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Sir: The rabbit syndrome is a distinct antipsychotic-induced extrapyramidal syndrome, described by Villeneuve as the rapid, rhythmic involuntary movements of the oral and masticatory muscles except for the tongue, with a frequency of about 5.0 Hz. It is often misdiagnosed as tardive dyskinesia because it appears late in antipsychotic therapy and involves the buccalmasticatory muscle group.
Background: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia.
Method: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGIC) scales.
Results: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean ± SE dose of risperidone was 0.95 ± 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p < .001). A similar improvement was also seen for the CMAI total non-aggression subscale (p < .002) and for the BEHAVE-AD total (p < .001) and psychotic symptoms subscale (p = .004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p < .001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups.
Conclusion: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.
Background: Patients with chronic schizophrenia (DSM-IV criteria) often receive depot antipsychotic medications to assure longer administration and better compliance with their treatment regimen. This study evaluated whether patients stabilized on depot antipsychotic medication could be successfully transitioned to oral olanzapine.
Method: In a 3-month open-label study, 26 clinically stable patients with schizophrenia taking depot antipsychotics for over 3 years were randomly assigned to continue on their current depot dose or to switch to oral olanzapine. Clinical ratings (Positive and Negative Syndrome Scale [PANSS], Global Assessment of Functioning [GAF] scale, and Clinical Global Impressions [CGI] scale) and side effect parameters (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Scale, AMDP-5 scale, vital signs, and weight) were obtained monthly.
Results: Oral olanzapine patients (N = 13) demonstrated significant clinical improvement over the depot control group (N = 13) from baseline to 3-month endpoint (PANSS total, p = .012; PANSS general, p = .068; PANSS negative, p = .098; CGI-Improvement, p = .007; CGI-Severity, p = .026; GAF, p = .015). Side effect rating scales showed no statistical differences between the 2 groups (AIMS, Barnes Akathisia Scale, AMDP-5, vital signs). The depot control group showed no statistical superiority in any measure except weight change (p = .0005). After 3 months, all olanzapine patients preferred olanzapine to their previous depot medications and chose to continue on olanzapine treatment.
Conclusion: Clinicians may expect clinical improvement when switching chronically psychotic patients from traditional depot antipsychotic drugs to oral olanzapine. Switching may be completed within a 4-week period with relative compliance being maintained and patients preferring oral olanzapine to their previous depot medications.
Background: Clozapine is indicated for the treatment of resistant schizophrenia, which is usually defined as failure to respond to adequate trials of 2 antipsychotics. It is thought that only clozapine is likely to be effective in such cases and that other drugs are ineffective. We sought to discover prior patterns of antipsychotic prescribing in schizophrenic patients eventually prescribed clozapine.
Method: Prescribing histories were obtained from prescription charts and case notes for all inpatients prescribed clozapine in 4 hospitals in southeast London during April 2001.
Results: 120 patients were identified, of whom 112 had been diagnosed with schizophrenia or schizoaffective disorder and whose data were analyzed. The mean duration of illness was 15.1 years. Subjects had experienced a mean of 9.2 (range, 2-35) episodes of antipsychotic prescription before clozapine was first used, with 5.7 (range, 0-25) episodes constituting adequate trials (drug used at therapeutic dose for 6 weeks). The mean number of different antipsychotics used was 5.5 (range, 1-13), with a mean of 4.0 (range, 0-12) given an adequate trial. Ninety percent of patients (N=101) had received an atypical antipsychotic before first use of clozapine, and 65% (N=73) had previously received antipsychotic polypharmacy. The mean maximum theoretical delay in using clozapine was 5.0 years (range, 0-11.1 years). Longer delay was significantly (p < .05) associated with being aged over 30 years at the time of the study, being diagnosed with psychotic illness before the introduction of clozapine, and completing adequate trials of 2 different antipsychotics before the introduction of clozapine or risperidone.
Conclusion: Clozapine treatment was quite likely delayed for longer than is clinically desirable. This delay may have important effects on quality of life, clinical outcome, and health resource utilization.
Letter to the Editor
Sir: Antipsychotic agents are the most effective pharmacologic treatment for tic disorders. However, tic-like symptoms, including motor and vocal variants, have been reported for patients treated with clozapine. We present a case in which a simple motor tic-like symptom emerged during quetiapine treatment.
Sir: Quetiapine is a relatively new third-generation antipsychotic with a labeled dose range of 400 to 800 mg/day. Quetiapine has demonstrated efficacy in the management of patients with a history of partial response to conventional antipsychotics. We report the case of a schizophrenic woman who achieved full clinical remission without significant side effects with a high dose of quetiapine (1600 mg/day). To our knowledge, evidence from daily clinical practice or controlled clinical trials has never been published on high doses of this new antipsychotic.
Background: It has been suggested that transiently high dopamine-2 (D2) receptor occupancy by antipsychotic medication may be sufficient for inducing an antipsychotic response. We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D2 receptor blockade, to determine if this would lead to an antipsychotic response.
Method: Fourteen patients with a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were treated with quetiapine titrated to a single daily dose (mean ± SD dose at the time of the positron emission tomography [PET] scan = 427 ± 69 mg) for 12 weeks. Peak D2 occupancy approximately 2 hours postdose and trough D2 occupancy approximately 20 hours postdose were determined using PET and [11C]raclopride. Clinical symptoms and side effects were measured at baseline and every 2 weeks during the treatment phase.
Results: Quetiapine administration led to a mean peak D2 occupancy of 62% ± 10% 2 hours postdose, which declined to 14% ± 8% approximately 20 hours postdose. Ten (71%) of 14 patients responded to treatment with quetiapine, scoring "much improved" or greater on the Clinical Global Impressions-Improvement scale. Plasma drug levels and peak D2 occupancy were highly correlated (r = 0.84; p = .003), as were prolactin and plasma drug levels when measured 2.5 hours after drug administration (r = 0.60; p < .05). Mean weight gain for the 10 subjects who completed the 12-week study was 4.2 ± 4.6 kg (9.3 ± 10.2 lb). No clinically relevant motor side effects occurred during the trial.
Conclusion: Patients with a first episode of schizophrenia responded to treatment with a single daily dose of quetiapine despite only transiently high D2 receptor occupancy. Our findings raise the question of whether continuously high D2 blockade is necessary for obtaining an antipsychotic response. Future studies aimed at evaluating the relative merits of "transiently high" versus "continuously high" D2 occupancy are warranted.
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