Schizophrenia resistance

Spina E, Avenoso A, Facciola G, et al. Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics. Psychopharmacoiogy (Berl) 2000 148 83-89. 

A 50-year-old man with symptoms of chronic paranoid schizophrenia resistant to typical neuroleptic drugs had a brief syncopal attack with significant electrocardiographic changes (sinus bradycardia and deep anteroseptal inverted T waves and minor ST... 

Sensky, T., Turkington, D., Kingdon, D., Scott, J. L., Scott, J., Siddle, R., O Carroll, M., Barnes, T.R. (2000). A randomized controlled trial of cognitive behavioral therapy for persistent symptoms in schizophrenia resistant to medication. Archives of General Psychiatry, 57, 165-172. 

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. 

Meltzer FiY, Cola P, Way L, et al (1995). Cost effectiveness of clozapine in neuroleptic-resistant schizophrenia. Am J Psychiatry 150, 1630-8. 

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. 

What are the best treatments for resistant schizophrenia If the disease has shown little or no improvement with the previous antipsychotics, then a trial of clozapine is warranted. This is a difficult and expensive medication that reqnires a motivated patient who is willing to report for weekly blood draws. Taken altogether, clozapine is a difficult drug. Nevertheless, it is the one antipsychotic that has clearly been shown to help schizophrenia that is resistant to other antipsychotics. 

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... 

Cognitive psychotherapeutic techniques have further been developed since their introduction by Beck et al. (1979), who demonstrated their effectiveness in the treatment of depression. Several studies have extended Beck s cognitive therapy to adulthood schizophrenia with encouraging clinical results. The efficacy of cognitive-behavioral approaches could be demonstrated in several key areas in schizophrenia, especially therapy-resistant hallucinations and delusions. Several approaches have also addressed therapeutic efforts in the treatment of associated symptoms such as anxiety and depression. In addition, cognitive-behavioral techniques have been shown to be effective in treatment of chronic schizophrenia, resulting in reduction of distress and disruption due to hallucinations and delusions. In some studies anxiety and depression associated with schizophrenia could also be reduced to some extent. The value of these techniques in children and adolescents has yet to be demonstrated. 

Turetz, M., Mozes, T, Toren, P., Chernauzan, N., Yoran-Hegesh, R., Mester, R., Wittenberg, N., Tyano, S., and Weizman, A. (1997) An open trial of clozapine in neuroleptic-resistant childhood-onset schizophrenia. Br J Psychiatry 170 507-510. 

ECT was generally inferior or equivalent to treatment with neuroleptics alone in terms of short-term outcome 2) in contrast, long-term outcome in these early studies appeared to favor ECT over medications 3] the combination of ECT and neuroleptic may be more effective than ECT or neuroleptic alone and 4] although we lack controlled studies, several reports have indicated that ECT may be of benefit in neuroleptic-resistant patients with schizophrenia. 

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... 

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