Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional significance of the interaction between serotonergic and dopaminergic neurotransmission is still uncertain. To document this interaction further, specific behavioral responses of rats to tryptamine and apomorphine were studied. The sequential injection of these agonists, at time intervals with minimal direct behavioral interference, was used to observe response changes with respect to a single challenge. The antagonists haloperidol, ritanserin and risperidone, with known actions on serotonin-S2 (5-HT2) and dopamine-D2 (D2) receptors were used to evaluate effective antagonism of single and sequential challenges. When tryptamine was preceded by an apomorphine challenge the effective doses of the 5-HT2 antagonists ritanserin and risperidone for 50% inhibition of the seizures increased by a factor of 2.5. The dose-response curve of haloperidol remained virtually unchanged, apparently because of the potent dopamine-D2 antagonism associated with these doses which may block the potentiating effect of apomorphine. When apomorphine was preceded by a tryptamine challenge, the total agitation score of the control animals increased by 59% on the average. Haloperidol was equally effective against the enhanced as against the unenhanced apomorphine response. Ritanserin reduced agitation only by the part corresponding to the tryptamine enhancement. Risperidone's activity against the enhanced agitation started at very low doses and was complete at a dose still about 2.5 times lower than that required against the single apomorphine challenge. Mutual enhancement of tryptamine and apomorphine appears to occur even at a time when the behavioral effects of the first agonist are no longer manifest. The enhanced agitation remains largely dopamine-D2-specific and the enhanced seizures serotonin 5-HT2-specific.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional interaction between serotonin-S2 and dopamine-D2 neurotransmission as revealed by selective antagonism of hyper-reactivity to tryptamine and apomorphine. 169 23

Tobacco withdrawal symptoms hamper smoking cessation. This was a pilot study of buspirone, a new azapirone anxiolytic, for tobacco withdrawal. Thirteen smokers entered an open clinical trial. Smokers were titrated to 30 mg/day of oral buspirone for 2 weeks prior to cessation. Tobacco withdrawal and Spielberger state-anxiety scales were used at baseline, on the quit date, and then at 24 hours, 48 hours, 1 week, and 2 weeks after abrupt cessation. At the final visit, smokers compared their withdrawal experience with previous cessation attempts. Two patients (15 percent) could not tolerate the medication and did not attempt smoking cessation. Of the remaining 11 smokers, 3 (27 percent) rated withdrawal relief "very definite," 6 (55 percent) "moderate," and 2 (18 percent) "slight." More than two-thirds of the smokers believed that their difficulty concentrating, craving, restlessness, and anxiety were improved compared with earlier tobacco withdrawal attempts. Five patients (46 percent) reported decreased smoking urges during the 2-week medication titration period. Tobacco withdrawal symptoms and state-anxiety scores changed significantly during the study (P less than 0.05). These results are encouraging, but they should be interpreted with caution because of the small sample size and lack of placebo control. Buspirone effect on tobacco withdrawal symptoms should be studied in a randomized, controlled clinical trial.
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PMID:Buspirone effect on tobacco withdrawal symptoms: a pilot study. 202 30

In 1965 the first study of this series reported different effects of neuroleptics in rats, supporting clinical differences. At the one end, haloperidol presented as a potent and specific antagonist of the psychostimulants amphetamine and apomorphine. Haloperidol-like neuroleptics have marked effects on psychomotor agitation, delusions and hallucinations and bind with high affinity to dopamine-D2 receptors. Pipamperone, at the other end, presented with weak "dopamine" antagonism and more striking tryptamine antagonism. Pipamperone is known to improve disturbed sleep, social withdrawal and other symptoms of chronic schizophrenia in the relative absence of extrapyramidal symptoms. These effects have been attributed to central serotonin-S2 antagonism, on the basis of the clinical effects of ritanserin. As shown by the present analysis of relative tryptamine versus apomorphine antagonism of 57 neuroleptics, in comparison to relative S2 vs. D2 binding, there is a continuity in the series. About 30% of the compounds can be considered to act primarily as serotonin antagonists, but few are markedly more potent than pipamperone. In amphetamine-challenged rats pipamperone-like activity is reflected in preferential inhibition of the excessive oxygen consumption rather than of agitation. Risperidone inhibits oxygen consumption (0.016 mg/kg) at the same dose as haloperidol inhibits agitation. Other low-dose effects of risperidone include reversal of amphetamine-induced withdrawal, antagonism of agitation induced by a sequential tryptamine and apomorphine challenge and LSD-antagonism. In dogs, the antiemetic activity of risperidone is characterized by high oral effectiveness which lasts one day and agrees with pharmacokinetic data when allowance is made for the active metabolite 9-hydroxyrisperidone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is it possible to predict the clinical effects of neuroleptics from animal data? Part V: From haloperidol and pipamperone to risperidone. 751 73

Standard antipsychotics are ineffective in some geriatric patients. In addition, they are not helpful for apathy and withdrawal. Studies have demonstrated that 5HT2 antagonists improve affective symptoms and anxiety; therefore, the efficacy of risperidone on agitation and withdrawal was considered. The literature on risperidone was reviewed, and the efficacy and limitations of risperidone observed in two geriatric patients, one with agitation and another with apathy and withdrawal. Risperidone proved to be effective in controlling disruptive behavior in geriatric patients. Combined antagonism of D2 and 5HT2 receptors might be effective in improving agitation and withdrawal. Risperidone, with both D2 and 5HT2 antagonistic properties, seems to have potential as an alternative agent in controlling agitation and withdrawal in geriatric patients. Caution and need for further observation is recommended.
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PMID:Efficacy of risperidone for behavioral disorders in the elderly: a clinical observation. 757 39

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.
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PMID:Efficacy and safety of risperidone in psychotic patients: an open study. 872 91

Risperidone is a recently approved atypical antipsychotic that offers the advantages over existing typical antipsychotics of improved efficacy against negative symptoms and a decreased incidence of extrapyramidal side effects. However, risperidone is much more expensive than other antipsychotics. A drug use evaluation (DUE) was undertaken to assess the prescribing practices of risperidone in a large public adult psychiatric outpatient clinic. After a through literature review, criteria describing the appropriate prescribing of risperidone were approved after consultation with the medical staff. Criteria were developed to delineate appropriate patient selection, laboratory and clinical monitoring parameters, documentation, and outcome measures. After a chart review was conducted to evaluate existing prescribing practices, the criteria and results were presented to the medical staff and the appropriateness of the criteria were discussed. After 1 month, a second chart review was conducted to evaluate changes in prescribing practices in response to these criteria. Risperidone was prescribed to 44 patients in the outpatient clinic. Sixteen of these patients were resistant to treatment with traditional antipsychotics, 19 had developed intolerable extrapyramidal side effects during treatment with traditional antipsychotics, 10 had developed tardive dyskinesia, and 11 were noncompliant with other treatment regimens (some patients fell into more than one category). In 35 patients able to be evaluated for side effects, the most common were termed "activating side effects" and included restlessness, anxiety, insomnia, and unspecified activation. These side effects occurred in 9 patients. Another 5 patients developed extrapyramidal side effects and 3 patients developed a tremor. The initial chart review showed deficiencies in several areas, including laboratory and clinical monitoring and documentation. After presentation of these results to the staff, a second review was conducted; the results demonstrated improvements in many of the areas that were originally deficient. In conclusion, it was shown that the criteria developed had an overall positive impact on the appropriate prescribing of risperidone.
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PMID:Development and implementation of drug use evaluation (DUE) criteria for risperidone in an outpatient psychiatric setting. 899 94

Many nursing home residents are candidates for antipsychotic pharmacotherapy for dementia-related behavioral disturbances that include physical agitation and aggression, verbal outbursts, anxiety, and depression. These patients are often resistant to or intolerant of standard neuroleptics and are usually receiving multiple medications for concurrent psychiatric or medical conditions. New medications must be carefully considered because they may interact with concurrent medications or aggravate concurrent medical problems. Low doses of risperidone may be better tolerated in the elderly because the drug poses little risk of extrapyramidal side effects or blood disorders. One hundred and nine patients with dementia-related behavioral disturbances were studied in 9 nursing homes; most initially received 0.25 to 0.5 mg of risperidone twice daily. Their behavior was recorded for up to 6 months on questionnaires completed by a nursing staff member at each home. Risperidone was well tolerated overall and nursing staff viewed it as helpful in 38 of 100 patients, moderately helpful in 26, slightly helpful in 17, and not helpful in 19.
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PMID:Risperidone for dementia-related disturbed behavior in nursing home residents: a clinical experience. 919 80

Risperidone, a novel atypical neuroleptic agent, was used to treat a psychotic disorder secondary to ischemic brain damage in a 19-year-old adolescent, who had been treatment-refractory to two conventional antipsychotic agents and valproate. Clinically significant reductions in behavioral agitation and psychotic thinking initially appeared within the first 4 days of treatment with risperidone 3 mg twice daily. Risperidone was well tolerated despite this adolescent's severe cardiac and pulmonary illnesses. There was no evidence of increased neurotoxic symptoms in the presence of the ischemic brain damage. With its favorable side effect profile, risperidone may hold promise in the treatment of patients with psychotic disorders due to general medical conditions.
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PMID:Use of risperidone in psychotic disorder following ischemic brain damage. 923 1

A series of 14 children and adolescents (ages 9-17 years, 10 males) were treated with risperidone for pervasive developmental disorder. The rationale for using an atypical neuroleptic agent is based on its ability to target both positive and negative symptoms of schizophrenia. It was postulated that symptoms similar to the positive and negative symptoms of schizophrenia may be observed in the pervasive developmental disorders and might respond favorably to risperidone. Twelve of the 14 youths had been treated previously with several psychotropic drugs, often concurrently. Risperidone was initiated at a starting dose of 0.25 mg twice daily and increased in 0.25 mg/day increments every 5-7 days. Optimal dosages ranged from 0.75 to 1.5 mg daily in divided doses. Thirteen of the 14 youths appeared to benefit from risperidone. Improvement in functionality on the Children's Global Assessment Scale was demonstrated in 13 of 14 cases. Disruptive behaviors, when present, markedly decreased on risperidone. Ten patients showed a marked reduction in agitation and anxiety. Social awareness improved markedly in 10 patients, moderately in 3, and only slightly in 1. All but 1 patient demonstrated a lessening in obsessional behaviors. Effects on attention were uniformly positive. Side effects were minimal at the dosages used in this study; 5 patients had initial sedation. Neither extrapyramidal side effects nor agitation was observed in any case. Ten of 14 youths could be managed with risperidone monotherapy. During the follow-up period (mean 7 months), none of the patients experienced a major relapse while taking risperidone. Positive and negative symptoms, as typically characterized in schizophrenia, were both found to improve equally well with risperidone treatment. Based on these findings, a prospective clinical trial with a randomized controlled design is warranted.
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PMID:Use of risperidone in pervasive developmental disorders: a case series. 923 11

Open-label buspirone was studied in 25 prepubertal psychiatric inpatients (age 8.0 +/- 1.8 years, 76% boys) presenting with anxiety symptoms and moderately aggressive behavior. Patients with severe aggression, requiring rapid treatment with mood stabilizers or neuroleptics, were excluded. A 3-week titration (maximum 50 mg daily) preceded a 6-week maintenance phase at optimal dose. Buspirone was discontinued in 6 children (25%): 4 developed increased aggression and agitation, and 2 developed euphoric mania. For the 19 patients who completed the study, mean optimal dose was 28 mg daily. Among completers, depressive symptoms were reduced 52% by Week 6 on Children's Depression Inventory (p < or = 0.001). Decreased aggressivity was reflected in a 29% reduction on Measure of Aggression, Violence, and Rage in Children [MAVRIC] ratings (p < or = 0.02) and in 86% less time in seclusion or physical restraints (p < or = 0.02). Clinical Global Assessment scores improved (CGAS 41 vs. 54, p < or = 0.01). Only 3 children improved sufficiently to continue buspirone after the study. Residual aggressivity and global functioning remained problematic. Buspirone may pose behavioral risks in treating moderate aggressivity in 24% of children with anxiety; in the others, the therapeutic effects on aggression, anxiety, and depression were limited but significant.
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PMID:Buspirone treatment of psychiatrically hospitalized prepubertal children with symptoms of anxiety and moderately severe aggression. 946 32


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