Schizophrenics fully remitted on neuroleptics for 3-5 years--to stop or continue drugs? [Adjuvant treatment of schizophrenic illness with carbamazepine]. Prophylactic effect of neuroleptics in symptom-free schizophrenics. Clozapine versus perphenazine: the value of the biochemical mode of action of neuroleptics in predicting their therapeutic activity. Initial improvement as a criterion for drug choice in acute schizophrenia. Technique for training schizophrenic patients in illness self-management: a controlled trial. Long-term treatment effects of vitamin E for tardive dyskinesia. Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia. [Carbamazepine: an efficient adjuvant treatment in schizophrenia]. Episodic and residual thought pathology in chronic schizophrenics: effect of neuroleptics. The treatment of acute psychosis without neuroleptics: six-week psychopathology outcome data from The Soteria Project.
A double-blind comparison between benzodiazepines and neuroleptics was carried out for 1 1/2 years on 30 schizophrenics who had hitherto continuously received neuroleptics and remained apparently in full remission for at least 3-5 years. The benzodiazepine-group had a significantly higher relapse rate than the neuroleptic-group, meaning that we cannot stop neuroleptics for these patients yet. Three possible reasons for this are (1) demand of the natural course of the illness, (2) the fact that the patients agreed to stay in therapy for so long may signify a need for therapy, (3) some of the relapses on stopping neuroleptics may be 'withdrawal psychosis' after prolonged neuroleptic therapy. If withdrawal of neuroleptics is really needed, however, it may be considered for a subgroup of female patients whose illness started after the age of 40. Very few controlled clinical trials have been assessing the interaction of antipsychotics and antiepileptics. However, schizophrenic patients frequently receive a combination therapy consisting of haloperidol and carbamazepine. The data for this treatment strategy are contradictory and may depend on the initial plasma concentration of the antipsychotic. There is convincing evidence that after addition of carbamazepine the plasma concentration of neuroleptics drops due to hepatic enzyme induction. In this study, we treated 18 schizophrenic patients either with haloperidol alone or in combination with carbamazepine. The use of carbamazepine was associated with a dramatic fall in haloperidol plasma levels and a worse clinical outcome compared to the monotherapy group. These results, together with a review of the literature, lead us to the conclusion that there are no obvious advantages of carbamazepine co-medication in schizophrenia compared to an optimized neuroleptic monotherapy. Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the "first assigned drugs" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics. The chemical structure of a neuroleptic does not relaibly predict the exact profile of its therapeutic action. We considered the question whether the biochemical action of a neuroleptic, and specifically the ratio between DA-receptor block and NA-receptor block, might have a higher predictive value in this respect. In this context we carried out a double-blind study of the therapeutic value of clozapine and perphenazine in acute psychoses of varying symptomatology anc aetiology. There are strong indications that clozapine has only a slight inhibitory effect on transmission in central DA-ergic neurons, but markedly inhibits transmission in central NA-ergic neurons, and that the reverse applies to perphenazine. In view of these data we expected perphenazine to be a stronger antipsychotic and a weaker sedative than clozapine, and vice versa. The plausibility of this hypothesis was demonstrated. Partly also on the basis of earlier research, we concluded that the biochemical action of a neuroleptic is a more faithful predictor of its therapeutic action profile than the chemical structure. Several investigators have found that the initial improvement of acute schizophrenia after some days of neuroleptic treatment is correlated in a statistically significant way to the outcome after four weeks. In all these studies the question arises as to whether the correlation between early response and subsequent outcome is due to a specific response to a certain neuroleptic, or whether patients who respond early simply have a better prognosis. In order to isolate the specific drug effect from prognostic influences we performed a controlled double-blind study in 50 newly admitted schizophrenic inpatients. All patients were treated over three days with 15 mg haloperidol i.v., following which they were classified as 'early responders (ER)' (markedly improved or improved) or as 'early nonresponders (EN)' and then randomly assigned to group 1 (3 x 5 mg haloperidol p.o./d) or to group 2 (3 x 100 mg perazin p.o./d). If there was a specific drug effect on the correlation between early response and subsequent outcome a therapeutic superiority of perazin in EN and no superiority in ER was expected. Independently of the treatment condition the mean BPRS score had decreased from 61.2 (Sx = 12.1) to 38.1 (Sx = 13.9) at the end of the study. ER and EN were evenly distributed in the haloperidol and perazin group. The analysis of variance revealed no significant interactions of the factors 'treatment condition' x 'duration' x 'early response' (p = 0.27) and 'treatment condition' x 'early response' (p = 0.88) on the outcome (BPRS, CGI). This means that the initial hypothesis of this study has to be rejected.(ABSTRACT TRUNCATED AT 250 WORDS) To determine whether schizophrenic outpatients receiving low-dose neuroleptic therapy could learn and retain complex information and skills related to self-management of their illness, a novel technique of teaching, using cognitive and behavioral methods, was designed to compensate for the patients' learning disabilities.
                The subjects were 41 patients with DSM-III-R schizophrenia who were receiving constant maintenance neuroleptic drug therapy. They were randomly assigned to structured, modularized skills training or to supportive group psychotherapy.
                The patients who received skills training made significant gains in each of the areas taught, while those participating in group therapy did not. The skills learned during training were retained without significant erosion over a 1-year follow-up period.
                The effectiveness of modularized teaching of illness self-management skills to schizophrenic patients appears to be largely independent of baseline psychology and symptom improvement. Such an approach is useful for overcoming or compensating for the enduring cognitive and information processing deficits commonly found in schizophrenia. Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment.
                To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo.
                Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score.
                The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo. The authors investigated the clinical effects of D-cycloserine when added to treatment with conventional neuroleptics, olanzapine, or risperidone for treatment-resistant schizophrenia.
                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.
                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.
                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. Different studies published in the last years have focused on the psychotropic effects of carbamazepine (CBZ). This study tries to investigate the efficacity of CBZ as an adjunct treatment of schizophrenia. 20 patients with a diagnosis of paranoid schizophrenia, according to the RDC, have been investigated by double-blind method. Subjects are divided in two groups (n = 10). The first one is treated with CBZ (with dose in order to reach a plasma level between 8-12 mg /l) and Haloperidol (oral fixed dose: 30 mg /day). The second group only with Haloperidol (same dose). Clinic and psychopathological disturbances are evaluated with the BPRS, and secondary effects with the UKU scale. A clinical improvement (90%, measured by the BPRS) was observed for both groups, without significant differences. Patients treated with CBZ show an important reduction of neurological secondary effects related to neuroleptics (Haloperidol). Carbamazepine appears to be a useful treatment, combined with neuroleptics, for acute schizophrenic episodes. We sought to determine the effect of neuroleptic treatment on thought disorder in chronic schizophrenics, using the Thought Disorder Index (TDI). We were able to demonstrate that high levels of thought disorder are found in chronic schizophrenic and schizoaffective patients, while in both bipolar patients and normal controls thought pathology is minimal. Moreover, the TDI appears to be particularly well suited to the characterization of thought disorder in chronic schizophrenics. For total scores on the TDI, we were unable to demonstrate a significant reduction in thought pathology, although it was evident that thought disorder as reflected in the Conceptual Disorganization and Unusual Thought Content subscales of the Brief Psychiatric Rating Scale is significantly reduced by neuroleptics. In analyses of subscores of the TDI reflecting four levels of severity, we were able to show that more severe forms of thought pathology are normalized by neuroleptics, while less severe pathology is largely unaffected. Our results suggest that neuroleptic treatment reduces thought pathology associated with acute episodes, but that somewhat milder, though still disabling, residual thought pathology persists after clinical remission has been attained. Today's treatment of acute psychosis usually includes short-term hospitalization and anti-psychotic drug treatment. The Soteria project compared this form of treatment (control) with that of a small, home-like social environment, usually without neuroleptics (experimental).
                Newly diagnosed, young, unmarried persons with DSM-II schizophrenia were randomly assigned to treatment in two experimental and two control settings. Subjects and families were assessed at admission on 29 independent variables. Treatment environments were studied by means of Moos', COPES or WAS scales. Three dependent six week psychopathology outcome measures were collected.
                The groups were comparable on 25 of 29 admission variables. The environments of the two experimental and two control settings were different from each other. The milieus were similar to each other within each condition. At six weeks, psychopathology in both groups had improved significantly, and similarly, and overall change was the same.
                Specially designed, replicable milieus were able to reduce acute psychotic symptomatology within six weeks, usually without antipsychotic drugs, as effectively as usual hospital ward treatment that included routine neuroleptic drug use.
Limited data from small studies using neuroleptic reduction or specific neuroleptic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration in order to fully investigate this area.