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Treating Schizophrenia Now and Developing Strategies for the Next Decade

Published online by Cambridge University Press:  07 November 2014

Carol A. Tamminga
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Abstract

This paper focuses on treatments for schizophrenia (SZ)—treatments we have now and those we hope to have in the future. The treatments we have are based on serendipity, but are effective nonetheless. Pharmacologic characteristics of the most-prescribed drugs are reviewed. It is apparent that a spectrum of effective drugs exist to support individualized therapy. With a view to future discovery, a strategy is proposed for rational antipsychotic drug development. A few concrete examples from the author's own laboratory illustrate an application of the proposal. These data would support the existence of a drugtarget in the anterior cingulate and/or hippocampal cortex. The studies suggest a focus on the limbic cortex for SZ pathophysiology. It would depend on future discovery to test whether this proposal will be productive. For sure, the rapid advance of basic neuroscience provides untold promise for the future.

Type
Feature Articles
Information
CNS Spectrums , Volume 6 , Issue 12: The White Paper Issue 2001 , December 2001 , pp. 987 - 991, 1000
Copyright
Copyright © Cambridge University Press 2001

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References

REFERENCES

1. Tamminga, CA. Neuropsychiatric aspects of schizophrenia. In: Yudofsky, SC, Hales, RE, eds. The American Psychiatric Press Textbook of Neuropsychiatry. 3rd ed. Washington, DC: American Psychiatric Press; 1997:855–882.Google Scholar
2. Carpenter, WT, Buchanan, RW. Schizophrenia: introduction and overview. In: Kaplan, HI, Sadock, BJ, eds. Comprehensive Textbook of Psychiatry. 6th ed. Baltimore, Md: Williams & Wilkins; 1995:889–942.Google Scholar
3. Andreasen, NC. Schizophrenia: the characteristic symptoms [review]. Schizophr Bull. 1991;17:27–49.CrossRefGoogle ScholarPubMed
4. Klein, DF, Davis, JM. Diagnosis and Drug Treatment of Psychiatric Disorders. Baltimore, Md: Williams & Wilkins; 1969.Google Scholar
5. Andreasen, NC. American Journal of Psychiatry celebrates 150th anniversary [editorial]. Am J Psychiatry. 1994;151(supp 16):1–4.Google ScholarPubMed
6. Kutcher, SP. Child and adolescent psychopharmacology. In: Breier, A, Tran, PV, Hen-era, JM, Tollefson, GD, Bymaster, FP, eds. Current Issues in the Psychopharmacology of Schizophrenia. Philadelphia, Pa: W.B. Saunders & Company; 1997:223–272.Google Scholar
7. Schneider, L, Pollock, VE, Lyness, SA. A meta-analysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc. 1990;38:553–563.CrossRefGoogle ScholarPubMed
8. Tohen, M, Zarate, CA Jr., Antipsychotic agents and bipolar disorder. J Clin Psychiatry. 1998;59(suppl 1):38–48.Google ScholarPubMed
9. Davis, JM. Review of antipsychotic drug literature. In: Klein, DF, Davis, JM, eds. Diagnosis and Drug Treatment of Psychiatric Disorders. Baltimore, Md: Williams & Wilkins; 1969:52–138.Google Scholar
10. Carlsson, A, Lindquist, L. Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenh). 1963;20:140–145.CrossRefGoogle ScholarPubMed
11. Anden, NE, Butcher, SG, Corrodi, H, Fuxe, K, Ungerstedt, U. Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur J Pharmacol. 1970;11:303–314.CrossRefGoogle ScholarPubMed
12. Tamminga, CA. Principles of the pharmacotherapy of schizophrenia. In: Bunney, BS, ed. Neurobiology of Psychiatric Disorders. New York, NY: Oxford University Press; 1998:272–285.Google Scholar
13. Purdon, SE, Jones, BD, Stip, E, et al. Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia. Arch Gen Psychiatry. 2000;57:249–258.CrossRefGoogle ScholarPubMed
14. Fink-Jensen, A, Kristensen, P. Effects of typical and atypical neuroleptics on Fos protein expression in the rat forebrain. Neurosci Lett. 1994; 182:115–118.CrossRefGoogle ScholarPubMed
15. Harding, CM, Brooks, GW, Ashikaga, T, Strauss, JS, Breier, A. The Vermont longitudinal study of persons with severe mental illness, II: long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. Am J Psychiatry. 1987;144:727–735.Google ScholarPubMed
16. Tamminga, CA, Conley, RR, Wong, DF. Human brain receptors, IV: human in vivo receptor imaging. Am J Psychiatry. 1994;151:639–639.Google ScholarPubMed
17. Zimbroff, DL, Kane, JM, Tamminga, CA, et al. A controlled, dose-response study of sertindole and haloperidol in schizophrenia. Am J Psychiatry. 1997;154:782–791.Google ScholarPubMed
18. VanPutten, T, Marder, SR, Wirshing, WC, Aravagiri M, Chabert N. Neuroleptic plasma levels. Schizophr Bull. 1991;17:197–216.CrossRefGoogle Scholar
19. Kane, J, Honigfeld, G, Singer, J, Meltzer, H. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45:789–796.CrossRefGoogle ScholarPubMed
20. Kane, JM. Pharmacologic teatment of schizophrenia. Biol Psychiatry. 1999;46:1396–1408.CrossRefGoogle Scholar
21. Miller, DD. Clozapine's effect on negative symptoms in treatment-refractory schizophrenics. Compr Psychiatry. 1994; 35:8–15.CrossRefGoogle ScholarPubMed
22. Leysen, JE, Janssen, PM, Megens, AA, Schotte, A. Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994;55 (suppl):5–12.Google ScholarPubMed
23. Conley, RR, Carpenter, WT Jr, Tamminga, CA. Time to clozapine response in a standardized trial. Am J Psychiatry. 1997;154:1243–1247.Google Scholar
24. Miller, DD, Andreasen, NC, O'Leary, DS, et al. Comparison of the effects of risperidone and haloperidol on regional cerebral blood flow in schizophrenia. Biol Psychiatry. 2001;49:704–715.CrossRefGoogle ScholarPubMed
25. Bymaster, FP, Calligaro, DO, Falcone, JF, et al. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996;14:87–96.CrossRefGoogle ScholarPubMed
26. Nyberg, S, Farde, L, Halldin, C. A PET study of 5-HT2 and D2 dopamine receptor occupancy induced by olanzapine in healthy subjects. Neuropsychopharmacology. 1997;16:1–7.CrossRefGoogle ScholarPubMed
27. Gao, XM, Sakai, K, Tamminga, CA. Chronic olanzapine or sertindole treatment results in reduced oral chewing movements in rats compared to haloperidol. Neuropsychopharmacology. 1998;19:428–433.CrossRefGoogle ScholarPubMed
28. Arvanitis, LA, Miller, BG. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and place bo. Biol Psychiatry. 1997;42:233–246.CrossRefGoogle Scholar
29. Cowan, WM, Harter, DH, Kandel, ER. The emergence of modem neuroscience: some implications for neurology and psychiatry. Ann Rev Neurosci 2000;23:343–391.CrossRefGoogle Scholar
30. Nasar, S. A Beautiful Mind: A Biography of John Forbes Nash, Jr. New York, NY: Simon & Schuster; 1998.Google Scholar
31. Lachenmeyer, N. The Outsider. New York, NY: Broadway Books; 2000.Google Scholar
32. Andreasen, NC. Symptoms, signs, and diagnosis of schizophrenia [review]. Lancet. 1995;346:477–481.CrossRefGoogle ScholarPubMed
33. Andreasen, NC, Arndt, S, Alliger, RJ, Miller, D, Flaum, M. Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch Gen Psychiatry. 1995;52:341–351.CrossRefGoogle ScholarPubMed
34. Carpenter, WT Jr, Buchanan, RW. Schizophrenia. N Engl J Med. 1994;330:681–690.CrossRefGoogle ScholarPubMed
35. Liddle, PF, Friston, KJ, Frith, CD, Hirsch, SR, Jones, T, Frackowiak, RS. Patterns of cerebral blood flow in schizophrenia. Br J Psychiatry. 1992;160:179–186.CrossRefGoogle ScholarPubMed
36. Liddle, PF. Syndromes of chronic schizophrenia. Br J Psyctary. 1990;157:558–561.CrossRefGoogle ScholarPubMed
37. Stevens, JR. An anatomy of schizophrenia? Arch Gen Psychiatry. 1973;29:177–189.CrossRefGoogle ScholarPubMed
38. Carter, CS, Braver, TS, Barch, DM, et al. Anterior cingulate cortex, error detection, and the on-line monitoring of performance. Science. 1998;280:747–749.CrossRefGoogle Scholar
39. Harrison, PJ. The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain. 1999;122(pt 4):593–624.CrossRefGoogle ScholarPubMed
40. Lewis, DA. GAB Aergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Brain Res Rev. 2000;31:270–276.CrossRefGoogle Scholar
41. Holcomb, HH, Links, JM, Smith, C, Wong, DF. Positron emission tomography: measuring the metabolic and neurochemical characteristics of the living human nervous system. In: Andreasen, NC, ed. Brain Imaging Applications in Psychiatry. Washington, DC: American Psychiatric Press; 1989:235–370.Google Scholar
42. Tamminga, CA, Thaker, GK, Buchanan, R, et al. Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Arch Gen Psychiatry. 1992;49:522–530.CrossRefGoogle ScholarPubMed
43. Holcomb, HH, Lahti, AC, Medoff, DR, et al. Brain activation patterns in schizophrenic and comparison volunteers during a matched-performance auditory recognition task. Am J Psychiatry. 2000;157:1634–1645.CrossRefGoogle ScholarPubMed
44. Lahti, AC, Holcomb, HH, Medoff, DR, Tamminga, CA. Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport. 1995;6:869–872.CrossRefGoogle ScholarPubMed
45. Lahti, AC, Holcomb, HH, Weiler, MA, Kile, I, Tamminga, CA. Time course of rCBF changes after acute haloperidol in patients with schizophrenia. Schizophr Res. 1998;29:173.CrossRefGoogle Scholar
46. Andreasen, NC, Amdt, S, Swayze, VW, et al. Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science. 1994;266:294–298.CrossRefGoogle ScholarPubMed
47. Buchsbaum, MS, Nuechterlein, KH, Haier, RJ, et al. Glucose metabolic rate in normals and schizophrenics during the continuous performance test assessed by positron emission tomography. Br J Psychiatry. 1990;156:216–227.CrossRefGoogle ScholarPubMed
48. Silbersweig, DA, Stern, E, Frith, C, et al. A functional neuroanatomy of hallucinations in schizophrenia. Nature. 1995;378:176–179.CrossRefGoogle ScholarPubMed
49. Weinberger, DR, Berman, KF, Suddath, R, Torrey, EF. Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry. 1992;149:890–897.Google ScholarPubMed
50. Gao, XM, Sakai, K, Roberts, RC, et al. Inotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in subregions of human hippocampus: effects of schizophrenia. Am J Psychiatry. 2000;157:1141–1149.CrossRefGoogle Scholar
51. Medoff, DR, Holcomb, HH, Lahti, AC, Tamminga, CA. Probing the human hippocampus using rCBF: contrasts in schizophrenia. Hippocampus. 2001. In press.Google ScholarPubMed