The psychopharmacology algorithm project at the harvard south shore program: An update on schizophrenia

Harvard Review of Psychiatry

Volumn 21, Issue 1, 2013, Pages 18-40

  Osser, David N ^a   Roudsari, Mohsen Jalali ^b,c   Manschreck, Theo ^a,b,c  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b Laboratory for Clinical and Experimental Psychopathology   (United States)

^c BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Algorithms; Antipsychotics; Psychopharmacology; Schizophrenia

Indexed keywords

AMISULPRIDE; ARIPIPRAZOLE; BENZODIAZEPINE; CITALOPRAM; CLOZAPINE; HALOPERIDOL; HALOPERIDOL DECANOATE; IMIPRAMINE; LAMOTRIGINE; LURASIDONE; OLANZAPINE; QUETIAPINE; RISPERIDONE; ZIPRASIDONE;

AGGRESSION; AGITATION; ALGORITHM; DRUG BIOAVAILABILITY; ELECTROCONVULSIVE THERAPY; HEART DISEASE; HUMAN; MAJOR DEPRESSION; MONOTHERAPY; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; SUBSTANCE ABUSE; TREATMENT REFUSAL;

ALGORITHMS; ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; ANTIPSYCHOTIC AGENTS; BENZODIAZEPINES; CLINICAL PROTOCOLS; COMBINED MODALITY THERAPY; DRUG THERAPY, COMBINATION; ELECTROCONVULSIVE THERAPY; HUMANS; PIPERAZINES; QUINOLONES; RISPERIDONE; SCHIZOPHRENIA; SULPIRIDE; THIAZOLES;

EID: 84875544927     PISSN: 10673229     EISSN: 14657309     Source Type: Journal    
DOI: 10.1097/HRP.0b013e31827fd915     Document Type: Review

References (222)

1. Eack SM, Hogarty GE, Cho RY, et al. Neuroprotective effects of cognitive enhancement therapy against gray matter loss in early schizophrenia: results from a 2-year randomized controlled trial. Arch Gen Psychiatry 2010;67:674-82.
2. Osser DN. Treatment resistant problems. In: Tupin JP, Shader RI, Harnett DS, eds. Clinical handbook of psychopharmacology. New York: Jason Aronson, 1988:269-328.
3. Osser DN. A systematic approach to pharmacotherapy in patients with neuroleptic-resistant psychoses. Hosp Community Psychiatry 1989;40:921-7.
4. Osser DN, Patterson RD. Pharmacotherapy of schizophrenia I: acute treatment. In: Soreff S, ed. Handbook for the treatment of the seriously mentally ill. Toronto: Hogrefe & Huber, 1996:91-119.
5. Osser DN, Patterson RD. Pharmacotherapy of schizophrenia II: an algorithm for neuroleptic resistant patients. In: Soreff S, ed. Handbook for the treatment of the seriously mentally ill. Toronto: Hogrefe & Huber, 1996:121-55.
6. Osser DN, Zarate CJ. Consultant for the pharmacotherapy of schizophrenia. Psychiatr Ann 1999;29:252-69.
7. Osser DN, Sigadel R. Short-term inpatient pharmacotherapy of schizophrenia. Harv Rev Psychiatry 2001;9:89-104.
8. Hamoda HM, Osser DN. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an update on psychotic depression. Harv Rev Psychiatry 2008;16: 235-47.
9. Ansari A, Osser DN. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an update on bipolar depression. Harv Rev Psychiatry 2010;18:36-55.
10. Osser DN, Dunlop LR. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an update on generalized social anxiety disorder. Psychopharm Rev 2010;45:91-8.
11. Bajor L, Ticlea A, Osser DN. The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an update on posttraumatic stress disorder. Harv Rev Psychiatry 2011;19:240-58.
12. Gelenberg AJ. The catatonic syndrome. Lancet 1976;1: 1339-41.
13. Manschreck TC, Petri M. The paranoid syndrome. Lancet 1978;2:251-3.
14. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry 2003;60: 82-91.
15. Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: A meta-analysis. Schizophr Res 2005;73: 139-45.
16. Tiihonen J, Suokas JT, Suvisaari JM, Haukka J, Korhonen P. Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiatry 2012;69:476-83.
17. Krakowski MI, Czobor P, Citrome L, Bark N, Cooper TB. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2006;63:622-9.
18. Volavka J, Czobor P, Nolan K, et al. Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychopharmacol 2004;24:225-8.
19. Volavka J, Czobor P, Derks EM, et al. Efficacy of antipsychotic drugs against hostility in the European First-Episode Schizophrenia Trial (EUFEST). J Clin Psychiatry 2011;72: 955Y61.
20. Battaglia J, Moss S, Rush J, et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Am J Emerg Med 1997;15:335-40.
21. Garza-Trevino ES, Hollister LE, Overall JE, Alexander WF. Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. Am J Psychiatry 1989;146:1598-601.
22. Breier A, Meehan K, Birkett M, et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry 2002;59: 441-8.
23. Andrezina R, Josiassen RC, Marcus RN, et al. Intramuscular aripiprazole for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder: A doubleblind, placebo-controlled comparison with intramuscular haloperidol. Psychopharmacology (Berl) 2006;188:281-92.
24. Satterthwaite TD, Wolf DH, Rosenheck RA, Gur RE, Caroff SN. A meta-analysis of the risk of acute extrapyramidal symptoms with intramuscular antipsychotics for the treatment of agitation. J Clin Psychiatry 2008;69:1869-79.
25. Zeller SL, Rhoades RW. Systematic reviews of assessment measures and pharmacologic treatments for agitation. Clin Ther 2010;32:403-25.
26. Thapa PB, Palmer SL, Owen RR, Huntley AL, Clardy JA, Miller LH. P.R.N. (as-needed) orders and exposure of psychiatric inpatients to unnecessary psychotropic medications. Psychiatr Serv 2003;54:1282-6.
27. Carpenter WT, Heinrichs DW, Wagman AMI. Deficit and nondeficit forms of schizophreniaVthe concept. Am J Psychiatry 1988;145:578-83.
28. Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: A meta-analysis. Lancet 2009;373:31-41.
29. Buchanan RW, Breier A, Kirkpatrick B, Ball P, Carpenter WT Jr. Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am J Psychiatry 1998;155:751-60.
30. Rado JT. Treatment of negative symptoms in schizophrenia. Psychopharm Rev 2011;46:33-9.
31. Singh SP, Singh V, Kar N, Chan K. Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. Br J Psychiatry 2010;197:174-9.
32. Bodkin JA, Siris SG, Bermanzohn PC, Hennen J, Cole JO. Double-blind, placebo-controlled, multicenter trial of selegiline augmentation of antipsychotic medication to treat negative symptoms in outpatients with schizophrenia. Am J Psychiatry 2005;162:388-90.
33. Strous RD, Maayan R, Lapidus R, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry 2003;60:133-41.
34. Doruk A, Uzun O, Ozsahin A. A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia. Int Clin Psychopharmacol 2008;23:223-7.
35. Levkovitz Y, Mendlovich S, Riwkes S, et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 2010;71:138-49.
36. Whitehead C, Moss S, Cardno A, Lewis G. Antidepressants for people with both schizophrenia and depression. Cochrane Database Syst Rev 2002;(2):CD002305.
37. Siris SG, Bermanzohn PC, Mason SE, Shuwall MA. Maintenance imipramine therapy for secondary depression in schizophrenia. A controlled trial. Arch Gen Psychiatry 1994; 51:109-15.
38. Kirli S, Caliskan M. A comparative study of sertraline versus imipramine in postpsychotic depressive disorder of schizophrenia. Schizophr Res 1998;33:103-11.
39. Moller HJ. Antidepressive effects of traditional and second generation antipsychotics: A review of the clinical data. Eur Arch Psychiatry Clin Neurosci 2005;255:83-93.
40. Zisook S, Kasckow JW, Golshan S, et al. Citalopram augmentation for subsyndromal symptoms of depression in middle-aged and older outpatients with schizophrenia and schizoaffective disorder: A randomized controlled trial. J Clin Psychiatry 2009;70:562-71.
41. Trixler M, Gati A, Fekete S, Tenyi T. Use of antipsychotics in the management of schizophrenia during pregnancy. Drugs 2005;65:1193-206.
42. Gentile S. Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophr Bull 2010;36:518-44.
43. Collins KO, Comer JB. Maternal haloperidol therapy associated with dyskinesia in a newborn. Am J Health Syst Pharm 2003;60:2253-5.
44. Diav-Citrin O, Shechtman S, Ornoy S, et al. Safety of haloperidol and penfluridol in pregnancy: A multicenter, prospective, controlled study. J Clin Psychiatry 2005;66:317-22.
45. Reis M, Kallen B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol 2008;28:279-88.
46. Newham JJ, Thomas SH, MacRitchie K, McElhatton PR, McAllister-Williams RH. Birth weight of infants after maternal exposure to typical and atypical antipsychotics: prospective comparison study. Br J Psychiatry 2008;192:333-7.
47. Ernst CL, Goldberg JF. The reproductive safety profile of mood stabilizers, atypical antipsychotics, and broad-spectrum psychotropics. J Clin Psychiatry 2002;63 suppl 4:42-55.
48. McKenna K, Koren G, Tetelbaum M, et al. Pregnancy outcome of women using atypical antipsychotic drugs: A prospective comparative study. J Clin Psychiatry 2005;66:444-9.
49. Spyropoulou AC, Zervas IM, Soldatos CR. Hip dysplasia following a case of olanzapine exposed pregnancy: A questionable association. Arch Womens Ment Health 2006;9: 219-22.
50. Arora M, Praharaj SK. Meningocele and ankyloblepharon following in utero exposure to olanzapine. Eur Psychiatry 2006;21:345-6.
51. National Institute for Health and Clinical Excellence. Antenatal and postnatal mental health. Clinical management and service guideline. 2007. http://guidance.nice.org.uk/CG45/NICEGuidance/pdf/English.
52. Taylor D, Paton C, Kapur S. The Maudsley prescribing guidelines in psychiatry. 11th ed. Padstow, UK:Wiley-Blackwell, 2012.
53. Kirchner JE, Owen RR, Nordquist C, Fischer EP. Diagnosis and management of substance use disorders among inpatients with schizophrenia. Psychiatr Serv 1998;49:82-5.
54. Kerfoot KE, Rosenheck RA, Petrakis IL, et al. Substance use and schizophrenia: adverse correlates in the CATIE study sample. Schizophr Res 2011;132:177-82.
55. Kelly DL, McMahon RP, Wehring HJ, et al. Cigarette smoking and mortality risk in people with schizophrenia. Schizophr Bull 2011;37:832-8.
56. Phansalkar S, Osser DN. Optimizing clozapine treatment, part one. Psychopharm Rev 2009;44:1-7.
57. Petrakis IL, O-Malley S, Rounsaville B, Poling J, McHugh- Strong C, Krystal JH. Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia. Psychopharmacology (Berl) 2004;172:291-7.
58. Tsoi DT, Porwal M, Webster AC. Efficacy and safety of bupropion for smoking cessation and reduction in schizophrenia: systematic review and meta-analysis. Br J Psychiatry 2010;196:346-53.
59. Weiner E, Buchholz A, Coffay A, et al. Varenicline for smoking cessation in people with schizophrenia: A double blind randomized pilot study. Schizophr Res 2011;129: 94-5.
60. Chung AK, Chua SE. Effects on prolongation of Bazetts corrected QT interval of seven second-generation antipsychotics in the treatment of schizophrenia: A meta-analysis. J Psychopharmacol 2011;25:646-66.
61. Chahine LM, Acar D, Chemali Z. The elderly safety imperative and antipsychotic usage. Harv Rev Psychiatry 2010; 18:158-72.
62. Pollock BG, Mulsant BH, Rosen J, et al. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. Am J Geriatr Psychiatry 2007;15:942-52.
63. Crossley NA, Constante M, McGuire P, Power P. Efficacy of atypical v. typical antipsychotics in the treatment of early psychosis: meta-analysis. Br J Psychiatry 2010;196:434-9.
64. Emsley RA. Risperidone in the treatment of first-episode psychotic patients: A double-blind multicenter study. Risperidone Working Group. Schizophr Bull 1999;25:721-9.
65. Lieberman JA, Phillips M, Gu H, et al. Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: A 52-week randomized trial of clozapine vs chlorpromazine. Neuropsychopharmacology 2003;28: 995-1003.
66. Schooler N, Rabinowitz J, Davidson M, et al. Risperidone and haloperidol in first-episode psychosis: A long-term randomized trial. Am J Psychiatry 2005;162:947-53.
67. Green AI, Lieberman JA, Hamer RM, et al. Olanzapine and haloperidol in first episode psychosis: two-year data. Schizophr Res 2006;86:234-43.
68. Kahn RS, Fleischhacker WW, Boter H, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008;371:1085-97.
69. Alvarez-Jimenez M, Parker AG, Hetrick SE, McGorry PD, Gleeson JF. Preventing the second episode: A systematic reviewandmeta-analysis of psychosocial and pharmacological trials in first-episode psychosis. Schizophr Bull 2011;37: 619-30.
70. Lieberman JA, Tollefson G, Tohen M, et al. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: A randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry 2003; 160:1396-404.
71. Correll CU, Leucht S, Kane JM. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: A systematic review of 1-year studies. Am J Psychiatry 2004; 161:414-25.
72. Gharabawi GM, Bossie CA, Zhu Y. New-onset tardive dyskinesia in patients with first-episode psychosis receiving risperidone or haloperidol. Am J Psychiatry 2006;163: 938-9.
73. Novick D, Haro JM, Bertsch J, Haddad PM. Incidence of extrapyramidal symptoms and tardive dyskinesia in schizophrenia: thirty-six-month results from the European schizophrenia outpatient health outcomes study. J Clin Psychopharmacol 2010;30:531-40.
74. Minzenberg MJ, Poole JH, Benton C, Vinogradov S. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am J Psychiatry 2004;161:116-24.
75. Tandon R, DeQuardo JR, Goodson J, Mann NA, Greden JF. Effect of anticholinergics on positive and negative symptoms in schizophrenia. Psychopharmacol Bull 1992;28:297-302.
76. Oosthuizen PP, Emsley RA, Maritz JS, Turner JA, Keyter N. Incidence of tardive dyskinesia in first-episode psychosis patients treated with low-dose haloperidol. J Clin Psychiatry 2003;64:1075-80.
77. Woods SW, Morgenstern H, Saksa JR, et al. Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: A prospective cohort study. J Clin Psychiatry 2010;71:463-74.
78. McEvoy JP, Lieberman JA, Perkins DO, et al. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: A randomized, double-blind 52-week comparison. Am J Psychiatry 2007;164:1050-60.
79. Robinson DG, Woerner MG, Napolitano B, et al. Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes. Am J Psychiatry 2006;163:2096-102.
80. Buchanan RW, Kreyenbuhl J, Kelly DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull 2010;36:71-93.
81. Zipursky RB, Gu H, Green AI, et al. Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol. Br J Psychiatry 2005;187: 537-43.
82. Fernandez-Egea E, Miller B, Garcia-Rizo C, Bernardo M, Kirkpatrick B. Metabolic effects of olanzapine in patients with newly diagnosed psychosis. J Clin Psychopharmacol 2011;31:154-9.
83. Sanger TM, Lieberman JA, Tohen M, Grundy S, Beasley C Jr, Tollefson GD. Olanzapine versus haloperidol treatment in first-episode psychosis. Am J Psychiatry 1999;156:79-87.
84. Patel JK, Buckley PF, Woolson S, et al. Metabolic profiles of second-generation antipsychotics in early psychosis: findings from the CAFE study. Schizophr Res 2009;111:9-16.
85. Kreyenbuhl J, Slade EP, Medoff DR, et al. Time to discontinuation of first- and second-generation antipsychotic medications in the treatment of schizophrenia. Schizophr Res 2011;131:127-32.
86. Kasper S, Brecher M, Fitton L, Jones AM. Maintenance of long-term efficacy and safety of quetiapine in the open-label treatment of schizophrenia. Int Clin Psychopharmacol 2004;19:281-9.
87. Hatta K, Sato K, Hamakawa H, et al. Effectiveness of second-generation antipsychotics with acute-phase schizophrenia. Schizophr Res 2009;113:49-55.
88. McCue RE, Waheed R, Urcuyo L, et al. Comparative effectiveness of second-generation antipsychotics and haloperidol in acute schizophrenia. Br J Psychiatry 2006;189:433-40.
89. Suzuki T, Uchida H, Watanabe K, et al. How effective is it to sequentially switch among olanzapine, quetiapine and risperidone? A randomized, open-label study of algorithmbased antipsychotic treatment to patients with symptomatic schizophrenia in the real-world clinical setting. Psychopharmacology (Berl) 2007;195:285-95.
90. Malik P, Kemmler G, Hummer M, Riecher-Roessler A, Kahn RS, Fleischhacker WW. Sexual dysfunction in first-episode schizophrenia patients: results from European First Episode Schizophrenia Trial. J Clin Psychopharmacol 2011;31: 274-80.
91. Spollen JJ 3rd, Wooten RG, Cargile C, Bartztokis G. Prolactin levels and erectile function in patients treated with risperidone. J Clin Psychopharmacol 2004;24:161-6.
92. HoltRI, Peveler RC. Antipsychotics and hyperprolactinaemia: mechanisms, consequences and management. Clin Endocrinol (Oxf) 2011;74:141-7.
93. Komossa K, Rummel-Kluge C, Schmid F, et al. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009;(4):CD006569.
94. Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009;302:1765-73.
95. RayWA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009;360:225-35.
96. Komossa K, Rummel-Kluge C, Hunger H, et al. Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009;(4):CD006627.
97. Grootens KP, van Veelen NM, Peuskens J, et al. Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial. Schizophr Bull 2011;37:352-61.
98. Taylor D. Ziprasidone in the management of schizophrenia : the QT interval issue in context. CNS Drugs 2003;17: 423-30.
99. Citrome L. Using oral ziprasidone effectively: the food effect and dose-response. Adv Ther 2009;26:739-48.
100. Komossa K, Rummel-Kluge C, Hunger H, et al. Amisulpride versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010;(1):CD006624.
101. Marino J, Caballero J. Iloperidone for the treatment of schizophrenia. Ann Pharmacother 2010;44:863-70.
102. Janicak PG, Rado JT. Asenapine: A review of the data. Psychopharm Rev 2009;44:89-96.
103. Meyer JM, Loebel AD, Schweizer E. Lurasidone: A new drug in development for schizophrenia. Expert Opin Investig Drugs 2009;18:1715-26.
104. Potkin SG, Ogasa M, Cucchiaro J, Loebel A. Double-blind comparison of the safety and efficacy of lurasidone and ziprasidone in clinically stable outpatients with schizophrenia or schizoaffective disorder. Schizophr Res 2011;132:101-7.
105. Meltzer HY, Cucchiaro J, Silva R, et al. Lurasidone in the treatment of schizophrenia: A randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry 2011;168:957-67.
106. Harvey PD, Ogasa M, Cucchiaro J, Loebel A, Keefe RS. Performance and interview-based assessments of cognitive change in a randomized, double-blind comparison of lurasidone vs. ziprasidone. Schizophr Res 2011;127:188-94.
107. Kopala LC, Good KP, Honer WG. Extrapyramidal signs and clinical symptoms in first-episode schizophrenia: response to low-dose risperidone. J Clin Psychopharmacol 1997;17: 308-13.
108. McEvoy JP, Hogarty GE, Steingard S. Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. Arch Gen Psychiatry 1991;48:739-45.
109. Merlo MC, Hofer H, Gekle W, et al. Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning. J Clin Psychiatry 2002;63:885Y91.
110. Reilly JL, Harris MS, Keshavan MS, Sweeney JA. Adverse effects of risperidone on spatial working memory in firstepisode schizophrenia. Arch Gen Psychiatry 2006;63:1189-97.
111. Lambert M, Conus P, Eide P, et al. Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence. Eur Psychiatry 2004;19:415-22.
112. Leucht S, Busch R, KisslingW, Kane JM. Early prediction of antipsychotic nonresponse among patients with schizophrenia. J Clin Psychiatry 2007;68:352-60.
113. Gallego JA, Robinson DG, Sevy SM, et al. Time to treatment response in first-episode schizophrenia: should acute treatment trials last several months? J Clin Psychiatry 2011;72:1691-6.
114. Li C, Xia J, Wang J. Risperidone dose for schizophrenia. Cochrane Database Syst Rev 2009;(4):CD007474.
115. Kinon BJ, Volavka J, Stauffer V, et al. Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: A randomized, double-blind, fixed-dose study. J Clin Psychopharmacol 2008;28:392-400.
116. Davis JM, Chen N. Dose response and dose equivalence of antipsychotics. J Clin Psychopharmacol 2004;24: 192-208.
117. Citrome L, Yang R, Glue P, Karayal ON. Effect of ziprasidone dose on all-cause discontinuation rates in acute schizophrenia and schizoaffective disorder: A post-hoc analysis of 4 fixed-dose randomized clinical trials. Schizophr Res 2009;111:39-45.
118. Sparshatt A, Taylor D, Patel MX, Kapur S. A systematic review of aripiprazoleVdose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry 2010;71:1447-56.
119. Citrome L, Stauffer VL, Chen L, et al. Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol 2009;29:278-83.
120. Patel MX, Bowskill S, Couchman L, et al. Plasma olanzapine in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 1999Y2009. J Clin Psychopharmacol 2011;31:411-7.
121. Sparshatt A, Taylor D, Patel MX, Kapur S. AmisulprideV dose, plasma concentration, occupancy and response: implications for therapeutic drug monitoring. Acta Psychiatr Scand 2009;120:416-28.
122. Sparshatt A, Taylor D, Patel MX, Kapur S. Relationship between daily dose, plasma concentrations, dopamine receptor occupancy, and clinical response to quetiapine: A review. J Clin Psychiatry 2011;72:1108-23.
123. Olfson M, Marcus SC, Ascher-Svanum H. Treatment of schizophrenia with long-acting fluphenazine, haloperidol, or risperidone. Schizophr Bull 2007;33:1379-87.
124. Rosenheck RA, Krystal JH, Lew R, et al. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med 2011;364:842-51.
125. Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011;168:603-9.
126. Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. Oral versus depot antipsychotic drugs for schizophreniaVa critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res 2011;127: 83-92.
127. Haddad PM, Taylor M, Niaz OS. First-generation antipsychotic long-acting injections v. oral antipsychotics in schizophrenia: systematic reviewof randomised controlled trials and observational studies. Br J Psychiatry Suppl 2009;52:S20Y8.
128. Taylor D. Psychopharmacology and adverse effects of antipsychotic long-acting injections: A review. Br J Psychiatry Suppl 2009;52:S13-9.
129. Adams CE, Fenton MK, Quraishi S, David AS. Systematic meta-review of depot antipsychotic drugs for people with schizophrenia. Br J Psychiatry 2001;179:290-9.
130. Boaz TL, Constantine RJ, Robst J, Becker MA, Howe AM. Risperidone long-acting therapy prescribing patterns and their impact on early discontinuation of treatment in a large Medicaid population. J Clin Psychiatry 2011;72:1079-85.
131. Covell NH, McEvoy JP, Schooler NR, et al. Effectiveness of switching from long-acting injectable fluphenazine or haloperidol decanoate to long-acting injectable risperidone microspheres: an open-label, randomized controlled trial. J Clin Psychiatry 2012;73:669-75.
132. Citrome L. Paliperidone palmitateVreview of the efficacy, safety and cost of a new second-generation depot antipsychotic medication. Int J Clin Pract 2010;64:216-39.
133. Bishara D. Once-monthly paliperidone injection for the treatment of schizophrenia. Neuropsychiatr Dis Treat 2010; 6:561-72.
134. Kane JM, Detke HC, Naber D, et al. Olanzapine long-acting injection: A 24-week, randomized, double-blind trial of maintenance treatment in patients with schizophrenia. Am J Psychiatry 2010;167:181-9.
135. Detke HC, McDonnell DP, Brunner E, Zhao F, Sorsaburu S, Stefaniak VJ, Corya SA. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry 2010;10:43.
136. Glasgow RE, Vogt TM, Boles SM. Evaluating the public health impact of health promotion interventions: the REAIM framework. Am J Public Health 1999;89:1322-7.
137. Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002;63:763-71.
138. Lindenmayer JP, Citrome L, Khan A, Kaushik S. A randomized, double-blind, parallel-group, fixed-dose, clinical trial of quetiapine at 600 versus 1200 mg/d for patients with treatment-resistant schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 2011;31:160-8.
139. Miller CH, Fleischhacker WW. Managing antipsychoticinduced acute and chronic akathisia. Drug Saf 2000;22: 73-81.
140. Levinson DF, Simpson GM, Singh H, et al. Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment. Arch Gen Psychiatry 1990;47:761-8.
141. Sachdev P. The development of the concept of akathisia: A historical overview. Schizophr Res 1995;16:33-45.
142. Crowner ML, Douyon R, Convit A, Gaztanaga P, Volavka J, Bakall R. Akathisia and violence. Psychopharmacol Bull 1990;26:115-7.
143. Hansen L. A critical review of akathisia, and its possible association with suicidal behaviour. Hum Psychopharmacol 2001;16:495-505.
144. Kane JM, Fleischhacker WW, Hansen L, Perlis R, Pikalov A 3rd, Assuncao-Talbott S. Akathisia: an updated review focusing on second-generation antipsychotics. J Clin Psychiatry 2009;70:627-643.
145. Hirose S. The causes of underdiagnosing akathisia. Schizophr Bull 2003;29:547-58.
146. Farde L. Selective D1- and D2-dopamine receptor blockade both induce akathisia in humans: A PET study with [11C]SCH 23390 and [11C]raclopride. Psychopharmacology (Berl) 1992;107:23-9.
147. Adler LA, Peselow E, Rosenthal M, Angrist B. A controlled comparison of the effects of propranolol, benztropine, and placebo on akathisia: an interim analysis. Psychopharmacol Bull 1993;29:283-6.
148. Fischel T, Hermesh H, Aizenberg D, et al. Cyproheptadine versus propranolol for the treatment of acute neurolepticinduced akathisia: A comparative double-blind study. J Clin Psychopharmacol 2001;21:612-5.
149. Poyurovsky M, Pashinian A, Weizman R, Fuchs C, Weizman A. Low-dose mirtazapine: A new option in the treatment of antipsychotic-induced akathisia. A randomized, doubleblind, placebo- and propranolol-controlled trial. Biol Psychiatry 2006;59:1071-7.
150. Van Putten T, Marder SR. Behavioral toxicity of antipsychotic drugs. J Clin Psychiatry 1987;48 suppl:13-9.
151. Sachdev P, Loneragan C. Intravenous benztropine and propranolol challenges in acute neuroleptic-induced akathisia. Clin Neuropharmacol 1993;16:324-31.
152. Rathbone J, Soares-Weiser K. Anticholinergics for neuroleptic- induced acute akathisia. Cochrane Database Syst Rev 2006;(4):CD003727.
153. Stryjer R, Rosenzcwaig S, Bar F, Ulman AM, Weizman A, Spivak B. Trazodone for the treatment of neurolepticinduced acute akathisia: A placebo-controlled, double-blind, crossover study. Clin Neuropharmacol 2010;33:219-22.
154. Avital A, Gross-Isseroff R, Stryjer R, Hermesh H, Weizman A, Shiloh R. Zolmitriptan compared to propranolol in the treatment of acute neuroleptic-induced akathisia: A comparative double-blind study. Eur Neuropsychopharmacol 2009;19:476-82.
155. Miodownik C, Lerner V, Statsenko N, et al. Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: A randomized, double-blind, controlled study. Clin Neuropharmacol 2006;29:68-72.
156. Gandelman K, Alderman JA, Glue P, et al. The impact of calories and fat content of meals on oral ziprasidone absorption: A randomized, open-label, crossover trial. J Clin Psychiatry 2009;70:58-62.
157. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-23.
158. Mazure CM, Nelson JC, Jatlow PI, Kincare P, Bowers MB Jr. The relationship between blood perphenazine levels, early resolution of psychotic symptoms, and side effects. J Clin Psychiatry 1990;51:330-4.
159. Hansen LB, Larsen NE. Therapeutic advantages of monitoring plasma concentrations of perphenazine in clinical practice. Psychopharmacology (Berl) 1985;87:16-9.
160. Janicak PG, Marder SR, Pavuluri MN. Principles and practice of psychopharmacotherapy. 5th ed. New York: Lippincott Williams & Wilkins, 2011.
161. Janicak PG, Javaid JI, Sharma RP, Leach A, Dowd S, Davis JM. A two-phase, double-blind randomized study of three haloperidol plasma levels for acute psychosis with reassignment of initial non-responders. Acta Psychiatr Scand 1997; 95:343-50.
162. Stroup TS, Lieberman JA, McEvoy JP, et al. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry 2006;163:611Y22.
163. Essock SM, Covell NH, Davis SM, Stroup TS, Rosenheck RA, Lieberman JA. Effectiveness of switching antipsychotic medications. Am J Psychiatry 2006;163:2090-5.
164. Kane JM, Cohen M, Zhao J, Alphs L, Panagides J. Efficacy and safety of asenapine in a placebo- and haloperidolcontrolled trial in patients with acute exacerbation of schizophrenia. J Clin Psychopharmacol 2010;30:106-15.
165. Ashih HW. Saphris and Fanapt: two new antipsychotics. Carlat Psychiatry Rep 2009;7:1-3.
166. Narula PK, Rehan HS, Unni KE, Gupta N. Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: A double-blind, placebocontrolled trial. Schizophr Res 2010;118:218-23.
167. Klein DJ, Cottingham EM, Sorter M, Barton BA, Morrison JA. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Am J Psychiatry 2006;163:2072-9.
168. Wu RR, Zhao JP, Guo XF, et al. Metformin addition attenuates olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: A double-blind, placebo- controlled study. Am J Psychiatry 2008;165:352-8.
169. Smith RC. Metformin as a treatment for antipsychotic drug side effects: special focus on women with schizophrenia. Am J Psychiatry 2012;169:774-6.
170. Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997;23:663-74.
171. Meltzer HY. Treatment-resistant schizophreniaVthe role of clozapine. Curr Med Res Opin 1997;14:1-20.
172. Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988;45: 789-96.
173. Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: A review and meta-analysis of randomized trials. Am J Psychiatry 2001;158:518-26.
174. Essock SM, Hargreaves WA, Covell NH, Goethe J. Clozapines effectiveness for patients in state hospitals: results from a randomized trial. Psychopharmacol Bull 1996;32:683-97.
175. 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.
176. Lewis SW, Barnes TR, 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.
177. Conley RR, Kelly DL, Richardson CM, Tamminga CA, Carpenter WT Jr. The efficacy of high-dose olanzapine versus clozapine in treatment-resistant schizophrenia: A double-blind crossover study. J Clin Psychopharmacol 2003;23:668-71.
178. Meltzer HY. Dimensions of outcome with clozapine. Br J Psychiatry Suppl 1992;26:46-53.
179. Perry PJ, Miller DD, Arndt SV, Cadoret RJ. Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients. Am J Psychiatry 1991;148:231-5.
180. Kronig MH, Munne RA, Szymanski S, et al. Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients. Am J Psychiatry 1995;152: 179-82.
181. Hasegawa M, Gutierrez-Esteinou R, Way L, Meltzer HY. Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: effect of smoking. J Clin Psychopharmacol 1993;13:383-90.
182. Potkin SG, Bera R, Gulasekaram B, et al. Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia. J Clin Psychiatry 1994;55 suppl B:133-6.
183. Freudenreich O, Weiner RD, McEvoy JP. Clozapine-induced electroencephalogram changes as a function of clozapine serum levels. Biol Psychiatry 1997;42:132-7.
184. Lu ML, Lane HY, Lin SK, Chen KP, Chang WH. Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances. J Clin Psychiatry 2004;65:766-71.
185. Faisal I, lindenmayer JP, Taintor Z, Cancro R. Clozapinebenzodiazepine interactions. J Clin Psychiatry 1997;58: 547-8.
186. Phansalkar S, Osser DN. Optimizing clozapine treatment; part II. Psychopharm Rev 2009;44:9-16.
187. Meltzer HY. Treatment of the neuroleptic-nonresponsive schizophrenic patient. Schizophr Bull 1992;18:515Y42.
188. Meltzer HY, Bastani B, Kwon KY, Ramirez LF, Burnett S, Sharpe J. A prospective study of clozapine in treatmentresistant schizophrenic patients. I. Preliminary report. Psychopharmacology (Berl) 1989;99 suppl:S68-72.
189. Buckley P, Miller A, Olsen J, Garver D, Miller DD, Csernansky J. When symptoms persist: clozapine augmentation strategies. Schizophr Bull 2001;27:615-28.
190. Barbui C, Signoretti A, Mule S, Boso M, Cipriani A. Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophr Bull 2009;35:458-68.
191. Taylor DM, Smith L. Augmentation of clozapine with a second antipsychoticVameta-analysis of randomized, placebocontrolled studies. Acta Psychiatr Scand 2009;119:419-25.
192. Sommer IE, Begemann MJ, Temmerman A, Leucht S. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: A quantitative literature review. Schizophr Bull 2012;38:1003-11.
193. Freudenreich O, Henderson DC, Walsh JP, Culhane MA, Goff DC. Risperidone augmentation for schizophrenia partially responsive to clozapine: A double-blind, placebocontrolled trial. Schizophr Res 2007;92:90-4.
194. Honer WG, Thornton AE, Chen EY, et al. Clozapine alone versus clozapine and risperidone with refractory schizophrenia. N Engl J Med 2006;354:472-82.
195. 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.
196. Josiassen 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.
197. Weiner E, Conley RR, Ball MP, et al. Adjunctive risperidone for partially responsive people with schizophrenia treated with clozapine. Neuropsychopharmacology 2010;35: 2274-83.
198. Henderson DC, Kunkel L, Nguyen DD, et al. An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia. Acta Psychiatr Scand 2006;113:142-7.
199. Barbui C, Accordini S, Nose M, et al. Aripiprazole versus haloperidol in combination with clozapine for treatmentresistant schizophrenia in routine clinical care: A randomized, controlled trial. J Clin Psychopharmacol 2011;31: 266-73.
200. Tiihonen J, Wahlbeck K, Kiviniemi V. The efficacy of lamotrigine in clozapine-resistant schizophrenia: A systematic review and meta-analysis. Schizophr Res 2009;109: 10-4.
201. 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.
202. Havaki-Kontaxaki BJ, Ferentinos PP, Kontaxakis VP, Paplos KG, Soldatos CR. Concurrent administration of clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia. Clin Neuropharmacol 2006;29:52-6.
203. Moore TA, Buchanan RW, Buckley PF, et al. The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry 2007;68: 1751-62.
204. De Lucena D, Fernandes BS, Berk M, et al. 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.
205. Amminger GP, Schafer MR, Papageorgiou K, et al. Longchain omega-3 fatty acids for indicated prevention of psychotic disorders: A randomized, placebo-controlled trial. Arch Gen Psychiatry 2010;67:146-54.
206. Peet M, Horrobin DF. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. J Psychiatr Res 2002;36: 7-18.
207. Raja M. Improvement or worsening of psychotic symptoms after treatment with low doses of aripiprazole. Int J Neuropsychopharmacol 2007;10:107-10.
208. Tadokoro S, Okamura N, Sekine Y, Kanahara N, Hashimoto K, Iyo M. Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis. Schizophr Bull 2012;38: 1012-20.
209. Jong-Yih L. Successful switch from clozapine to aripiprazole: A case report. J Clin Psychopharmacol 2009;29:93-5.
210. Kane JM, Meltzer HY, Carson WH Jr, McQuade RD, Marcus RN, Sanchez R. Aripiprazole for treatment-resistant schizophrenia: results of a multicenter, randomized, doubleblind, comparison study versus perphenazine. J Clin Psychiatry 2007;68:213-23.
211. Meltzer HY, Jayathilake K. Low-dose loxapine in the treatment of schizophrenia: is it more effective and more Batypical[ than standard-dose loxapine? J Clin Psychiatry 1999;60 suppl 10:47-51.
212. Joffe G, Terevnikov V, Joffe M, Stenberg JH, Burkin M, Tiihonen J. Add-on mirtazapine enhances antipsychotic effect of first generation antipsychotics in schizophrenia: A double-blind, randomized, placebo-controlled trial. Schizophr Res 2009;108:245Y51.
213. Terevnikov V, Stenberg JH, Joffe M, et al. More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial. Hum Psychopharmacol 2010;25:431-8.
214. Berk M, Gama CS, Sundram S, et al. Mirtazapine add-on therapy in the treatment of schizophrenia with atypical antipsychotics: A double-blind, randomised, placebo-controlled clinical trial. Hum Psychopharmacol 2009;24:233-8.
215. Laan W, Grobbee DE, Selten JP, Heijnen CJ, Kahn RS, Burger H. 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.
216. Riedel M, Strassnig M, Schwarz MJ, Muller N. COX-2 inhibitors as adjunctive therapy in schizophrenia: rationale for use and evidence to date. CNS Drugs 2005;19:805-19.
217. Chan J, Sweeting M. Review: Combination therapy with non-clozapine atypical antipsychotic medication: A review of current evidence. J Psychopharmacol 2007;21:657-64.
218. Lerner V, Libov I, Kotler M, Strous RD. Combination of Batypical[ antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder. Prog Neuropsychopharmacol Biol Psychiatry 2004;28: 89-98.
219. Kane JM, Correll CU, Goff DC, et al. 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.
220. Leucht S, Heres S, Kissling W, Davis JM. Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacol 2011;14:269-84.
221. National Institute for Health and Clinical Excellence. Schizophrenia: core interventions in the treatment and management of schizophrenia in adults in primary and secondary care (update). 2009. http://www.nice.org.uk/CG82.
222. Osser DN. Why physicians do not follow some guidelines and algorithms. Drug Benefit Trends 2009;21:345-54.