Role of long-acting neuroleptics in the treatment of schizophrenia]

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.     

Medico-economic assessment of neuroleptics in schizophrenia. Amisulpride versus haloperidol]

The aim of this study is to assess the economic impact of neuroleptic strategies in the long-term treatment of schizophrenic patients. In this respect a new neuroleptic strategy (amisulpride) was compared to a reference drug (haloperidol) using a cost minimization method. Clinical, demographic and economic (direct medical costs) data were obtained retrospectively from patients' charts. Patients (n = 160) were randomly selected according to diagnosis (schizophrenia, DSM III-R), treatment (outpatient, amisulpride or haloperidol) and follow up period (at least 6 months). The health insurance point of view was selected for the economic analysis. We found a significant reduction of the annual number of days of relapse when patients were treated with amisulpride compared to haloperidol. This reduction was associated with a significant reduction of direct costs mainly related to shorter length of hospitalization. This result was only partly explained by demographic and clinical variables such as the severity of the disease. The differences remained significant when populations were matched. This finding illustrates the validity of the concept of efficiency in psychiatry.     

氟西汀合并抗精神病药物治疗具有强迫症状的精神分裂症的疗效分析

目的 探讨抗精神病药物合并氟丁汀治疗具有强迫症状的精神分裂症的临床疗效。方法 对原用抗精神病药物治疗的以强迫症状为主的36例精神分裂症患者随机分成两组,一组加用氟西汀(研究组),另一组仍用原抗精神病药物(对照组)治疗8周,用PANSS、Y-BOCS、TESS评定两组精神症状变化和副反应,用t检验对照分析。结果 研究组的PANSS、Y-BOCS总分比对照组明显下降,且有显著性差异(P<0.01)。结论 强迫症状明显的精神分裂症患者,采用抗精神病药物合并氟西汀治疗,可提高疗效。     

The effect of neuroleptics in a attempt at understanding the vulnerability to schizophrenia]

Animal and human data suggest that neuroleptic drugs act by decreasing the special significance of some stimulations, especially those of importance for the subject. The two following hypotheses are therefore considered as a basis for the work presented in this paper: 1) the target of neuroleptic drugs is a neuro-psychological mechanism whose function is to focalize the subject on important stimulations and to involve the subject in responding; 2) schizophrenia vulnerability could imply an excessive and abnormal propensity to be over-involved, especially in existentially loaded problems. A careful clinical study of the mode of decrease, and sometimes of disappearance, of schizophrenic delusions under the influence of neuroleptic treatment confirms the hypotheses. Results are of interest for clinical treatment and for research.     

Gender and the use of neuroleptics in schizophrenia

INTRODUCTION: The oestrogen hypothesis proposes that the lower need for neuroleptic drugs in female schizophrenia patients is caused by the antidopaminergic effect of oestrogens, and that when oestrogen production decreases at menopause, the need for neuroleptic drugs increases in female schizophrenia patients. SUBJECTS AND METHOD: The oestrogen hypothesis was tested in a sample of 4338 schizophrenia patients (DSM III R), who were discharged from hospital and followed up for 3 years. Prescribed daily doses of neuroleptics (DDN) were recorded and converted to chlorpromazine equivalents. RESULTS: Males had higher DDN than females. When the age at first admission (AFA) was controlled, DDNs were higher in males than in females in all age groups. In addition to AFA, DDNs were associated with duration of illness (DUI), education, smoking and clinical status as well as with concurrently prescribed antidepressants, anti-manics, sedatives and hypnotics, but these factors did not explain the gender differences in DDN. CONCLUSIONS: The results did not support the original oestrogen hypothesis. It is proposed that testosterone secretion may explain why male schizophrenia patients are prescribed higher DDNs than female patients. Ageing processes in the central nervous system (CNS) may explain why DDNs decrease after middle age in both genders.     

利培酮与氯氮平治疗难治性精神分裂症对照研究

目的 比较利培酮与氯氮平治疗难治性精神分裂症的疗效和副反应。方法 将符合入组条件的病人随机分为2组,分别服用利培酮和氯氮平治疗12周,用PANSS和TESS评定疗效和副反应情况。结果 利培酮组总有效率为62.9％,氯氮平组为60.0％,经统计学处理无显著性差异(P>0.05)。结论 利培酮对难治性精神分裂症的疗效与氯氮平相当,副作用轻,易被病人接受。     

Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia

OBJECTIVE: The authors investigated the clinical effects of D-cycloserine when added to treatment with conventional neuroleptics, olanzapine, or risperidone for treatment-resistant schizophrenia. METHOD: Twenty-four patients participated in a double-blind, placebo-controlled, 6-week crossover trial with D-cycloserine, 50 mg/day, added to their fixed dose of antipsychotic medication. Clinical ratings were performed every 2 weeks. RESULTS: D-Cycloserine treatment was well tolerated and resulted in a significant reduction in negative symptoms (mean=15%). The degree of improvement did not differ between patients treated with conventional neuroleptics and those treated with olanzapine or risperidone. CONCLUSIONS: These data support the efficacy of the addition of 50 mg/day of D-cycloserine to treatment with conventional neuroleptics and suggest that therapeutic benefits may also be attained when D-cycloserine is added to olanzapine or risperidone.     

Limitations of efficacy of chemotherapies in schizophrenia]

The concept of treatment-resistant schizophrenia cannot be defined as this of resistant depression: schizophrenia is a long-term illness; its evolution is almost always influenced by neuroleptics--but complete recovery is rare. French psychiatry tends to use clinical-empirical criteria, while english speaking studies prefer quantitative criteria, by extended use of clinical and psycho-social scales. The definition of resistant schizophrenia by Kane et al. is a typical example of this method of work. We propose to overview the limits of neuroleptics efficiency in schizophrenia from three groups of studies: a) The effects of maintenance therapy: 24 studies of the last twenty years show that 2/3 of schizophrenics under neuroleptics maintain their remission over one or two years, opposed to less than 1/3 of those who discontinue their treatment. These data seem to be independant from the method of the study, the choice of the neuroleptic drug, the dose and the way of administration (per os or depot treatment). b) A second group of studies tries to define the clinical characteristics of treatment-resistant schizophrenia. French psychiatry uses an empirical graduation of neuroleptics clinical efficiency: these drugs are more effective on hallucinations than on delusional ideas--they are more effective on recent and acute hallucinations and delusions than on those of which course is chronic. Other studies specify predictive factors of poor response to neuroleptics, as few affective symptoms and presence of negative symptoms--a controversed factor. c) Not clinical factors of poor neuroleptics efficiency in schizophrenia begin to be studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective attention and schizophrenia before the administration of neuroleptics

In recent years, the presence of attention deficits has been recognized as a key feature of schizophrenia. Past studies reveal that selective attention, or the ability to select relevant information while ignoring simultaneously irrelevant information, is disturbed in schizophrenic patients. According to Treisman feature-integration theory of selective attention, visual search for conjunctive targets (e.g., shape and color) requires controlled processes, that necessitate attention and operate in a serial manner. Reaction times (RTs) are therefore function of the number of stimuli in the display. When subjects are asked to detect the presence or absence of a target in an array of a variable number of stimuli, different performance patterns are expected for positive (present target) and negative trials (absent target). For positive trials, a self-terminating search is triggered, that is, the search is ended when the target is encountered. For negative trials, an exhaustive search strategy is displayed, where each stimulus is examined before the search can end; the RT slope pattern is thus double that of the positive trials. To assess the integrity of these processes, thirteen drug naive schizophrenic patients were compared to twenty normal control subjects. Neuroleptic naive patients were chosen as subjects to avoid the potential influence of medication and chronicity-related factors on performance. The subjects had to specify as fast as possible the presence or absence of the target in an array of a variable number of stimuli presented in a circular display, and comprising or not the target. Results showed that the patients can use self-terminating search strategies as well as normal control subjects. However, their ability to trigger exhaustive search strategies is impaired. Not only were patients slower than controls, but their pattern of RT results was different. These results argue in favor of an early impairment in selective attention capacities in schizophrenia, which appears before the introduction of neuroleptics. The attention performance was also shown to present some association to clinical symptoms.     

Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia

This study examines whether the duration of treatment with antipsychotic drugs influences the regional distribution of cerebral [18F]2-fluoro-2-deoxy-D-glucose utilization as measured by positron emission tomography. Two groups of schizophrenic patients are compared with normal volunteers (n = 10). One group (n = 5) consisted of patients treated for one year, and the second (n = 12) of patients medicated for four to 14 years (mean +/- SD duration, 7.4 +/- 3.4 years). The first group was also examined before patients received their first dose ever of antipsychotic medication. One year of medication was not sufficient to alter the schizophrenic profile of cerebral cortical glucose activity but did elevate activity of the corpus striatum. Medication for 7.4 years also did not alter the schizophrenic pattern of frontal hyperactivity and posterior hypoactivity, although deviations from control values appeared less marked than after one year. On the other hand, in patients medicated for 7.4 years, there was perhaps an even greater increase in the activity of the corpus striatum and of the thalamus. Thus, duration of exposure to antipsychotic medication may affect the pattern of cerebral glucose activity; possibly, even longer exposure may contribute to the hypofrontality noted by others, although this can be confounded with the duration of illness as a factor. In considering the biological significance of the observed profile of cortical glucose activity, we introduce the concept of cerebral metabolic tone. We suggest that a disturbance of this tonus may account for some symptoms of schizophrenia and could be consistent with the hypothesis of abnormal developmental changes in the brains of schizophrenics.     

Effect of methadone plus neuroleptics on treatment-resistant chronic paranoid schizophrenia

In a placebo-controlled single-crossover study, seven patients with treatment-resistant chronic paranoid schizophrenia who received methadone plus neuroleptic showed significant improvement. Methadone may be a useful adjunctive treatment in a subpopulation of patients with chronic paranoid schizophrenia.     

Combination of neuroleptics and psychosocial therapies in schizophrenia

Sven Jonas Dencker och Ulf Malm är överläkare på klinik 11, Lillhagens sjukhus i Göteborg. Bägge är intresserade av utvecklingsarbete inom området psykiatrisk rehabilitering. De har här gjort en datasökning to m hösten 1982 omfattande kontrollerade studier avseende jämförelse mellan olika behandlingsmetoder vid schizofreni. Relativt få studier hittades. Neuroleptika enbart var överlägset psykosocial terapi endast i 3 av 10 arbeten mot ingen skillnad i 6. När neuroleptika kombinerades med olika psykosociala åtgärder blev effekten av ett sådant kombinationsprogram i 13 av 18 arbeten överlägset behandling med enbart neuroleptika.     

Treatment of negative symptoms in schizophrenia with neuroleptics

Different concepts of negative symptoms in schizophrenia are reviewed. The beneficial effects of neuroleptics are discussed. The results of a pharmacokinetic and pharmacodynamic study with Amisulpride in healthy volunteers are reported. Preliminary findings of a study with Amisulpride in schizophrenic patients with predominately negative symptoms are presented. The utility of various rating scales for documenting the clinical state of these patients during therapy, and correlations of negative symptoms with psychometric and psychophysiological data are discussed. Finally, therapeutic consequences suggested by different hypothesized etiological factors causing negative symptoms are considered.     

利培酮与氯丙嗪治疗难治性精神分裂症对照研究

目的：比较利培酮与氯丙嗪治疗难治性精神分裂分裂症的疗效。方法：将符合入组条件的病人随机分为2组,分别服用利培酮或氯丙嗪治疗12周,用阳性与阴性症状量表（PANSS）和副反应量表（TESS）评定疗效和副反应情况。结果：利培且总有效率为71．4％,明显高于氯丙嗪组42．9％,经统计学处理差异有显著性（P＜0．05）,结论：利培酮对难治性精神分裂症的 疗效优于氯丙嗪,对阴性症状效果更佳。     

Reducing the dose of depot neuroleptics in stable schizophrenia.

In order to determine the safety of reducing maintenance neuroleptic dose in long-term ambulatory schizophrenia, a step-wise depot reduction study was carried out on patients over a six month period. Doses were reduced by 1/8 of original approximately every two months for a total of three reductions. At the end of dose reduction and at six month follow-up, relapse rate was calculated. Relapse in this study was defined as the clinical decision to either increase neuroleptic dose or to hospitalize. Approximately 50% of the patients relapsed. There was no association with life events as measured by the Paykel scale. Where relapse occurred, it was usually seen subsequent to the second dose reduction. Patients who survived dose reduction had been maintained for a significantly longer period on depot neuroleptics and tended to suffer from a form of schizophrenia which required the co-administration of antidepressants. The findings show that, for a population on long-term depot medication, the risk of symptom exacerbation after gradual step-wise neuroleptic reduction is 50%. The results help to delineate which patients will fall into that 50%.     

Comments on the long-term outcome of schizophrenia

Among the many technical issues dealt with in this symposium, two clinical problems are preeminent--how is schizophrenia defined and what is meant by outcome? Each problem is highly complex. Even given adequate designs, sampling, and analysis, the generalizability of the results depends on the extent to which the diagnostic and outcome criteria are independent of each other and reproducible. The authors amply demonstrate how far we are from achieving such comparability. Schizophrenia, at the moment, is diagnosable only on its manifestations, which can be influenced for better or worse by environmental conditions. Several standardized diagnostic systems are available but they recommend different sets of rules. It is premature, therefore, to speak of a "natural" long-term course. It is even doubtful whether further long-term studies (except perhaps of birth cohorts) should be attempted until more discriminating and reliable methods have been found. Short-term studies, however, focused on specific hypotheses, still hold out promise of yielding fruitful results.     

Therapy of the adverse effects of neuroleptics]

The authors analyzed 65 women patients treated with neuroleptics and evaluated the results in accordance the SARS scale with regard to side-effects of the neuroleptic therapy. They dealt with the problem of convenience of treatment with antiparkinsonics to minimize side-effects of neuroleptics.