Treatment Of Schizophrenic Patients Research Articles

Uso de neurolépticos atípicos en esquizofrénicos consumidores de cannabis

The increasing research about comorbidity shows the growing importance of this topic in the current development of psychiatry. The mayority of these papers discuss the importance of psychological treatment in these kind of patients, but there are a few number dealing with the pharmacological treatment. There are some references on the benefit of the atypical neuroleptics in the treatment of schizophrenic patients using cannabis. The aim of the present paper is trying to verify this hypothesis. Material and Methods: Three groups of patients with paranoid schizophrenia, two of them cannabis users, were included in this study. We made a one year follow-up after treatment with a classic (group ED) or an atypical (group AT) neuroleptic treatment Results: Group AT shows a lower frequency of cannabis use and a greater insight. Conclusions: Atypical neuroleptics could be useful in the management of schizophrenic patients with current cannabis use.

Evidence for an Association between Polymorphism in the Serotonin-2A Receptor Variant (102T/C) and Increment of N100Am plitude in Schizophrenics Treated with Clozapine

Using event-related potentials (ERPs), a reduction in the auditory N100, N200 and P300 amplitude has been found in schizophrenic patients and may represent some pathophysiological deficit. Therefore, we investigated whether the genetic variant of the serotonin-2A receptor is associated with ERP change after clozapine treatment in schizophrenic patients. Ninety-nine schizophrenic patients were included in the study. The results demonstrated that patients with 102C/C genotype have higher N100 amplitude than other patients after clozapine treatment. Our findings suggested that serotonin-2A receptor polymorphism may relate to clozapine response in schizophrenic patients. An objective and reliable tool like ERPs to assess patients’ treatment response may afford more consistent results in pharmacogenetic studies.

Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine

Background: The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest. Methods: The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the “noninferiority” of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total). Results: Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the “noninferiority” of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts ( p = .022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients. Conclusions: Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.

Actigraphy to measure day structure as a therapeutic variable in the treatment of schizophrenic patients

A component of social skills is the ability to adapt to the social rhythms of the environment. Patients with schizophrenia are often disabled in this adaptation. Thus, structuring activities throughout the day has long been known as part of psychosocial treatments. Actigraphy as a tool to measure acitvity and circadian rhythms may even serve as an indicator for the day-structuring of schizophrenic patients. Actigraphy was used in a patient with affective disorder and one with chronic schizophrenia for more than 2 weeks. In comparison to a regular 24-hour rest-activity cycle in a depressed patient, the actigraph of the patient with schizophrenia presents active phases at night, irregular activity levels at day and signs of a delayed-sleep-phase syndrome. Actigraphy could serve as a tool to investigate activity levels and circadian rest-activity phases, even in schizophrenia. There may be some further benefit of actigraphy as a tool in psychosocial treatments.

Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial

Background. A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication. Methods. Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men). Results. An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone ( P=0.025), while the parkinsonism total score tended to be better with risperidone ( P<0.10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication. Conclusions. In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.

The effect of augmentation with moclobemide on symptoms of schizophrenia

The effectiveness of adding moclobemide to antipsychotic treatment in schizophrenic patients with prominent negative symptoms was examined. Eleven chronic schizophrenic patients had their regular antipsychotic treatment augmented by the addition of moclobemide 450 mg/day for 8 weeks. A significant improvement was seen on the Positive and Negative Syndrome Scale (PANSS) negative factor and for the Scale for the Assessment of Negative Symptoms (SANS) scores, PANSS total score, PANSS general factor score and Hamilton Depression Scale scores. Positive symptoms were not altered. Moclobemide augmentation may ameliorate negative, depressive and general symptoms in schizophrenia. Int Clin Psychopharmacol 14:193–195 © 1999 Lippincott Williams & Wilkins

The effect of augmentation with moclobemide on symptoms of schizophrenia

The effectiveness of adding moclobemide to antipsychotic treatment in schizophrenic patients with prominent negative symptoms was examined. Eleven chronic schizophrenic patients had their regular antipsychotic treatment augmented by the addition of moclobemide 450 mg/day for 8 weeks. A significant improvement was seen on the Positive and Negative Syndrome Scale (PANSS) negative factor and for the Scale for the Assessment of Negative Symptoms (SANS) scores, PANSS total score, PANSS general factor score and Hamilton Depression Scale scores. Positive symptoms were not altered. Moclobemide augmentation may ameliorate negative, depressive and general symptoms in schizophrenia.

Some remarks on etiological aspects of early-onset schizophrenia.

Neurophysiological, neuropsychological, neuroanatomical, and neuroradiological findings in schizophrenic psychoses demonstrate that subcortical (e.g., mesolimbic and diencephalic regions) as well as neocortical structures (e.g., dorsolateral prefrontal cortex, superior temporal and inferior parietal cortices) are involved. Special significance is accorded to the neuroanatomical connection between limbic structures and the dorsolateral prefrontal cortex. Here myelinization begins relatively late in humans, during the second and third decade of life - a particularly vulnerable period for schizophrenic onset. The nature of prepsychotic behavioral abnormalities in patients with early-onset schizophrenia as well as the existence of typical cognitive dysfunctions preceding the manifestation of psychotic symptoms points to the importance of a dynamic imbalance of neocortical-subcortical interactions in the etiology of schizophrenia. Based on the crucial importance of the prefrontal-hippocampal circuitry a stimulus barrier model of schizophrenic psychoses is elaborated, which integrates recent neurobiological findings as well as results of research in modern developmental psychology. One of the implications of this model is the multidimensional treatment of schizophrenic patients.

Striatal enlargement in rats chronically treated with neuroleptic

Background: Striatal enlargement with chronic neuroleptic treatment in schizophrenic patients has been reported by several investigators. Longitudinal magnetic resonance imaging studies of patients suggest that changes in striatal volume may be caused by treatment with antipsychotic medication. Methods: We have examined the effects of chronic neuroleptic treatment on postmortem striatal volume in the laboratory rat and have examined the relationship between striatal volume and vacuous chewing movements (VCMs). Autoradiographs of 50 rats treated with haloperidol (1.5 mg/kg/day) or drug free for varying durations of time (1–12 months) were utilized in this analysis. Results: Chronic treatment with neuroleptics (1 month or greater) was associated with larger striatal volumes. The increase in striatal volume was present at 1 month of treatment and was sustained to 12 months of treatment. Rats that developed the high-VCM syndrome had larger striatal volumes than both drug-free and low-VCM rats, while low-VCM rats had larger striatal volumes than drug-free rats. Conclusions: These data suggest that chronic neuroleptic treatment is the cause of striatal enlargement in the laboratory rat, and that this enlargement is most prominent in rats that have the high-VCM syndrome.

53 EEG-reactivity before and during treatment in schizophrenic patients: Differences between responders and non-responders?

53 EEG-reactivity before and during treatment in schizophrenic patients: Differences between responders and non-responders?

Sertindole: Targeting the optimal dosage for the treatment of schizophrenic patients

Sertindole: Targeting the optimal dosage for the treatment of schizophrenic patients

P.2.059 New perspectives in the treatment of schizophrenic patients

P.2.059 New perspectives in the treatment of schizophrenic patients

P.2.044 Clozapine, norclozapine plasma levels during a long term treatment of schizophrenic patients

P.2.044 Clozapine, norclozapine plasma levels during a long term treatment of schizophrenic patients

Vulnerability to Schizophrenia and Psychotherapeutic Treatment of Schizophrenic Patients: Towards an Integrated View

My approach to schizophrenia and its treatment has evolved gradually over my forty-year experience as a family researcher and a psychotherapist to schizophrenic patients. I am convinced that we must maintain a comprehensive view, both with regard to the factors contributing to vulnerability to schizophrenia and concerning our treatment activities, and not limit our views with studies focusing on restricted spheres of interest. I will present some viewpoints concerning both the biological and the psychosocial factors contributing to the vulnerability to schizophrenia. My aim is to indicate that these factors are heterogeneous and differently weighted in different cases. However, an integrated notion of the pathways leading to schizophrenia can be proposed. I will also review the therapeutic approach-the need-adapted treatment of schizophrenic psychoses-which I and my coworkers have developed in Finland and which, in many respects, is related to these views.

Lack of allelic association between 102T/C polymorphism of serotonin receptor type 2A gene and schizophrenia in Chinese.

Recent studies have reported an association between a 102T/C polymorphism of serotonin receptor type 2A gene (5-HT2A) and schizophrenia. In addition, an association was detected between a 102T/C polymorphism of the 5-HT2A receptor gene and drug response to clozapine in the treatment of schizophrenic patients. These studies suggest an important role of the 5-HT2A gene in schizophrenia. To study the possible involvement of the 5-HT2A gene in the pathogenesis of schizophrenia, a case-control association study was carried out in a Chinese population from Taiwan. No significant differences of genotype distributions, allele frequencies and homozygosity were detected between schizophrenic patients (n = 177) and nonpsychiatric controls (n = 98). When subjects were divided into subgroups according to sex, still no differences of allele frequencies or genotype distributions were noted between patients and controls. Our data do not support an allelic association between the 102T/C polymorphism of the 5-HT2A receptor gene and schizophrenia in Chinese population.

EPOS: Increasing our understanding of the treatment of schizophrenia; Start of a prospective referenced cohort study of sertindole in clinical practice

Sertindole is a new limbic-selective antipsychotic agent which has recently received marketing authorization in several countries across Europe for the treatment of schizophrenia. The experience gained in around 2200 patients treated with sertindole in controlled clinical trials has enabled optimal targeting of sertindole to those patient groups who will benefit most and who are least likely to experience adverse effects. Ultimately, it is how a new medicinal product is used in clinical practice, how it performs in everyday life, and how the patient who takes it feels and functions that determine the real benefit/risk ratio of a new medicinal product. The European Post-marketing Observational Serdolect® project (EPOS) is a post-marketing, referenced, observational, cohort, safety study in the treatment of schizophrenic patients initiated earlier this year. It is planned to recruit over 12 000 patients in two cohorts in centres throughout Europe. The aims are to provide a full safety evaluation of sertindole under marketed conditions at the relevant clinical dosage, and further, to provide epidemiological data on schizophrenic patients receiving sertindole or other treatment under the usual clinical conditions in Europe. At the moment, the study is the only one of its kind to be undertaken in schizophrenia and will provide important new data for psychiatrists around the world.

A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables

The benefit of neuroleptic drugs in the treatment of schizophrenic patients is objectively beyond any doubt. However, most patients discontinue their neuroleptic drugs within some months. This low compliance might be caused by the lack of insight into the disease and the necessity of therapy. Also of major importance are adverse effects, not restricted to motor symptoms, but also affecting cognition and emotion. They are often too subtle to be detected by objective examination, but reported by patients who complain of a reduced quality of life with restrictions of emotionality, straight thinking and spontaneity. This syndrome, similar to negative symptoms of schizophrenia, has been named 'pharmacogenic depression' or 'neuroleptic-induced deficit syndrome'. To investigate this issue of major clinical relevance, a self-rating scale was developed to measure subjective well-being under neuroleptic treatment (SWN). First analyses indicate good practicability, reliability, validity and sensitivity. Data obtained from 280 remitted schizophrenic patients showed that the SWN was significantly correlated to objective psychopathology (Positive and Negative Symptom Scale, PANSS; r = -0.35), quality of life (r = 0.60) and other self-ratings of mood states [Profile of Mood Scale (POMS), Self-rating Depression Scale (SDS), Befindlichkeits Scale (BFS); r = 0.25-0.75]. A repeated application after 3 months in 53 patients did not show any change in SWN in those with constant neuroleptic medication, but there were marked alterations if the dosage or the drug was changed. The SWN in 28 patients treated with clozapine because of therapy resistance or major side effects was, despite negative selection, significantly better (t = 1.79, p = 0.03) than in 38 patients under classical neuroleptics. Moreover, even at dismissal, patients who were non-compliant 4-6 months later (n = 14) differed significantly (t = 3.21, p = 0.02) in SWN, but not in PANSS, from those who remained compliant (n = 34). These data indicate that the SWN is a useful tool for investigating a hitherto neglected psychopathological dimension. Subjective effects of neuroleptics are measurable, affect patients' quality of life and should be considered more thoroughly in clinical routine as well as in clinical trials of potential neuroleptic drugs.

Depot neuroleptics in relapse prevention

Non-compliance is a major problem in the treatment of schizophrenic patients, a problem which is due to the patient's mental condition, to disturbing side effects of the medication, to a defective doctor-patient relationship, and to a general scepticism towards chemical treatment of mental symptoms. The major advantage of depot administration of neuroleptic drugs is the assurance of compliance leading to fewer relapses and rehospitalizations. Depot neuroleptics also eliminate bioavailability problems related to absorption and first pass metabolism and give a stable plasma concentration. Finally, depot neuroleptics provide a better and safer way to use the lowest effective dose principle thereby reducing the frequency of side effects, including the subjectively distressing mental side effects such as akathisia, dysphoria and neuroleptic-induced deficit syndrome. Disadvantages include delayed disappearance of potentially irreversible and unpleasant side effects after discontinuation and, for many patients, a feeling of being controlled. Administered in the proper way, with suitable information to the patient and relatives, depot neuroleptics improve the quality of antipsychotic treatment, reduce relapse frequency, stabilize the therapeutic effect and diminish the level of side effects.

New diagnostic vistas.

There are many difficulties in establishing criteria for better drug compliance and improved quality assurance in the treatment of schizophrenic patients. The most serious problem (especially with first episodes) is that of diagnosis. Since no biological markers for schizophrenia have been found the clinician is referred to "symptom collecting"--including collecting social data. In spite of many attempts there is still no general agreement of the concept of schizophrenia. This deplorable fact is reflected in the everchanging subdivisions of the schizophrenias over the decades: from a division of acute and chronic dementia praecox via a classification of simple, hebephrenic, catatonic, paranoid forms, on to new classifications based on positive/negative manifestations, divisions of type I/type II forms etc. The many different rating scales are reflections of the same problem, as are the different diagnostic systems (e.g. DSM-III and ICD-10). The recent attempts to make a synthesis of these systems seem promising but raise new problems related to etiological and pathogenetic views of psychiatric disorders.

A Double-Blind Controlled Study of Intramuscular Zuclopenthixol Acetate and Liquid Oral Haloperidol in the Treatment of Schizophrenic Patients With Acute Exacerbation

We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. A parallel-group design was used with stratification by sex. Zuclopenthixol acetate (50 to 150 mg) was given intramuscularly every 3 days, whereas liquid haloperidol (10 to 30 mg daily) was given orally three times a day, with supplementary doses of each medication given under double-blind conditions when needed for agitation. No other sedative drugs, including benzodiazepines, were administered. The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol. The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale. Both drugs induced similar extrapyramidal side effects. However, more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval. Sedation was higher with zuclopenthixol acetate than with haloperidol. Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections. The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia.