Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mood disorders in schizophrenia are common and are associated with a poor outcome, an increased risk of relapse and a high rate of suicide. Consequently, treatment strategies need to take mood disorders into account. In depressed and actively psychotic schizophrenic and schizoaffective patients, treatment with neuroleptic plus antidepressant may be less effective than neuroleptic alone. However, patients with post-psychotic depression on maintenance neuroleptics respond well to tricyclic antidepressants. Mood disorders can be caused by neuroleptics and if so will often improve if the dose is reduced or if the drug is changed. Anticholinergics may also help. In schizoaffective disorder, lithium is usually beneficial, especially for patients with classical affective disorder. Carbamazepine may be more effective in patients with schizoaffective and schizophreniform disorders. At doses comparable with those effective in schizophrenia, clozapine may be as good or better than conventional neuroleptics in schizophrenic patients with psychotic mood disorder or schizoaffective disorder. In patients with high BPRS anxiety/depression scores, risperidone (8 mg/day) was more effective than haloperidol (10 mg/day). Risperidone at a mean dose of 8.6 mg/day was also more effective than haloperidol (mean dose 9.2 mg/day) or levomepromazine (methotrimeprazine -- mean dose 125 mg/day) on the Psychotic Anxiety Scale. Mood-related symptoms are therefore amenable to treatment. Risperidone and clozapine appear to be good candidates for the long-term treatment of mood disorders in schizophrenia, although long-term, double-blind, controlled studies are needed to confirm this.
 ...
PMID:Long-term treatment of mood disorders in schizophrenia. 754 99

Antipsychotic medication remains the mainstay of both acute and long-term treatment for schizophrenia. Recent research has underscored the need for optimum dosing strategies. Relatively few patients benefit from high doses (e.g. greater than 15-20 mg per day of haloperidol or 500-800 mg/day of chlorpromazine). In poor or partial responders clozapine continues to be the treatment of choice. Risperidone is an effective antipsychotic with a good safety profile. Its potential advantages in terms of efficacy need to be further studied. An expanded data base from maintenance trials supports the use of continuing maintenance medication and provides guidelines for dosage requirements.
 ...
PMID:Antipsychotic medication in the treatment of schizophrenia. 754 42

Risperidone is a benzisoxazole derivative with antipsychotic activity that is chemically unrelated to other currently available antipsychotic agents. Its neuropharmacological properties, characterized by potent central antagonism of both serotonin 5-HT2 and dopamine D2 receptors, also differ from those of most other antipsychotic drugs. The pharmacokinetics of risperidone are well understood, having been studied in healthy subjects as well as in psychotic patients. The absolute oral bioavailability of risperidone is nearly 70%, and after oral administration, it is rapidly absorbed with the plasma level reaching a peak at about 1 h. 9-Hydroxyrisperidone, one of the metabolites of risperidone, is equally active with the parent compound and so the clinical activity of a dose of risperidone is due to the combined actions of both moieties. The plasma concentrations of risperidone and its active metabolite remain dose proportional even at doses exceeding the therapeutic range. In clinical trials with chronic schizophrenia patients, risperidone has an overall therapeutic activity comparable with that of haloperidol, but at doses that produce similar improvements in the positive symptoms of schizophrenia, risperidone has a greater effect on the negative symptoms and produces less extrapyramidal side effects than does haloperidol. However, additional controlled clinical studies are needed before the claims that risperidone is therapeutically superior to haloperidol can be considered to be established firmly. Although risperidone is effective in acute schizophrenia and in non-treatment-resistant schizophrenics, studies adequately comparing risperidone with clozapine in treatment-resistant schizophrenic patients remain to be published. In addition, risperidone has been reported to be of value in patients with schizodepressive disorders. The clinical success of risperidone suggests that the development of compounds with selective affinity for 5-HT2 or other serotonin receptors may result in even further improvements in the pharmacotherapy of psychiatric disorders.
 ...
PMID:A pharmacological, pharmacokinetic and clinical overview of risperidone, a new antipsychotic that blocks serotonin 5-HT2 and dopamine D2 receptors. 754 76

The objective was to examine effects of risperidone on hostility and compare these effects with those of haloperidol. On the basis of risperidone's pharmacologic profile, we hypothesized that risperidone has a selective effect on hostility and that this effect is greater than that of haloperidol. The data were obtained in a multicenter clinical trial of risperidone under placebo-controlled, double-blind conditions (duration, 9 weeks). The patients were 139 patients with the diagnosis of DSM-III-R schizophrenia. Hostility was measured by the "hostility" item of the Positive and Negative Syndrome Scale. Change in hostility served as a dependent variable in the analyses. Change in "psychosis" was applied as a covariate; it helped us examine changes in hostility that were unrelated to change in psychosis (selective effect). Risperidone had a greater selective effect on hostility than did haloperidol or placebo. This finding should encourage tests of risperidone as a treatment for patients who show frequent overt physical aggression.
 ...
PMID:Effect of risperidone on hostility in schizophrenia. 759 6

A parallel group double-blind comparative trial was conducted to study the efficacy and safety of risperidone compared with haloperidol. After a one-week wash-out, 35 chronic schizophrenic patients (17 males, 18 females) were randomly assigned to one of two groups for eight weeks of double-blind treatment. The patients' psychopathology was assessed by means of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and the Clinical Global Impression (CGI). Safety assessments included the Extrapyramidal Symptom Rating Scale (ESRS), the UKU Side Effect Rating Scale, vital signs, body weight, ECG and laboratory screening. Thirty-two patients completed the trial: there were 3 dropouts in the risperidone group. The results on the PANSS and CGI indicate that the mean changes from baseline on the total PANSS score and on the total BPRS score were comparable in both treatment groups. The number of patients where a clinical improvement at least 20% reduction in baseline score was also similar in both treatment groups. Risperidone caused less extrapyramidal symptoms and less side effects in UKU scale than haloperidol. No significant ECG changes were induced, no relevant changes in blood pressure or clinical laboratory parameters were observed. This study has demonstrated that the combined serotonin 5-HT2 and dopamine-D2 antagonist risperidone is an antipsychotic as potent as haloperidol. Risperidone causes less extrapyramidal symptoms, and is better tolerated than haloperidol.
 ...
PMID:Risperidone versus haloperidol in the treatment of chronic schizophrenic patients: a parallel group double-blind comparative trial. 769 Oct 17

Before the dopamine hypothesis of schizophrenia became established, a serotonin (5-hydroxy-tryptamine) 5-HT hypothesis was popular. This was based on the hallucinogenic properties of lysergic acid diethlyamide and abnormal serotonin levels in schizophrenics. Suggestions that serotonin might be involved in the cause of schizophrenia or could be a target for antipsychotic drug action began with the discovery that the antipsychotic agent clozapine is a potent serotonin 5-HT2A antagonist, as well as being a dopamine D2 antagonist. This led to the formulation of the serotonin-dopamine antagonist (SDA) concept for antipsychotics, with wider spectrums of activity and lower extrapyramidal side effects (EPS) liability. The principle of the SDAs is that the drug should be a potent serotonin 5-HT2A antagonist, with slightly less potent dopamine D2 receptor-blocking properties. The clinical experience with risperidone, the first member of the new class of antipsychotics, seems to offer the promise that the SDAs have significant advantages over both the conventional dopamine-blocking neuroleptics and the atypical antipsychotic clozapine. Risperidone has efficacy against both the positive and negative symptoms of schizophrenia and has a low tendency to produce EPS. Only time will tell whether other SDAs will have the same advantages.
 ...
PMID:The evolution of the serotonin-dopamine antagonist concept. 773 Apr 99

Clozapine is a great advance in the treatment of schizophrenia. It should be tried in any neuroleptic-resistant schizophrenic as well as some who are neuroleptic intolerant. If progress is made in controlling its agranulocytosis, clozapine could be the drug of choice for all types of schizophrenia and perhaps other conditions as well for which neuroleptic drugs are employed, e.g., mania resistant to mood stabilizers. Its advantage with regard to lower risk of tardive dyskinesia indicates that potent antipsychotic activity and liability to cause tardive dyskinesia can be dissociated. This must be the object of future antipsychotic drug development. Risperidone could be the next clozapine but at the time of this writing, there is too little data to pass judgment on this. Its low EPS profile and apparent effects on negative symptoms at lower doses are promising. Remoxipride may be useful because of its low EPS profile. How much better tolerated it is than currently available drugs, especially thioridazine, is not clear. Many other novel agents are being tested. Clinicians will be challenged to follow this emerging field closely and identify the most promising new agents that may be indicated for specific stages of, or subtypes of, schizophrenia.
 ...
PMID:New drugs for the treatment of schizophrenia. 810 73

Since the average lifespan is becoming longer, the number of older patients with psychoses is expected to increase. Late-life schizophrenia is prototypical of these chronic psychotic disorders. Antipsychotic drugs are the most effective symptomatic treatment. Pharmacotherapy in older patients, however, is complicated by alterations in pharmacokinetics and pharmacodynamics. The risk of many adverse effects is considerably higher in the elderly. For example, we found the cumulative annual incidence of tardive dyskinesia among patients over age 45 to be 26%, which was five to six times greater than that reported in younger patients. Studies suggest that most patients with schizophrenia relapse without neuroleptic maintenance therapy, exemplifying the need for improved pharmacologic regimens. Data concerning the use of the newer serotonin-dopamine antagonists in patients with late-life psychoses are limited. Initial studies suggested that clozapine is efficacious, but its use is limited by side effects. Risperidone is also clinically beneficial and is generally well tolerated, but needs to be prescribed in lower doses than those recommended for younger adults. Antipsychotic use in the elderly should be accompanied by careful conservative dosing and close patient monitoring.
 ...
PMID:Management of late-life psychosis. 862 69

Buspirone, an azaspirone serotonin (5-HT) 1A partial agonist, has been approved by the FDA as an anxiolytic. It has been tested for use in depression, panic disorder, obsessive-compulsive disorder, and schizophrenia as well. Several trials have indicated that it may prove to be a useful agent for augmentation of other psychotropic medications in these disorders. We review the literature supporting the potential use of buspirone as an augmenting agent.
 ...
PMID:Augmentation with buspirone: a review. 864 75

This open prospective study was undertaken to determine the efficacy and safety of a fixed dose (6 mg) of risperidone in psychotic patients. Hospital in-patients who fulfilled DSM-111-R criteria for schizophrenia, schizoaffective and bipolar disorders were eligible for entry into the study (n = 15). Patients who were on other antipsychotics had a washout period of 1 week before they were started on the drug. A fixed dose of risperidone was administered (6 mg). The Brief Psychiatric Rating Scale (BPRS), Negative Symptom Rating Scale (NSRS) and Abnormal Involuntary Movement Scale were used to measure psychopathology and extrapyramidal side-effects. Five patients dropped out of the study. Two patients became very agitated and potentially aggressive, one patient became very restless and did not respond to benzodiazepines, and one dropped out because of restlessness that did not respond to clonazepam. Of the 10 patients who completed the study, 50 per cent reduction on BPRS and NSRS was achieved by five and six patients respectively. There was a marginally significant trend towards a greater reduction in the magnitude of negative symptoms. Four patients required treatment with anticholinergic drugs. Risperidone was effective in resistent psychotic patients, but agitated and impulsive psychotic patients with positive symptoms may not be best candidates for treatment with risperidone. On average, negative symptoms respond better than positive symptoms.
 ...
PMID:Efficacy and safety of risperidone in psychotic patients: an open study. 872 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>