Le concept de résistance évoque, dans une perspective évolutive concernant le schizophrène et son psychiatre, un mode d'interaction assimilable à une lutte dont l'enjeu serait le symptôme, sa présence ou sa disparition. La notion de schizophrénie résistante pourrait ainsi être traduite suivant deux axes de compréhension : d'une part, comme la persistance des symptômes schizophréniques chez un patient soumis à un traitement médicamenteux supposé efficace ; ou, d'autre part, comme l'inefficacité des traitements disponibles dans certaines formes de schizophrénies non clairement étiquetées. En considérant le premier axe évoqué, on pourrait incriminer des facteurs de résistance indépendants des caractéristiques pharmacodynamiques et pharmacocinétiques des molécules utilisées, alors que le second axe donnerait à penser que la pathologie schizophrénique regorge encore de nombreux cônes d'ombres qu'il conviendrait d'explorer. Dans l'un ou l'autre cas, apparaît l'incapacité pour le thérapeute de parvenir aux résultats escomptés. Cette notion de schizophrénie résistante a de façon récurrente fait l'objet de nombreuses réflexions et constitue encore de nos jours une préoccupation forte. L'une des constatations majeures ressortant du parcours d'un grand nombre de travaux récents est la difficulté à recruter de nos jours, pour des études standardisées, des patients répondant aux critères explicites de schizophrénie résistante tels qu'énoncés par Kane. En revanche, dans la pratique quotidienne, la notion de schizophrénie résistante reste présentée comme un problème de santé publique. Dans ce contexte, elle répond à une caractérisation plutôt implicite, dont l'appréciation est souvent variable d'un psychiatre à un autre. La plupart des études utilisent comme critère d'efficacité antipsychotique une baisse d'au moins 20 % du score de la BPRS. On peut s'interroger sur la pertinence actuelle des seuils utilisés dans l'interprétation des différentes échelles. Seuils demeurés constants malgré les évolutions thérapeutiques et le passage d'une caractérisation explicite vers une caractérisation plus implicite de la résistance. Face aux innovations dans le champ pharmacologique, qu'atteste la mise sur le marché de nouvelles molécules antipsychotiques dénuées de la plupart des effets secondaires décrits avec les neuroleptiques classiques, il m'a paru essentiel de revisiter la notion de schizophrénie résistante sous un angle pharmacologique, et d'en rediscuter les abords physiopathologiques.

The “treatment-resistant” concept etymologically may be referring to an opposition to a force, to an action. Considering the dynamic relationship between a patient with schizophrenia and his psychiatrist, this concept can evoke an interaction looking like a fight which stake might be the symptom, it is persisting or disappearing. The “treatment-resistant” concept can be explored in two main lines: on one hand, as the persistence of schizophrenic symptoms at a patient taking suitable drugs with no doubt on efficacy and, on the other hand, as the inefficacy of available drugs on some schizophrenia cases not yet identified. The first hypothesis is in accordance with the existence of other resisting factors not related to drug's pharmacokinetic and pharmacodynamic while the second one shows the remaining field of research on schizophrenia. In each line, one can notice the difficulties of psychiatrists to achieve for their patients proper results. The “treatment-resistant” concept has very often been shielded and still constitutes a major field of research. But, the hope of a better curing appeared with innovations in the field of research. New and more efficient antipsychotic drugs with low adverse effects are now available. After few years of using them, I found it necessary to get the new look of the “treatment-resistant” concept and its supporting physiopathology. I gathered around one hundred articles on that subject in general and I reminded the various characterizations done so far such as Kane's criteria. I stopped on an article published on July 2000 by Wahlbeck. This article is an illustration of what might be the reality of that concept at year 2002. He defined in his work the “treatment-resistant” concept as the persistence of psychotic symptoms for a period of 6 months in spite of a treatment with two antipsychotic drugs of different chemical classes during at least 6 weeks each at dosages superior or equal to 1000 mg of chlorpromazine per day. By selecting patients according to these criteria which one could find less rigorous compared to those Kane stated 14 years ago, Wahlbeck found among 9000 admissions for schizophrenic symptoms in two years, only 1% of them fitting his description of a “treatment-resistant” patient. There would be a great temptation to infer from this observation that, by applying thoroughly Kane's criteria today, we have no chance to diagnose a case of “treatment-resistant” schizophrenia. The new drugs, without any doubt played an important role in the “shortage” of “treatment-resistant” patients, researchers might be facing today. That is a sign which can be claimed as very positive for future of schizophrenics, but the optimal response the psychiatrist could expect from schizophrenics remains unknown. For instance, the “treatment-resistant” schizophrenia is still presented today as a public health concern. In the studies, the efficacy of an antipsychotic drug is based on at least 20% decrease of the Brief Psychiatric Rating Scale (BPRS). One can wonder about the current pertinence of thresholds used for scale's interpretation. Thresholds which remained the same over the years in spite of therapeutic changes and moving from an explicit on an implicit characterization of “treatment-resistant” schizophrenia. Have these scales formerly used by Kane and others kept over the years and changes sufficient reliability for “treatment-resistant” assessment? In daily practice and out of the context of standardized studies, one may observe that, the prevalence of patient with schizophrenia whose responses to treatment appeared not satisfactory for their psychiatrists is stable over years. On the other hand, most clinicians unanimously recognize the quality improvement of the daily relationship with schizophrenics benefiting the new drugs. The percentage of resistant patients with schizophrenia showing a favourable response to clozapine is around 30% as previously shown by Kane in his study and it, whatever the definition given to “treatment-resistant” concept. One can evoke a sort of “1/3 rule” that means: one schizophrenic over three might be resistant to his treatment and among “treatment-resistant” schizophrenics, one over three might show a favourable response to clozapine. This informal rule, while reinforcing the idea that there are many other factors participating to resistance, set back the “treatment-resistant” concept in the core of the specific relation that links the schizophrenic to his psychiatrist. The remaining questions on that subject are numerous, so new hypothesis will be therefore of great importance.