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Home » Schizophrenia

Psychiatric Times. Vol. 26 No. 8
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TREATMENT RESISTANCE 

Treatment-Resistant Schizophrenia

Strategies for Recognizing Schizophrenia and Treating to Remission

By Seong S. Shim, MD, PhD | August 17, 2009
Dr Shim is assistant professor in the department of psychiatry at Case Western Reserve University School of Medicine in Cleveland and a staff psychiatrist at the Cleveland VA Medical Center, Psychiatric Services. He is currently conducting preclinical and clinical research on the neuroplasticity of psychotropic medications related to schizophrenia, bipolar disorder, and Alzheimer disease. He reports no conflicts of interest concerning the subject matter of this article.

Psychotherapy

Pharmacological treatment alone is not adequate for patients with treatment-resistant schizophrenia. Up to 60% of patients have persistent psychotic and cognitive symptoms and are at high risk for suicide despite active pharmacological therapy.1,2 Comprehensive treatment strategies that integrate pharmacological, psychological, and psychosocial approaches should be used (Table 4).

(MORE: Psychodynamic Psychopharmacology)

Among various models (including personal therapy, psychodynamic psychotherapy, and family treatment), cognitive-behavioral therapy (CBT) is considered most effective.34,35 The primary aim of CBT is to improve understanding and insight of schizophrenia and enhance coping mechanisms for psychotic and depressive symptoms. Furthermore, CBT is used to reinforce psychosocial skills and thereby alleviate psychological and physical distress. CBT can also help with illness-associated compromised psychosocial behavior. CBT in conjunction with antipsychotic drugs is particularly effective in reducing the intensity of delusions and depressive symptoms and the risk of suicide. CBT also alleviates hallucinations, improves quality of life, and reduces the risk of suicide attempts and other violent behaviors. Long-term CBT is much more effective than the short-term therapy and provides long-lasting and cost-effective results.36 CBT has not been shown to be significantly effective in the treatment of acute psychotic relapse and severe impairment in cognitive insight.

Several psychosocial treatment models—including social skill improvement, stress reduction, cognitive reframing, and vocational rehabilitation—have also been used in conjunction with pharmacological treatment.35 Psychosocial treatment should be fully integrated into the care of patients with treatment-resistant schizophrenia to maximize the effects of therapeutic strategies. A variety of psychosocial interventions have been shown to enhance treatment adherence, improve medication management, reduce chances of relapse, provide for faster and longer- lasting recovery, and improve social coping skills.

A 10-year follow-up study clearly demonstrated the effectiveness of integrated psychosocial strategies in treatment-resistant schizophrenia.37 That study used need-adapted treatment—a comprehensive psychosocial strategy that integrates pharmacological, psychological, and psy- chosocial models. The study showed that the number of psychiatric hospitalizations and the duration of hospital stay were reduced more than 50% in patients who received need-adapted treatment for 10 years. The long-term outcome of these patients was very favorable, their quality of life was improved, and the overall cost was reduced. Thus, multidisciplinary care systems that integrate diverse clinical expertise are essential not only in treating schizophrenic symptoms but also in helping patients achieve an independent psychosocial life.35

Conclusion

The clinical management of patients with treatment-resistant schizophrenia is still challenging despite years of extensive research. As shown in the Figure, at least 2 antipsychotic drugs should be tried at adequate dosage and for an adequate period, and various factors that interfere with adherence should be ruled out before making a diagnosis of treatment-resistant schizophrenia.

Clozapine should be used only when it is confirmed that patients have treatment-resistant schizophrenia and their condition fails to respond to atypical antipsychotics or typical antipsychotics.

The same rule applies in identifying clozapine(Drug information on clozapine)-resistant schizophrenia. Pharmacological augmentation strategies for managing clozapine-resistant schizophrenia are widely used in clinical practice. However, there is no strong evidence that supports augmentation as an effective treatment option. ECT may be an effective augmentation strategy in the treatment of clozapine-resistant schizophrenia. It should be emphasized that psychological and psychosocial care combined with medication treatment are the key factors in maximizing the effectiveness in the treatment of patients with treatment-resistant schizophrenia.

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by Meredith Hinds | June 27, 2011 6:23 PM EDT

So, just the same old same old. Hopefully those of us in the profession are already well aware of the CATIE studies. What I want to know (and maybe there are no answers) is what to do with my severely ill patients who have already exhausted all the avenues outlined above.

Also in this Special Report

Introduction Underlying Causes and Implications

Chronic Eating Disorders

Treatment-Resistant Bipolar Disorder

Treatment-Resistant Depression

Borderline Personality Disorder and Resistance to Treatment

Psychodynamic Psychopharmacology

Treatment-Resistant Schizophrenia





References

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3. Brenner HD, Merlo MC. Definition of therapy-resistant schizophrenia and its assessment. Eur Psychiatry. 1995;10(suppl 1):11s-17s.
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17. Conley RR, Kelly DL, Richardson CM, et al. The efficacy of high-dose olanzapine versus clozapine in treatment-resistant schizophrenia: a double-blind crossover study. J Clin Psychopharmacol. 2003;23: 668-671.
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19. Geddes J, Freemantle N, Harrison P, Bebbington P. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ. 2000;321:1371-1376.
20. Leucht S, Komossa K, Rummel-Kluge C, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009;166:152-163.
21. Leucht S, Corves C, Arbter D, et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009;373: 31-41.
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23. Rosenheck RA, Leslie DL, Sindelar J, et al; CATIE Study Investigators. Cost-effectiveness of second-generation antipsychotgics and perphenazine in a randomized trial of treatment for chronic schizophrenia. Am J Psychiatry. 2006;163:2080-2089.
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28. Shiloh R, Zemishlany Z, Aizenberg D, et al. Sulpiride augmentation in people with schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled study. Br J Psychiatry. 1997;171:569-573.
29. Honer WG, Thornton AE, Chen EY, et al; Clozapine and Risperidone Enhancement (CARE) Study Group. Clozapine alone versus clozapine and risperidone with refractory schizophrenia. N Engl J Med. 2006;354: 472-482.
30. 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;66:63-67.
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32. Dossenbach MRK, Beuzen JN, Avnon M, et al. The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine. Clin Ther. 2000;22:1021-1034.
33. Kho KH, Blansjaar BA, de Vries S, et al. Electroconvulsive therapy for the treatment of clozapine nonresponders suffering from schizophrenia: an open label study. Eur Arch Psychiatry Clin Neurosci. 2004; 254:372-379.
34. Rathod S, Kingdon D, Weiden P, Turkington D. Cognitive-behavioral therapy for medication-resistant schizophrenia: a review. J Psychiatr Pract. 2008;14: 22-33.
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37. Tuori T, Lehtinen V, Hakkarainen A, et al. The Finnish National Schizophrenia Project 1981-1987: 10-year evaluation of its results. Acta Psychiatr Scand. 1998;97:10-17.


 
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