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J Clin Psychiatry. 2019 Mar 5;80(2). pii: 18com12123. doi: 10.4088/JCP.18com12123.

Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia.

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75-59 263rd St, Kaufmann Bldg, Ste 103, The Zucker Hillside Hospital, Glen Oaks, NY 11004.
Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
The Zucker Hillside Hospital, Glen Oaks, New York, USA.
The Feinstein Institute for Medical Research, Psychiatric Neuroscience Center of Excellence, Manhasset, New York, USA.
Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Department of Economics, W. P. Carey School of Business, Arizona State University, Tempe, Arizona, USA.
Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom.
MRC London Institute of Medical Sciences, Imperial College, London, United Kingdom.
Department of Psychiatry, New York University School of Medicine, New York, New York, USA.
The Semel Institute for Neuroscience at UCLA, Los Angeles, California, USA.
The VA Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, California, USA.
Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.
Department of Psychiatry and Human Behavior, University of California at Irvine, Irvine, California, USA.
Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.


Treatment-resistant schizophrenia (TRS) occurs in approximately 30% of individuals diagnosed with schizophrenia. The identification and management of TRS in clinical practice are inconsistent and not evidence based. No established clinically relevant criteria for defining and treating TRS exist, although guidelines have been promulgated for clozapine use among TRS patients. This report summarizes the consensus from a roundtable that focused on defining and identifying TRS, pathways to treatment resistance, current treatments, unmet needs, and disease burden. Nine clinical experts in schizophrenia and TRS participated in a closed meeting on June 23, 2017, sponsored by Lundbeck, at which published literature in key areas of TRS research was reviewed. The findings from published studies were synthesized by experts in each area and presented to the group for review and discussion. It was agreed that inadequate response to 2 different antipsychotics, each taken with adequate dose and duration, is required to establish TRS. This recommendation is consistent with guidelines for clozapine use. For each trial, objective symptom measures should be used to assess treatment response, with medication adherence ensured. Once nonresponse is established (after ≥ 12 weeks for positive symptoms [2 trials of ≥ 6 weeks]), the treatment plan should be reevaluated and alternative pharmacologic or nonpharmacologic treatments considered. With increased awareness, those involved in the care of patients with schizophrenia will be able to identify TRS earlier in its course, thus supporting more informed treatment decisions by clinicians, patients, and caregivers to reduce the overall disease burden.

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