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PubMed2005

Antipsychotic use in the elderly: shifting trends and increasing costs.

OBJECTIVE: The purpose of this study was to assess trends in utilization and costs of antipsychotic drugs among a population of older adults over time, with respect to the prevalence of users, shifts in prescribing patterns, and related financial implications. DESIGN: Cross-sectional time series of quarterly and annual antipsychotic utilization and cost were obtained from administrative databases for calendar years 1993 through 2002. SETTING AND PARTICIPANTS: A population-based study of more than 1.4 million residents of the province of Ontario aged 65 years or older. MEASUREMENTS: Data sources used included the Ontario Drug Benefits (ODB) database and Statistics Canada census data. RESULTS: The prevalence of antipsychotic users increased by 34.8% over the study period from 2.2% at the beginning of 1993 to 3.0% of the elderly at the end of 2002 (p < 0.01). This was associated with a 749% increase in total cost (from $3.7 million in 1993 to $31.4 million in 2002; p < 0.01). The atypical antipsychotics, which were not available in 1993, made up 82.5% of the antipsychotics dispensed and 95.2% of costs in 2002. CONCLUSIONS: The modest increase in antipsychotic prevalence in the elderly over the last ten years has been associated with a substantial increase in cost, with a significant shift towards use of the atypical antipsychotics. As the atypical antipsychotics are increasingly used for patients with dementia, which is becoming more prevalent in the aging population, an understanding of the benefits of these medications must be balanced with a detailed understanding of the material and financial implications.

Aged↗
PubMed2007

Quetiapine indication shift in the elderly: diagnosis and dosage in 208 psychogeriatric patients from 2000 to 2006.

RATIONALE: Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum. METHODS: Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed. RESULTS: Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly. DISCUSSION: Since the decision of the German Federal Court in 2002 'off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its 'off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect. CONCLUSION: In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians.

Aged↗
PubMed2006

Synergetic effects of quetiapine and venlafaxine in preventing the chronic restraint stress-induced decrease in cell proliferation and BDNF expression in rat hippocampus.

Clinical studies show better response rates of patients with depression and schizophrenia to combinations of atypical antipsychotics and antidepressants, compared to responses to either type of drugs alone. Animal studies demonstrate that some antipsychotics and antidepressants increase neurogenesis and BDNF expression in the hippocampus, which is reduced in volume in patients with depression or schizophrenia. We hypothesized that the better therapeutic effects of combined treatment seen in schizophrenia and depression patients are related to the additive or synergistic effects of combined treatment on hippocampal neurogenesis and BDNF expression. To test this hypothesis, we investigated the effects of chronic administration of quetiapine, venlafaxine, and their combination, on hippocampal cell proliferation and BDNF expression in rats, when subjected to chronic restraint stress (CRS) during the last 2 weeks of a 3-week drug administration period. We found (1) CRS decreased hippocampal cell proliferation and BDNF expression; (2) chronic administration of quetiapine or venlafaxine dose-dependently prevented these decreases in hippocampal cell proliferation and BDNF expression caused by CRS (6 h/day for 14 days); (3) the combination of lower doses of quetiapine (5 mg/kg) and venlafaxine (2.5 mg/kg) increased hippocampal cell proliferation and prevented BDNF decrease in stressed rats, whereas each of the drugs exerted mild or no effects; (4) individual higher doses of quetiapine (10 mg/kg) or venlafaxine (5 mg/kg) exerted effects comparable to those produced by their combination. These results support our hypothesis and can lead to future studies to develop new therapeutic approaches for treatment-resistant depression and the negative symptoms of schizophrenia.

Animals↗
PubMed2002

Pharmacotherapy of bipolar disorder: the role of atypical antipsychotics and experimental strategies.

Bipolar disorder, despite being a common and debilitating illness, has remarkably few pharmacological therapeutic options, the majority of which, with the exception of lithium, have been borrowed from other medical indications. Furthermore the quantity and quality of controlled clinical data are considerably smaller than in conditions of comparable severity and frequency. Not surprisingly, the clinical outcome of bipolar disorder is frequently suboptimal. Fortunately there are a growing number of novel therapeutic options for its treatment such as atypical antipsychotics, calcium channel blockers and omega-3 fatty acids. This paper summarizes some of the data regarding these "experimental" therapeutic options, focusing principally on atypical antipsychotics as these are now widely prescribed in the management of bipolar disorder.

Antipsychotic Agents↗
PubMed2004

Nizatidine for the treatment of patients with quetiapine-induced weight gain.

It has been reported that nizatidine may reduce weight gain in schizophrenic patients on olanzapine treatment. Leptin has been reported to be associated with antipsychotic-induced weight gain. Thus, the purpose of the study was to evaluate whether nizatidine might be useful for the treatment of quetiapine-induced weight gain. Among the patients on the quetiapine monotherapy, 47 participated in the study for the two and half months of the open-label screening period. However, 28 patients who gained considerable weight in this period entered the 8-week, double-blind and placebo-controlled phase. These patients were randomly divided into two groups; quetiapine plus nizatidine (group I) and quetiapine plus placebo (group II) for the 8-week double-blind phase. The patients were evaluated at the baseline and at week 8 with respect to the positive and negative syndrome scale, body mass index, weight and serum leptin levels. The mean weight and leptin levels exhibited modest increases in both groups for the open-label screening period. In the double-blind period, in group I, a minimal, but not statistically significant, decrease in weight was observed, with a mean of 1.0 +/- 0.6 kg. The weight increased in group II. The leptin levels decreased by a mean of 0.6 +/- 0.6 ng/ml in group I, and increased by 1.0 +/- 0.9 ng/ml in group II. At evaluation at week 8, a trend toward statistical significance in the mean serum leptin levels between groups was detected. The results suggest that nizatidine treatment may stop but not reduce the weight gain and is correlated with leptin levels in patients with schizophrenia on quetiapine treatment.

Adult↗
PubMed2003

Comparison of three antipsychotics in the emergency psychiatric setting.

In the present naturalistic study, the effectiveness and safety of quetiapine, risperidone and olanzapine were compared in the treatment of non selected acutely psychotic patients. It was observed that the rate of antipsychotic switch because of a lack of efficacy or side effects was higher in the quetiapine treated cases in comparison with the risperidone or olanzapine treated cases. The proportion of cases concomitantly treated with typical neuroleptics was significantly higher in the quetiapine group compared with the other two groups. In the outcome of non crossover cases, there were more improvements in the risperidone and olanzapine groups than in the quetiapine group. The results of this study suggest that quetiapine is not as efficacious as risperidone or olanzapine in the emergency psychiatric setting. Due to the methodological limitations of the study, these results must be considered preliminary and need confirmation.

Acute Disease↗
PubMed2003

EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects.

In this study the effects of the atypical antipsychotics quetiapine and olanzapine, and the typical antipsychotic haloperidol on EEG patterns were retrospectively investigated in 81 patients under stable monotherapy with either drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three subgroups were compared with a control group of healthy subjects (n=30) which were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM-IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There were no statistically significant differences regarding demographic characteristics between the groups. Digital EEG recordings were retrieved from a database and visually assessed by two independent investigators, and one blinded regarding medication. One patient from the quetiapine group (5%), 13 olanzapine patients (35%), five of the haloperidol patients (23%) and two subjects of the control group (7%) had an abnormal EEG. Epileptiform activity was observed in four patients (11%) of the olanzapine group, and none in the others. EEG abnormalities were statistically significantly increased with dose in the olanzapine group, in contrast to patients treated with haloperidol, quetiapine or healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in patients treated with quetiapine comparable to the control group, but significantly more often with haloperidol and olanzapine, possibly due to different receptor profiles of these substances. To our knowledge, this is the first electrophysiological investigation comparing the new atypical antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.

Adolescent↗
PubMed2004

Switching to quetiapine in patients with acute mania who were intolerant to risperidone.

This study evaluated the overall efficacy and tolerability of quetiapine in the treatment of inpatients with acute mania who are intolerant to risperidone in combination with a mood stabilizer. Eighteen patients completed this 3-week trial. The efficacy and tolerability was assessed upon admission, at baseline, and 1 and 3 weeks later. The Young mania rating scale (YMRS) and clinical global impression-severity (CGI-s) scores from the baseline to the endpoint, decreased by 39.8% and 40.0%, respectively. Fifteen (78.9%) and 18 (94.7%) patients exhibited at least a 50% improvement in the YMRS and CGI-s scores by the end of the trial. Measurements taken through the Barnes akathisia rating scale (BARS), the Simpson-Angus rating scale (SARS) and the drug attitude inventory shortened version-10 (DAI-10) also showed significant improvement. This study suggests that quetiapine may hold promise as an alternative regimen that does not worsen the psychopathology, particularly for those vulnerable to the side effects of drugs, including atypical agents such as risperidone, in naturalistic treatment settings.

Acute Disease↗
PubMed2004

A pilot trial of quetiapine for the treatment of patients with delirium.

Twenty-two Korean inpatients with delirium were administered prospectively a flexible dose of quetiapine. The delirium rating scale-revised-severity 98 (DRS-R-98) and clinical global impression scale-severity (CGI-s) scores were assessed at the time of pre- and post-treatment. The DRS-R-98 and CGI-s scores were significantly reduced by 57.3% and 55.1%, respectively. Quetiapine was effective and safe for the treatment of patients with delirium, and could be a useful alternative agent to classical antipsychotics in the treatment of delirium.

Aged↗
PubMed2004

Maintenance treatment for schizophrenia with quetiapine.

With the majority of current information being derived from short-term clinical trials, the impact of atypical antipsychotics during maintenance treatment of schizophrenia is of considerable interest, although only limited data are available at present. The present report is an analysis of data that are available up to 156 weeks after the start of an open-label extension (OLE) phase of three, double-blind randomized trials in quetiapine-treated patients who responded to an initial 6-week treatment period. The mean daily quetiapine dose (range 150-750 mg) was 439.5 mg for patients included in the brief psychiatric rating scale (BPRS) and 438.5 mg for patients included in the clinical global impression (CGI) analyses. The initial mean acute phase BPRS total score (40.67; n=258) and CGI severity of illness score (4.81; n=259) were reduced at the start of the OLE to 13.94 and 3.00, respectively. After 156 weeks, endpoint scores were 9.04 for BPRS and 2.43 for CGI severity of illness. Although limited by patient attrition, these OLE data suggest that an initial beneficial response with quetiapine treatment can be maintained over a long-term period.

Brief Psychiatric Rating Scale↗
PubMed2004

Combination of mood stabilizers with quetiapine for treatment of acute bipolar disorder: an open label study.

OBJECTIVES: The atypical antipsychotics are being increasingly used to control acute manic episodes, and data are emerging to support their mood-stabilizing and antidepressant properties. This study investigated the short-term efficacy of quetiapine as an add-on therapy in the treatment of acute mania. METHOD: This study was a 4-week, open-label, add-on, prospective investigation using quetiapine in addition to mood stabilizers. Data on 18 patients fulfilling DSM-IV diagnostic criteria for bipolar I disorder were analysed. The Young mania rating scale (YMRS), the Hamilton scale for depression (HDRS), the brief psychiatric rating scale (BPRS) and extrapyramidal symptom rating scale (ESRS) were applied at baseline and at weeks 1, 2 and 4. The clinical global impression scale (CGI) was evaluated at baseline and week 4. RESULTS: The addition of quetiapine produced a statistically significant improvement on the YMRS, HDRS, BPRS and CGI score at week 4 from baseline (p<0.005). Quetiapine was well tolerated, with no subjects discontinuing because of side effects. CONCLUSIONS: The combination of quetiapine was associated with a substantial symptomatic improvement in patients with acute mania. Randomized placebo-controlled prospective studies are needed.

Adult↗
PubMed2004

Quetiapine has a direct effect on the negative symptoms of schizophrenia.

Second-generation 'atypical' antipsychotics appear to be more effective than first-generation 'typical' antipsychotics in improving negative symptoms in schizophrenia; it is unclear, however, if this greater improvement represents a direct beneficial effect or is mediated indirectly by an antidepressant effect or the absence of extrapyramidal symptoms (EPS). To address this issue with reference to quetiapine ('Seroquel'), data were evaluated from four randomized, controlled clinical studies involving 1106 patients employing a path analysis model. The total effect of quetiapine on negative symptoms was measured using the Scale for Assessment of Negative Symptoms (SANS) total score. Indirect effects on negative symptoms via positive, depressive and EPS were assessed using appropriate instruments. Effect sizes were calculated by path analysis for the difference between treatment groups in change from baseline to endpoint in SANS total score. Analysis confirmed that quetiapine produced a greater overall improvement in negative symptoms than placebo (effect size 1.96); this was explained by a significant direct effect (p = 0.001; 44.2% of total improvement), and a secondary effect of improved positive symptoms (p < 0.001; 47.5% of total improvement), but was not a consequence of changes in depressive symptoms or EPS. Within the constraints of the path analysis methodology, these results indicate that quetiapine has a substantial direct effect on improving the negative symptoms of schizophrenia.

Antipsychotic Agents↗
PubMed2005

The effect of quetiapine on aggression and hostility in patients with schizophrenia.

A post hoc analysis of data from three placebo-controlled, double-blind, randomized trials was carried out to determine the efficacy of quetiapine in aggression and hostility in patients with schizophrenia. Quetiapine treatment induced statistically significantly greater improvements in BPRS positive symptom cluster scores and three measures of hostility derived from the BPRS, compared with placebo, in patients symptomatic at baseline. A path analysis showed that the improvements in hostility were highly correlated with improvements in positive symptoms and there was no consistent relationship between sedation and hostility. Aggressive behaviour appears to be related to positive symptoms of schizophrenia. Quetiapine may be a suitable option for patients with schizophrenia and aggressive behaviour.

Adult↗
PubMed2005

Mood stabilization in the treatment of bipolar disorder: focus on quetiapine.

The use of at least one mood-stabilizing agent is common clinical practice in the treatment of bipolar disorder, regardless of the treatment setting or disease phase. However, a consensus definition of 'mood stabilizer' remains to be established. A mood stabilizer has been operationally described as an agent that is useful in at least one phase of bipolar disorder while not worsening any other phase of the illness. More stringent definitions have been proposed, and it can be argued that a clinically effective mood stabilizer would have efficacy in a broad range of affective, psychotic, behavioral and cognitive domains in all phases of bipolar disorder and would be well tolerated across a range of doses for sustained periods. Clinically effective mood stabilizers should treat mania and depression, while preventing recurrence and improving quality of life. Effective treatment should not precipitate mania, depression, or rapid cycling, and should minimize the burden of treatment-emergent side effects. Data from clinical studies of quetiapine are reviewed in context with the literature discussing traditional and emerging mood stabilizers. Using a liberal definition, the evidence for quetiapine qualifies it as a bimodal mood stabilizer based on its demonstrated effectiveness in the treatment of bipolar mania and depression. Further data suggest that quetiapine has promise across all phases of bipolar disorder with the potential to meet even the most stringent definitions of a mood stabilizer.

Affect↗