Hostname: page-component-848d4c4894-8bljj Total loading time: 0 Render date: 2024-06-20T01:42:59.822Z Has data issue: false hasContentIssue false

Pharmacologic Treatment of Schizophrenia: What the Future Holds

Published online by Cambridge University Press:  07 November 2014

Abstract

The advent of the newer “atypical” antipsychotics has revolutionized pharmacologic treatment of schizophrenia (SZ) and other psychotic disorders. In contrast to the first-generation conventional neuroleptics, these second-generation antipsychotic agents possess a broader spectrum of efficacy and cause fewer motor side effects such as extrapyramidal symptoms and tardive dyskinesia. Despite their substantial advantages, however, these second-generation agents also have significant limitations in terms of both efficacy and adverse effects. Several strategies to address these shortcomings are currently under study and some of these are likely to become part of our therapeutic armamentarium in the future. Current shortcomings in the pharmacologic treatment of SZ and strategies under investigation to address each of these deficiencies are reviewed. New formulations of existing medications and new antipsychotics under development are discussed. Developing adjunctive treatment strategies to address each of the major psychopathologic domains in SZ are summarized. The potential application of genetic information to treatment-matching in SZ is reviewed and likely refinements in the practice of evidence-based medicine in the pharmacotherapy of SZ are considered.

Type
Feature Articles
Copyright
Copyright © Cambridge University Press 2001

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Cancro, R, Lehmann, HE. Schizophrenia: clinical features. In: Sadock, BJ, Sadock, VA, eds. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000:11691199.Google Scholar
2. Tandon, R, Jibson, MD, Taylor, SF, DeQuardo, JR. Conceptual models of the relation-ship between positive and negative symptoms. In: Shriqui, CL, Nasrallah, HA, eds. Contemporary Issues in the Treatment of Schizophrenia. Washington, DC: American Psychiatric Press; 1995:109124.Google Scholar
3. Kraepelin, E. Dementia praecox. In: Cutting, J, Shepherd, M, eds. The Clinical Roots of the Schizophrenic Concept. New York, NY: Cambridge University Press; 1987.Google Scholar
4. Cerletti, U, Bini, L. A new method of shock therapy: electro-convulsive therapy. Bolletino deU'Accademia di Roma. 1938;64:136138.Google Scholar
5. Delay, J, Deniker, P. Le traitement des psychoses par une methode neurolyque derivee de rhibernotherapie. In: Congres des Medicim Alienistes et Neurologlstes de France. Paris, France: Masson Editeurs Libraires de France; 1952:497502.Google Scholar
6. Tandon, R. Antipsychotic agents. In: Klein, DF, Rowland, LP, eds. Current Psychotherapeutic Drugs. New York, NY: Brunner/Mazel Publishers; 1998:120154.Google Scholar
7. Kane, JM. Pharmacologic treatment of schizophrenia. Biol Psychiatry. 1999;46:13961408.CrossRefGoogle ScholarPubMed
8. Jibson, MD, Tandon, R. New atypical antipsychotic medications. J Psychiatr Res. 1998;32:215228.CrossRefGoogle ScholarPubMed
9. Andrew, H. Clinical relationship of extrapyramidal symptoms and tardive dyskinesia. Can J Psychiatry. 1994;39(suppl 2):7680.Google ScholarPubMed
10. Casey, DE. Motor and mental aspects of EPS. Int Clin Psychopharmacol. 1995;10:105114.Google Scholar
11. Haase, HJ, Janssen, PAJ. The Action of Neuroleptk Drugs: A Psychiatric, Neurologic, and Pharmacological Investigation. Amsterdam, Netherlands: Elsevier; 1958.Google Scholar
12. Meltzer, HY. The concept of atypical antipsychotics. In: den Boer, JA, Westenberg, HGM, van Praag, HM, eds. Advances in the Neurobiology of Schizophrenia. Chichester, England: Wiley; 1995:265273.Google Scholar
13. Tandon, R, Milner, K, Jibson, MD. Antipsychotics from theory to practice: integrating clinical and basic data. J Clin Psychiatry. 1999;60(suppl 8):2028.Google ScholarPubMed
14. Jibson, MD, Tandon, R. Treatment of schizophrenia. Psychiatr Clin North Am Ann Drug Ther. 2000;7:83113.Google Scholar
15. DeQuardo, JR, Tandon, R. Do atypical antipsychotic medications favorably alter the long-term course of schizophrenia? J Psychiatr Res. 1998;32:229242.CrossRefGoogle ScholarPubMed
16. Marder, SR, Meibach, RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry. 1994;151:825835.Google ScholarPubMed
17. Kane, JM, Woerner, MG, Pollack, S, Safferman, AZ, Lieberman, JA. Does clozapine cause tardive dyskinesia? J Clin Psychiatry. 1993;54:327330.Google ScholarPubMed
18. Harvey, PD, Keefe, RSE. Cognitive impairment in schizophrenia and implications of atypical neuroleptic treatment. CNS Spectrums. 1997;2:4155.CrossRefGoogle Scholar
19. Meltzer, HY, Casey, DE, Garver, DL, et al. Assessing the effects of atypical antipsychotics on negative symptoms. J Clin Psychiatry. 1998;59(suppl 12):2834.Google Scholar
20. Kane, J, Honigfeld, G, Singer, J, Meltzer, H. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45:789796.CrossRefGoogle ScholarPubMed
21. Meltzer, HY. Treatment-resistant schizophrenia: the role of clozapine. Curr Med Res Opin. 1997;14:120.CrossRefGoogle ScholarPubMed
22. Chakos, M, Lieberman, J, Hoffman, E, Bradford, D, Sheitman, B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia. Am J Psychiatry. 2001;158:518526.CrossRefGoogle ScholarPubMed
23. Conley, RR, Tamminga, C, Bartko, JJ, et al. Olanzapine compared to chlorpromazine in treatment-resistant schizophrenia. Am J Psychiatry. 1998;155:914920.CrossRefGoogle ScholarPubMed
24. Breier, A, Hamilton, SH. Comparative efficacy of olanzapine and haloperidol for patients with treatment-resistant schizophrenia. Biol Psychiatry. 1999;45:403411.CrossRefGoogle ScholarPubMed
25. Hegarty, JD, Baldessarini, RJ, Tohen, M, Waternaux, C, Open, G. One hundred years of schizophrenia: a meta-analysis of the outcome literature. Am J Psychiatry. 1994;151:14091416.Google ScholarPubMed
26. Keefe, RSE, Silva, SG, Perkins, DO, Lieberman, JA. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull. 1999;25:201222.CrossRefGoogle ScholarPubMed
27. Breier, A, Buchanan, RW, Kirkpatrick, B, et al. Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. Am J Psychiatry. 1994;151:2026.Google ScholarPubMed
28. Bilder, RM. Neurocognitive impairment in schizophrenia and how it affects treatment options. Can J Psychiatry. 1997;42:255264.CrossRefGoogle ScholarPubMed
29. Geddes, JR, Harrison, PJ, Closing the gap between research and practice. Br J Psychiatry. 1997;171:220225.CrossRefGoogle Scholar
30. Lehman, AF, Steinwachs, DM. Translating research into practice: the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations. Schizophr Bull. 1998;24:110.CrossRefGoogle ScholarPubMed
31. Mellman, TA, Miller, AL, Weissman, EM, Crismon, ML, Essock, SM, Marder, SR. Evidence-based pharmacological treatment for people with severe mental illness: a focus on guidelines and algorithms. Psychiatr Serv. 2001;52:619625.CrossRefGoogle ScholarPubMed
32. Tandon, R. Implementing evidence-based pharmacotherapy practice for schizophrenia. J Psychotic Disord. 2001;6:1415.Google Scholar
33. Jones, B, Taylor, CC, Meehan, K. The efficacy of a rapid-acting intramuscular formulation of olanzapine for positive symptoms. J Clin Psychiatry. 2001;61(suppl 2):2224.Google Scholar
34. Swift, RH, Harrigan, EP, van Kammen, DP. A comparison of intramuscular ziprasidone and intramuscular haloperidol. Paper presented at: 9th Congress of the Association of European Psychiatrists; September 20-24, 1998; Copenhagen, Denmark.Google Scholar
35. Corbett, R, Griffiths, L, Shipley, JE. Iloperidone. Cent New Syst Drug Rev. 1997;3:120147.Google Scholar
36. Jain, KK. An assessment of iloperidone in the treatment of schizophrenia. Expert Opin Investig Drugs. 2000;9:29352943.CrossRefGoogle ScholarPubMed
37. Lawler, CP, Prioleau, C, Lewis, MM, Mak, C, Jiang, D, Schetz, JA. Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology. 1999;20:612627.CrossRefGoogle ScholarPubMed
38. Aripiprazole overview. Drug Future. 2000;25:961963.Google Scholar
39. Carson, WH, Sana, A, Ali, M, Dunbar, GC, Ingenito G. Aripiprazole and risperidone vs. placebo in schizophrenia and schizoaffective disorder. Paper presented at: Annual Meeting of the American Psychiatric Association; May 7-12,2001; New Orleans, La.Google Scholar
40. Carson, WH, Ali, M, Saha, GC, Dunbar, GC, Ingenito G. A double-blind, placebo-controlled trial of aripiprazole and haloperidol. Paper presented at: Annual Meeting of the American Psychiatric Association; May 7-12,2001; New Orleans, La.Google Scholar
41. Miller, DD, Tandon, R. The biology and pathophysiology of negative symptoms. In: Keefe, R, McEvoy, J, eds. Negative Symptoms of Schizophrenia. Washington, DC: American Psychiatric Press; 2000.Google Scholar
42. Goff, DC, Coyle, JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry. 2001;158:13671377.CrossRefGoogle ScholarPubMed
43. Goff, DC, Leahy, L, Berman, I, et al. A placebo-controlled pilot study of the ampakine C516 added to clozapine in schizophrenia. J Clin Psychopharmacol. 2001;21:484487.CrossRefGoogle Scholar
44. Tandon, R. Cholinergic aspects of schizophrenia. Br J Psychiatry. 1999;174(suppl 37):711.CrossRefGoogle Scholar
45. Bymaster, FP. Possible role of muscarinic receptor agonists as therapeutic agents for psychosis. In: Breier, A, Tran, PV, Herrea, JM, Tollefson, GD, Bymaster, FP, eds. Current Issues in the Psychopharmacology of Schizophrenia. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001;333348.Google Scholar
46. Tandon, R, Taylor, SF, DeQuardo, JR, Eiser, A, Jibson, MD, Goldman, M. The cholinergic system in schizophrenia reconsidered. Neuropsychopharmacology. 1999;22:S189202.CrossRefGoogle Scholar
47. Sumiyoshi, T, Matsui, M, Yamashita, I. The effect of tandospirone, a serotonin (1A) agonist, on memory function in schizophrenia. Biol Psychiatry. 2001;49:861868.CrossRefGoogle ScholarPubMed
48. Sumiyoshi, T, Matsui, M, Nohara, S, et al. Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment. Am J Psychiatry. 2001;158:17221724.CrossRefGoogle ScholarPubMed
49. Binder, E, Owens, MJ, Kilts, CD, Nemeroff, CB. Involvement of neurotensin in latent inhibition. Soc Neurosd Abstracts. 1998;24:8288.Google Scholar
50. Binder, EB, Kinkead, B, Nemeroff, CB. Neuropeptides. In: Breier, A, Tran, PV, Herrea, JM, Tollefson, GD, Bymaster, FP, eds. Current Issues in the Psychopharmacology of Schizophrenia. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:349371.Google Scholar
51. Gillies, D, Beck, A, McCloud, A. Benzodiazepines alone or in combination with antipsychotic drugs for acute psychosis [database online]. Cochrane Database of Syst Rev. Protocol.Google Scholar
52. Casey, DE, Daniel, D, Tracy, K, Wozniak, P, Sommerville, K. Improved antipsychotic effect of divalproex combined with risperidone or olanzapine for schizophrenia. Paper presented at: World Assembly of Mental Health; July 22-27,2001; Vancouver, Canada.Google Scholar
53. Leucht, S, McGrath, J, White, P, Kissling, W. Carbamazepine for schizophrenia and schizoaffective psychoses [database online]. Cochrane Database Syst Rev. 2001:2134.Google Scholar
54. Arranz, MJ, Munro, J, Birkett, J. Pharmacogenetic prediction of clozapine response. Lancet. 2000;355:16151616.CrossRefGoogle ScholarPubMed
55. Eichhammer, P, Albus, M, Bormann-Hassenbach, M. Association of dopamine D3-receptor gene variants with neuroleptic-induced akathisia in schizophrenic patients: a generalization of Steen's study on DRD3 and tardive dyskinesia. Am J Med Genet. 2000;96:187191.3.0.CO;2-8>CrossRefGoogle Scholar
56. Otani, K, Aoshima, T. Pharmacogenetics of classical and new antipsychotic drugs. Ther Drug Monk. 2000;22:118121.CrossRefGoogle ScholarPubMed
57. Tandon, R, Glick, I, Goldman, M, Jibson, MD, Marder, SR, Mellman, T. Managing Schizophrenia: A Comprehensive Primer. New York, NY: McMahon Publishing; 2001.Google Scholar
58. Carpenter, WT Jr.Phase IV industry-sponsored trials are of little or no value. J Psychotic Disord. 2001;5:24.Google Scholar
59. Conley, RR. Phase IV industry-sponsored trials provide useful information. J Psychotic Disord. 2001;5:45.Google Scholar
60. Tandon, R. Industry-sponsored phase IV clinical trials: promises and pitfalls, information and misinformation. J Psychotic Disord. 2001;5:1415.Google Scholar
61. Mojtabai, R, Nicholson, RA, Carpenter, BN. Role of psychosocial treatments in management of schizophrenia: a meta-analytic review of controlled outcome studies. Schizophr Bull. 1998;24:569587.CrossRefGoogle ScholarPubMed
62. Slade, M, Priebe, S. Are randomized controlled trials the only gold that glitters? Br J Psychiatry. 2001;179:286287.CrossRefGoogle ScholarPubMed