Barcelona snapshots

Prof. John M. Kane

John M. Kane psiquiatra Controversias Psiquiatria Barcelona
Hofstra University, EUA
Ponència Clozapina i més enllà
Data Divendres, 26 d'Abril, 2019
Hora 11:45 a 12:30
Taula rodona Resistència al tractament en esquizofrènia


John M. Kane, MD, is Senior Vice President for Behavioral Health Services at Northwell Health. He is Professor and Chairman of Psychiatry at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He also serves as Chairman of Psychiatry at The Zucker Hillside Hospital in Glen Oaks, New York. Dr. Kane received a BA from Cornell University and earned his medical degree from New York University School of Medicine. He completed his residency in Psychiatry at The Zucker Hillside Hospital. He is a Diplomate of the American Board of Psychiatry and Neurology.

Dr. Kane is the recipient of many awards, including: the Lieber Prize; The APA's Kempf Award, the Gralnick Award and Foundations Prize; the New York State Office of Mental Health Lifetime Achievement Award; and The Dean Award from the American College of Psychiatrists. He has served as President of the American Society of Clinical Psychopharmacology, the Psychiatric Research Society and the Schizophrenia International Research Society. Dr. Kane has been the principal investigator for research projects focusing on schizophrenia psychobiology, treatment and recovery, as well as improving the quality and cost of care. He is the author of 600 peer-reviewed papers and serves on the editorial boards of numerous journals.


The management of treatment resistant schizophrenia (TRS) remains an enormous challenge. Operational criteria and epidemiologic data have been inconsistent, but conservative estimates suggest that as many as one out three patients with schizophrenia will experience treatment resistance during the course of illness.

After three decades, clozapine remains the only treatment with regulatory approval for TRS. However, after all of these years debate even continues as to clozapine's superiority over other “second generation” antipsychotics, with a clinical trial data base limited by methodological shortcomings. In addition, the mechanism for clozapine's seemingly unique therapeutic potential remains elusive.

Data from large naturalistic studies reveal impressive advantages for clozapine over other potential treatments in reducing rates of hospitalization, suicide and mortality. Though guidelines for identifying TRS and guidelines for the use of clozapine are not necessarily one in the same, there is considerable commonality and failure to achieve adequate response of positive symptoms with two or more antipsychotics given in adequate doses for six weeks each and with evidence of good adherence in medication taking generally apply to both.

Though 10-20% of patients with schizophrenia manifest TRS at the onset of illness, generally a small proportion of such patients are given a trial of clozapine and the delay in even offering such a trial is often years rather than months. Though some experts have recently recommended clozapine after only one previous antipsychotic failure, we should first effectively move toward its more rapid and consistent utilization after two failures. Even among more chronically ill individuals with a history of multiple hospitalizations and significant decrements in functioning, clozapine is grossly underutilized. The reasons for this are varied, but too often patient refusal is cited as the basis, when it is most often physician ambivalence and lack of training that serve as the greatest impediments.

In my opinion, given the adverse effect profile of clozapine and the need for weekly blood monitoring during the early stages of use, coupled with the unpredictability of a range of potential therapeutic responses, it is impossible for a patient to make an adequately informed benefit to risk judgment without actually having a therapeutic trial. If an individual experiences the dramatic improvement that can occur with clozapine this creates a very different scenario than that for a patient with only modest if any benefit. Missing the potential opportunity for a “life changing” effect is something that we should strive to avoid.

Currently in the U.S., and many countries around the world, the level of training for its use and experience with clozapine varies enormously from setting to setting. Therefore, highly disparate rates of utilization are not surprising. We need to address this issue with more consistent training and strategies to increase appropriate utilization, while also working to identify biomarkers of potential response.

Though considerable efforts are underway to map out the possibilities beyond clozapine, we need to take full advantage of the opportunities that clozapine provides for many thousands of suffering patients and families in the here and now.


[PDF] Kane JM, Correll CU (2016). The Role of Clozapine in Treatment-Resistant Schizophrenia. JAMA Psychiatry. 2016 Mar;73(3):187-8. doi: 10.1001/jamapsychiatry.2015.2966.

[PDF] Nielsen J, Correll CU, Manu P, Kane JM (2013). Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided?. J Clin Psychiatry. 2013 Jun;74(6):603-13; quiz 613. doi: 10.4088/JCP.12r08064.

[PDF] Kane JM et al (2001). Clozapine and Haloperidol in Moderately Refractory Schizophrenia. Arch Gen Psychiatry. 2001 Oct;58(10):965-72.

[web] Kane JM et al (1988). Clozapine for the Treatment-Resistant Schizophrenic. A Double-blind Comparison With Chlorpromazine. Arch Gen Psychiatry. 1988;45(9):789-796. doi:10.1001/archpsyc.1988.01800330013001.