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G Remington

Publications and source records attributed to G Remington.

At least 19 recordsLinked to original sources
PubMed2004

Healthcare resource utilization during 1-year treatment with long-acting, injectable risperidone.

BACKGROUND: Schizophrenia is associated with disproportionately high costs, mainly due to hospitalization rates. This study assessed healthcare resource use in patients with schizophrenia and schizoaffective disorder during treatment with long-acting risperidone. METHODS: Patients (n = 397 [inpatients, 24%; outpatients, 76%]) receiving stable doses of an antipsychotic for >or=4 weeks were eligible to enter this 1-year, open-label study. Following a 2-week run-in period (oral risperidone 1-6 mg/day), patients received intramuscular long-acting risperidone (25 or 50 mg modal dose) every 2 weeks. Healthcare resource use in the previous 12 weeks was assessed at baseline and 12-weekly intervals. RESULTS: Patients needing hospitalization decreased significantly and continuously from 38% during the 12 weeks before study entry to 12% during the last 12 weeks. Mean hospitalization length during the study was 30.5 days (outpatients, 4.9 days; inpatients, 110 days). This included 28 patients (7%) who remained in hospital throughout the study. During treatment, 71% of those hospitalized at baseline were discharged. Partial hospitalization decreased significantly from 7% of patients during the 12 weeks before treatment to 3% during the last 12 weeks. Outpatient consultations also decreased significantly from 70% of patients to 30% in the first 12 weeks of treatment and remained stable thereafter. Only 9% of patients required an emergency room visit; mostly for non-psychiatric conditions. CONCLUSION: Healthcare resource use is significantly reduced in patients with stable schizophrenia or schizoaffective disorder receiving long-acting risperidone. It is highly likely that these reductions will decrease healthcare costs in patients receiving long-acting risperidone.

Adult↗
PubMed2003

Clinical characteristics and associated factors in antipsychotic-induced akathisia of Asian patients with schizophrenia.

OBJECTIVE: We studied the prevalence of akathisia and its relationship to a number of sociodemographic and clinical factors in a population of Chinese inpatients with Schizophrenia. METHOD: Six-hundred and forty-five patients were recruited for the study. Akathisia was assessed using the Barnes Akathisia Rating Scale (BARS), dyskinesia by the Abnormal Involuntary Movement Scale (AIMS) and extrapyramidal side effects (EPSE) were assessed by the Simpson-Angus Rating Scale (SARS). RESULTS: Only 35 (5%) patients were assessed to have akathisia. There was no gender or ethnic difference in the rates of akathisia. However, the majority of the patients (65%) were receiving an anticholinergic agent at the time of the study. CONCLUSION: Our findings of an overlap between TD and EPSE support the suggestion that there may be a common vulnerability for these movement disorders. The finding of a low rate of akathisia among our Asian patients suggests an inter-ethnic difference in the vulnerability for the development of akathisia. However, comparing our results with the rates reported from other countries may be hampered by the diagnostic and methodological differences across studies.

Akathisia, Drug-Induced↗
PubMed2002

Significant dissociation of brain and plasma kinetics with antipsychotics.

Current dosing regimens of psychotropic drugs are based on plasma kinetic considerations, although it is unclear whether plasma levels faithfully reflect brain kinetics of drugs.(1,2) To examine this, we compared the kinetics of plasma levels of two widely used antipsychotics, olanzapine and risperidone, vs the time course of their effects in the brain. We used positron emission tomography (PET) and [(11)C]-labeled ligands to quantify striatal and extra-striatal dopamine-2 (D(2)), and cortical serotonin-2A (5-HT(2A)) receptor occupancy in healthy subjects after a single dose, and in patients chronically treated for psychosis. We found a significant dissociation of brain and plasma kinetics. Mean plasma elimination half-lives of single doses of olanzapine and risperidone were 24.2 and 10.3 h, respectively, whereas it took on average 75.2 h with olanzapine, and 66.6 h with risperidone to decline to 50% of their peak striatal D(2) receptor occupancy. We found similar discrepancies between the time course of plasma levels and extra-striatal D(2) as well as 5-HT(2A) receptor occupancy. Our results question the current reliance on plasma kinetics as the main basis for dosing regimens of antipsychotics. Studies of brain kinetics may provide a sounder basis for determining dosing schedules of psychotropic medications.

Adult↗
PubMed2001

Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient.

"Atypical" antipsychotics are associated with a much lower propensity for extrapyramidal side effects and, with some exceptions, a lack of sustained prolactin elevation. The authors propose that a low-affinity and fast dissociation (in molecular terms) from the dopamine D(2) receptor, along with administration of the drug in doses that lead to appropriate levels of dopamine D(2) receptor blockade, are the most important requirements for atypicality. Actions at other receptors (5-HT(2), D(4), etc.) may not be necessary to achieve atypicality, and while action at these receptors may have benefits on symptoms such as mood and cognition, this is as yet to be conclusively proven. Why clozapine is effective in refractory patients is still elusive and efforts to make antipsychotics that are devoid of effects on the dopamine D(2) receptors so far have been unsuccessful. In light of this, the authors provide a heuristic model linking pathophysiology and therapeutics and suggest that the ideal treatment for schizophrenia is unlikely to be single-drug with multireceptor blockade (a sort of one-size-fits-all polypharmacy) but will require several specific and targeted treatment strategies that are titrated to match the variable expression of different dimensions of schizophrenia in each patient.

Amisulpride↗
PubMed2001

Health care utilization in patients with schizophrenia maintained on atypical versus conventional antipsychotics.

1. Patients with schizophrenia who had been stabilized on their antipsychotic medication and subsequently maintained on it for a period of at least 18 months were identified: clozapine (N=15); risperidone (N=15); depot conventional (N=18); oral conventional (N=18). 2. Groups were compared on a clinical measure as well as the use of various health care services: hospitalizations; days in hospital, emergency room visits; physician and non-physician visits. 3. No differences between groups were found for hospitalizations, days in hospital, or emergency room visits, while physician and non-physician visits were highest in the clozapine group, in keeping with the need for routine hematologic monitoring in this population. The clozapine group had the highest baseline clinical scores and greatest number of previous hospitalizations. These treatment groups may reflect different clinical populations. However, the findings suggest that in drawing conclusions regarding long-term benefits of different agents, clinical or economic, it would prove useful to include in the evaluation a comparison of patients who have been stabilized on each of the treatments.

Administration, Oral↗
PubMed2001

Awareness of tardive dyskinesia in Asian patients with schizophrenia.

While ethnocultural differences in risk of tardive dyskinesia (TD) have been suggested, no previous studies have examined whether this factor also plays a role in lack of awareness of TD. This study examined this question in an Asian population with schizophrenia. Six hundred seven patients in a state mental hospital in Singapore were assessed using the Abnormal Involuntary Movement Scale (AIMS) and the Simpson-Angus Rating Scale. Of the 607 patients, 242 (39.9%) met criteria for TD, and 163 (67.4%) patients were not aware of the presence of TD. No significant differences in terms of age, gender, and duration of illness were found between those aware of their TD and those not aware. Daily neuroleptic doses and scores for the AIMS and Simpson-Angus Rating Scale were significantly different, although after logistic regression, only the Simpson-Angus Rating Scale scores remained significant. The finding that a large proportion of our patients lacked awareness of their TD is consistent with other reports in the West and provides evidence that this feature is characteristic of the illness rather than of a specific ethnocultural group. We found an association between lack of awareness and greater severity of extrapyramidal symptoms (EPS), suggesting that there may be a subtype of TD in which lack of awareness and greater vulnerability of developing EPS are features.

Adult↗
PubMed2001

Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study.

Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.

Adolescent↗
PubMed2001

Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia.

"Atypical" antipsychotics represent a new generation of antipsychotics with a significantly lower incidence of extrapyramidal side effects (EPS), as well as little or no effect on prolactin elevation. These advantages constitute a major improvement in the treatment of patients with schizophrenia. The exact mechanisms that make these drugs atypical is not clear. However, a preferential action on serotonin 5-HT2 or D4 receptors, or a more rapid dissociation from the dopamine D2 receptor, may account for atypicality. Although the atypical antipsychotics have overcome EPS, other side effects such as weight gain and impaired glucose tolerance/lipid abnormalities have come to the fore. Thus, the challenges are far from over. The current atypicals are much more effective against the psychosis of schizophrenia than against the other, more enduring aspects of this disorder, e.g. negative symptoms and cognitive dysfunction. At present, the atypicals use a "pharmacological shotgun" strategy to treat aspects of the disease in all patients. A more sophisticated and perhaps effective approach to schizophrenia may lie in independently targeting the pathophysiological mechanisms of each clinical dimension (i.e. positive, negative, cognitive, and affective) with more selective drugs that can be combined and individually titrated to the needs of each patient.

Amisulpride↗
PubMed2001

Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine.

OBJECTIVE: The authors added haloperidol, a potent D(2) blocker, to ongoing treatment with clozapine in patients with schizophrenia to determine the effects of this combination on dopamine D(2) receptor blockade, prolactin level, and extrapyramidal side effects. METHOD: At baseline and 4-8 weeks after the addition of haloperidol (4 mg/day) to ongoing clozapine treatment, five patients were examined for prolactin elevation, extrapyramidal side effects, drug plasma levels, and D(2) receptor occupancy measured with [(11)C]raclopride and positron emission tomography imaging. RESULTS: Adding haloperidol significantly increased D(2) receptor occupancy, from a mean of 55% to 79%, and significantly increased the prolactin level. One patient developed akathisia, and another manifested mild extrapyramidal side effects. CONCLUSIONS: Adding a modest dose of haloperidol to clozapine results in the high D(2) receptor occupancy and sustained prolactin elevation usually associated with typical antipsychotics. These findings suggest that the lack of prolactin elevation associated with clozapine derives mainly from low D(2) receptor occupancy and not from the medication's effects on other receptors.

Adult↗
PubMed2001

A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.

OBJECTIVE: This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response. METHOD: Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study. RESULTS: The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group. CONCLUSIONS: Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.

Adolescent↗
PubMed2001

Antipsychotic dosing patterns for schizophrenia in three treatment settings.

Daily dosages of antipsychotic medications were evaluated to determine whether current guidelines advocating lower dosing are being followed. A chart review of 163 outpatients with schizophrenia was undertaken in three outpatient hospital settings-a general community hospital, a provincial hospital, and an academic teaching hospital. The daily dosage in chlorpromazine equivalents was significantly higher in the provincial hospital (773.8 mg) than in the community hospital (355 mg) or the academic hospital (424.8 mg). A greater proportion of patients at the provincial hospital received conventional antipsychotics than novel antipsychotics or depot antipsychotics, and a greater proportion received more than one antipsychotic.

Adult↗
PubMed2001

SB-277011 GlaxoSmithKline.

It is presumed that GlaxoSmithKline has taken over from SmithKline Beecham in investigating the highly selective dopamine D3 antagonist SB-277011 and its analogs for the potential treatment of schizophrenia [284490] following the merger of Glaxo Wellcome and SmithKline Beecham in December 2000 [394715]. In June 2000, it was reported that novel 2,3,4,5-tetrahydro-1H-benzazepines and 2,3-dihydro-1H-isoindoles, including SB-277011, had shown high affinity and selectivity for the dopamine D3 receptor. All compounds were suggested to have further potential roles in the treatment of drug abuse and psychosis [372205]. In November 2000, data presented at the 30th Neuroscience meeting in New Orleans, LA, demonstrated that D3 receptor blockade with SB-277011 specifically altered neurochemical effects in the nucleus accumbens without the non-selective effects, such as catalepsy, seen with some other antagonists [390460].

Animals↗
PubMed2000

A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy.

BACKGROUND: Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile. METHODS: Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. After 3 weeks of treatment, D2 and 5-HT2a occupancy were measured using positron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were included to examine the effects of the drug 2 to 3 hours after last dose. RESULTS: Quetiapine was an effective antipsychotic and improved the extrapyramidal symptoms and prolactin level elevation noted at baseline. It achieved these results with minimal (0%-27%) D2 occupancy 12 hours after the last dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours. CONCLUSIONS: Quetiapine shows a transiently high D2 occupancy, which decreases to very low levels by the end of the dosing interval. Quetiapine's low D2 occupancy can explain its freedom from extrapyramidal symptoms and prolactin level elevation. The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect. Future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.

Adult↗
PubMed2000

Atypical antipsychotics: are some more atypical than others?

On the heels of clozapine, we now have a number of newer agents (risperidone, olanzapine, quetiapine, sertindole, and ziprasidone). Are they all the same? What are the differences? How do we best understand them? In this article we review current clinical evidence to compare these issues on four measures of atypicality: EPS, prolactin elevation, superior efficacy in refractory/positive symptoms and efficacy against negative symptoms. All the newer agents are superior on EPS and, with the exception of risperidone, avoid prolactin elevation. Clozapine shows the most convincing efficacy in refractory schizophrenia, although comparative data concerning risperidone's benefit in this respect are also emerging. It is unclear, however, whether any of the agents produce a greater effect than conventional antipsychotics against positive symptoms in responsive patients. Both clozapine and olanzapine have demonstrated superior efficacy against negative symptoms, although it remains controversial whether this is an effect on primary or secondary symptoms. The precise pharmacologic mechanisms underlying "atypicality" remain unclear, but several conceptual frameworks are highlighted that characterize, and perhaps differentiate, these newer agents.

Antipsychotic Agents↗
PubMed2000

Predicting haloperidol occupancy of central dopamine D2 receptors from plasma levels.

Positron emission tomography (PET) is increasingly being used to study dopamine receptor occupancy and the clinical effects of antipsychotic medication. Dopamine D2 receptor occupancy has been shown to predict several clinical effects of antipsychotic medication including therapeutic response, motor and endocrine side-effects. Plasma levels may be used as a surrogate marker for central occupancy if the relationship between these two measures may be accurately described. This study was designed to test the capacity of a previously derived relationship equation (%D2 occupancy=plasma level/ED50+plasma level, where ED50= 0.40 ng/ml) to predict striatal D2 occupancy from plasma level. Twenty-one patients receiving treatment with low dose haloperidol underwent a 11C-raclopride PET scan to measure D2 occupancy. The D2 occupancy levels were accurately predicted by use of the previously generated equation with only a small degree of error (3.89% CI 0.45-7.33). Predicted and measured D2 occupancy values correlated closely (Pearson's r=0.864, P=0.003). The study indicates that reliable prediction of D2 occupancy from plasma levels is possible. This provides a potentially useful surrogate measure of D2 occupancy for research and possibly clinical practice, as the routine use of PET to measure occupancy levels is not feasible.

Adult↗
PubMed2000

Instrumentally detected changes in motor functioning in patients with low levels of antipsychotic dopamine D2 blockade.

Extrapyramidal side-effects (EPSE) of antipsychotic medication are related to the occupancy of dopamine D2 receptors and there appears to be a threshold of D2 occupancy below which clinically EPSE are unlikely to occur. It is unclear whether there are motor changes produced by 'subthreshold' levels of D2 occupancy that are not detectable by clinical examination. This study was designed to investigate whether a number of electromechanical instrumental techniques could detect 'subthreshold' motor changes and whether these changes correlate with dopamine D2 occupancy as measured by [11C]-raclopride PET scan. Twenty medication naïve patients were studied before and during treatment with low dose haloperidol. Instrumental techniques detected an asymmetrical worsening in motor function with drug treatment despite the failure of the group to experience significant EPSE. These changes did not correlate with D2 occupancy and measurements of rigidity, tremor, and bradykinesia did not closely inter-correlate.

Adult↗