Skip to main content
Indian Journal of Psychiatry logoLink to Indian Journal of Psychiatry
. 2004 Apr-Jun;46(2):125–134.

Concept and Management of Treatment Resistant Schizophrenia (TRS)

Nitesh Painuly 1, Nitin Gupta 2, Ajit Avasthi 3,*
PMCID: PMC2949927  PMID: 21408038

Abstract

Treatment resistance in schizophrenia is a fairly common problem faced by psychiatrists worldwide. The concept and definition of Treatment Resistant Schizophrenia (TRS) is still far from satisfactory. Data suggests the presence of biological factors underlying TRS. Second generation antipsychotics are advocated for patients with TRS. However, till date, clozapine remains the treatment of choice. Evidence for other pharmacological measures and ECT is accumulating. Psychosocial interventions do form an integral component of management of TRS. It can be concluded that, with advances in sychopharmacology, TRS needs to be better researched and managed in the future.

Keywords: Schizophrenia, treatment resistant, clozapine, a typical antipsychotics, difficult to treat schizophrenia

Full Text

The Full Text of this article is available as a PDF (101.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Azorin J. M., Spiegel R., Remington G., Vanelle J. M., Péré J. J., Giguere M., Bourdeix I. A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia. Am J Psychiatry. 2001 Aug;158(8):1305–1313. doi: 10.1176/appi.ajp.158.8.1305. [DOI] [PubMed] [Google Scholar]
  2. Barnes T. R., McEvedy C. J. Pharmacological treatment strategies in the non-responsive schizophrenic patient. Int Clin Psychopharmacol. 1996 May;11 (Suppl 2):67–71. doi: 10.1097/00004850-199605002-00011. [DOI] [PubMed] [Google Scholar]
  3. Bondolfi G., Dufour H., Patris M., May J. P., Billeter U., Eap C. B., Baumann P. Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group. Am J Psychiatry. 1998 Apr;155(4):499–504. doi: 10.1176/ajp.155.4.499. [DOI] [PubMed] [Google Scholar]
  4. Breier A., Buchanan R. W., Irish D., Carpenter W. T., Jr Clozapine treatment of outpatients with schizophrenia: outcome and long-term response patterns. Hosp Community Psychiatry. 1993 Dec;44(12):1145–1149. doi: 10.1176/ps.44.12.1145. [DOI] [PubMed] [Google Scholar]
  5. Breier A., Hamilton S. H. Comparative efficacy of olanzapine and haloperidol for patients with treatment-resistant schizophrenia. Biol Psychiatry. 1999 Feb 15;45(4):403–411. doi: 10.1016/s0006-3223(98)00291-1. [DOI] [PubMed] [Google Scholar]
  6. Brenner H. D., Dencker S. J., Goldstein M. J., Hubbard J. W., Keegan D. L., Kruger G., Kulhanek F., Liberman R. P., Malm U., Midha K. K. Defining treatment refractoriness in schizophrenia. Schizophr Bull. 1990;16(4):551–561. doi: 10.1093/schbul/16.4.551. [DOI] [PubMed] [Google Scholar]
  7. Carman J. S., Bigelow L. B., Wyatt R. J. Lithium combined with neuroleptics in chronic schizophrenic and schizoaffective patients. J Clin Psychiatry. 1981 Mar;42(3):124–128. [PubMed] [Google Scholar]
  8. Chakos M. H., Alvir J. M., Woerner M. G., Koreen A., Geisler S., Mayerhoff D., Sobel S., Kane J. M., Borenstein M., Lieberman J. A. Incidence and correlates of tardive dyskinesia in first episode of schizophrenia. Arch Gen Psychiatry. 1996 Apr;53(4):313–319. doi: 10.1001/archpsyc.1996.01830040049009. [DOI] [PubMed] [Google Scholar]
  9. 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 Apr;158(4):518–526. doi: 10.1176/appi.ajp.158.4.518. [DOI] [PubMed] [Google Scholar]
  10. Chanpattana W., Chakrabhand M. L., Sackeim H. A., Kitaroonchai W., Kongsakon R., Techakasem P., Buppanharun W., Tuntirungsee Y., Kirdcharoen N. Continuation ECT in treatment-resistant schizophrenia: a controlled study. J ECT. 1999 Sep;15(3):178–192. [PubMed] [Google Scholar]
  11. Chanpattana W. Maintenance ECT in treatment-resistant schizophrenia. J Med Assoc Thai. 2000 Jun;83(6):657–662. [PubMed] [Google Scholar]
  12. Chouinard G., Vainer J. L., Bélanger M. C., Turnier L., Beaudry P., Roy J. Y., Miller R. Risperidone and clozapine in the treatment of drug-resistant schizophrenia and neuroleptic-induced supersensitivity psychosis. Prog Neuropsychopharmacol Biol Psychiatry. 1994 Nov;18(7):1129–1141. doi: 10.1016/0278-5846(94)90116-3. [DOI] [PubMed] [Google Scholar]
  13. Christison G. W., Kirch D. G., Wyatt R. J. When symptoms persist: choosing among alternative somatic treatments for schizophrenia. Schizophr Bull. 1991;17(2):217–245. doi: 10.1093/schbul/17.2.217. [DOI] [PubMed] [Google Scholar]
  14. Claghorn J., Honigfeld G., Abuzzahab F. S., Sr, Wang R., Steinbook R., Tuason V., Klerman G. The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol. 1987 Dec;7(6):377–384. [PubMed] [Google Scholar]
  15. Conley R. R., Buchanan R. W. Evaluation of treatment-resistant schizophrenia. Schizophr Bull. 1997;23(4):663–674. doi: 10.1093/schbul/23.4.663. [DOI] [PubMed] [Google Scholar]
  16. Conley R. R., Kelly D. L. Management of treatment resistance in schizophrenia. Biol Psychiatry. 2001 Dec 1;50(11):898–911. doi: 10.1016/s0006-3223(01)01271-9. [DOI] [PubMed] [Google Scholar]
  17. Conley R. R., Tamminga C. A., Kelly D. L., Richardson C. M. Treatment-resistant schizophrenic patients respond to clozapine after olanzapine non-response. Biol Psychiatry. 1999 Jul 1;46(1):73–77. doi: 10.1016/s0006-3223(99)00029-3. [DOI] [PubMed] [Google Scholar]
  18. Crow T. J., Ferrier I. N., Johnstone E. C. The two-syndrome concept and neuroendocrinology of schizophrenia. Psychiatr Clin North Am. 1986 Mar;9(1):99–113. [PubMed] [Google Scholar]
  19. Dean C. E. Severe self-injurious behavior associated with treatment-resistant schizophrenia: treatment with maintenance electroconvulsive therapy. J ECT. 2000 Sep;16(3):302–308. doi: 10.1097/00124509-200009000-00014. [DOI] [PubMed] [Google Scholar]
  20. Dossenbach MRK, Beuzen J. N., Avnon M., Belmaker R. H., Elizur A., Mark M., Munitz H., Schneidman M., Shoshani D., Kratky P. The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine. Clin Ther. 2000 Sep;22(9):1021–1034. doi: 10.1016/s0149-2918(00)80082-x. [DOI] [PubMed] [Google Scholar]
  21. Drapalski A. L., Rosse R. B., Peebles R. R., Schwartz B. L., Marvel C. L., Deutsch S. I. Topiramate improves deficit symptoms in a patient with schizophrenia when added to a stable regimen of antipsychotic medication. Clin Neuropharmacol. 2001 Sep-Oct;24(5):290–294. doi: 10.1097/00002826-200109000-00006. [DOI] [PubMed] [Google Scholar]
  22. Dursun S. M., Deakin J. F. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J Psychopharmacol. 2001 Dec;15(4):297–301. doi: 10.1177/026988110101500409. [DOI] [PubMed] [Google Scholar]
  23. Dursun S. M., Devarajan S. Clozapine weight gain, plus topiramate weight loss. Can J Psychiatry. 2000 Mar;45(2):198–198. [PubMed] [Google Scholar]
  24. Emsley R. A., Raniwalla J., Bailey P. J., Jones A. M. A comparison of the effects of quetiapine ('seroquel') and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. PRIZE Study Group. Int Clin Psychopharmacol. 2000 May;15(3):121–131. doi: 10.1097/00004850-200015030-00001. [DOI] [PubMed] [Google Scholar]
  25. Essock S. M., Hargreaves W. A., Dohm F. A., Goethe J., Carver L., Hipshman L. Clozapine eligibility among state hospital patients. Schizophr Bull. 1996;22(1):15–25. doi: 10.1093/schbul/22.1.15. [DOI] [PubMed] [Google Scholar]
  26. Falloon I. R., Boyd J. L., McGill C. W., Razani J., Moss H. B., Gilderman A. M. Family management in the prevention of exacerbations of schizophrenia: a controlled study. N Engl J Med. 1982 Jun 17;306(24):1437–1440. doi: 10.1056/NEJM198206173062401. [DOI] [PubMed] [Google Scholar]
  27. Falloon I. R., Boyd J. L., McGill C. W., Williamson M., Razani J., Moss H. B., Gilderman A. M., Simpson G. M. Family management in the prevention of morbidity of schizophrenia. Clinical outcome of a two-year longitudinal study. Arch Gen Psychiatry. 1985 Sep;42(9):887–896. doi: 10.1001/archpsyc.1985.01790320059008. [DOI] [PubMed] [Google Scholar]
  28. Farde L., Nordström A. L., Wiesel F. A., Pauli S., Halldin C., Sedvall G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry. 1992 Jul;49(7):538–544. doi: 10.1001/archpsyc.1992.01820070032005. [DOI] [PubMed] [Google Scholar]
  29. Friedman J., Ault K., Powchik P. Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine. Biol Psychiatry. 1997 Sep 15;42(6):522–523. doi: 10.1016/S0006-3223(97)00227-8. [DOI] [PubMed] [Google Scholar]
  30. Garety P. A., Fowler D., Kuipers E. Cognitive-behavioral therapy for medication-resistant symptoms. Schizophr Bull. 2000;26(1):73–86. doi: 10.1093/oxfordjournals.schbul.a033447. [DOI] [PubMed] [Google Scholar]
  31. Goswami Utpal, Kumar Unnati, Singh Baljit. Efficacy of Electroconvulsive Therapy in Treatment Resistant Schizophreinia : A double-blind study. Indian J Psychiatry. 2003 Jan;45(1):26–29. [PMC free article] [PubMed] [Google Scholar]
  32. Green M. F., Marshall B. D., Jr, Wirshing W. C., Ames D., Marder S. R., McGurk S., Kern R. S., Mintz J. Does risperidone improve verbal working memory in treatment-resistant schizophrenia? Am J Psychiatry. 1997 Jun;154(6):799–804. doi: 10.1176/ajp.154.6.799. [DOI] [PubMed] [Google Scholar]
  33. Gupta S., Sonnenberg S. J., Frank B. Olanzapine augmentation of clozapine. Ann Clin Psychiatry. 1998 Sep;10(3):113–115. doi: 10.1023/a:1022350221192. [DOI] [PubMed] [Google Scholar]
  34. Hegarty J. D., Baldessarini R. J., Tohen M., Waternaux C., Oepen G. One hundred years of schizophrenia: a meta-analysis of the outcome literature. Am J Psychiatry. 1994 Oct;151(10):1409–1416. doi: 10.1176/ajp.151.10.1409. [DOI] [PubMed] [Google Scholar]
  35. Hollister L. E., Trevino E. S. Calcium channel blockers in psychiatric disorders: a review of the literature. Can J Psychiatry. 1999 Sep;44(7):658–664. doi: 10.1177/070674379904400702. [DOI] [PubMed] [Google Scholar]
  36. Hosák L., Libiger J. Antiepileptic drugs in schizophrenia: a review. Eur Psychiatry. 2002 Nov;17(7):371–378. doi: 10.1016/s0924-9338(02)00696-x. [DOI] [PubMed] [Google Scholar]
  37. James D. V., Gray N. S. Elective combined electroconvulsive and clozapine therapy. Int Clin Psychopharmacol. 1999 Mar;14(2):69–72. doi: 10.1097/00004850-199903000-00002. [DOI] [PubMed] [Google Scholar]
  38. Johns C. A., Thompson J. W. Adjunctive treatments in schizophrenia: pharmacotherapies and electroconvulsive therapy. Schizophr Bull. 1995;21(4):607–619. doi: 10.1093/schbul/21.4.607. [DOI] [PubMed] [Google Scholar]
  39. Juarez-Reyes M. G., Shumway M., Battle C., Bacchetti P., Hansen M. S., Hargreaves W. A. Effects of stringent criteria on eligibility for clozapine among public mental health clients. Psychiatr Serv. 1995 Aug;46(8):801–806. doi: 10.1176/ps.46.8.801. [DOI] [PubMed] [Google Scholar]
  40. Kales H. C., Dequardo J. R., Tandon R. Combined electroconvulsive therapy and clozapine in treatment-resistant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Apr;23(3):547–556. doi: 10.1016/s0278-5846(99)00015-9. [DOI] [PubMed] [Google Scholar]
  41. Kane J. M. Management strategies for the treatment of schizophrenia. J Clin Psychiatry. 1999;60 (Suppl 12):13–17. [PubMed] [Google Scholar]
  42. Kane J. M., Marder S. R. Psychopharmacologic treatment of schizophrenia. Schizophr Bull. 1993;19(2):287–302. doi: 10.1093/schbul/19.2.287. [DOI] [PubMed] [Google Scholar]
  43. Kane J. M. Treatment-resistant schizophrenic patients. J Clin Psychiatry. 1996;57 (Suppl 9):35–40. [PubMed] [Google Scholar]
  44. Kane J., Honigfeld G., Singer J., Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988 Sep;45(9):789–796. doi: 10.1001/archpsyc.1988.01800330013001. [DOI] [PubMed] [Google Scholar]
  45. Keck P. E., Jr, Wilson D. R., Strakowski S. M., McElroy S. L., Kizer D. L., Balistreri T. M., Holtman H. M., DePriest M. Clinical predictors of acute risperidone response in schizophrenia, schizoaffective disorder, and psychotic mood disorders. J Clin Psychiatry. 1995 Oct;56(10):466–470. [PubMed] [Google Scholar]
  46. Kee K. S., Kern R. S., Marshall B. D., Jr, Green M. F. Risperidone versus haloperidol for perception of emotion in treatment-resistant schizophrenia: preliminary findings. Schizophr Res. 1998 May 25;31(2-3):159–165. doi: 10.1016/s0920-9964(98)00026-7. [DOI] [PubMed] [Google Scholar]
  47. Kinon B. J., Kane J. M., Johns C., Perovich R., Ismi M., Koreen A., Weiden P. Treatment of neuroleptic-resistant schizophrenic relapse. Psychopharmacol Bull. 1993;29(2):309–314. [PubMed] [Google Scholar]
  48. Leff J., Berkowitz R., Shavit N., Strachan A., Glass I., Vaughn C. A trial of family therapy v. a relatives group for schizophrenia. Br J Psychiatry. 1989 Jan;154:58–66. doi: 10.1192/bjp.154.1.58. [DOI] [PubMed] [Google Scholar]
  49. Leff J., Berkowitz R., Shavit N., Strachan A., Glass I., Vaughn C. A trial of family therapy versus a relatives' group for schizophrenia. Two-year follow-up. Br J Psychiatry. 1990 Oct;157:571–577. doi: 10.1192/bjp.157.4.571. [DOI] [PubMed] [Google Scholar]
  50. Lerner V., Chudakova 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 Sep-Oct;23(5):284–286. doi: 10.1097/00002826-200009000-00009. [DOI] [PubMed] [Google Scholar]
  51. Leucht Stefan, McGrath John, White Paul, Kissling Werner. Carbamazepine augmentation for schizophrenia: how good is the evidence? J Clin Psychiatry. 2002 Mar;63(3):218–224. doi: 10.4088/jcp.v63n0308. [DOI] [PubMed] [Google Scholar]
  52. Levinson D. F., Simpson G. M., Singh H., Yadalam K., Jain A., Stephanos M. J., Silver P. Fluphenazine dose, clinical response, and extrapyramidal symptoms during acute treatment. Arch Gen Psychiatry. 1990 Aug;47(8):761–768. doi: 10.1001/archpsyc.1990.01810200069010. [DOI] [PubMed] [Google Scholar]
  53. Lieberman J. A., Safferman A. Z., Pollack S., Szymanski S., Johns C., Howard A., Kronig M., Bookstein P., Kane J. M. Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome. Am J Psychiatry. 1994 Dec;151(12):1744–1752. doi: 10.1176/ajp.151.12.1744. [DOI] [PubMed] [Google Scholar]
  54. Lieberman J., Jody D., Geisler S., Alvir J., Loebel A., Szymanski S., Woerner M., Borenstein M. Time course and biologic correlates of treatment response in first-episode schizophrenia. Arch Gen Psychiatry. 1993 May;50(5):369–376. doi: 10.1001/archpsyc.1993.01820170047006. [DOI] [PubMed] [Google Scholar]
  55. Marder S. R. Management of treatment-resistant patients with schizophrenia. J Clin Psychiatry. 1996;57 (Suppl 11):26–30. [PubMed] [Google Scholar]
  56. Martín J., Gómez J. C., García-Bernardo E., Cuesta M., Alvarez E., Gurpegui M. Olanzapine in treatment-refractory schizophrenia: results of an open-label study. The Spanish Group for the Study of Olanzapine in Treatment-Refractory Schizophrenia. J Clin Psychiatry. 1997 Nov;58(11):479–483. [PubMed] [Google Scholar]
  57. Mauri Massimo C., Volonteri Lucia S., Dell'Osso Bernardo, Regispani Francesca, Papa Pietro, Baldi Marialuisa, Bareggi Silvio R. Predictors of clinical outcome in schizophrenic patients responding to clozapine. J Clin Psychopharmacol. 2003 Dec;23(6):660–664. doi: 10.1097/01.jcp.0000095351.32154.3a. [DOI] [PubMed] [Google Scholar]
  58. McEvoy J. P., Hogarty G. E., Steingard S. Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. Arch Gen Psychiatry. 1991 Aug;48(8):739–745. doi: 10.1001/archpsyc.1991.01810320063009. [DOI] [PubMed] [Google Scholar]
  59. McFarlane W. R., Lukens E., Link B., Dushay R., Deakins S. A., Newmark M., Dunne E. J., Horen B., Toran J. Multiple-family groups and psychoeducation in the treatment of schizophrenia. Arch Gen Psychiatry. 1995 Aug;52(8):679–687. doi: 10.1001/archpsyc.1995.03950200069016. [DOI] [PubMed] [Google Scholar]
  60. McGlashan T. H. A selective review of recent North American long-term followup studies of schizophrenia. Schizophr Bull. 1988;14(4):515–542. doi: 10.1093/schbul/14.4.515. [DOI] [PubMed] [Google Scholar]
  61. Meltzer H. Y. An overview of the mechanism of action of clozapine. J Clin Psychiatry. 1994 Sep;55 (Suppl B):47–52. [PubMed] [Google Scholar]
  62. Meltzer H. Y. Defining treatment refractoriness in schizophrenia. Schizophr Bull. 1990;16(4):563–565. doi: 10.1093/schbul/16.4.563. [DOI] [PubMed] [Google Scholar]
  63. Meltzer H. Y., Lee M., Cola P. The evolution of treatment resistance: biologic implications. J Clin Psychopharmacol. 1998 Apr;18(2 Suppl 1):5S–11S. doi: 10.1097/00004714-199804001-00003. [DOI] [PubMed] [Google Scholar]
  64. Miller A. L., Chiles J. A., Chiles J. K., Crismon M. L., Rush A. J., Shon S. P. The Texas Medication Algorithm Project (TMAP) schizophrenia algorithms. J Clin Psychiatry. 1999 Oct;60(10):649–657. doi: 10.4088/jcp.v60n1002. [DOI] [PubMed] [Google Scholar]
  65. Miller R., Chouinard G. Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia. Biol Psychiatry. 1993 Nov 15;34(10):713–738. doi: 10.1016/0006-3223(93)90044-e. [DOI] [PubMed] [Google Scholar]
  66. Molina Vicente, Reig Santiago, Sarramea Fernando, Sanz Javier, Francisco Artaloytia Juan, Luque Rogelio, Aragüs María, Pascau Javier, Benito Carlos, Palomo Tomás. Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia. Psychiatry Res. 2003 Nov 30;124(3):153–161. doi: 10.1016/s0925-4927(03)00108-2. [DOI] [PubMed] [Google Scholar]
  67. Moncrieff Joanna. Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination. Br J Psychiatry. 2003 Aug;183:161–166. doi: 10.1192/bjp.183.2.161. [DOI] [PubMed] [Google Scholar]
  68. Mowerman S., Siris S. G. Adjunctive loxapine in a clozapine-resistant cohort of schizophrenic patients. Ann Clin Psychiatry. 1996 Dec;8(4):193–197. doi: 10.3109/10401239609147759. [DOI] [PubMed] [Google Scholar]
  69. Muijen M., Marks I. M., Connolly J., Audini B., McNamee G. The daily living programme. Preliminary comparison of community versus hospital-based treatment for the seriously mentally ill facing emergency admission. Br J Psychiatry. 1992 Mar;160:379–384. doi: 10.1192/bjp.160.3.379. [DOI] [PubMed] [Google Scholar]
  70. Murray R. M., O'Callaghan E., Castle D. J., Lewis S. W. A neurodevelopmental approach to the classification of schizophrenia. Schizophr Bull. 1992;18(2):319–332. doi: 10.1093/schbul/18.2.319. [DOI] [PubMed] [Google Scholar]
  71. Pato C. N., Wolkowitz O. M., Rapaport M., Schulz S. C., Pickar D. Benzodiazepine augmentation of neuroleptic treatment in patients with schizophrenia. Psychopharmacol Bull. 1989;25(2):263–266. [PubMed] [Google Scholar]
  72. Peuskens J. The evolving definition of treatment resistance. J Clin Psychiatry. 1999;60 (Suppl 12):4–8. [PubMed] [Google Scholar]
  73. Quitkin F., Rifkin A., Klein D. F. Very high dosage vs standard dosage fluphenazine in schizophrenia. A double-blind study of nonchronic treatment-refractory patients. Arch Gen Psychiatry. 1975 Oct;32(10):1276–1281. doi: 10.1001/archpsyc.1975.01760280074007. [DOI] [PubMed] [Google Scholar]
  74. Raskin S., Katz G., Zislin Z., Knobler H. Y., Durst R. Clozapine and risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation. Acta Psychiatr Scand. 2000 Apr;101(4):334–336. [PubMed] [Google Scholar]
  75. Revicki D. A., Luce B. R., Weschler J. M., Brown R. E., Adler M. A. Cost-effectiveness of clozapine for treatment-resistant schizophrenic patients. Hosp Community Psychiatry. 1990 Aug;41(8):850–854. doi: 10.1176/ps.41.8.850. [DOI] [PubMed] [Google Scholar]
  76. Rodriguez V. M., Catalina M. L., García-Noblejas J. A., Cuesta P. Schizophrenic syndromes and clozapine response in treatment-resistant schizophrenia. Psychiatry Res. 1998 Jan 16;77(1):21–28. doi: 10.1016/s0165-1781(97)00129-7. [DOI] [PubMed] [Google Scholar]
  77. Rosberg J., Stunden A. A. The use of direct confrontation: the treatment-resistant schizophrenic patient. Acta Psychiatr Scand. 1990 Apr;81(4):352–358. doi: 10.1111/j.1600-0447.1990.tb05463.x. [DOI] [PubMed] [Google Scholar]
  78. Ruskin P., Averbukh I., Belmaker R. H., Dasberg H. Benzodiazepines in chronic schizophrenia. Biol Psychiatry. 1979 Jun;14(3):557–558. [PubMed] [Google Scholar]
  79. Sajatovic M., Meltzer H. Y. The Effect of Short-Term Electroconvulsive Treatment Plus Neuroleptics in Treatment-Resistant Schizophrenia and Schizoaffective Disorder. Convuls Ther. 1993;9(3):167–175. [PubMed] [Google Scholar]
  80. Sanders R. D., Mossman D. An open trial of olanzapine in patients with treatment-refractory psychoses. J Clin Psychopharmacol. 1999 Feb;19(1):62–66. doi: 10.1097/00004714-199902000-00012. [DOI] [PubMed] [Google Scholar]
  81. Schooler N. R., Keith S. J., Severe J. B., Matthews S. M., Bellack A. S., Glick I. D., Hargreaves W. A., Kane J. M., Ninan P. T., Frances A. Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment. Arch Gen Psychiatry. 1997 May;54(5):453–463. doi: 10.1001/archpsyc.1997.01830170079011. [DOI] [PubMed] [Google Scholar]
  82. Schulz S. C., Thompson P. A., Jacobs M., Ninan P. T., Robinson D., Weiden P. J., Yadalam K., Glick I. D., Odbert C. L. Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients. J Clin Psychiatry. 1999 Jun;60(6):366–372. [PubMed] [Google Scholar]
  83. Seeley William W., Turetsky Neil, Reus Victor I., Wolkowitz Owen M. Benzodiazepines in schizophrenia: prefrontal cortex atrophy predicts clinical response to alprazolam augmentation. World J Biol Psychiatry. 2002 Oct;3(4):221–224. doi: 10.3109/15622970209150625. [DOI] [PubMed] [Google Scholar]
  84. Shalev A., Hermesh H., Rothberg J., Munitz H. Poor neuroleptic response in acutely exacerbated schizophrenic patients. Acta Psychiatr Scand. 1993 Feb;87(2):86–91. doi: 10.1111/j.1600-0447.1993.tb03335.x. [DOI] [PubMed] [Google Scholar]
  85. Shiloh R., Zemishlany Z., Aizenberg D., Radwan M., Schwartz B., Dorfman-Etrog P., Modai I., Khaikin M., Weizman A. Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study. Br J Psychiatry. 1997 Dec;171:569–573. doi: 10.1192/bjp.171.6.569. [DOI] [PubMed] [Google Scholar]
  86. Shore D., Matthews S., Cott J., Lieberman J. A. Clinical implications of clozapine discontinuation: report of an NIMH workshop. Schizophr Bull. 1995;21(2):333–338. doi: 10.1093/schbul/21.2.333. [DOI] [PubMed] [Google Scholar]
  87. Small J. G., Kellams J. J., Milstein V., Moore J. A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Am J Psychiatry. 1975 Dec;132(12):1315–1317. doi: 10.1176/ajp.132.12.1315. [DOI] [PubMed] [Google Scholar]
  88. Small Joyce G., Klapper Marietta H., Malloy Frederick W., Steadman Timothy M. Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder. J Clin Psychopharmacol. 2003 Jun;23(3):223–228. doi: 10.1097/01.jcp.0000084026.22282.5f. [DOI] [PubMed] [Google Scholar]
  89. Smith T. E., Docherty J. P. Standards of care and clinical algorithms for treating schizophrenia. Psychiatr Clin North Am. 1998 Mar;21(1):203–220. doi: 10.1016/s0193-953x(05)70367-1. [DOI] [PubMed] [Google Scholar]
  90. Stahl S. M. Antipsychotic polypharmacy, Part 1: Therapeutic option or dirty little secret? J Clin Psychiatry. 1999 Jul;60(7):425–426. doi: 10.4088/jcp.v60n0701. [DOI] [PubMed] [Google Scholar]
  91. Tarrier N., Barrowclough C., Porceddu K., Fitzpatrick E. The Salford Family Intervention Project: relapse rates of schizophrenia at five and eight years. Br J Psychiatry. 1994 Dec;165(6):829–832. doi: 10.1192/bjp.165.6.829. [DOI] [PubMed] [Google Scholar]
  92. Tarrier N., Barrowclough C., Vaughn C., Bamrah J. S., Porceddu K., Watts S., Freeman H. Community management of schizophrenia. A two-year follow-up of a behavioural intervention with families. Br J Psychiatry. 1989 May;154:625–628. doi: 10.1192/bjp.154.5.625. [DOI] [PubMed] [Google Scholar]
  93. Tarrier N., Barrowclough C., Vaughn C., Bamrah J. S., Porceddu K., Watts S., Freeman H. The community management of schizophrenia. A controlled trial of a behavioural intervention with families to reduce relapse. Br J Psychiatry. 1988 Oct;153:532–542. doi: 10.1192/bjp.153.4.532. [DOI] [PubMed] [Google Scholar]
  94. Tarrier N., Lowson K., Barrowclough C. Some aspects of family interventions in schizophrenia. II: Financial considerations. Br J Psychiatry. 1991 Oct;159:481–484. doi: 10.1192/bjp.159.4.481. [DOI] [PubMed] [Google Scholar]
  95. Taylor C. G., Flynn S. W., Altman S., Ehmann T., MacEwan G. W., Honer W. G. An open trial of risperidone augmentation of partial response to clozapine. Schizophr Res. 2001 Mar 1;48(1):155–158. doi: 10.1016/s0920-9964(00)00104-3. [DOI] [PubMed] [Google Scholar]
  96. Telles C., Karno M., Mintz J., Paz G., Arias M., Tucker D., Lopez S. Immigrant families coping with schizophrenia. Behavioral family intervention v. case management with a low-income Spanish-speaking population. Br J Psychiatry. 1995 Oct;167(4):473–479. doi: 10.1192/bjp.167.4.473. [DOI] [PubMed] [Google Scholar]
  97. Terkelsen K. G., Grosser R. C. Estimating clozapine's cost to the nation. Hosp Community Psychiatry. 1990 Aug;41(8):863–869. doi: 10.1176/ps.41.8.863. [DOI] [PubMed] [Google Scholar]
  98. Thomas S. G., Labbate L. A. Management of treatment-resistant schizophrenia with olanzapine. Can J Psychiatry. 1998 Mar;43(2):195–196. [PubMed] [Google Scholar]
  99. Torrey E. F. Management of chronic schizophrenic outpatients. Psychiatr Clin North Am. 1986 Mar;9(1):143–151. [PubMed] [Google Scholar]
  100. Van Putten T., Marder S. R., Mintz J. A controlled dose comparison of haloperidol in newly admitted schizophrenic patients. Arch Gen Psychiatry. 1990 Aug;47(8):754–758. doi: 10.1001/archpsyc.1990.01810200062009. [DOI] [PubMed] [Google Scholar]
  101. Wassef A. A., Dott S. G., Harris A., Brown A., O'Boyle M., Meyer W. J., 3rd, Rose R. M. Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia. J Clin Psychopharmacol. 2000 Jun;20(3):357–361. doi: 10.1097/00004714-200006000-00011. [DOI] [PubMed] [Google Scholar]
  102. Weinberger D. R. From neuropathology to neurodevelopment. Lancet. 1995 Aug 26;346(8974):552–557. doi: 10.1016/s0140-6736(95)91386-6. [DOI] [PubMed] [Google Scholar]
  103. Wirshing D. A., Marshall B. D., Jr, Green M. F., Mintz J., Marder S. R., Wirshing W. C. Risperidone in treatment-refractory schizophrenia. Am J Psychiatry. 1999 Sep;156(9):1374–1379. doi: 10.1176/ajp.156.9.1374. [DOI] [PubMed] [Google Scholar]
  104. Wolkowitz O. M., Turetsky N., Reus V. I., Hargreaves W. A. Benzodiazepine augmentation of neuroleptics in treatment-resistant schizophrenia. Psychopharmacol Bull. 1992;28(3):291–295. [PubMed] [Google Scholar]

Articles from Indian Journal of Psychiatry are provided here courtesy of Wolters Kluwer -- Medknow Publications

RESOURCES