Treatment Resistant Schizophrenia

Davies LM, Drummond MF (1993). Assessment of costs and benefits of drug therapy for treatment-resistant schizophrenia in the United Kingdom. Br JPsychiatry 162, 38-42. 

Conley RR, Tamminga CA, Bartko JJ, et al (1998). Olanzapine compared with chlorpromazine in treatment resistant schizophrenia. Am J... 

For approximately 20% to 30% of people with schizophrenia, drug treatment is ineffective. A standard definition of treatment resistance includes patients who have persistent positive symptoms despite treatment with at least two different antipsychotics given at adequate doses (at least 600 chlorpro-mazine equivalents) for an adequate duration (4 to 6 weeks). In addition, patients must have a moderately severe illness as defined by rating instruments, and have a persistence of illness for at least 5 years.40 These patients are often highly symptomatic and require extensive periods of hospital care. 

Conley RR, Kelly DL. Management of treatment resistance in schizophrenia. Biol Psychiatry 2001 50 898-911. 

Only clozapine has shown superiority over other antipsychotics in randomized clinical trials for the management of treatment-resistant schizophrenia. 

Clozapine (Clozaril). Clozapine was introduced over 30 years ago but has only been available in the United States since 1990. It remains the medication of choice for treatment-resistant schizophrenia. Since its introduction, it has been used to treat acute mania with excellent results. Furthermore, it avoids the potential for tardive dyskinesia posed by haloperidol and the other typical antipsychotics. 

In addition to being effective in the treatment of schizophrenia, clozapine also is effective in the treatment of the manic phase of bipolar disorder. Although not a first-line treatment for mania, clozapine is useful for patients who are not responding well to more traditional treatments. Finally, clozapine is the one antipsychotic proven to help treatment-resistant schizophrenia. Fully one-third of patients who do not respond to other antipsychotics will respond to clozapine. 

Clozapine can certainly be a difficult and expensive medication to take. However, for the treatment-resistant patient with schizophrenia, clozapine is often well worth the trouble. 

Clozapine was the first atypical antipsychotic released in the United States. However, clozapine is associated with the risk of leukopenia and, potentially, lethal agranulocytosis. Because of these concerns, hematological monitoring during clozapine pharmacotherapy is required (Alphs and Anand, 1999). Due to these hematological risks, clozapine is indicated only for patients with treatment-resistant schizophrenia. The other atypical antipsychotics, risperidone, olanzapine, quetiapine, and ziprasidone, that are marketed in the United States can be used as first-line treatments for adults with schizophrenia. 

Clozapine Dibenzodiazepine 25-900 Low 100 Treatment-resistant illnesses Schizophrenia Bipolar disorder Autistic disorder Kumra et ah, 1996 Kowatch et ah, 1995 Zuddas et ah, 1996... 

Utman RE, Su TP, Potter WZ, et al Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia comparison with the atypical neuroleptic, clozapine. Br J Psychiatry 168 571-579, 1996 Uttle A, Levy R, Chuaqui-Kidd P, et al A double-blind placebo-controlled trial of high-dose lecithin in Alzheimer s disease. J Neurol Neurosurg Psychiatry 12 110-118, 1985... 

Lieberman JA, Sheitman B, Chakos M, et al The development of treatment resistance in patients with schizophrenia a clinical and pathophysiologic perspective. J Clin Psychopharmacol 18 (2, suppl 1) 20S-24S, 1998... 

Heresco-Lewy, U., Javitt, D.C., Ermilov, M., et al. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Br. J. Psychiatry 169, 610-617, 1996. 

Buckley P, Thompson P, Way L, et al. Substance abuse among patients with treatment-resistant schizophrenia characteristics and implications for clozapine theory. Am J Psychiatry 1994 151 385-389. 

Bondolfi G, Baumann P, Paths M, et al. A randomized double-blind trial of risperidone versus clozapine for treatment-resistant chronic schizophrenia. Presented at the 148th Annual Meeting of the American Psychiatric Association, Miami, May 1995. 

Potkin SG, Bera R, Gulasekaram B, et al. Plasma clozapine concentrations predict clinical response in treatment resistant schizophrenia. J Clin Psychiatry 1994 55(9, suppi B) 117-121. 

Chanpattana W, Chakrabhand MLS, Kongsakon R, et al. Short-term effect of combined ECT and neuroleptic therapy in treatment-resistant schizophrenia. J ECT 1999 15 129-139. 

Schizophrenia is the primary indication for antipsychotic agents. Antipsychotic drugs are also used very extensively in patients with psychotic bipolar disorder (BP1), psychotic depression, and treatment resistant depression. 

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