Advertisement

CNS Drugs

, Volume 19, Issue 10, pp 843–872 | Cite as

Augmentation Strategies in Clozapine-Resistant Schizophrenia

  • Gary Remington
  • Amitabha Saha
  • Siow-Ann Chong
  • Chekkera Shammi
Review Article

Abstract

.The introduction of antipsychotics in the 1950s revolutionised the treatment of schizophrenia, but it soon became apparent that a substantial number of patients demonstrated a suboptimal response to these antipsychotics. Clozapine proved to be beneficial in patients whose symptoms were treatment resistant, but it too had limitations, with as many as 40–70% of those treated with clozapine demonstrating inadequate response to this drug as well. The availability of other ‘atypical’ antipsychotics offers options, but clozapine appears to remain the most effective option in treatment-resistant schizophrenia. This, of course, raises the question of what to do when clozapine is only partially effective.

To address the issue of treatment in patients who have demonstrated a suboptimal response to clozapine, efforts have focused on a variety of augmentation strategies, including numerous medications and electroconvulsive therapy. The current body of evidence consists largely of data from smaller open trials and case series/reports, although data from a limited number of controlled studies are now available. Not surprisingly, the evidence drawn from the former is more supportive of augmentation strategies, although the controlled trials are not without positive findings.

The available information is certainly not so overwhelming as to endorse any single augmentation approach. Indeed, it argues for more controlled data and cautions us regarding the cost-benefit ratio in adopting this strategy. Over and above the added adverse effects of another treatment, there is evidence to indicate that actual clinical worsening can occur.

Without compelling evidence, clinicians must resort to guiding principles. The potential benefits of augmentation cannot be ruled out, but it should be approached with caution and in a systematic fashion. Factors compromising clozapine response should first be ruled out, and any augmentation trials should be guided by existing evidence and a treatment plan that incorporates a clear understanding of target symptoms. A means of evaluating outcome effectively needs to be in place, and the trial should be circumscribed to prevent needless polypharmacy. A priori, an endpoint needs to be established and the trial discontinued unless results firmly support added benefits.

Keywords

Schizophrenia Clozapine Risperidone Olanzapine Lamotrigine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Brenner HD, Dencker SJ, Goldstein MJ, et al. Defining treatment refractoriness in schizophrenia. Schizophr Bull 1990; 16: 551–61PubMedCrossRefGoogle Scholar
  2. 2.
    Kane JM. Treatment-resistant schizophrenic patients. J Clin Psychiatry 1996; 57: 35–40PubMedGoogle Scholar
  3. 3.
    Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlor-promazine. Arch Gen Psychiatry 1988; 45: 789–96PubMedCrossRefGoogle Scholar
  4. 4.
    Hippius H. A historical perspective of clozapine. J Clin Psychiatry 1999; 60: 22–3PubMedCrossRefGoogle Scholar
  5. 5.
    Deniker P. From chlorpromazine to tardive dyskinesia (brief history of neuroleptics). Psychiatr J Univ Ott 1989; 14: 253–9PubMedGoogle Scholar
  6. 6.
    Deniker P. The neuroleptics: a historical survey. Acta Psychiatr Scand Suppl 1990; 358: 83–7PubMedCrossRefGoogle Scholar
  7. 7.
    Meltzer H. Atypical antipsychotic drugs. In: Bloom FE, Kupfer D, editors. Psychopharmacology: the fourth generation of progress. New York (NY): Raven Press, 1995: 1277–86Google Scholar
  8. 8.
    Blin O. A comparative review of new antipsychotics. Can J Psychiatry 1999; 44: 235–44PubMedGoogle Scholar
  9. 9.
    Fleischhacker WW. Second generation antipsychotics. Psychopharmacology 2002; 162: 90–1PubMedCrossRefGoogle Scholar
  10. 10.
    Potkin SG, Saha AR, Kujawa MJ, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaf-fective disorder. Arch Gen Psychiatry 2003; 60: 681–90PubMedCrossRefGoogle Scholar
  11. 11.
    Cole JO, Goldberg SC, Klerman GL. Phenothiazine treatment in acute schizophrenia. Arch Gen Psychiatry 1964; 10: 246–61CrossRefGoogle Scholar
  12. 12.
    Cole JO, Goldberg SC, Davis JM. Drugs in the treatment of psychosis. In: Solomon P, editor. Psychiatric drugs. New York (NY): Grune & Stratton, 1966: 153–80Google Scholar
  13. 13.
    VanRossum J. The significance of dopamine-receptor blockade for the action of neuroleptic drugs. In: Brill H, Cole J, Deniker P, et al., editors. Neuropsychopharmacology, procedings of the 5th Collegium Internationale Neuro-psycho-pharmacologicum. Amsterdam: Excerptica Medica, 1967: 321–9Google Scholar
  14. 14.
    Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997; 23: 663–74PubMedCrossRefGoogle Scholar
  15. 15.
    Vanelle J. Refractory schizophrenia: historical and currently prevailing criteria and definitions. Eur Psychiatry 1997; 12: 321S–6SPubMedCrossRefGoogle Scholar
  16. 16.
    Peuskens J. The evolving definition of treatment resistance. J Clin Psychiatry 1999; 60: 4–8PubMedGoogle Scholar
  17. 17.
    Conley RR, Kelly DL. Management of treatment resistance in schizophrenia. Biol Psychiatry 2001; 50: 898–911PubMedCrossRefGoogle Scholar
  18. 18.
    Remington G, Kapur S. Atypical antipsychotics: are some more atypical than others? Psychopharmacology (Berl) 2000; 148: 3–15CrossRefGoogle Scholar
  19. 19.
    Wahlbeck K, Cheine M, Essali A, et al. Evidence of clozapine’s effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials. Am J Psychiatry 1999; 156: 990–9PubMedGoogle Scholar
  20. 20.
    Moncrieff J. Clozapine vs conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination. Br J Psychiatry 2003; 183: 161–6PubMedCrossRefGoogle Scholar
  21. 21.
    Kane JM, Marder SR, Schooler NR, et al. Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison. Arch Gen Psychiatry 2001; 58: 965–72PubMedCrossRefGoogle Scholar
  22. 22.
    Howanitz E, Pardo M, Smelson DA, et al. The efficacy and safety of clozapine versus chlorpromazine in geriatric schizophrenia. J Clin Psychiatry 1999; 60: 41–4PubMedCrossRefGoogle Scholar
  23. 23.
    Ciapparelli A, Dell’Osso L, Bandettini di Poggio A, et al. Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: a naturalistic 48-month follow-up study. J Clin Psychiatry 2003; 64: 451–8PubMedCrossRefGoogle Scholar
  24. 24.
    Essock SM, Drake RE, Frank RG, et al. Randomized controlled trials in evidence-based mental health care: getting the right answer to the right question. Schizophr Bull 2003; 29: 115–23PubMedCrossRefGoogle Scholar
  25. 25.
    Roy-Byrne PP, Sherbourne CD, Craske MG, et al. Moving treatment research from clinical trials to the real world. Psychiatr Serv 2003; 54: 327–32PubMedCrossRefGoogle Scholar
  26. 26.
    Conley RR, Schulz SC, Baker RW, et al. Clozapine efficacy in schizophrenic nonresponders. Psychopharmacol Bull 1988; 24: 269–74PubMedGoogle Scholar
  27. 27.
    Pickar D, Owen RR, Litman RE, et al. Clinical and biologic response to clozapine in patients with schizophrenia: crossover comparison with fluphenazine. Arch Gen Psychiatry 1992; 49: 345–53PubMedCrossRefGoogle Scholar
  28. 28.
    Breier A, Buchanan RW, Kirkpatrick B, et al. Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. Am J Psychiatry 1994; 151: 20–6PubMedGoogle Scholar
  29. 29.
    Hong CJ, Chen JY, Chiu HJ, et al. A double-blind comparative study of clozapine versus chlorpromazine on Chinese patients with treatment-refractory schizophrenia. Int Clin Psychopharmacol 1997; 12: 123–30PubMedCrossRefGoogle Scholar
  30. 30.
    Rosenheck R, Cramer J, Xu W, et al. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. N Engl J Med 1997; 337: 809–15PubMedCrossRefGoogle Scholar
  31. 31.
    Essock SM, Hargreaves WA, Covell NH, et al. Clozapine’s effectiveness for patients in state hospitals: results from a randomized trial. Psychopharmacol Bull 1996; 32: 683–97PubMedGoogle Scholar
  32. 32.
    Heinrich K, Klieser E, Lehmann E, et al. Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18: 129–37PubMedCrossRefGoogle Scholar
  33. 33.
    Bondolfi G, Dufour H, Patris M, et al. Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. Am J Psychiatry 1998; 155: 499–504PubMedGoogle Scholar
  34. 34.
    Breier AF, Malhotra AK, Su TP, et al. Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkin-sonian side effects, and neuroendocrine response. Am J Psychiatry 1999; 156: 294–8PubMedGoogle Scholar
  35. 35.
    Azorin JM, Spiegel R, Remington G, et al. A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia. Am J Psychiatry 2001; 158: 1305–13PubMedCrossRefGoogle Scholar
  36. 36.
    Meyer-Lindenberg A, Gruppe H, Bauer U, et al. Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study. Pharmacopsychiatry 1997; 30: 35–42PubMedCrossRefGoogle Scholar
  37. 37.
    Tollefson GD, Birkett MA, Kiesler GM, et al. Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine. Biol Psychiatry 2001; 49: 52–63PubMedCrossRefGoogle Scholar
  38. 38.
    Volavka J, Czobor P, Sheitman B, et al. Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am J Psychiatry 2002; 159: 255–62PubMedCrossRefGoogle Scholar
  39. 39.
    Conley RR, Kelly DL, Richardson CM, et al. The efficacy of high-dose olanzapine versus clozapine in treatment-resistant schizophrenia: a double-blind crossover study. J Clin Psychopharmacol 2003; 23: 668–71PubMedCrossRefGoogle Scholar
  40. 40.
    Fleischhacker WW. Clozapine: a comparison with other novel antipsychotics. J Clin Psychiatry 1999; 60Suppl. 12: 30–4PubMedGoogle Scholar
  41. 41.
    Tuunainen A, Wahlbeck K, Gilbody S. Newer atypical antipsychotic medication in comparison to clozapine: a systematic review of randomized trials. Schizophr Res 2002; 56: 1–10PubMedCrossRefGoogle Scholar
  42. 42.
    Kane JM, Leucht S, Carpenter D, et al. Optimizing pharmacologic treatment of psychotic disorders. J Clin Psychiatry 2003; 64Suppl. 12: 5–19PubMedGoogle Scholar
  43. 43.
    Lieberman JA, Safferman AZ, Pollack S, et al. Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome. Am J Psychiatry 1994; 151: 1744–52PubMedGoogle Scholar
  44. 44.
    Meltzer HY, Bastani B, Kwon KY, et al. A prospective study of clozapine in treatment-resistant schizophrenic patients: I. Pre-liminary report. Psychopharmacology (Berl) 1989; 99: S68–72CrossRefGoogle Scholar
  45. 45.
    Juul Povlsen U, Noring U, Fog R, et al. Tolerability and therapeutic effect of clozapine: a retrospective investigation of 216 patients treated with clozapine for up to 12 years. Acta Psychiatr Scand 1985; 71: 176–85PubMedCrossRefGoogle Scholar
  46. 46.
    Marinkovic D, Timotijevic I, Babinski T, et al. The side-effects of clozapine: a four year follow-up study. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18: 537–44PubMedCrossRefGoogle Scholar
  47. 47.
    Wang PS, Glynn RJ, Ganz DA, et al. Clozapine use and risk of diabetes mellitus. J Clin Psychopharmacol 2002; 22: 236–43PubMedCrossRefGoogle Scholar
  48. 48.
    Young CR, Bowers Jr MB, Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull 1998; 24: 381–90PubMedCrossRefGoogle Scholar
  49. 49.
    Potkin SG, Bera R, Gulasekaram B, et al. Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia. J Clin Psychiatry 1994; 55Suppl. B: 133–6PubMedGoogle Scholar
  50. 50.
    Centorrino F, Baldessarini RJ, Kando J, et al. Serum concentrations of clozapine and its major metabolites: effects of cotreatment with fluoxetine or valproate. Am J Psychiatry 1994; 151: 123–5PubMedGoogle Scholar
  51. 51.
    Centorrino F, Baldessarini RJ, Kando JC, et al. Clozapine and metabolites: concentrations in serum and clinical findings during treatment of chronically psychotic patients. J Clin Psychopharmacol 1994; 14: 119–25PubMedCrossRefGoogle Scholar
  52. 52.
    Kronig MH, Munne RA, Szymanski S, et al. Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients. Am J Psychiatry 1995; 152: 179–82PubMedGoogle Scholar
  53. 53.
    Perry PJ, Miller DD, Arndt SV, et al. Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients. Am J Psychiatry 1991; 148: 231–5PubMedGoogle Scholar
  54. 54.
    Hasegawa M, Gutierrez-Esteinou R, Way L, et al. Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: effect of smoking. J Clin Psychopharmacol 1993; 13: 383–90PubMedCrossRefGoogle Scholar
  55. 55.
    VanderZwaag C, McGee M, McEvoy JP, et al. Response of patients with treatment-refractory schizophrenia to clozapine within three serum level ranges. Am J Psychiatry 1996; 153: 1579–84PubMedGoogle Scholar
  56. 56.
    Meltzer HY. Clozapine: is another view valid? Am J Psychiatry 1995; 152: 821–5PubMedGoogle Scholar
  57. 57.
    Carpenter Jr WT, Conley RR, Buchanan RW, et al. Clozapine conflict. Am J Psychiatry 1996; 153: 1505–7PubMedGoogle Scholar
  58. 58.
    Carpenter Jr WT, Conley RR, Buchanan RW, et al. Patient response and resource management: another view of clozapine treatment of schizophrenia. Am J Psychiatry 1995; 152: 827-32PubMedGoogle Scholar
  59. 59.
    Conley RR, Carpenter Jr WT, Tamminga CA. Time to clozapine response in a standardized trial. Am J Psychiatry 1997; 154: 1243–7PubMedGoogle Scholar
  60. 60.
    Fabrazzo M, La Pia S, Monteleone P, et al. Is the time course of clozapine response correlated to the time course of clozapine plasma levels? A one-year prospective study in drug-resistant patients with schizophrenia. Neuropsychopharmacology 2002; 27: 1050–5PubMedCrossRefGoogle Scholar
  61. 61.
    Wilson WH. Time required for initial improvement during clozapine treatment of refractory schizophrenia. Am J Psychiatry 1996; 153: 951–2PubMedGoogle Scholar
  62. 62.
    Rosenheck R, Evans D, Herz L, et al. How long to wait for a response to clozapine: a comparison of time course of response to clozapine and conventional antipsychotic medication in refractory schizophrenia. Schizophr Bull 1999; 25: 709–19PubMedCrossRefGoogle Scholar
  63. 63.
    Chong SA, Remington G. Clozapine augmentation: safety and efficacy. Schizophr Bull 2000; 26: 421–40PubMedCrossRefGoogle Scholar
  64. 64.
    Williams L, Newton G, Roberts K, et al. Clozapine-resistant schizophrenia: a positive approach. Br J Psychiatry 2002; 181: 184–7PubMedCrossRefGoogle Scholar
  65. 65.
    Buckley P, Miller A, Olsen J, et al. When symptoms persist: clozapine augmentation strategies. Schizophr Bull 2001; 27: 615–28PubMedCrossRefGoogle Scholar
  66. 66.
    Lerner V, Libov I, Kotier M, et al. Combination of “atypical” antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 89–98PubMedCrossRefGoogle Scholar
  67. 67.
    Buchanan RW, Kirkpatrick B, Bryant N, et al. Fluoxetine augmentation of clozapine treatment in patients with schizophrenia. Am J Psychiatry 1996; 153: 1625–7PubMedGoogle Scholar
  68. 68.
    Zoccali R, Muscatello MR, Cedro C, et al. The effects of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study. Clin Psychopharmacol 2004; 19: 71–6CrossRefGoogle Scholar
  69. 69.
    Shiloh R, Zemishlany Z, Aizenberg D, et al. Sulpiride augmentation in people with schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled study. Br J Psychiatry 1997; 171: 569–73PubMedCrossRefGoogle Scholar
  70. 70.
    Yagcioglu AEA, Akdede BBK, Turgut TI, et al. A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety. J Clin Psychiatry 2005; 66: 63–72CrossRefGoogle Scholar
  71. 71.
    Josiassen RC, Joseph A, Kohegyi E, et al. Clozapine augmented with risperidone in the treatment of schizophrenia: a random-ized, double-blind, placebo-controlled trial. Am J Psychiatry 2005; 162: 130–6PubMedCrossRefGoogle Scholar
  72. 72.
    Small JG, Klapper MH, Malloy FW, et al. Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder. J Clin Psychopharmacol 2003; 23: 223–8PubMedGoogle Scholar
  73. 73.
    Tiihonen J, Hallikainen T, Ryynanen OP, et al. Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial. Biol Psychiatry 2003; 54: 1241–8PubMedCrossRefGoogle Scholar
  74. 74.
    Tsai GE, Yang P, Chung LC, et al. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry 1999; 156: 1822–5PubMedGoogle Scholar
  75. 75.
    Potkin SG, Jin Y, Bunney BG, et al. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. Am J Psychiatry 1999; 156: 145–7PubMedGoogle Scholar
  76. 76.
    Goff DC, Tsai G, Manoach DS, et al. D-cycloserine added to clozapine for patients with schizophrenia. Am J Psychiatry 1996; 153: 1628–30PubMedGoogle Scholar
  77. 77.
    Goff DC, Leahy L, Berman I, et al. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J Clin Psychopharmacol 2001; 21: 484–7PubMedCrossRefGoogle Scholar
  78. 78.
    Goff DC, Henderson DC, Evins AE, et al. A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia. Biol Psychiatry 1999; 45: 512–4PubMedCrossRefGoogle Scholar
  79. 79.
    Evins AE, Fitzgerald SM, Wine L, et al. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry 2000; 157: 826–8PubMedCrossRefGoogle Scholar
  80. 80.
    Diaz P, Bhaskara S, Dursun SM, et al. Double-blind, placebo-controlled, crossover trial of clozapine plus glycine in refractory schizophrenia: negative results [letter]. J Clin Psychopharmacol 2005; 25: 277–8PubMedCrossRefGoogle Scholar
  81. 81.
    Potter WZ, Ko GN, Zhang LD, et al. Clozapine in China: a review and preview of US/PRC collaboration. Psychopharma-cology (Berl) 1989; 99: S87–91CrossRefGoogle Scholar
  82. 82.
    Leucht S, Pitschel-Walz G, Abraham D, et al. 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: 51–68PubMedCrossRefGoogle Scholar
  83. 83.
    Wyatt RJ. Early intervention for schizophrenia: can the course of the illness be altered? Biol Psychiatry 1995; 38: 1–3PubMedCrossRefGoogle Scholar
  84. 84.
    Kontaxakis VP, Ferentinos PP, Havaki-Kontaxakis BJ, et al. Case studies of adjunctive agents in clozapine-resistant schizophrenic patients. Clin Neuropharmacol 2005; 28: 50–3PubMedCrossRefGoogle Scholar
  85. 85.
    Weissman EM. Antipsychotic prescribing practices in the Veterans Healthcare Administration-New York metropolitan region. Schizophr Bull 2002; 28: 31–42PubMedCrossRefGoogle Scholar
  86. 86.
    Covell NH, Jackson CT, Evans AC, et al. Antipsychotic prescribing practices in Connecticut’s public mental health system: rates of changing medications and prescribing styles. Schizophr Bull 2002; 28: 17–29PubMedCrossRefGoogle Scholar
  87. 87.
    Peacock L, Gerlach J. Clozapine treatment in Denmark: concomitant psychotropic medication and hematologic monitoring in a system with liberal usage practices. J Clin Psychiatry 1994; 55: 44–9PubMedGoogle Scholar
  88. 88.
    Tapp A, Wood AE, Secrest L, et al. Combination antipsychotic therapy in clinical practice. Psychiatr Serv 2003; 54: 55–9PubMedCrossRefGoogle Scholar
  89. 89.
    Procyshyn RM, Kennedy NB, Tse G, et al. Antipsychotic polypharmacy: a survey of discharge prescriptions from a tertiary care psychiatric institution. Can J Psychiatry 2001; 46: 334–9PubMedGoogle Scholar
  90. 90.
    Miller AL, Craig CS. Combination antipsychotics: pros, cons, and questions. Schizophr Bull 2002; 28: 105–9PubMedCrossRefGoogle Scholar
  91. 91.
    Stahl SM. Antipsychotic polypharmacy, Part 1: Therapeutic option or dirty little secret? J Clin Psychiatry 1999; 60: 506–7PubMedCrossRefGoogle Scholar
  92. 92.
    Stahl SM. Antipsychotic polypharmacy, Part 2: Tips on use and misuse. J Clin Psychiatry 1999; 60: 425–6PubMedCrossRefGoogle Scholar
  93. 93.
    Freudenreich O, Goff DC. Antipsychotic combination therapy in schizophrenia: a review of efficacy and risks of current combinations. Acta Psychiatr Scand 2002; 106: 323–30PubMedCrossRefGoogle Scholar
  94. 94.
    Stahl SM. Antipsychotic polypharmacy: evidence based or eminence based? Acta Psychiatr Scand 2002; 106: 321–2PubMedCrossRefGoogle Scholar
  95. 95.
    Mowerman S, Siris SG. Adjunctive loxapine in a clozapine-resistant cohort of schizophrenic patients. Ann Clin Psychiatry 1996; 8: 193–7PubMedCrossRefGoogle Scholar
  96. 96.
    Friedman J, Ault K, Powchik P. Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine. Biol Psychiatry 1997; 42: 522–3PubMedCrossRefGoogle Scholar
  97. 97.
    Rajarethinam R, Gilani S, Tancer M, et al. Augmentation of clozapine partial responders with conventional antipsychotics [letter]. Schizophr Res 2003; 60: 97–8PubMedCrossRefGoogle Scholar
  98. 98.
    Kapur S, Roy P, Daskalakis J, et al. Increased dopamine D2 receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. Am J Psychiatry 2001; 158: 311–4PubMedCrossRefGoogle Scholar
  99. 99.
    de Groot IW, Heck AH, van Harten PN. Addition of risperidone to clozapine therapy in chronically psychotic inpatients [letter]. J Clin Psychiatry 2001; 62: 129–30PubMedCrossRefGoogle Scholar
  100. 100.
    Henderson DC, Goff DC. Risperidone as an adjunct to clozapine therapy in chronic schizophrenics. J Clin Psychiatry 1996; 57: 395–7PubMedGoogle Scholar
  101. 101.
    Taylor CG, SW, Altman S, et al. An open trial of risperidone augmentation of partial response to clozapine. Schizophr Res 2001; 48: 155–8PubMedCrossRefGoogle Scholar
  102. 102.
    Morera AL, Barreiro P, Cano-Munoz JL. Risperidone and clozapine combination for the treatment of refractory schizophrenia. Acta Psychiatr Scand 1999; 99: 305–6PubMedCrossRefGoogle Scholar
  103. 103.
    Raskin S, Katz G, Zislin Z, et al. Clozapine and risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation. Acta Psychiatr Scand 2000; 101: 334–6PubMedGoogle Scholar
  104. 104.
    Raju GVL, Kumar R, Khanna S: Clozapine-risperidone combination in treatment-resistant schizophrenia [letter]. Aust N Z J Psychiatry 2001; 35: 543PubMedGoogle Scholar
  105. 105.
    Adesanya A, Pantelis C. Adjunctive risperidone treatment in patients with ‘clozapine-resistant schizophrenia’ [letter]. Aust N Z J Psychiatry 2000; 34: 533–4PubMedCrossRefGoogle Scholar
  106. 106.
    McCarthy RH, Terkelsen KG. Risperidone augmentation of clozapine. Pharmacopsychiatry 1995; 28: 61–3PubMedCrossRefGoogle Scholar
  107. 107.
    Tyson SC, Devane CL, Risch SC. Pharmacokinetic interaction between risperidone and clozapine [letter]. Am J Psychiatry 1995; 152: 1401–2PubMedGoogle Scholar
  108. 108.
    Chong SA, Tan CH, Lee HS. Hoarding and clozapine-risperidone combination [letter]. Can J Psychiatry 1996; 41: 315–6PubMedGoogle Scholar
  109. 109.
    Godleski LS, Sernyak MJ. Agranulocytosis after addition of risperidone to clozapine treatment [letter]. Am J Psychiatry 1996; 153: 735–6PubMedGoogle Scholar
  110. 110.
    Chong SA, Tan CH, Lee HS. Atrial ectopics with clozapine-risperidone combination [letter]. J Clin Psychopharmacol 1997; 17: 130–1PubMedCrossRefGoogle Scholar
  111. 111.
    Koreen AR, Lieberman JA, Kronig M, et al. Cross-tapering clozapine and risperidone [letter]. Am J Psychiatry 1995; 152: 1690PubMedGoogle Scholar
  112. 112.
    Beauchemin MA, Millaud F, Nguyen KA. A case of neuroleptic malignant syndrome with clozapine and risperidone [letter]. Can J Psychiatry 2002; 47: 886PubMedGoogle Scholar
  113. 113.
    Kontaxakis VP, Havaki-Kontaxaki BJ, Stamouli SS, et al. Toxic interaction between risperidone and clozapine: a case report. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 407–9PubMedCrossRefGoogle Scholar
  114. 114.
    Gupta S, Sonnenberg SJ, Frank B. Olanzapine augmentation of clozapine [letter]. Ann Clin Psychiatry 1998; 10: 113–5PubMedGoogle Scholar
  115. 115.
    Rhoads E. Polypharmacy of 2 atypical antipsychotics [letter]. J Clin Psychiatry 2000; 61: 678–80PubMedCrossRefGoogle Scholar
  116. 116.
    Flynn SW, Altman S, MacEwan GW, et al. Prolongation of clozapine-induced granulocytopenia associated with olanzapine [letter]. J Clin Psychopharmacol 1997; 17: 494–5PubMedCrossRefGoogle Scholar
  117. 117.
    Kaye NS. Ziprasidone augmentation of clozapine in 11 patients [letter]. J Clin Psychiatry 2003; 64: 215–6PubMedCrossRefGoogle Scholar
  118. 118.
    Reinstein MJ, Sirotovskaya LA, Jones LE, et al. Effect of clozapine-quetiapine combination therapy on weight and glycaemic control. Clin Drug Invest 1999; 18: 99–104CrossRefGoogle Scholar
  119. 119.
    Munro J, Matthiasson P, Osborne S, et al. Amisulpride augmentation of clozapine: an open non-randomized study in patients with schizophrenia partially responsive to clozapine. Acta Psychiatr Scand 2004; 110: 292–8PubMedCrossRefGoogle Scholar
  120. 120.
    George S, Cowan C. Effectiveness of amisulpride augmentation of clozapine in a non-responder to either drug alone: a case report [letter]. Acta Psychiatr Scand 2005; 111: 163PubMedCrossRefGoogle Scholar
  121. 121.
    Poyurovsky M, Hermesh H, Weizman A. Fluvoxamine treatment in clozapine-induced obsessive-compulsive symptoms in schizophrenic patients. Clin Neuropharmacol 1996; 19: 305–13PubMedCrossRefGoogle Scholar
  122. 122.
    Strous RD, Patel JK, Zimmet S, et al. Clozapine and paroxetine in the treatment of schizophrenia with obsessive-compulsive features [letter]. Am J Psychiatry 1999; 156: 973–4PubMedGoogle Scholar
  123. 123.
    Cassady SL, Thaker GK. Addition of fluoxetine to clozapine [letter]. Am J Psychiatry 1992; 149: 1274PubMedGoogle Scholar
  124. 124.
    Allen L, Tejera C. Treatment of clozapine-induced obsessive-compulsive symptoms with sertraline [letter]. Am J Psychiatry 1994; 151: 1096–7PubMedGoogle Scholar
  125. 125.
    Rahman MS, Grace JJ, Pato MT, et al. Sertraline in the treatment of clozapine-induced obsessive-compulsive behavior [letter]. Am J Psychiatry 1998; 155: 1629–30PubMedGoogle Scholar
  126. 126.
    Pallanti S, Quercioli L, Rossi A, et al. The emergence of social phobia during clozapine treatment and its response to fluoxetine augmentation. J Clin Psychiatry 1999; 60: 819–23PubMedCrossRefGoogle Scholar
  127. 127.
    Szegedi A, Anghelescu I, Wiesner J, et al. Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial. Pharmacopsychiatry 1999; 32: 148–53PubMedCrossRefGoogle Scholar
  128. 128.
    Lu ML, Lane HY, Chen KP, et al. Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients. J Clin Psychiatry 2000; 61: 594–9PubMedCrossRefGoogle Scholar
  129. 129.
    Spina E, Avenoso A, Facciola G, et al. Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia. Int Clin Psychopharmacol 1998; 13: 141–5PubMedCrossRefGoogle Scholar
  130. 130.
    Purdon SE, Snaterse M. Selective serotonin reuptake inhibitor modulation of clozapine effects on cognition in schizophrenia [letter]. Can J Psychiatry 1998; 43: 84–5PubMedGoogle Scholar
  131. 131.
    McGurk SR, Mueser KT, Harvey PD, et al. Cognitive and symptom predictors of work outcomes for clients with schizophrenia in supported employment. Psychiatr Serv 2003; 54: 1129–35PubMedCrossRefGoogle Scholar
  132. 132.
    Silver H, Kushnir M, Kaplan A. Fluvoxamine augmentation in clozapine-resistant schizophrenia: an open pilot study. Biol Psychiatry 1996; 40: 671–4PubMedCrossRefGoogle Scholar
  133. 133.
    Silver H, Kaplan A, Jahjah N. Fluvoxamine augmentation for clozapine-resistant schizophrenia [letter]. Am J Psychiatry 1995; 152: 1098PubMedGoogle Scholar
  134. 134.
    Kuo FJ, Lane HY, Chang WH. Extrapyramidal symptoms after addition of fluvoxamine to clozapine [letter]. J Clin Psychopharmacol 1998; 18: 483–4PubMedCrossRefGoogle Scholar
  135. 135.
    Hiemke C, Weigmann H, Hartter S, et al. Elevated levels of clozapine in serum after addition of fluvoxamine [letter]. J Clin Psychopharmacol 1994; 14: 279–81PubMedCrossRefGoogle Scholar
  136. 136.
    Dequardo JR, Roberts M. Elevated clozapine levels after fluvoxamine initiation [letter]. Am J Psychiatry 1996; 153: 840–1PubMedGoogle Scholar
  137. 137.
    Centorrino F, Baldessarini RJ, Frankenburg FR, et al. Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors [letter]. Am J Psychiatry 1996; 153: 820–2PubMedGoogle Scholar
  138. 138.
    Brosen K, Skjelbo E, Rasmussen BB, et al. Fluvoxamine is a potent inhibitor of cytochrome P4501A 2. Biochem Pharmacol 1993; 45: 1211–4PubMedCrossRefGoogle Scholar
  139. 139.
    Armstrong SC, Stephans JR. Blood clozapine levels elevated by fluvoxamine: potential for side effects and lower clozapine dosage [letter]. J Clin Psychiatry 1997; 58: 499PubMedCrossRefGoogle Scholar
  140. 140.
    Chong SA, Tan CH, Lee HS. Worsening of psychosis with clozapine and selective serotonin reuptake inhibitor combination: two case reports [letter]. J Clin Psychopharmacol 1997; 17: 68–9PubMedCrossRefGoogle Scholar
  141. 141.
    Kingsbury SJ, Puckett KM. Effects of fluoxetine on serum clozapine levels [letter]. Am J Psychiatry 1995; 152: 473–4PubMedGoogle Scholar
  142. 142.
    Sloan D, O’Boyle J. Hypertension and increased serum clozapine associated with clozapine and fluoxetine in combination. Ir J Psychol Med 1997; 14: 151–2Google Scholar
  143. 143.
    Wetzel H, Anghelescu I, Szegedi A, et al. Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol 1998; 18: 2–9PubMedCrossRefGoogle Scholar
  144. 144.
    Bryois C, Ferrero F. Clinical observation of 11 patients under clozapine-lithium association. Eur Psychiatry 1993; 8: 213–8Google Scholar
  145. 145.
    Bender S, Linka T, Wolstein J, et al. Safety and efficacy of combined clozapine-lithium pharmacotherapy. Int J Neuropsychopharmacol 2004; 7: 59–63PubMedCrossRefGoogle Scholar
  146. 146.
    Naber D, Holzbach R, Perro C, et al. Clinical management of clozapine patients in relation to efficacy and side-effects. Br J Psychiatry 1992; 17: 54–9Google Scholar
  147. 147.
    Lemus CZ, Lieberman JA, Johns CA. Myoclonus during treatment with clozapine and lithium: the role of serotonin. Hillside J Cin Psychiatry 1989; 11: 127–30Google Scholar
  148. 148.
    Garcia G, Crismon ML, Dorson PG. Scizures in two patients after the addition of lithium to a clozapine regimen [letter]. J Clin Psychopharmacol 1994; 14: 426–8PubMedGoogle Scholar
  149. 149.
    Blake LM, Marks RC, Luchins DJ. Reversible neurologic symptoms with clozapine and lithium [letter]. J Clin Psychopharmacol 1992; 12: 297–9PubMedCrossRefGoogle Scholar
  150. 150.
    Lee SH, Yang YY. Reversible neurotoxicity by a combination of clozapine and lithium. Zhonghua Yi Xue Za Zhi (Tapei) 1999; 62: 184–7Google Scholar
  151. 151.
    Peterson GA, Byrd SL. Diabetic ketoacidosis from clozapine and lithium cotreatment [letter]. Am J Psychiatry 1996; 153: 737–8PubMedGoogle Scholar
  152. 152.
    Pope Jr HG, Cole JO, Choras PT, et al. Apparent neuroleptic malignant syndrome with clozapine and lithium. J Nerv Ment Dis 1986; 174: 493–5PubMedCrossRefGoogle Scholar
  153. 153.
    Kando JC, Tohen M, Castillo J, et al. Concurrent use of clozapine and valproate in affective and psychotic disorders. J Clin Psychiatry 1994; 55: 255–7PubMedGoogle Scholar
  154. 154.
    Suppes T, Rush AJ. Medication optimization during clozapine treatment [letter]. J Clin Psychiatry 1996; 57: 307–8PubMedGoogle Scholar
  155. 155.
    Hofer A, Fleischhacker WW, Hummer M. Worsening of psychosis after replacement of adjunctive valproate with topiramate in a schizophrenia patient [letter]. J Clin Psychiatry 2003; 64: 1267–8PubMedCrossRefGoogle Scholar
  156. 156.
    Costello LE, Suppes T. A clinically significant interaction between clozapine and valproate [letter]. J Clin Psychopharmacol 1995; 15: 139–41PubMedCrossRefGoogle Scholar
  157. 157.
    Madeb R, Hirschmann S, Kurs R, et al. Combined clozapine and valproic acid treatment-induced agranulocytosis [letter]. Eur Psychiatry 2002; 17: 238–9PubMedCrossRefGoogle Scholar
  158. 158.
    Pantelis C, Adesanya A. Increased risk of neutropenia and agranulocytosis with sodium valproate used adjunctively with clozapine [letter]. Aust N Z J Psychiatry 2001; 35: 544–5PubMedCrossRefGoogle Scholar
  159. 159.
    Wirshing WC, Ames D, Bisheff S, et al. Hepatic encephalopathy associated with combined clozapine and divalproex sodium treatment [letter]. J Clin Psychopharmacol 1997; 17: 120–1PubMedCrossRefGoogle Scholar
  160. 160.
    Finley P, Warner D. Potential impact of valproic acid therapy on clozapine disposition. Biol Psychiatry 1994; 36: 487–8PubMedCrossRefGoogle Scholar
  161. 161.
    Taylor D. Pharmacokinetic interactions involving clozapine. Br J Psychiatry 1997; 171: 109–12PubMedCrossRefGoogle Scholar
  162. 162.
    Longo LP, Salzman C. Valproic acid effects on serum concentrations of clozapine and norclozapine [letter]. Am J Psychiatry 1995; 152: 650PubMedGoogle Scholar
  163. 163.
    Okuma T. Treatment of schizophrenic and schizoaffective disorders with carbamazepine. Int Clin Psychopharmacology 1990; 5Suppl. 1: 27–34Google Scholar
  164. 164.
    Simhandl C, Meszaros K. The use of carbamazepine in the treatment of schizophrenic and schizoaffective psychoses: a review. J Psychiatry Neurosci 1992; 17: 1–14PubMedGoogle Scholar
  165. 165.
    Junghan U, Albers M, Woggon B. Increased risk of hematological side-effects in psychiatric patients treated with clozapine and carbamazepine? [letter]. Pharmacopsychiatry 1993; 26: 262PubMedCrossRefGoogle Scholar
  166. 166.
    Jerling M, Lindstrom L, Bondesson U, et al. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 1994; 16: 368–74PubMedCrossRefGoogle Scholar
  167. 167.
    Tiihonen J, Vartiainen H, Hakola P. Carbamazepine-induced changes in plasma levels of neuroleptics. Pharmacopsychiatry 1995; 28: 26–8PubMedCrossRefGoogle Scholar
  168. 168.
    Muller T, Becker T, Fritze J. Neuroleptic malignant syndrome after clozapine plus carbamazepine [letter]. Lancet 1988; II: 1500CrossRefGoogle Scholar
  169. 169.
    Dursun SM, McIntosh D, Milliken H. Clozapine plus lamotrigine in treatment-resistant schizophrenia [letter]. Arch Gen Psychiatry 1999; 56: 950PubMedCrossRefGoogle Scholar
  170. 170.
    Saba G, Dumortier G, Kalalou K, et al. Lamotrigine-clozapine combination in refractory schizophrenia: three cases [letter]. J Neuropsychiatry Clin Neurosci 2002; 14: 86PubMedCrossRefGoogle Scholar
  171. 171.
    Dursun SM, Deakin JF. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J Psychopharmacol 2001; 15: 297–301PubMedCrossRefGoogle Scholar
  172. 172.
    de Camargo OA, Bode H. Agranulocytosis associated with lamotrigine [letter]. BMJ 1999; 318: 1179PubMedCrossRefGoogle Scholar
  173. 173.
    Solvason HB. Agranulocytosis associated with lamotrigine [letter]. Am J Psychiatry 2000; 157: 1704PubMedCrossRefGoogle Scholar
  174. 174.
    Kossen M, Selten JP, Kahn RS. Elevated clozapine plasma level with lamotrigine [letter]. Am J Psychiatry 2001; 158: 1930PubMedCrossRefGoogle Scholar
  175. 175.
    Shorvon S, Stefan H. Overview of the safety of newer antiepileptic drugs. Epilepsia 1997; 38Suppl. 1: S45–51PubMedCrossRefGoogle Scholar
  176. 176.
    Millson RC, Owen JA, Lorberg GW, et al. Topiramate for refractory schizophrenia [letter]. Am J Psychiatry 2002; 159: 675PubMedCrossRefGoogle Scholar
  177. 177.
    Wilson WH. Do anticonvulsants hinder clozapine treatment? Biol Psychiatry 1995; 37: 132–3PubMedCrossRefGoogle Scholar
  178. 178.
    Wolkowitz OM, Pickar D. Benzodiazepines in the treatment of schizophrenia: a review and reappraisal. Am J Psychiatry 1991; 148: 714–26PubMedGoogle Scholar
  179. 179.
    Frankenburg F, Baldessarini RJ. Clozapine — a novel antip-sychotic [letter]. N Engl J Med 1991; 325: 518CrossRefGoogle Scholar
  180. 180.
    Kanofsky JF, Lindenmayer JP, Konafsky D. Relapse in a clozapine responder following lorazepam withdrawal [letter]. Am J Psychiatry 1993; 150: 348–9PubMedGoogle Scholar
  181. 181.
    Klimke A, Klieser E. Sudden death after intravenous application of lorazepam in a patient treated with clozapine [letter]. Am J Psychiatry 1994; 151: 780PubMedGoogle Scholar
  182. 182.
    Jackson CW, Markowitz JS, Brewerton TD. Delirium associated with clozapine and benzodiazepine combinations. Ann Clin Psychiatry 1995; 7: 139–41PubMedCrossRefGoogle Scholar
  183. 183.
    Friedman LJ, Tabb SE, Worthington JJ, et al. Clozapine: a novel antipsychotic agent [letter]. N Engl J Med 1991; 325: 518–9PubMedCrossRefGoogle Scholar
  184. 184.
    Faisal I, Lindenmayer JP, Taintor Z, et al. Clozapine-benzodiazepine interactions [letter]. J Clin Psychiatry 1997; 58: 547–8PubMedCrossRefGoogle Scholar
  185. 185.
    Grohmann R, Ruther E, Sassim N, et al. Adverse effects of clozapine. Psychopharmacology (Berl) 1989; 99: S101–4CrossRefGoogle Scholar
  186. 186.
    Sassim N, Grohmann R. Adverse drug reactions with clozapine and simultaneous application of benzodiazepines. Pharmacopsychiatry 1988; 21: 306–7PubMedCrossRefGoogle Scholar
  187. 187.
    Baldessarini RJ, Frankenburg FR. Clozapine: a novel antipsychotic agent. N Engl J Med 1991; 324: 746–54PubMedCrossRefGoogle Scholar
  188. 188.
    Bredbacka PE, Paukkala E, Kinnunen E, et al. Can severe cardiorespiratory dysregulation induced by clozapine monotherapy be predicted? Int Clin Psychopharmacol 1993; 8: 205–6PubMedCrossRefGoogle Scholar
  189. 189.
    Javitt DC, Zylberman I, Zukin SR, et al. Amelioration of negative symptoms in schizophrenia by glycine. Am J Psychiatry 1994; 151: 1234–6PubMedGoogle Scholar
  190. 190.
    Heresco-Levy U, Javitt DC, Ermilov M, et al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry 1999; 56: 29–36PubMedCrossRefGoogle Scholar
  191. 191.
    Tsai G, Yang P, Chung LC, et al. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 1998; 44: 1081–9PubMedCrossRefGoogle Scholar
  192. 192.
    Fink M. Clozapine and electroconvulsive therapy [letter]. Arch Gen Psychiatry 1990; 47: 290–1PubMedCrossRefGoogle Scholar
  193. 193.
    Benatov R, Sirota P, Megged S. Neuroleptic-resistant schizophrenia treated with clozapine and ECT. Convuls Ther 1996; 12: 117–21PubMedGoogle Scholar
  194. 194.
    Bhatia SC, Bhatia SK, Gupta S. Concurrent administration of clozapine and ECT: a successful therapeutic strategy for a patient with treatment-resistant schizophrenia. J ECT 1998; 14: 280–3PubMedCrossRefGoogle Scholar
  195. 195.
    Frankenburg F, Suppes T, McLean PE. Combined clozapine and electroconvulsive therapy. Convuls Ther 1993; 9: 176–80PubMedGoogle Scholar
  196. 196.
    Cardwell BA, Nakai B. Scizure activity in combined clozapine and ECT: a retrospective view. Convuls Ther 1995; 11: 110–3PubMedGoogle Scholar
  197. 197.
    Kales HC, Dequardo JR, Tandon R. Combined electroconvulsive therapy and clozapine in treatment-resistant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 1999; 23: 547–56PubMedCrossRefGoogle Scholar
  198. 198.
    James DV, Gray NS. Elective combined electroconvulsive and clozapine therapy [letter]. Int Clin Psychopharmacol 1999; 14: 69–72PubMedCrossRefGoogle Scholar
  199. 199.
    Husni M, Haggarty J, Peat C. Clozapine does not increase ECT-seizure duration. Can J Psychiatry 1999; 44: 190–1PubMedGoogle Scholar
  200. 200.
    Safferman AZ, Munne R. Case report: combining clozapine with ECT. Convuls Ther 1992; 8: 141–3PubMedGoogle Scholar
  201. 201.
    Kupchik M, Spivak B, Mester R, et al. Combined electroconvul-sive-clozapine therapy. Clin Neuropharmacol 2000; 23: 14–6PubMedCrossRefGoogle Scholar
  202. 202.
    Koh KH, Blansjaar BA, de Vries S, et al. Electroconvulsive therapy for the treatment of clozapine nonresponders suffering from schizophrenia: an open label study. Eur Arch Psychiatry Clin Neurosci 2004; 254: 372–9CrossRefGoogle Scholar
  203. 203.
    Dickson RA, Williams R, Dalby JT. The use of chloral hydrate and sodium amytal during clozapine initiation. Can J Psychiatry 1994; 39: 132–4PubMedGoogle Scholar
  204. 204.
    Healy DJ, Dalack GW, Meador-Woodruff JH. Clozapine-reser-pine combination for refractory psychosis. Schizophr Res 1997; 25: 259–60PubMedCrossRefGoogle Scholar
  205. 205.
    al-Semaan Y. Bromocriptine as adjunctive therapy to clozapine in treatment-resistant schizophrenia [letter]. Can J Psychiatry 1996; 41: 484–5PubMedGoogle Scholar
  206. 206.
    Briskin JK, Curtis JL. Augmentation of clozapine therapy with ondansetron [letter]. Am J Psychiatry 1997; 154: 1171PubMedGoogle Scholar
  207. 207.
    Henderson DC, Nasrallah RA, Goff DC. Switching from clozapine to olanzapine in treatment-refractory schizophrenia: safety, clinical efficacy, and predictors of response. J Clin Psychiatry 1998; 59: 585–8PubMedCrossRefGoogle Scholar
  208. 208.
    Lindenmayer JP, Czobor P, Volavka J, et al. Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: an open-label switch study. J Clin Psychiatry 2002; 63: 931–5PubMedCrossRefGoogle Scholar
  209. 209.
    Littrell KH, Johnson CG, Hilligoss NM, et al. Switching clozapine responders to olanzapine. J Clin Psychiatry 2000; 61: 912–5PubMedCrossRefGoogle Scholar
  210. 210.
    Dossenbach MRK, Beuzen JN, Avnon M, et al. The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine. Clin Ther 2000; 22: 1021–34PubMedCrossRefGoogle Scholar
  211. 211.
    Weiss EL, Longhurst JG, Bowers Jr MB, et al. Olanzapine for treatment-refractory psychosis in patients responsive to, but intolerant of, clozapine [letter]. J Clin Psychopharmacol 1999; 19: 378–80PubMedCrossRefGoogle Scholar
  212. 212.
    Millson RC, Delva NJ. Clozapine to olanzapine [letter]. Am J Psychiatry 1999; 156: 1121PubMedGoogle Scholar
  213. 213.
    Rafal S, Tsuang MT, Carpenter Jr WT. A dilemma born of progress: switching from clozapine to a newer antipsychotic. Am J Psychiatry 1999; 156: 1086–90PubMedGoogle Scholar
  214. 214.
    Fogelson DL, Sternbach H, Payne D. A naturalistic pilot study comparing haloperidol, clozapine, sertindole, and risperidone in partially responsive chronic schizophrenia or schizoaffec-tive disorder [letter]. J Clin Psychopharmacol 1997; 17: 492–4PubMedCrossRefGoogle Scholar
  215. 215.
    Gardner DM, Baldessarini RJ, Benzo J, et al. Switching between clozapine and risperidone treatment [letter]. Can J Psychiatry 1997; 42: 430–1PubMedGoogle Scholar
  216. 216.
    Lacey RL, Preskorn SH, Jerkovich GS. Is risperidone a substitute for clozapine for patients who do not respond to neuroleptics? [letter]. Am J Psychiatry 1995; 152: 1401PubMedGoogle Scholar
  217. 217.
    Avnon M, Kunin A. Risperidone response after no clozapine response [letter]. Br J Psychiatry 1995; 167: 699PubMedCrossRefGoogle Scholar
  218. 218.
    Robinson D, Woerner MG, Alvir MG, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 1999; 56: 241–7PubMedCrossRefGoogle Scholar
  219. 219.
    American Psychiatric Association. Practice guidelines for the treatment of patients with schizophrenia. 2nd ed. Am J Psychiatry 2004; 161 Suppl. 2: 24–5Google Scholar
  220. 220.
    Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry 2003; 60: 553–64PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Gary Remington
    • 1
    • 2
  • Amitabha Saha
    • 3
  • Siow-Ann Chong
    • 3
  • Chekkera Shammi
    • 1
    • 2
  1. 1.Schizophrenia ProgramCentre for Addiction and Mental HealthTorontoCanada
  2. 2.University of TorontoTorontoCanada
  3. 3.Institute of Mental HealthWoodbridge HospitalSingapore

Personalised recommendations