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From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

The robust and specific associations between cognitive abilities and the functional prognosis of patients suffering from schizophrenia lead to a major concern for cognitive impairment in this disorder. Among the strategies considered to correct or enhance cognition in schizophrenia, drugs hold a pivotal place. Evidently, antipsychotic drugs, which are inextricable from patients' management, have generated considerable scrutiny in this topic. This paper first aims to outline the current views on the impact of antipsychotic drugs in schizophrenia. The distinction between conventional and atypical drugs is reminded in order to more precisely review existing data comparing the impact of these two types of molecules on cognitive impairment. More specifically, an elementary framework is proposed to facilitate the recognition of methodological flaws and offer a critical examination of previous findings. It emerges subsequently that differences between atypical and conventional drugs appear far less contrasted than initially suggested. Also, atypical antipsychotics compose a disparate pharmacological class and much clarification could be obtained by differentiating the individual effects of these molecules rather than considering them as a group. Finally, the relevance of these cognitive measures is also considered. In particular, we address alternative measures closer to real life situations as well as the growing interest in the broad field of social cognition. A last part of this article deals with strategies relying on adjunctive therapies. The fairly modest results obtained with these approaches is evoked and briefly reviewed., (Copyright © 2011 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

On the occasion of the Clozapine symposium we have had cause to reflect on the social life-histories of schizophrenic patients. After an analysis of a cohort of 40 patients aged over 65 years, whose medical records had been kept up since the start of their disease, we have set up a methodology which enables us to study the social life-histories of these patients. Our aim is ultimately to compare the course of the disease with the treatments received by these patients and the therapeutic structures they have been offered. For this purpose, we shall study three criteria of social exposure: 1) Autonomy, 2) Integration into the family, 3) Integration through work. The aim of the present paper is to record our initial analytical findings in these three years.

This study reports a clinical experience among twenty schizophrenic patients treated by clozapine during two years and eight months within a range extending from three months to seven years. These twenty patients had previously shown long-term resistance to usual neuroleptics but three out of them met the diagnosis of mental retardation or childhood disintegrative disorder (F.84.3-ICD 10). These patients were put under clozapine for their violent behavior. The methodology was retrospective, descriptive with intra-individual comparison, each patient being his own reference before and after treatment. Diagnosis met CD 10 criteria and were assessed without using standard examination. This study aimed at assessing once more clozapine efficacy and tolerance upon a long time follow up. Single therapy has been the rule and dosages have been progressively increased reaching a mean daily dosage of 350 mg per day. The efficacy, assessed by the way of BPRS, GAF (DSM III-R) and simplified form of CGIS, has been verified in approximately 30% of the patients, mainly concerning positive symptoms. Clozapine was also able to alleviate severe behavior troubles brought about by delusional states, without this latter being markedly softened when it was a long term one. Clozapine tolerance has shown it to be satisfactory, however we noticed the occurrence of a leucopenia with neutropenia after seventeen weeks of treatment, followed, some days later, by a Quincke oedema, which forced to interrupt the treatment. White blood cells came back in a normal range fifteen days later. The other side effects (transitory hypersialorrhea, tachycardia, without clinical and ECG perturbations) have been usually well tolerated and have never caused treatment interruption. No extrapyramidal side effect have been noticed among our twenty patients. The end of this paper consists in the presentation of four clinical cases: one about the efficacy of clozapine upon violent antisocial behaviour in a schizotypital disorder; one delusional chronic schizophrenic patient whose violence has been controlled despite of the delusion; one paranoid schizophrenic patient who has been able to maintain a satisfactory professional and family adaptation; and finally a childhood disintegrative disorder (F.84.3-ICD 10) in whom occurred the only leucopenia side effect of our study. These four clinical cases have seemed particularly meaningful regarding our clinical experience of clozapine which has been lasting for almost seven years now.

Various pharmacologic agents have been reported to be effective in treating negative symptoms of schizophrenia. European schools of psychiatry and especially the French one assumed the opinion that part of negative symptoms of schizophrenia do respond to neuroleptics. In light of effects of reserpine and some phenothiazines on negative schizophrenia, various pharmacologic agents have been studied focusing on these properties. Various papers devoted to this question concluded that some drugs, particularly neuroleptics, can be considered as disinhibitors: phenothiazines (thiotixene, trifluoperazine, fluphenazine, pipotiazine), butyrophenones (trifluperidol, risperidone), diphenylbutylpiperidines (pimozide) and benzamides (sulpiride, amisulpiride). Major part of controlled studies concluded to the better efficacy of low doses of such drugs on negative symptoms, while high doses are almost inefficient. Some studies concluded in the activity of clozapine on negative symptoms of schizophrenic patients. To answer the question whether negative symptoms of schizophrenia are improved concomitantly or independently of improvement in positive symptoms or of decrease in extrapyramidal side effects and/or depressive symptoms, the authors prospectively followed up for 30 months, 13 DSM-IV resistant schizophrenics. Symptoms were assessed by means of 18 item Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale and Extrapyramidal Symptom Rating Scale (ESRS). Improvement in negative symptoms was significantly correlated to improvement in positive ones and to scores in ESRS. Many open studies concerning anti-depressants and other drugs have been published; however controlled studies are necessary to confirm these data.

This paper summarizes the presentations made during the Lucca symposium (1-3 October, 1977) on long-acting neuroleptics. The authors tried to present advantages and inconveniences of this therapeutic compared to the "classical" neuroleptic therapeutics: - in patients with an acute symptomatology; - in stabilized patients. The main advantage is that one can be ensured that the drug has been or not been taken.