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Contents

Preface

References

Concepts and Assessment

History and Current Definitions of Treatment-Resistant Schizophrenia

Abstract

Prevalence, Clinical and Psychopathological Aspects

Operational Definitions

Definitions of TRS Based on Algorithms

Incomplete Response to Clozapine (‘Super-Refractory Schizophrenia’)

Conclusions

References

Assessment of Therapy-Resistant Schizophrenia

Abstract

History and Development of TRS

Definitions of TRS

Correlates of TRS

Assessment Steps for Patients with Suspected TRS

Conclusions

References

Neuropsychology of Treatment-Resistant Schizophrenia

Abstract

Domains of Neuropsychological Functioning

Neuropsychological Impairment in Schizophrenia

Relationship between Neuropsychological Functioning and Clinical Symptoms

Neuropsychological Impairment in Treatment-Resistant Schizophrenia

Consequences of Neuropsychological Impairment

Pharmacological Approaches to Improving Cognition in Schizophrenia

Conclusions

References

Etiology and Neurobiology

Genetic Studies in Treatment-Resistant Schizophrenia

Abstract

Definitions of Resistance to Antipsychotic Treatment

What Influences Resistance to Antipsychotic Medications?

Pharmacogenetics of Resistant Schizophrenia

Defining Candidate Genes: The Pharmacology of Antipsychotics and Results of Genetic Analysis

Gene-Gene Interaction Model

Conclusions

References

Neuroimaging of Treatment-Resistant Schizophrenia

Abstract

Neuroimaging of Schizophrenia

Structural Neuroimaging

Functional Neuroimaging

Molecular Neuroimaging

Conclusions

References

Duration of Untreated Psychosis and Premorbid Functioning: Relationship with Treatment Response and Treatment-Resistant Schizophrenia

Abstract

DUP and Treatment-Resistant Schizophrenia

Poor Premorbid Adjustment

Conclusions

Acknowledgments

References

Disease Management and Treatment Strategies

Disease Management: Multidimensional Approaches to Incomplete Recovery in Psychosis

Abstract

Resistance to Treatment versus Treatment-Resistant Schizophrenia

Use of LAIs to Help Determine RTT vs. TRS Status

Modified Academic Detailing

Conclusion

References

Role of Clozapine in Treatment-Resistant Schizophrenia

Abstract

Discovery of Typical Antipsychotic Drugs

Discovery of Clozapine

First Report of Agranulocytosis

US Clozaril Study: Demonstration of Efficacy in Treatment-Resistant Schizophrenia

Additional Evidence for Clozapine Efficacy in Treatment-Resistant Schizophrenia

Comparison of Efficacy of Clozapine and Other Atypical Antipsychotic Drugs in Treatment-Resistant Schizophrenia

Mechanism of Action of Clozapine

Effect of Clozapine on Cognition, Level of Functioning, and Quality of Life

Suicide as an Indication for Clozapine in Treatment-Resistant Patients

Clozapine and Agranulocytosis

Achieving Optimal Benefit with Clozapine

Conclusions

Acknowledgments

Disclosure Statement

References

Augmenting Clozapine Response in Treatment-Resistant Schizophrenia

Abstract

Defining TRS

Clozapine versus First-Generation Antipsychotics

Clozapine versus Second-Generation Antipsychotics

Switching from Clozapine to Another Antipsychotic

Clozapine Augmentation

Benzodiazepines

Electroconvulsive Therapy

Repetitive Transcranial Magnetic Stimulation

Glutamatergic Agents

Nootropics

Conclusion

References

New Therapeutic Strategies for Resistance to Clozapine and Treatment-Resistant Schizophrenia

Abstract

Meta-Analyses of Clozapine Augmentation with Antipsychotics and Lamotrigine

Memantine

Cognitive-Behavioral Therapy

New Strategies for TRS: SGA versus Clozapine

Risperidone versus Clozapine

Olanzapine versus Clozapine

Other SGA versus Clozapine

Pragmatic Studies

Conclusions

References

Electroconvulsive Therapy for Treatment-Refractory Schizophrenia

Abstract

Previous Studies on the Efficacy of ECT

Prediction of Response to ECT

ECT Treatment Technique

Continuation/Maintenance ECT in TRS

Quality of Life after Acute and M-ECT

Discussion

Acknowledgments

References

Treatment of Therapy-Resistant Auditory Verbal Hallucinations in Schizophrenia Patients by Repetitive Transcranial Magnetic Stimulation

Abstract

Auditory Verbal Hallucinations – A Major Symptom of Schizophrenia Spectrum Disorders

Repetitive Transcranial Magnetic Stimulation in Treating AVH

Definition of ‘Treatment-Refractory Hallucinations’

The First Studies

Later and More Comprehensive Trials

Probing Multiple Cortical Regions by Means of fMRI-Guided Trials

rTMS and Brain Functions in AVH

Meta-Analyses

Prospects and Suggestions for Future Clinical Trials

Acknowledgements

References

Author Index

Subject Index

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