Efficacy and tolerability of quetiapine in patients with schizophrenia who switched from haloperidol, olanzapine or risperidone

A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n = 43); olanzapine (n = 66); or risperidone (n = 55) monotherapy. Patients were initiated with quetiapine to 400 mg/day over 7 days, and then flexibly dosed (300-750 mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138) mg/day in the haloperidol subgroup, 472 (147) mg/day in the olanzapine subgroup and 485 (141) mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of -32.5, -15.4, and -18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p < 0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p < 0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p < 0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone.     

Quetiapine. A review of its use in the management of schizophrenia

Quetiapine (Seroquel), a dibenzothiazepine derivative, is an atypical antipsychotic with demonstrated efficacy in acute schizophrenia. In short-term, randomised, double-blind trials, it was usually more effective than placebo, and was generally effective against both positive and negative symptoms. Overall, quetiapine (up to 750 mg/day) was at least as effective as chlorpromazine (up to 750 mg/day) and had similar efficacy to haloperidol (up to 16 mg/day) in patients with acute schizophrenia in randomised, double-blind trials; it was at least as effective as haloperidol 20 mg/day in patients with schizophrenia unresponsive or partially responsive to previous antipsychotic treatment. Improvements in overall psychopathology and positive and negative symptoms with quetiapine (up to 800 mg/day) were similar to those with risperidone (up to 8 mg/day) or olanzapine (15 mg/day) [interim analysis]. Efficacy was maintained for at least 52 weeks in open-label follow-up studies in adult and elderly patients. Quetiapine improved cognitive function versus haloperidol, and depressive symptoms and hostility/aggression versus placebo. Quetiapine is well tolerated. It is associated with placebo-level incidence of extrapyramidal symptoms (EPS) across its entire dose range, appears to have a low risk for EPS in vulnerable patient groups (e.g. the elderly, adolescents or patients with organic brain disorders) and has a more favourable EPS profile than risperidone. Irrespective of dose, quetiapine, unlike risperidone and amisulpride, does not elevate plasma prolactin levels compared with placebo, and previously elevated levels may even normalise. Quetiapine appears to have minimal short-term effects on bodyweight and a favourable long-term bodyweight profile. Preliminary studies indicate that there is a high level of patient acceptability and satisfaction with quetiapine. In conclusion, quetiapine has shown efficacy against both positive and negative symptoms of schizophrenia, and has benefits in improving cognitive deficits, affective symptoms and aggression/hostility. The beneficial effects of quetiapine have been maintained for at least 52 weeks. Quetiapine was effective and well tolerated in hard-to-treat patients, and may be of particular use in these individuals. It is at least as effective as standard antipsychotics and appears to have similar efficacy to risperidone and olanzapine. The relative risk/benefit profile of quetiapine compared with other atypical antipsychotics requires further research in head-to-head trials, although quetiapine's relatively benign tolerability profile distinguishes it from other commonly used atypical agents, particularly with respect to bodyweight, EPS and plasma prolactin levels. Overall, quetiapine has an excellent risk/benefit profile and is a suitable first-line option for the treatment of schizophrenia.     

国产奎硫平与利培酮治疗老年人脑血管病所致精神障碍的对照研究

目的比较国产奎硫平和利培酮治疗老年人脑血管病所致精神障碍的疗效和安全性。方法将64例老年人脑血管病所致精神障碍随机分为国产奎硫平组和利培酮组,分别给予启维50~500mg.d-1及维思通1~4mg.d-1治疗,连续治疗6周。分别在治疗前进行PANSS量表评分,治疗后2、4、6周末进行PANSS评分及TESS评分,以评估二者疗效及不良反应。结果两组治疗老年人脑血管病所致精神障碍,有效率为71%和70%,两组疗效差异无统计学意义。两组治疗前后比较PANSS得分均有显著下降,差异有统计学意义。副反应：国产奎硫平副反应发生率35.5%,利培酮组副反应发生率48.5%,两组副反应均较轻微,利培酮组锥体外系反应、内分泌改变明显多于国产奎硫平组。结论两药对老年人脑血管病所致精神障碍均有肯定疗效,且疗效相当,安全性好,但因锥体外系及内分泌方面的副反应更少,故国产奎硫平较利培酮更适合老年人脑血管病所致精神障碍的治疗。     

喹硫平单药治疗伴强迫症状精神分裂症的开放性研究

目的:探讨喹硫平单药治疗伴强迫症状精神分裂症患者的疗效和安全性。方法:采用多中心、自身前后对照研究,选择58例符合ICD-10诊断标准的精神分裂症患者,接受可变剂量的喹硫平(思瑞康()治疗8周。疗效评定用耶鲁-布朗强迫症状量表(Y-BOCS)、阳性及阴性症状量表(PANSS)量表。安全性评价用不良事件和严重不良事件记录表等。结果:采用独立样本t检验、重复测量方差检验显示,完成治疗患者的Y-BOCS量表评分[(21.31±7.33)vs.(9.29±6.09),F=102.36,P<0.01]和PANSS量表评分[(88.47±16.39)vs.(52.92±14.92),F=134.98,P<0.01]在治疗前后均差异有统计学意义,两两比较发现Y-BOCS量表和PANSS量表评分,基线期、2周末、4周末、6周末和8周末之间均两两差异有统计学意义(均P<0.01)。8周末强迫症状的有效率为63.3%;精神病性症状有效率为65.3%。相关分析显示强迫症状在基线期与阳性因子呈弱相关(r=0.264,P<0.05),而治疗到6周末,与阳性因子(r=0.403,P<0.05)、阴性因子分(r=0.340,P<0.05)...     

Choosing an atypical antipsychotic

The atypical antipsychotics vary in terms of their pharmacological profiles, particularly in relation to their tolerability, effects on safety parameters and patient acceptability. Olanzapine, risperidone and ziprasidone are associated with extrapyramidal symptoms (EPS) in a dose-dependent manner, whereas quetiapine has been shown to produce a significantly lower incidence of substantial EPS effects than haloperidol, and less EPS requiring treatment than risperidone. Similarly, unlike risperidone and haloperidol, quetiapine treatment has been associated with a significant reduction in serum prolactin levels, and has normalized raised prolactin levels after discontinuation of previous treatment. Weight gain is also one of the major unwanted adverse effects of treatment with many antipsychotic drugs but, in contrast, quetiapine has demonstrated a neutral or 'normalizing' effect on body weight. In comparison with other antipsychotics, quetiapine has been shown to possess a favourable safety profile, with no requirement for routine blood, thyroid, or liver monitoring during treatment. Overall, quetiapine therapy has produced high levels of patient satisfaction and compliance and this, coupled with its efficacy in reducing psychoses of various origins, has made it an attractive treatment option in both patients at increased risk of EPS, and the general population.     

Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy

In this 6-week, open-label trial, combat veterans meeting DSM-IV criteria for posttraumatic stress disorder (PTSD) were treated with the atypical antipsychotic quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Primary outcome was measured using the Clinician Administered PTSD Scale (CAPS). Secondary assessments of efficacy included the Positive and Negative Symptom Scale (PANSS), the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Safety and tolerability evaluations included neurologic ratings, vital signs, and assessment of treatment-emergent side effects. Eighteen of 20 patients enrolled in the study completed 6 weeks of open-label treatment. The dose range of quetiapine was 25 to 300 mg daily, with an average of 100+/-70 mg/d. There was significant improvement in CAPS scores, from 89.8+/-15.7 to 67.5+/-21.0 (t=4.863, df=18, <0.005), and composite PANSS ratings from baseline to endpoint. General psychopathology (PANSS) and depressive symptoms (HRSD) were also reduced at the 6-week end point. There were no serious adverse events and no clinically significant changes in vital signs or neurologic ratings. This preliminary open trial suggests that quetiapine is well tolerated and may have efficacy in reducing PTSD symptoms in patients who have not had an adequate response other medications. Studies utilizing a randomized, controlled trial design and larger sample sizes are needed to better define the potential role of quetiapine and other atypical antipsychotics in the treatment of PTSD.     

喹硫平治疗精神分裂症伴抑郁症状的疗效

目的 :观察喹硫平治疗精神分裂症伴抑郁的疗效 ,并与利培酮作对照。方法 :对 5 2例精神分裂症伴抑郁病人分成喹硫平组与利培酮组 ,其中喹硫平组 2 7例 ,给予喹硫平 30 0～ 70 0mg·d- 1治疗。利培酮组 2 5例 ,给予利培酮 2～ 5mg·d- 1治疗。观察时间 6wk ,采用PANSS ,HAMD ,CGI等量表 ,分别于治疗前及治疗后wk 1,2 ,4 ,6末评定疗效 ,用TESS观察不良反应。结果 :经 6wk治疗后 ,喹硫平组与利培酮组疗效比较 ,经Ridit分析 ,差异无显著意义 (P >0 .0 5 )。但HAMD评分 ,喹硫平组治疗后减分率大于利培酮组 ,差异有非常显著意义 (P <0 .0 1)。结论 :喹硫平治疗精神分裂症伴抑郁与利培酮疗效相似 ,提示喹硫平除了具有抗精神病性症状作用外 ,还可能具有情感稳定的作用     

喹硫平治疗精神分裂症的随机、平行对照和多中心临床研究

目的 :评价喹硫平治疗精神分裂症的疗效及安全性。方法 :精神分裂症病人 12 5例 ,其中喹硫平组 6 5例 ,给喹硫平 30 0～ 6 0 0mg·d- 1治疗 ;利培酮组 6 0例 ,给利培酮 3～ 6mg·d- 1治疗。观察时间6wk。疗效评定用PANSS ,BPRS ,CGI。安全性评价用TESS等。结果 :经 6wk治疗后 ,喹硫平组总有效率为 80 % ,利培酮组为 88% ,2组相比P >0 .0 5;喹硫平组血清催乳素浓度为 399IU±s 4 50IU ,利培酮组为 1351IU± 76 3IU ,P <0 .0 1。喹硫平组不良反应有失眠 (9% )、ECG轻度异常 (8% )、兴奋或激越 (8% )等。喹硫平组静坐不能的发生率 (0 )显著低于利培酮组 (10 % )。结论 :喹硫平治疗精神分裂症疗效与利培酮相当 ,但对血清催乳素的影响小 ,锥体外系症状少     

Risperidone (Risperdal): clinical experience with a new antipsychosis drug

Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha- adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic effects. Early studies demonstrated risperidone to be an effective medication for psychotic symptoms, probably more so than the older neuroleptics for both positive and negative symptoms. At clinically effective doses, risperidone causes no more extrapyramidal side-effects (EPS) than placebo; at higher doses EPS frequency increases in a dose-dependent manner. Since it became available in 1994, extensive experience with the drug supports favourable early impressions of efficacy and tolerability. Minimal sedation, relatively little weight gain and absence of anticholinergic manifestations contribute to the relative tolerability of risperidone as compared to older neuroleptics. However, risperidone is associated with hyperprolactinaemia which can result in amenorrhoea and sexual dysfunction. Compared to older neuroleptics, pharmacoeconomic studies have shown that use of risperidone is associated with reduced hospitalisation and direct cost savings. A recent study found equivalent efficacy between risperidone and clozapine for treatment-resistant patients. Two studies comparing risperidone and olanzapine have yielded positive but conflicting findings. The overall positive experience with risperidone has resulted in the drug being widely recommended as a first line treatment option for psychoses.     

An analysis of safety and tolerability data from controlled, comparative studies of quetiapine in patients with schizophrenia, focusing on extrapyramidal symptoms

AIM: This analysis evaluated the tolerability profile of quetiapine using data from all comparative controlled studies in patients with schizophrenia or related disorders in the AstraZeneca clinical trials database, focusing on extrapyramidal symptoms (EPS). METHODS: Adverse event (AE) data from randomised, double-blind, controlled studies in the AstraZeneca clinical trials database were pooled, allowing comparison of quetiapine (mean daily doses 357-496 mg/day) with placebo, haloperidol (10.4 mg/day), risperidone (5.5 mg/day) or chlorpromazine (552 mg/day). Incidence of EPS-related AEs in relation to quetiapine dose was also analysed using a subset of data from fixed-dose studies. RESULTS: Data from 4956 patients were analysed. Quetiapine was well tolerated, and did not increase EPS-related AEs when compared with placebo (9.6 vs. 10.6%, respectively). The incidence of EPS-related AEs with quetiapine was consistent across the dose range (4.2-13.2% vs. 11.1% with placebo). Patients receiving haloperidol, risperidone and chlorpromazine experienced significantly higher levels of EPS-related AEs than those on quetiapine. The most common quetiapine- associated AEs, with significantly higher incidence than placebo, were sedation, somnolence and orthostatic hypotension. CONCLUSION: Quetiapine is generally well tolerated in patients with schizophrenia or related disorders, with placebo-level EPS-related AEs. Quetiapine has a more favourable EPS profile than haloperidol, chlorpromazine or risperidone.     

奎硫平与利培酮治疗女性首发精神分裂症疗效比较

目的比较利培酮与奎硫平治疗女性首发精神分裂症的疗效和不良反应。方法将80例符合CCMD一3诊断标准的精神分裂症按数字表法随机分为两组（奎硫平组和利培酮组各40例）,分别给予奎硫平（300—750mg／d）和利培酮（2～5mg／d）治疗8周。用阳性与阴性症状量表评定疗效,并观察两组不良反应发生情况。结果两组治疗2、4、8周阳性与阴性症状量表评分比较差异均无统计学意义（均P〉0．05）,奎硫平组和利培酮组治疗临床有效率分别为90．O％和87．5％,差异无统计学意义（P〉0．05）,利培酮组发生震颤、肌强直、静坐不能、月经改变及泌乳等不良反应发生率显著高于奎硫平组（均P〈0．05）。结论奎硫平与利培酮治疗女性首发精神分裂症的临床疗效相当,但奎硫平不良反应小。     

The efficacy and tolerability of once-daily extended release quetiapine fumarate in hospitalized patients with acute schizophrenia: a 6-week randomized, double-blind, placebo-controlled study

Objectives: This study aimed to demonstrate efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in patients with acute schizophrenia. Methods: In this 6-week, randomized, double-blind study (5077IL/0041) patients were randomized to receive quetiapine XR (300, 600, or 800 mg/day), quetiapine fumarate immediate release (quetiapine IR) [300 or 600 mg/day], or placebo. Primary endpoint was change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Day 42. Secondary variables included PANSS response rate at Day 42 (>/=30% decrease in PANSS total score from baseline) and Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures. Results: Of 532 patients randomized, 222 (41.7%) completed the study. Improvements in PANSS total scores from baseline to Day 42 across treatment groups were: quetiapine XR 300 mg/day -5.01, 600 mg/day -13.01 and 800 mg/day -11.17, quetiapine IR 300 mg/day -9.42 and 600 mg/day -6.97, and placebo -5.19; the difference in change was statistically significant only for quetiapine XR 600 mg/day (p = 0.033). There were no statistically significant differences between active treatment groups and placebo for PANSS response rates. Several post hoc analyses were conducted to explain the study efficacy outcome but these were inconclusive. Quetiapine XR was generally well tolerated with the majority of AEs being mild or moderate in intensity and no unexpected AEs. Conclusions: Superior efficacy of quetiapine XR versus placebo in patients with schizophrenia was demonstrated for quetiapine XR 600 mg/day. The safety and tolerability profile of quetiapine XR was similar to that of quetiapine IR.     

Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia

Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores, and several other measures of psychopathology and general functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale (SAS) compared between treatment groups. The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary Movement Scale (AIMS). The average mean daily doses were 3.8 mg (s.d.=1.5) for risperidone and 3.7 mg (s.d.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [SAS: risperidone 36.5% of patients; haloperidol 51.5% of patients; likelihood ratio test, chi2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%; haloperidol n=79, drop-out rate=54.1%, chi2(1)=7.1, p=0.009] and a longer non-discontinuation time [risperidone: average of 50.8 d to drop-out; haloperidol: average of 44.0 d to drop-out; log rank test, chi2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.     

Lack of impact of race on the efficacy and safety of long-acting risperidone versus placebo in patients with schizophrenia or schizoaffective disorder

This analysis aimed to assess the relationship between race and clinical response to long-acting, injectable risperidone treatment in patients with schizophrenia or schizoaffective disorder. In a 12-week, randomized, double-blind study, patients with schizophrenia or schizoaffective disorder received placebo or long-acting risperidone (25, 50 or 75 mg every 2 weeks). Data were stratified by race as identified by demographic information: Caucasian, African-American or Other. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS); movement disorders by the Extrapyramidal Symptom Rating Scale (ESRS); adverse events (AEs) were reported spontaneously. Data were available for 439 patients: 193 Caucasian (44%), 174 (40%) African-American and 72 (16%) Other patients. Baseline characteristics were similar between racial groups, as were study completion rates (overall: 30% placebo; 48% long-acting risperidone). There was a significant effect of treatment (P<0.001), but not of race, on improvement in PANSS total scores from baseline to endpoint. ESRS scores were low throughout the study, and no significant impact of race was observed. Overall rates of AEs were similar among the racial groups. Race did not appear to impact the efficacy and tolerability of long-acting risperidone.     

Tolerability of atypical antipsychotics.

Atypical antipsychotics are expected to be better tolerated than older antipsychotics because of their lower propensity to cause certain adverse effects. All atypical drugs have been shown to cause fewer acute extrapyramidal symptoms (EPS) than a standard typical agent (usually haloperidol) and some (clozapine, sertindole and quetiapine) appear to cause these effects no more often than placebo. In the longer term, clozapine, olanzapine and (less robustly) other atypical antipsychotics are thought to cause less tardive dyskinesia than typical antipsychotics. Problems caused by hyperprolactinaemia occur less often with some atypical antipsychotics than with typical drugs although risperidone and amisulpride appear to have no advantages in this respect. Other adverse effects may occur as frequently with some atypical antipsychotics as with some typical drugs. Clozapine, risperidone and quetiapine are known to cause postural hypotension; clozapine, olanzapine and quetiapine are clearly sedative; and anticholinergic effects are commonly seen with clozapine, and, much less frequently, with olanzapine. Some adverse effects are more frequent with atypical drugs. Idiosyncratic effects seem particularly troublesome with clozapine and, to a lesser extent, sertindole, olanzapine and zotepine. Bodyweight gain is probably more problematic with atypical antipsychotics than with typical drugs. Overall tolerability, as judged by withdrawals from therapy, is not clearly proven to be better with atypical drugs, although some individual trials do indicate an advantage with atypical agents. Differences in tolerability between individual atypical antipsychotics have not been clearly shown. The tolerability profile of atypical drugs certainly benefits from a lower incidence of acute EPS effects, along with less certain or less uniform benefits in symptomatic hyperprolactinaemia or tardive dyskinesia. Other, perhaps more trivial, adverse effects militate against their good tolerability, and effects such as bodyweight gain may severely reduce tolerability. Without clear advantages in tolerability in patient groups used in trials, drug choice in regard to adverse effects should continue to be on a patient to patient basis.     

A comparison of the effects of quetiapine ('seroquel') and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. PRIZE Study Group

Quetiapine ('Seroquel') is a well-tolerated, novel, atypical antipsychotic with consistent efficacy in the treatment of schizophrenia. To date, no clinical studies have evaluated the effect of quetiapine in patients who only partially respond to conventional antipsychotics, yet this type of patient is most frequently seen by psychiatrists. Therefore, this international, multicentre, double-blind study was conducted to compare the efficacy and tolerability of 8 weeks' treatment of quetiapine 600 mg/day with haloperidol 20 mg/day in 288 patients who had a history of partial response to conventional antipsychotics and displayed a partial or no response to 1 month of fluphenazine (20 mg/day) treatment. Patients on quetiapine tended to have greater improvement than those on haloperidol in the primary efficacy measure, mean Positive and Negative Symptom Scale (PANSS) score, after 4 weeks' treatment (-9.05, -5.82, respectively, P = 0.061) and at study end (-11.50, -8.87, respectively, P = 0.234). Similarly, there was a trend towards patients on quetiapine demonstrating greater improvements in the secondary efficacy measures (Clinical Global Impression, PANSS subscale and Brief Psychiatric Rating Scale scores) [week 4 (baseline) to week 12 (end)], but the difference between treatments did not reach significance. Significantly more patients on quetiapine than on haloperidol showed a clinical response-patient response rates, defined as > 20% reduction in PANSS total score between weeks 4 and 12, were 52.2% for quetiapine and 38.0% for haloperidol (P = 0.043). Patients receiving quetiapine required less anticholinergic medication (P < 0.011), had greater reduction in extrapyramidal symptoms (EPS) (P = 0.005) and fewer treatment-emergent EPS-related adverse events compared to those on haloperidol (P < 0.001). Serum prolactin concentrations were elevated at the end of fluphenazine treatment in 73% of patients. Between weeks 4 and 12, elevated serum prolactin concentrations significantly decreased in quetiapine-treated patients compared to those receiving haloperidol (P < 0.001). At the end of quetiapine treatment, 83% of patients had normal prolactin levels while only 21% of patients receiving haloperidol were within the normal range. These results suggest that quetiapine may make a valuable contribution to the management of patients with a history of partial response to conventional antipsychotics.     

The safety and tolerability of atypical antipsychotics in bipolar disorder

Atypical antipsychotics (aAPs), have become a first-line treatment option, both in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy in acute mania, some also in bipolar depression and in maintenance treatment. This provides reliable data on their safety and tolerability in this particular group of patients. This review focuses on the safety and tolerability of aAPs in the treatment of bipolar disorders. Both tolerability, for example, extrapyramidal symptoms, and safety issues, for example, occurrence of weight gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine, risperidone, ziprasidone and aripiprazole.     

The safety and tolerability of atypical antipsychotics in bipolar disorder

Atypical antipsychotics (aAPs), have become a first-line treatment option, both in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy in acute mania, some also in bipolar depression and in maintenance treatment. This provides reliable data on their safety and tolerability in this particular group of patients. This review focuses on the safety and tolerability of aAPs in the treatment of bipolar disorders. Both tolerability, for example, extrapyramidal symptoms, and safety issues, for example, occurrence of weight gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine, risperidone, ziprasidone and aripiprazole.     

A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.