Pharmacotherapy for treatment-refractory schizophrenia

Expert Opinion on Pharmacotherapy

Volumn 12, Issue 3, 2011, Pages 411-434

  Van Sant, Scott P ^a   Buckley, Peter F ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

pharmacotherapy; refractory; schizophrenia; treatment resistant

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; ACETYLCYSTEINE; ACETYLSALICYLIC ACID; AMISULPRIDE; ARIPIPRAZOLE; BENZATROPINE MESILATE; CARBAMAZEPINE; CELECOXIB; CHLORPROMAZINE; CLOZAPINE; DEXTRO SERINE; FLUMAZENIL; GLYCINE; HALOPERIDOL; LAMOTRIGINE; LITHIUM; MEMANTINE; MK 0777; OLANZAPINE; PLACEBO; PREGABALIN; QUETIAPINE; RISPERIDONE; SEROTONIN UPTAKE INHIBITOR; SULPIRIDE; TOPIRAMATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROATE SEMISODIUM; ZIPRASIDONE; ZOTEPINE;

ADD ON THERAPY; AGRANULOCYTOSIS; CARDITIS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL (TOPIC); DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENTIATION; DRUG TOLERABILITY; ELECTROCONVULSIVE THERAPY; EXTRAPYRAMIDAL SYMPTOM; GLUTATHIONE METABOLISM; HUMAN; META ANALYSIS (TOPIC); METABOLIC DISORDER; MULTICENTER STUDY (TOPIC); PSYCHOPHARMACOTHERAPY; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCHIZOAFFECTIVE PSYCHOSIS; SCHIZOPHRENIA; SEXUAL DYSFUNCTION; SIDE EFFECT; TARDIVE DYSKINESIA; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT OUTCOME; TREATMENT RESPONSE; WEIGHT GAIN;

ANIMALS; ANTIPSYCHOTIC AGENTS; CLOZAPINE; DRUG RESISTANCE; ELECTROCONVULSIVE THERAPY; HEALTH CARE COSTS; HUMANS; QUALITY OF LIFE; SCHIZOPHRENIA; TRANSCRANIAL MAGNETIC STIMULATION;

EID: 79251469125     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.2011.528200     Document Type: Review

References (109)

1. Kane J, Honingfeld G, Singer J, Meltzer H. Clozapine for the treatment resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988;45:789-96
2. 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;151:1744-52
3. Buckley P, Miller A, Olsen J, et al. When symptoms persist: clozapine augmentationstrategies. Schizophr Bull 2001;27:615-28
4. Buckley PF, Miller BJ, Lehrer DS, et al. Psychiatric comorbities and schizophrenia. Schizophr Bull 2009;35:383-402
5. Poyuroovsky M, Fuchs C, Weizman A. Obsessive-compulsive disorder in patients with first-episode schizophrenia. Am J Psychiatry 1999;156:1998-2000
6. Poyurovsky M, Hramenkov S, Isakov V, et al. Obsessive-compulsive disorder in hospitalized patients with chronic schizophrenia. Psychiatry Res 2001;102:49-57
7. Kayahan B, Ozturk O, Veznedaroglu B, et al. Obsessive-compulsive symptoms in schizophrenia: prevelance and clinical correlates. Psychiatry Clin Neurosci 2005;59:291-5
8. Berman I, Kalinowski A, Berman SM, et al. Obsessive and compulsive symptoms in chronic symptoms in chronic schizophrenia. Compr Psychiatry 195;36:6-10
9. Keshavan MS, Tandon R, Boutros NN, Nasrallah HA. Schizophrenia, 'just the facts': what we know in 2008-part 3. Neurobiology Schizophr Res 106:89-107
10. Stahl SM, Buckley PF. Negative symptoms of schizophrenia: a problem that will not go away. Acta Psychiatr Scand 2007;115:4-11
11. van Winkel R, Mylin-Germeys L, De Hert M, et al. The association between cognition and functional outcome in first-episode patients with schizophrenia: mystery solved. Acta Psychiatr Scand 2007;116:119-24
12. Tandon R, Nasrallah HA, Keshavan MS. Schizophrenia, 'just the facts' 4: clinical features and conceptualization. Schizophr Res 2009;110:1-23
13. Hirsch SR, Weinberger DR, editors. Schizophrenia. Blackwell Sci, Oxford; 1995. p. 471
14. Kane JM, Leucht S, Carpenter D Docherty JP, editors, Optimizing pharmacologic treatment of psychotic disorders. J Clin Psychiatry 2003;64(Suppl 12):5-19
15. Troy M, Buchanan B, Buckley PF, et al. The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry 2007;68:1751-62
16. Kreyenbuhl J, Buchanan RW, Dickerson FB, Dixon LB. The schizophrenia patient outcomes research team (PORT): updated treatment recommendations 2009; Schizophr Bull 2010;36:94-103
17. Lehman AF, Leiberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004;161(2 Suppl):1-56
18. Jaffe AB, Levine J. Antipsychotic medication co-prescribing in a large state hospital system. Pharmacoepidemiol Drug Saf 2003;12:41-8
19. Clark RE, Bartels SJ, Mellman TA, Peacock WJ. Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorder: implications for state mental health policy. Schizophr Bull 2002;28:75-84
20. Weissman EM. Antipsychotic prescribing practices in the veterans healthcare administration-New York metropolitan region. Schizophr Bull 2002;28:31-42
21. Ganguly R, Kotzan JA, Miller S, et al. Prevalence, trends, and factors associated with antipsychotic polypharmacy among Medicaid-eligible schizophrenia patients, 1998-2000. J Clin Psychiatry 2004;65:1377-88
22. Pickar D, Vinik J, Bartko JJ. Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use. PLoSone 2008;3:1-5
23. Chue P, Welch R, Snaterse M. Combination risperidone and quetiapine therapy in refractory schizophrenia [Letter]. Can J Psychiatry 2001;46:86-7
24. Duggal SH. Aripiprazole-olanzapine combination for the treatment of schizophrenia. Can J Psychiatry 2004;49:151
25. Zink M, Henn FA, Thome J. Combination of amisulpride and olanzapine in treatment-resistant schizophrenia psychosis. Eur Psychiatry 2004;19:56-8
26. Lerner V, Chudakowa B, Kravets S, Polyakova I. Combined use of risperidone and olanzapine in the treatment of patients with resistant schizophrenia: a preliminary case series report. Clin Neuropharmacol 2000;23:284-6
27. Kane JM, Correll CU, Goff DC Kirpatrick B. 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 2009;70:1348-57
28. Correll CU, Rummel-Kluge C, Corves C, et al. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull 2009;35:443-57
29. Pierre JM, Rivard JM. High-dose quetiapine in treatment refractory schizophrenia. Schizophr Res 2005;73:373-5
30. Lerner V. High-dose olanzapine for treatment refractory schizophrenia. Clin Neuropharmacol 2003;26:58-61
31. Boggs DL, Nelson MW, Yu Y, Conly RR. Quetiapine at high doses for the treatment of refractory schizophrenia 2008. Schizophr Res 2008;101:347-8
32. Kumra S, Kranzler H, Gerbino-Rosen G, et al. Clozapine and 'high-dose' olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biol Psychiatry 2008;63:524-9
33. Basan A, Kissling W, Leucht S. Valproate as an adjunct to antipsychotics for schizophrenia: a systematic review of randomized trials. Schizophr Res 2004;70:33-7
34. Schwarz C, Volz A, Li C, Leucht S. Valproate for schizophrenia. Cochrane Database Syst Rev 2008;3:CD004028
35. Citrome L, Casey D, Daniel D, et al. Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone. Psychiatr Serv 2004;55:290-4
36. Casey DE, Daniel DG, Tamminga C, et al. Divalproex ER combined with olanzapine or risperidone for treatment of acute exacerbations of schizophrenia. Neuropsychopharmacology 2009;34:1330-8
37. Casey DE, Daniel DG, Wassef AA, et al. Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Neuropsychopharmacology 2003;28:182-92
38. Garver DL, Hirschowitz J, Fleischmann R, Djuric PE. Lithium response and psychoses: a double-blind, placebo-controlled study. Psychiatry Res 1984;12:57-68
39. Lerner Y, Mintzer Y, Schestatzky M. Lithium combined with haloperidol in schizophrenic patients. Br J Psychiatry 1988;153:359-62
40. Terao T, Oga T, Nozaki S, et al. Lithium addition to neuroleptic treatment in chronic schizophrenia: a randomized, double-blind, placebo-controlled, cross-over study. Acta Psychiatr Scand 1995;92:220-4
41. Collins PJ, Larkin EP, Shubsachs AP. lithium carbonate in chronic schizophrenia-a brief trial of lithium carbonate added to neuroleptics for treatment of resistant schizophrenic patients. Acta Psychiatr Scand 1991;84:150-4
42. Wilson WH. Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double-blind, placebo-controlled, parallel design clinical trial. Psychopharmacology 1993;111:359-66
43. Schulz SC, Thompson PA, Jacobs M, et al. Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients. J Clin Psychiatry 1999;60:366-72
44. Leucht S, Kissling W, McGrath J. Lithium for schizophrenia. Cochrane Database Syst Rev 2007;3:CD003834
45. Leucht S, McGrath J, White P, Kissling W. Carbamazepine augmentation for schizophrenia: how good is the evidence? J Clin Psychiatry 2002;63:218-24
46. Leucht S, Kissling W, McGrath J, White P. Carbamazepine for schizophrenia [Review]. Cochrane Database Syst Rev 2007;3:CD001258
47. Englisch S, Esser A, Enning F, et al. Augmentation with pregabalin in schizophrenia. J Clin Psychopharmacol 2010;30:437-40
48. Sepehry AA, Potvin S, Elie R, Stip E. Selective serotonin reuptake inhibitor (SSRI) add-on therapy for the negative symptoms of schizophrenia: a meta-analysis. J Clin Psychiatry 2007;68:604-10
49. McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine,and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006;163:600-10
50. Lewis SW, Barnes TRE, Davies L, et al. Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Schizophr Bull 2006;32:715-23
51. An FR, Xiang YT, Wang CY, et al. Change of psychotropic drug prescription for schizophrenia in a psychiatric institution in Beijing, China between 1999 and 2008. Int J Clin Pharmacol Ther 2010; 48: 270-4
52. Buckley PF. Dosing equivalency of second-generation antipsychotic medications. J Clin Psychopharmacol 2005;25:501-2
53. Tiihonen J, Lonnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009;374:620-7
54. Meltzer H, Alphs L, Green A, et al. Clozapine treatment for suicidality in schizophrenia. Arch Gen Psychiatry 2003;60:82-91
55. Chung C, Remington G. Predictors and markers of clozapine response. Psychopharmacology 2005;179:317-35
56. Mauri MC, Volonteri LS, Colasanti A, et al. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response. Clin Pharmacokinet 2007;46:359-88
57. Zink M, Englisch S, Meyer-Lindenberg A. Polypharmacy in schizophrenia. Curr Opin Psychiatry 2010;23:103-11
58. Paton C, Whittingham C, Barnes TR Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine. J Clin Psychopharmacol 2007;27:198-204
59. Cipriani A, Boso M, Barbui C. Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia. Cochrane Database Syst Rev 2009;3:CD006324
60. Anil Yagcioglu AE, Kivircik Akdede BB, 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;66:63-72
61. Joiassen RC, Joseph A, Kohegyi E, et al. Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo controlled trial. Am J Psychiatry 2005;162:130-6
62. Akdede BB, Anil Yagcioglu AE, Alptekin K, et al. A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition. J Clin Psychiatry 2006;67:1912-19
63. Freudenreich O, Henderson DC, Walsh JP, et al. Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial. Schizophr Res 2007;92:90-4
64. Honer WG, Allen ET, Thornton AE, et al. Clozapine versus clozapine and risperidone with refractory schizophrenia. N Engl J Med 2006;354:472-82
65. Zink M, Kuwilsky A, Krumm B, et al. Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomized controlled clinical trial. J Psychopharmacol 2009;23:305-14
66. Shiloh R, Zemishlany Z, Aizenberg D, Weizman A. Sulpride adjunction to clozapine in treatment-resistant schizophrenic patients: a preliminary case series study. Eur Psychiatry 1997;12:152-5
67. Shiloh R, Zemishlany Z, Aizenberg D, et al. Sulpride augmentation in people with schizophrenia partially responsive to clozapine: a double blind, placebo-controlled study. Br J Psychiatry 1997;717:569-73
68. Agelink MW, Kavuk I, Ak I. Clozapine with amisulpride for refractory schizophrenia. Am J Psychiatry 2004;161:924-5
69. Kampf P, Angelink MW, Naber D. Augmentation of clozapine with amisulpride: a promising therapeutic approach to refractory schizophrenic symptoms. Pharmacopsychiatry 2005;38:39-40
70. 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;10:292-8
71. Leucht S. Amisulpride-a selective dopamine antagonist and atypical antipsychotic: result of a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol 2004;7(Suppl 1):15-20
72. Genc Y, Taner E, Candansayar S. 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 2007;24:1-13
73. Assion HJ, Reinbold H, Lemanski S, et al. Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial. Pharmacopsychiatry 2008;41:24-8
74. Chang JS, Ahn YM, Park HJ, et al. Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2008;69:720-31
75. Fleischacker WW, Heikkinen ME, Olie JP, et al. 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 2010;12:1115-25
76. Tiihonen J, Hallikainen T, Ryynanen OP. Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial. Biol Psychiatry 2003;54:1241-8
77. Kremer I, Vass A, Gorelik I. Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia. Biol Psychiatry 2004;56:441-6
78. Zoccali R, Muscatello MR, Bruno A, et al. The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophr Res 2007;93:109-16
79. Goff DC, Keefe R, Citrome L, et al. Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials. J Clin Psychopharmacol 2007;27:582-9
80. Tiihonen J, Wahlbeck K, Kivineime V. The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophr Res 2009;109:10-4
81. Tiihonen J, Halonen P, Wahlbeck K, et al. Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychiatry 2005;66:1012-15
82. Afshar H, Roohafza H, Mousavi G, et al. Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial. J Psychopharmacol 2009;23:157-62
83. Kho 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;254:372-9
84. Levy-Rueff M, Gourevitch R, Loo H, et al. Maintenance electroconvulsive therapy: an alternative treatment for refractory schizophrenia and schizoaffective disorders. Psychiatry Res 2010;175:280-3
85. Shimizu E, Imai M, Fujisaki M, et al. Maintenance electroconvulsive therapy (ECT) for treatment-resistant disorganized schizophrenia. Prog Neuropschopharmacol Biol Psychiatry 2007;31:571-3
86. Masoudzadeh A, Khalilian AR Comparative study of clozapine, electroschock and the combination of ECT with clozapine in treatment-resistant schizophrenic patients. Pak J Biol Sci 2007;10:4287-90
87. Blumberger DM, Fitzgerald PB, Mulsant BH, et al. Repetitive transcranial magnetic stimulation for refractory symptoms in schizophrenia. Curr Opin Psychiatry 2010;23:85-90
88. Freitas C, Fregni F, Pascual-Leone A. Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia. Schizophr Res 2009;108:11-24
89. Carpenter WT, Koenig JI. The evolution of drug development in schizophrenia: past issues and future opportunities. Neuropsychopharmacology 2008;33:2061-79
90. Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antoagonist, ketamine, in humans: psychomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994;51:199-214
91. Malholtra AK, Pinals DA, Weingartner H, et al. NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 1996;14:301-7
92. Heresco-Levy U, Ermilov M, Lichtenberg P, et al. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biol Psychiatry 2004;55:165-71
93. Homayoun H, Moghaddam B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 2007;27:11496-500
94. Krivoy A, Weizman A, Laor L. Addition of memantine to antipsychotic treatment in schizophrenia inpatients with residual symptoms: a preliminary study. Eur Neuropsychopharmacol 2008;18:117-21
95. Lieberman JA, Papdakis K, Csernansky J, et al. A randomized, placebo-controlled study of memantine as adjunctive treatment in patients with schizophrenia. Neuropsychopharmacology 2009;34:1322-29
96. de Lucena D, Fernandes BS, Berk M. 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 2009;70:1416-23
97. 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;56:29-36
98. Heresco-Levy U, Ermilov M, Lichtenberg P, et al. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biol Psychiatry 2004;55:165-71
99. Heresco-Levy U, Javitt DC, Ebstein R, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry 2005;57:577-85
100. Patil ST, Zhang L, Martenyi F, et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med 2007;13:1102-7
101. Do KQ, Trabensinger AH, Kirsten-Kruger M, et al. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci 2000;12:3721-8
102. Matsuzawa D, Obata T, Shirayama Y, et al. Negative correlation between brain glutathione level and negative symptoms in schizophrenia: a 3T1H-MRS study. PLoS ONE 2008;3:e1944
103. Berk M, Copolov D, Dean O, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia-a double-blind, randomized, placebo-controlled trial. Biol Psychiatry 2008;64:361-8
104. Menzies L, Ooi C, Kamath S, et al. Effects of gamma-aminobutyric acid modulating drugs and working memory and brain function in patients with schizophrenia. Arch Gen Psychiatry 2007;64:156-67
105. Lewis DA, Cho RY, Carter CS, et al. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry 2008;165:1585-93
106. Muller N, Riedel M, Schwarz MJ, Engel RR. Clinical effects of COX-2 inhibitors on cognition in schizophrenia. Eur Arch Psychiatry Clin Neurosci 2005;255:149-51
107. Rapaport MH, Delrahim KK, Bresee CJ, et al. Celecoxib augmentation of continuously ill patients with schizophrenia. Biol Psychiatry 2005;57:1594-6
108. Akhondzadeh S, Tabatabaee M, Amini H. Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebo-controlled trial. Schizophr Res 2007;90:179-85
109. Laan W, Grobbee DE, Selten JP, et al. Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2010;71:520-7