipsychotics, J. Clin. Psychiatry, 61(9), 678–680
Risch SC, McGurk S, Horner MD, Nahas Z, Owens SD, Molloy M, Gilliard C, Christie S, Markowitz JS, DeVane CL, Mintzer J, George MS (2001) A double-blind placebo-controlled case study of the use of donepezil to improve cognition in a schizoaffective disorder patient: functional MRI correlates, Neurocase., 7(2), 105–110
Ritsner M, Gibel A, Perelroyzen G, Kurs R, Jabarin M, Ratner Y (2004) Quality of life outcomes of risperidone, olanzapine, and typical antipsychotics among schizophrenia patients treated in routine clinical practice: a naturalistic comparative study, J. Clin. Psychopharmacol., 24(6), 582–591
Rittmannsberger H, Leblhuber F (1992) Asterixis induced by carbamazepine therapy, Biol. Psychiatry, 32(4), 364–368
Rittmannsberger H, Leblhuber F, Sommer R (1991) Asterixis as a side effect of carbamazepine therapy, Klin. Wochenschr., 69(6), 279–281
Rocha FL, Hara C (2006) Benefits of combining aripiprazole to clozapine: three case reports, Prog. Neuropsychopharmacol. Biol. Psychiatry, 30(6), 1167–1169
Rothbard AB, Kuno E, Foley K (2003) Trends in the rate and type of antipsychotic medications prescribed to persons with schizophrenia, Schizophr. Bull., 29(3), 531–540
Rummel C, Kissling W, Leucht S (2006) Antidepressants for the negative symptoms of schizophrenia, Cochrane. Database. Syst. Rev., 3, CD005581
Rupnow MF, Greenspan A, Gharabawi GM, Kosik-Gonzalez C, Zhu Y, Stahl SM (2007) Incidence and costs of polypharmacy: data from a randomized, double-blind, placebo-controlled study of risperidone and quetiapine in patients with schizophrenia or schizoaffective disorder, Curr. Med. Res. Opin., 23(11), 2815–2822
Sacchetti E, Panariello A, Regini C, Valsecchi P (2004) Quetiapine in hospitalized patients with schizophrenia refractory to treatment with first-generation antipsychotics: a 4-week, flexible-dose, single-blind, exploratory, pilot trial, Schizophr. Res., 69(2–3), 325–331
Salokangas RK, Saarijarvi S, Taiminen T, Kallioniemi H, Lehto H, Niemi H, Tuominen J, Ahola V, Syvalahti E (1996) Citalopram as an adjuvant in chronic schizophrenia: a double-blind placebo-controlled study, Acta Psychiatr. Scand., 94(3), 175–180
Sands JR, Harrow M (1999) Depression during the longitudinal course of schizophrenia, Schizophr. Bull., 25(1), 157–171
Schulz SC, Thompson PA, Jacobs M, Ninan PT, Robinson D, Weiden PJ, Yadalam K, Glick ID, Odbert CL (1999) Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients, J. Clin. Psychiatry, 60(6), 366–372
Schumacher JE, Makela EH, Griffin HR (2003) Multiple antipsychotic medication prescribing patterns, Ann. Pharmacother., 37(7–8), 951–955
Schwarz C, Volz A, Li C, Leucht S (2008) Valproate for schizophrenia, Cochrane. Database. Syst. Rev.,(3), CD004028
Seger A, Lamberti JS (2001) Priapism associated with polypharmacy, J. Clin. Psychiatry, 62(2), 128
Sepehry A A, Potvin S, Elie R, Stip E (2007) Selective serotonin reuptake inhibitor (SSRI) add-on therapy for the negative symptoms of schizophrenia: a meta-analysis, J. Clin. Psychiatry, 68(4), 604–610
Sernyak MJ, Rosenheck R (2004) Clinicians' reasons for antipsychotic coprescribing, J. Clin. Psychiatry, 65(12), 1597–1600
Shiloh R, Zemishlany Z, Aizenberg D, Radwan M, Schwartz B, Dorfman-Etrog P, Modai I, Khaikin M, Weizman A (1997) Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study, Br. J. Psychiatry, 171, 569–573
Silver H (2001) Fluvoxamine as an adjunctive agent in schizophrenia, CNS. Drug Rev., 7(3), 283–304
Silver H (2003) Selective serotonin reuptake inhibitor augmentation in the treatment of negative symptoms of schizophrenia, Int Clin. Psychopharmacol., 18(6), 305–313
Sim K, Su A, Fujii S, Yang SY, Chong MY, Ungvari GS, Si T, Chung EK, Tsang HY, Chan YH, Heckers S, Shinfuku N, Tan CH (2004) Antipsychotic polypharmacy in patients with schizophrenia: a multicentre comparative study in East Asia, Br. J. Clin. Pharmacol., 58(2), 178–183
Simhandl C, Meszaros K (1992) The use of carbamazepine in the treatment of schizophrenic and schizoaffective psychoses: a review, J. Psychiatry Neurosci., 17(1), 1–14
Singh SP, Singh V (2011) Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia, CNS. Drugs, 25(10), 859–885
Singh SP, Singh V, Kar N, Chan K (2010) Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis, Br. J. Psychiatry, 197(3), 174–179
Siris SG (2000) Depression in schizophrenia: perspective in the era of "Atypical" antipsychotic agents, Am. J. Psychiatry, 157(9), 1379–1389
Siris SG, Bermanzohn PC, Mason SE, Shuwall MA (1994) Maintenance imipramine therapy for secondary depression in schizophrenia. A controlled trial, Arch. Gen. Psychiatry, 51(2), 109–115
Sivrioglu EY, Kirli S, Sipahioglu D, Gursoy B, Sarandol E (2007) The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study, Prog. Neuropsychopharmacol. Biol. Psychiatry, 31(7), 1493–1499
Small JG, Kellams JJ, Milstein V, Moore J (1975) A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients, Am. J. Psychiatry, 132(12), 1315–1317
Small JG, Klapper MH, Malloy FW, Steadman TM (2003) Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder, J Clin Psychopharmacol. 23(3), 223–8
Sommer IE, de Witte L, Begemann M, Kahn RS (2012) Nonsteroidal anti-inflammatory drugs in schizophrenia: ready for practice or a good start? A meta-analysis, J. Clin. Psychiatry, 73(4), 414–419
Sommer IE, van Westrhenen R, Begemann MJ, de Witte LD, Leucht S, Kahn RS (2014) Efficacy of Anti-inflammatory Agents to Improve Symptoms in Patients With Schizophrenia: An Update, Schizophr. Bull., 40(1), 181–191
Stahl SM (1999) Antipsychotic polypharmacy, Part 1: Therapeutic option or dirty little secret?, J. Clin. Psychiatry, 60(7), 425–426
Stahl SM, Grady MM (2004) A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation, Curr. Med. Chem., 11(3), 313–327
Stanley JA, Williamson PC, Drost DJ, Carr TJ, Rylett RJ, Morrison-Stewart S, Thompson RT (1994) Membrane phospholipid metabolism and schizophrenia: an in vivo 31P-MR spectroscopy study, Schizophr. Res., 13(3), 209–215
Strasser O, Schmauss M, Messer T (2004) Rehospitalization rates of newly diagnosed schizophrenic patients on atypical neuroleptic medication, Psychiatr. Prax., 31 Suppl 1, S38–S40
Strous RD, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M, Weizman A (2003) Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia, Arch. Gen. Psychiatry, 60(2), 133–141
Stubbs JH, Haw CM, Staley CJ, Mountjoy CQ (2000) Augmentation with sulpiride for a schizophrenic patient partially responsive to clozapine, Acta Psychiatr Scand. 102(5) : 390–3; discussion 393–4. Review.
Suzuki T, Remington G, Mulsant BH, Rajji TK, Uchida H, Graff-Guerrero A, Mamo DC (2011) Treatment resistant schizophrenia and response to antipsychotics: a review, Schizophr. Res., 133(1–3), 54–62
Suzuki T, Uchida H, Tanaka KF, Nomura K, Takano H, Tanabe A, Watanabe K, Yagi G, Kashima H (2004a) Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia, Int. J. Neuropsychopharmacol., 7(2), 133–142
Suzuki T, Uchida H, Watanabe K, Nakajima S, Nomura K, Takeuchi H, Tanabe A, Yagi G, Kashima H (2008) Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidone, Hum. Psychopharmacol., 23(6), 455–463
Suzuki T, Uchida H, Watanabe K, Yagi G, Kashima H (2004b) A clinical case series of switching from antipsychotic polypharmacy to monotherapy with a second-generation agent on patients with chronic schizophrenia, Prog. Neuropsychopharmacol. Biol. Psychiatry, 28(2), 361–369
Szegedi A, Anghelescu I, Wiesner J, Schlegel S, Weigmann H, Hartter S, Hiemke C, Wetzel H (1999) Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial, Pharmacopsychiatry, 32(4), 148–153
Szegedi A, Wiesner J, Hiemke C (1995) Improved efficacy and fewer side effects under clozapine treatment after addition of fluvoxamine, J Clin. Psychopharmacol., 15(2), 141–143
Takahashi H, Sugita T, Higuchi H, Shimizu T (2002) Fluvoxamine augmentation in risperidone-resistant schizophrenia: an open trial, Hum. Psychopharmacol., 17(2), 95–98
Takhar J (1999) Pimozide augmentation in a patient with drug-resistant psychosis previously treated with olanzapine, J. Psychiatry Neurosci., 24(3), 248–249
Tandon R, Jibson MD (2003) Efficacy of newer generation antipsychotics in the treatment of schizophrenia, Psychoneuroendocrinology, 28 Suppl 1, 9–26
Tapp A, Wood AE, Secrest L, Erdmann J, Cubberley L, Kilzieh N (2003) Combination antipsychotic therapy in clinical practice, Psychiatr. Serv., 54(1), 55–59
Taylor CG, Flynn SW, Altman S, Ehmann T, MacEwan GW, Honer WG (2001) An open trial of risperidone augmentation of partial response to clozapine, Schizophr Res. 48(1), 155–8
Terao T, Kojima H (2001) Risperidone addition and psychotic exacerbation, J. Neuropsychiatry Clin. Neurosci., 13(1), 114–115
Tiihonen J, Hallikainen T, Ryynanen OP, Repo-Tiihonen E, Kotilainen I, Eronen M, Toivonen P, Wahlbeck K, Putkonen A (2003) Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial, Biol. Psychiatry, 54(11), 1241–1248
Tiihonen J, Suokas JT, Suvisaari JM, Haukka J, Korhonen P (2012) Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia, Arch. Gen. Psychiatry, 69(5), 476–483
Tiihonen J, Wahlbeck K, Kiviniemi V (2009) The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis, Schizophr. Res., 109(1–3), 10–14
Tollefson GD, Sanger TM, Lu Y, Thieme ME (1998) Depressive signs and symptoms in schizophrenia: a prospective blinded trial of olanzapine and haloperidol, Arch. Gen. Psychiatry, 55(3), 250–258
Tuominen HJ, Tiihonen J, Wahlbeck K (2005) Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis, Schizophr. Res., 72(2–3), 225–234
Tuunainen A, Wahlbeck K, Gilbody S (2002) Newer atypical antipsychotic medication in comparison to clozapine: a systematic review of randomized trials, Schizophr. Res., 56(1–2), 1–10
Tyson SC, Devane CL, Risch SC (1995) Pharmacokinetic interaction between risperidone and clozapine, Am J Psychiatry. 152(9), 1401–2
Valevski A, Modai I, Lahav M, Weizman A (1993) Clozapine-lithium combined treatment and agranulocytosis, Int Clin Psychopharmacol. 8(1), 63–5
Volz A, Khorsand V, Gillies D, Leucht S (2007) Benzodiazepines for schizophrenia, Cochrane. Database. Syst. Rev.,(1), CD006391
Voruganti L, Cortese L, Owyeumi L, Kotteda V, Cernovsky Z, Zirul S, Awad A (2002) Switching from conventional to novel antipsychotic drugs: results of a prospective naturalistic study, Schizophr. Res., 57(2–3), 201–208
Voruganti L, Cortese L, Oyewumi L, Cernovsky Z, Zirul S, Awad A (2000) Comparative evaluation of conventional and novel antipsychotic drugs with reference to their subjective tolerability, side-effect profile and impact on quality of life, Schizophr. Res., 43(2–3), 135–145
Wang J, Omori IM, Fenton M, Soares B (2010) Sulpiride augmentation for schizophrenia, Cochrane. Database. Syst. Rev., (1), CD008125
Wassink TH, Flaum M, Nopoulos P, Andreasen NC (1999) Prevalence of depressive symptoms early in the course of schizophrenia, Am. J. Psychiatry, 156(2), 315–316
Weigmann H, Gerek S, Zeisig A, Muller M, Hartter S, Hiemke C (2001) Fluvoxamine but not sertraline inhibits the metabolism of olanzapine: evidence from a therapeutic drug monitoring service, Ther. Drug Monit., 23(4), 410–413
Weinmann S, Read J, Aderhold V (2009) Influence of antipsychotics on mortality in schizophrenia: systematic review, Schizophr. Res., 113(1), 1–11
Wetzel H, Anghelescu I, Szegedi A, Wiesner J, Weigmann H, Harter S, Hiemke C (1998) Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study, J Clin. Psychopharmacol., 18(1), 2–9
Wilson WH (1995) Do anticonvulsants hinder clozapine treatment?, Biol. Psychiatry, 37(2), 132–133
Wirshing WC, Ames D, Bisheff S, Pierre JM, Mendoza A, Sun A (1997) Hepatic encephalopathy associated with combined clozapine and divalproex sodium treatment, J. Clin. Psychopharmacol., 17(2), 120–121
Wolkowitz OM (1993) Rational polypharmacy in schizophrenia, Ann. Clin. Psychiatry, 5(2), 79–90
Xiang YT, Weng YZ, Leung CM, Tang WK, Ungvari GS (2007) Clinical and social determinants of antipsychotic polypharmacy for Chinese patients with schizophrenia, Pharmacopsychiatry, 40(2), 47–52
Yamauchi K, Baba K, Ikegami N, Miyaoka H, Kamijima K (1998) A survey of drug utilization in psychiatric hospitals in Japan: the basic analysis of the current status of prescription patterns, Seishin Shinkeigaku Zasshi, 100(1), 51–68
Zarate CA Jr, Daniel DG, Kinon BJ, Litman RE, Naber D, Pickar D, Sato M (1995) Algorithms for the treatment of schizophrenia, Psychopharmacol. Bull., 31(3), 461–467
Ziegenbein M, Kropp S, Kuenzel HE (2005) Combination of clozapine and ziprasidone in treatment-resistant schizophrenia: an open clinical study, Clin. Neuropharmacol., 28(5), 220–224
Ziegenbein M, Wittmann G, Kropp S (2006) Aripiprazole augmentation of clozapine in treatment-resistant schizophrenia: a clinical observation, Clin. Drug Investig., 26(3), 117–124
Zink M, Henn FA, Thome J (2004d) Combination of amisulpride and olanzapine in treatment-resistant schizophrenic psychoses, Eur Psychiatry. 19(1), 56–58
Zink M, Knopf U, Henn FA, Thome J (2004a) Combination of clozapine and amisulpride in treatment-resistant schizophrenia – case reports and review of the literature, Pharmacopsychiatry, 37(1), 26–31
Zink M, Kuwilsky A, Krumm B, Dressing H (2008) Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial, J. Psychopharmacol.
Zink M, Mase E, Dressing H (2004c) Ziprasidone-augmentation of clozapine, Psychiatr. Prax., 31(5), 259–261
Zink M, Mase E, Dressing H (2004b) Combination of ziprasidone and clozapine in treatment-resistant schizophrenia, Hum. Psychopharmacol., 19(4), 271–273
Zisook S, McAdams LA, Kuck J, Harris MJ, Bailey A, Patterson TL, Judd LL, Jeste DV (1999) Depressive symptoms in schizophrenia, Am. J. Psychiatry, 156(11), 1736–1743
Zoccali R, Muscatello MR, Bruno A, Cambria R, Mico U, Spina E, Meduri M (2007) The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study, Schizophr. Res., 93(1–3), 109–116
Zoccali R, Muscatello MR, Cedro C, Neri P, La Torre D, Spina E, Di Rosa AE, Meduri M (2004) The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study, Int Clin. Psychopharmacol., 19(2), 71–76
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer-Verlag Wien
About this chapter
Cite this chapter
Messer, T., Tiltscher, C., Schmauß, M. (2016). Behandlung der Schizophrenie. In: Messer, T., Schmauß, M. (eds) Polypharmazie in der Behandlung psychischer Erkrankungen. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1849-8_2
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1849-8_2
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1848-1
Online ISBN: 978-3-7091-1849-8
eBook Packages: Medicine (German Language)