Acute Phase Of Schizophrenia Research Articles

Endocannabinoid signalling in the blood of patients with schizophrenia

AimTo test the hypothesis that schizophrenia might be associated with alterations of the endogenous cannabinoid system in human blood.ResultsBlood from 20 healthy volunteers and 12 patients with schizophrenia, 5 of which both before and after a successful antipsychotic treatment, was analysed for: 1) the amounts of the endocannabinoid anandamide; 2) the levels of cannabinoid CB1 and CB2 receptor mRNAs, and 3) the levels of the mRNA encoding the enzyme fatty acid amide hydrolase (FAAH), responsible for anandamide degradation.The amounts of anandamide were significantly higher in the blood of patients with acute schizophrenia than in healthy volunteers (7.79 ± 0.50 vs. 2.58 ± 0.28 pmol/ml). Clinical remission was accompanied by a significant decrease of the levels of anandamide (3.88 ± 0.72 pmol/ml) and of the mRNA transcripts for CB2 receptors and FAAH.ConclusionThese findings indicate that endocannabinoid signalling might be altered during the acute phase of schizophrenia not only in the central nervous system but also in the blood. These changes might be related to the several immunological alterations described in schizophrenia.

Distractor cueing effects on choice reaction time and their relationship with schizotypal personality.

Although usually displaying increased distractibility, schizophrenic patients sometimes show a reduced influence of distractors during selective attention tasks. This study explored whether reduced distractor processing effects can also occur in healthy individuals with high levels of schizotypal personality traits. In all, 36 healthy volunteers completed schizotypal personality scales and a choice reaction time (RT) task in which they responded to the central letter of triads (XMX, YCY), ignoring the flanking distractors. RT increases on low-probability probe trials (YMY, XCX) measured distractor processing ('the distractor cueing effect'). Correlations between schizotypy scores and distractor cueing were evaluated. Healthy participants with high positive schizotypy scores (i.e. those reporting more hallucination-like experiences and delusion-like beliefs) showed smaller distractor cueing effects than those with lower scores. This association was independent of the influence of other schizotypal personality traits (disorganized, negative or asocial schizotypy) and was significant only for right-hand responses. These findings closely parallel the previously reported reduced distractor cueing effect, for right-hand responses, among acute-phase schizophrenic patients. Finding reduced distractor cueing effects in healthy participants with high levels of positive schizotypy increases confidence that reduced distractor cueing is a specific feature, rather than a non-specific consequence, of acute-phase schizophrenia.

Spotlight on amisulpride in schizophrenia.

Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D(2)/D(3) autoreceptors. At higher doses, amisulpride antagonises postsynaptic D(2) and D(3) receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or = 300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo. In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.

Efficacy and safety of long-term risperidone treatment

INTRODUCTION: While efficacy in treatment of the acute phase of schizophrenia is well established for so-called atypical antipsychotics, more data regarding long-term treatment are needed. METHOD: In a naturalistic, open-label study, 32 patients were included in order to investigate the efficacy and safety of risperidone over 3 years of treatment; 26 of them were treatment-resistant to the previously used antipsychotic drugs (except clozapine). RESULTS: At the end of the first year, 20 of these 26 patients showed at least partial improvement. At the end of the third year, 17 patients were still being treated with risperidone. While eight patients were lost to follow-up, six relapsed in spite of good compliance. All the adverse events which occurred during treatment were strictly dose-dependent and disappeared when the dose was lowered to 4 mg daily. CONCLUSIONS: Within the limits of naturalistic studies, it can be concluded that risperidone seemed to be an effective and safe drug for long-term treatment in the majority of our patients. (Int J Psych Clin Pract 2002; 6: 193-197 )

The changes of biological markers and treatment efficacy in schizophrenia

1. In a group of schizophrenic patients, the effect and selected parameters of biological markers were evaluated during the index hospitalisation in the acute phase of schizophrenia (n = 30) and then after one year of ambulatory treatment. 2. During the acute treatment, a significant drop in symptomatology was recorded in average; an analogical tendency was observed further on, too. Apart from that, a significant change was observed in 5/41 parameters being monitored (the pair t-test):I) decrease in the total NES score, II) decrease in the sensorial integration subscale NES score, III) increase in psychomotor speed, IV) decrease in auditory reaction time, V) increase in basal cortisol. 3. In the comparison of the successfully (severity of illness after one year = 1, 2) and unsuccessfully (severity of illness after one year ≥3) treated patients in the beginning of treatment in the acute phase, the unsuccessful group had a significantly higher score of negative symptomatology, and by the end of the acute treatment, again, a significantly higher score of negative symptomatology, a higher total PANSS score and a greater severity of illness. 4. In the acute phase, the successful group had a significantly better score in individual items of the Contemporary Memory Scale and a significantly worse performance and goal-aimed concentration in the Bourdon test than the unsuccessfully treated one; apart from that, it had a significantly higher cortisol leel after dexamethasone, which was also reflected in the lower percentage rate of dexamethasone nonsuppression. 5. In the course of the year, a drop in the total NES score for the individual subscales occurred; a significant drop was observed in the sensory integration subscale. The worse concentration items improved significantly in the successful group in contrast to the unsuccessful group, where they showed a downgrade tendency. Changes in Contemporary Memory Scale were negligible and mostly below statistical significance. Apart from that, a drop in basal cortisolemia occurred in the successful group and an increase in cortisolemia after administering dexamethasone was registered in the unsuccessful group. 6. The more successful group had a significantly lower NES score, a significantly better visual reaction time and a smaller forgetting item (in percentiles) after the one-year period.

Olanzapine

Olanzapine, a thienobenzodiazepine derivative, is a second generation (atypical) antipsychotic agent which has proven efficacy against the positive and negative symptoms of schizophrenia. Compared with conventional antipsychotics, it has greater affinity for serotonin 5-HT2A than for dopamine D2 receptors. In large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine 5 to 20 mg/day was significantly superior to haloperidol 5 to 20 mg/day in overall improvements in psychopathology rating scales and in the treatment of depressive and negative symptoms, and was comparable in effects on positive psychotic symptoms. The 1-year risk of relapse (rehospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8-week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder. Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval. The most common adverse effects reported with olanzapine are bodyweight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth) and transient asymptomatic liver enzyme elevations. In comparison with haloperidol, the adverse events reported significantly more frequently with olanzapine in > or = 3.5% of patients were dry mouth, bodyweight gain and increased appetite and compared with risperidone, only bodyweight gain occurred significantly more frequently with olanzapine. The high acquisition cost of olanzapine is offset by reductions in other treatment costs (inpatient and/or outpatient services) of schizophrenia. Pharmacoeconomic analyses indicate that olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Compared with risperidone, olanzapine has also been reported to decrease overall treatment costs, despite the several-fold higher daily acquisition cost of the drug. Olanzapine treatment improves quality of life in patients with schizophrenia and related psychoses to a greater extent than haloperidol, and to broadly the same extent as risperidone. Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first-episode or treatment-resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first-line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.

Risperidone: Efficacy and Safety

This article reviews the evidence for the efficacy and effectiveness of risperidone in persons with schizophrenia. Nine published double-blind studies compare risperidone with another antipsychotic medication and/or placebo. All were conducted in the acute phase of illness. Risperidone's antipsychotic efficacy is shown to be consistently superior to that of placebo and at least comparable to that of haloperidol and perphenazine for patients in the acute phase of schizophrenia. Further research is necessary to determine the effectiveness of risperidone and its efficacy both as a maintenance treatment and in treatment-refractory and deficit-state patients.

On the Delusional Experience of Controlling Other Persons in Acute Schizophrenics

I present cases in which patients feel that they are able to control other persons, and consider the features of this delusional experience and note some points concerning its treatment. This delusional experience does not continue for a long period and is accompanied by a suicidal tendency, a pathological consciousness of the disappearance of the self, and some catatonic experiences. These features are not accidental, but result from the essentially solipsistic quality of this delusional experience. So, from the symptomatic viewpoint, this experience can be considered as belonging to catatonic ones in the acute phase of schizophrenia. From the therapeutic point of view, the occurrence of this experience should be carefully examined, bearing in mind its short duration. And when we encounter this experience, we should make provision against its suicidal tendency that often inevitably impels us to carry out electroconvulsive therapy.

A neuroleptic-like effect of ceronapril on latent inhibition

Three experiments that used a latent inhibition procedure to investigate the effects of ceronapril on attentional processes in the rat are reported. Latent inhibition is a behavioural paradigm in which prior exposure to a stimulus with no significant consequences retards subsequent conditioning to that stimulus when it is paired with reinforcement. Latent inhibition reflects a process of learning to ignore, or tune out, irrelevant stimuli, and has been suggested as an animal model of the attentional processes disrupted in the acute phase of schizophrenia. In animals, latent inhibition is disrupted by the administration of low doses of amphetamine and enhanced by the administration of neuroleptics. Ceronapril is an angiotensin converting enzyme inhibitor that has been shown to retard the breakdown of central cholecystokinin. It has been proposed that elevation of cholecystokinin levels in the brain may possess neuroleptic-like properties. We assessed this possibility by determining the effects of ceronapril on latent inhibition using a conditioned emotional response procedure, consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus, a tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where latent inhibition was indexed by animals' suppression of licking during tone presentation. In Experiment 1, 20 tone pre-exposures were given, and conditioning consisted of five tone-shock pairings; we assessed the effects of 0.005 mg/kg, 0.05 mg/kg and 0.5 mg/kg ceronapril, compared with vehicle injections. In Experiment 2, five tone pre-exposures were given, and conditioning consisted of two tone-shock pairings: we assessed the effects of 0.05 mg/kg ceronapril, compared with vehicle injections. Both procedures have been shown to be insufficient to produce latent inhibition in normal animals, in the one case because there are enough conditioning trials to overcome the effects of pre-exposure, and, in the other, because there is insufficient pre-exposure to produce an effect. Accordingly, in the present experiments, latent inhibition was absent in vehicle controls, but, in marked contrast, animals treated with 0.05 mg/kg ceronapril exhibited latent inhibition. Experiment 3 used a procedure that yields latent inhibition in normal animals, consisting of 40 tone pre-exposures and two tone-shock pairings; we assessed the effects of 0.05 mg/kg ceronapril on latent inhibition as well as on the disruption of latent inhibition produced by 1 mg/kg amphetamine. Ceronapril (0.05 mg/kg) significantly enhanced latent inhibition with respect to vehicle controls. This enhancing effect was not seen in rats given 1 mg/kg d-amphetamine. Ceronapril thus produces effects on attentional learning that have hitherto been shown only with typical and atypical neuroleptics, and may therefore possess some antipsychotic properties.

Remoxipride and haloperidol in the treatment of acute phase schizophrenia

Remoxipride and haloperidol in the treatment of acute phase schizophrenia

A double‐blind comparative study of remoxipride and thioridazine in the acute phase of schizophrenia

Sixty-one patients with acute schizophrenia received either remoxipride (75-375 mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no statistically significant between-drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction, and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both were associated with cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests.

A clinical comparison of melperone and placebo in schizophrenic women on a milieu therapeutic ward

Twenty schizophrenic women participated in a double-blind comparison of melperone (300 mg daily) and placebo lasting 4 weeks. All the patients received milieu treatment. Two patients in the melperone and four in the placebo group were removed from the study due to unsatisfactory therapeutic response. In the melperone group, there were significant reductions in psychotic morbidity. In the placebo group, there were occasional significant reductions of psychotic morbidity during but not at the end of treatment. The melperone-treated patients exhibited significantly lower morbidity scores than the placebo group after treatment for two and four weeks. The melperone group demonstrated significantly more adverse reactions than placebo-treated patients at the end of the study. The results support the view that melperone exerts an antipsychotic effect. The study is consistent with the opinion that milieu therapy should be combined with neuroleptics to achieve an optimal result in the treatment of an acute phase of schizophrenia.