Treatment of the symptoms of schizophrenia: a combined analysis of double-blind studies comparing risperidone with haloperidol and other antipsychotic agents

Combined data on efficacy were available from 12 double-blind short-term (maximum 8 weeks) trials comparing risperidone and other antipsychotics in patients with chronic schizophrenia. Patients received risperidone (n = 1056) or other antipsychotics (n = 703). Haloperidol (n = 473) was the most frequently prescribed other antipsychotic. Efficacy assessments include the Positive and Negative Syndrome Scale (PANSS) total, subscale (positive symptoms, negative symptoms and general psychopathology), cluster (cognitive and affective symptoms) and item (anxiety and hostility) scores. At endpoint, the mean decrease from baseline in PANSS total scores was significantly greater for patients receiving risperidone (-20.9) than other antipsychotics (-16.2; P < 0.001), or the subset receiving haloperidol (-14.3; P < 0.001). Risperidone-treated patients showed a significantly greater decrease in the positive (P < 0.01), negative (P < 0.05) and general psychopathology (P < 0.001) scores than patients receiving other antipsychotics or haloperidol. Scores for cognition, affective symptoms, anxiety and hostility each improved significantly (P < 0.05) more for patients receiving risperidone than those receiving other antipsychotics or haloperidol. Efficacy data on patients with an acute exacerbation were available from seven trials (risperidone n = 372, other antipsychotics n = 285, including haloperidol n = 120). At endpoint, the mean decrease from baseline in PANSS total scores was significantly greater for patients receiving risperidone (-24.7) than other antipsychotics (-19.8, P < 0.01) including haloperidol (-19.8, P < 0.05). Risperidone-treated patients also showed a greater decrease in positive symptom scores (-7.8) than those receiving other antipsychotics (-6.3; P < 0.01) or haloperidol (-7.1). A > or = 20% reduction in PANSS total score with risperidone, haloperidol and other antipsychotics was achieved by 65.9%, 54.3% and 54.9%, respectively; a > or = 30% PANSS reduction by 54.0%, 46.6% and 46.5% of patients, respectively; and a > or = 40% reduction by 43.8%, 33.7% and 34.4% of patients, respectively. These findings are consistent with earlier findings that show risperidone is more efficacious than haloperidol for reducing the symptoms of schizophrenia.     

Differential effect of quetiapine on depressive symptoms in patients with partially responsive schizophrenia

While atypical antipsychotics appear to be effective in reducing depressive symptoms in the acute phase of schizophrenia, little is known about their efficacy in patients with ongoing symptoms. The present study assessed whether quetiapine (Seroquel) is more effective than haloperidol in treating depressive symptoms in patients with persistent positive symptoms, and investigated whether this effect is independent, or secondary to, reductions in other symptoms such as positive, negative or extrapyramidal symptoms. Patients with schizophrenia and a history of partial refractoriness to conventional antipsychotics who had not responded to 4 weeks of fluphenazine treatment (20 mg/day) were randomized to receive either quetiapine (600 mg/day) or haloperidol (20 mg/day) for a further 8 weeks. Change in the Positive and Negative Syndrome Scale depression factor score from baseline to endpoint was calculated and path analyses were performed on data from 269 patients. Quetiapine produced a greater reduction in depressive scores than haloperidol (-1.60 versus -0.54; p = 0.006). The path analyses indicated that this was a direct effect on depressive symptoms. These findings extend the evidence for an antidepressant effect for the novel antipsychotics in schizophrenia, and suggest that this is not limited to acutely psychotic patients.     

帕利哌酮缓释片与喹硫平治疗精神分裂症的对照研究

目的探讨帕利哌酮缓释片治疗精神分裂症的疗效及安全性。方法将67例精神分裂症患者随机分为帕利哌酮组(34例)和喹硫平组(33例),疗程8周,在治疗前及治疗后2,4,6,8周时采用阳性及阴性症状量表(PANSS)、治疗中出现的症状量表(TESS)评定疗效和不良反应。并于治疗前、中、后检测泌乳素水平。结果治疗结束时,帕利哌酮组显效率62%,有效率88%;喹硫平组显效率64%,有效率85%,两组间的疗效差异无显著性(P>0.05)。两组PANSS总分和各因子分均较治疗前明显下降(P<0.01),帕利哌酮组在第二周末的评分明显低于喹硫平组(P<0.05),余时点组间比较差异无显著性(P>0.05)。不良反应总体发生率两组间差异无显著性(P>0.05)。帕利哌酮组催乳素水平明显升高,喹硫平组则无影响,二组间比较有显著性差异(P<0.01)。结论帕利哌酮缓释片对精神分裂症患者的总体疗效与喹硫平相当,但起效更早,且耐受性更高。     

喹硫平与氯氮平治疗精神分裂症对照研究

目的：探讨国产喹硫平治疗精神分裂症的疗效和安全性。方法：将96例符合《中国精神障碍分类与诊断标准》第3版（CCMD-3）的精神分裂症患者随机分为两组,分别给予喹硫平（研究组,n=48）和氯氮平（对照组,n=48）治疗,疗程8周。分别于治疗前及治疗第2、4、6、8周末采用阳性和阴性症状量表（PANSS）和副反应量表（TESS）评定临床疗效和不良反应。结果：喹硫平组显效率70.8%,有效率91.7%。氯氮平组显效率72.9%,有效率93.7%。两组间显效率（X2=0.05,P〉0.05）有效率（X2=0.15,P〉0.05）的差异无统计学意义。两组间治疗后各时点PANSS总分、阳性症状、阴性症状以及一般病理症状各项分值均低于治疗前,而治疗后各时点组间差异无统计学意义（P〉0.05）。喹硫平组的嗜睡、便秘、头疼头晕、乏力、流涎的发生率分别为12.5%,4.17%,6.3%,4.2%和2.1%,明显低于氯氮平组（分别为45.8%,18.6%,20.8%,29.2%和39.6%）,两组差异均有统计学意义（X2=13.04,P〈0.01;X2=5.03,P〈0.05;X2=4.36,P〈0.05;X2=10.8,P〈0.01;X2=20.46,P〈0.05）结论：国产喹硫平治疗精神分裂症疗效确切,不良反应少,有利于患者对治疗的依从性,是一种安全有效的抗精神病药物。     

舒思与氟哌啶醇治疗精神分裂症疗效及依从性比较

目的 探讨评价舒思与氟哌啶醇治疗精神分裂症的疗效及依从性.方法 128例精神分裂症患者随机分为两组,分别给予舒思和氟哌啶醇治疗、均治疗18个月,于疗前,治疗后2个月、18个月采用阳性症状阴状量表(PANSS)、药物副反应量表(TESS)评价其疗效、副反应及依从性.结果 2个月后,舒思组有效率91.9%,氟哌啶醇组有效率89.8%,两组治疗前后比较有非常显著性的差异(P＜0.01),但两组间比较无显著性差异(P＞0.05);18个月后舒思有效率91.9%,氟哌啶醇组有效率69.4%.舒思组有非常显著性的疗效(P＜0.01),氟哌啶醇组有显著性疗效(P＜0.05),两组间比较具有显著性差异(P＜0.05).舒思组的不良反应发生率远低于氟哌啶醇组.结论 舒思与氟哌啶醇对精神分裂症患者均有较好的疗效,精神分裂症患者对舒思的依从性高主要是其疗效好和副反应轻.     

Extrapyramidal symptoms during treatment of first schizophrenia episode: Results from EUFEST

The European First Episode Schizophrenia Trial (EUFEST) included first-episode schizophrenia patients, assessing the efficacy of five antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine and ziprasidone) over one year. Baseline frequency of extrapyramidal symptoms (EPS) in this group of patients (n=490) was as follows: parkinsonism 10.8%, akathisia 10.0%, dystonia 1.8%, and dyskinesia 0.6%. The frequency of parkinsonism at baseline was greater in patients with a brief prior exposure to antipsychotics (≤2 weeks) compared with antipsychotic-naïve ones, and was positively correlated with the intensity of negative symptoms and negatively with depressive symptoms. After one month of treatment, the increase of parkinsonism was highest in patients receiving haloperidol (+13%), that of akathisia in patients treated with ziprasidone (+14%), and 10.1% of the patients were taking anticholinergic drugs, most frequently in the haloperidol group (24%). In 291 patients remaining on treatment after one year, both parkinsonism and akathisia had decreased: the frequency of parkinsonism was 3%, highest in the haloperidol group (9.1%), that of akathisia was 3%, highest in the quetiapine group (7.5%), and 4% of patients were taking anticholinergic drugs, most frequently those receiving haloperidol (10.5%). The results obtained suggest that in first-episode schizophrenia patients during the first year of antipsychotic treatment (in this case amisulpride, haloperidol in low doses, olanzapine, quetiapine and ziprasidone), EPS were present as manageable clinical problems.     

All-cause treatment discontinuation in schizophrenia during treatment with olanzapine relative to other antipsychotics: an integrated analysis

OBJECTIVES: Treatment continuation, as measured by time to all-cause treatment discontinuation, is a broad measure of overall treatment effectiveness. This integrated analysis compared the likelihood of discontinuation from olanzapine treatment versus other antipsychotics among patients with schizophrenia. METHODS: Clinical trials of all sponsors were included if they met the following criteria: double-blind, randomized, comparative; duration of 12 weeks or longer; no mandatory discontinuation before 12 weeks; and schizophrenia-spectrum disorders; 20 patients or more per treatment. Weighted mean hazard ratios and 95% confidence intervals were calculated from discontinuation time. Meta-analyses were performed for the following comparators that had at least 2 studies: haloperidol (5 studies), risperidone (5 studies), ziprasidone (2 studies), clozapine (3 studies), and perphenazine (2 studies) (13 studies in total; 3 included more than 1 comparator). Only 1 eligible published study was found for fluphenazine, amisulpride, and quetiapine; therefore, meta-analyses could not be performed for these comparators. RESULTS: Significantly (P < 0.05) greater likelihood of discontinuation relative to olanzapine treatment (hazard ratio [95% confidence interval]) was observed for haloperidol (1.4 [1.2-1.7]), risperidone (1.3 [1.1-1.6]), ziprasidone (1.6 [1.4-2.0]), and quetiapine (1.4 [1.1-1.9]), but not clozapine (1.2 [0.9-1.6]), fluphenazine (1.8 [0.8-4.3]), perphenazine (1.3 [0.7-2.1]), or amisulpride (1.1 [0.8-1.6]). CONCLUSIONS: These data suggest that patients with schizophrenia and related disorders may continue olanzapine treatment longer than haloperidol, risperidone, ziprasidone, or quetiapine treatment.     

The influence of the CYP2D6 polymorphism on psychopathological and extrapyramidal symptoms in the patients on long-term antipsychotic treatment

Poor response to antipsychotics treatment and extrapyramidal side effects (EPS) are the most challenging problems in the treatment of schizophrenia. Several studies were investigating the impact of polymorphic cytochrome P450 2D6 gene (CYP2D6) on EPS but the results were conflicting. There are practically no clinical studies of long-term treatment of schizophrenia and CYP2D6 polymorphism. Our aim was to evaluate the influence of CYP2D6 genotype on psychopathological symptoms and the occurrence of EPS in Slovenian outpatients with schizophrenia or schizoaffective disorder in stable remission, receiving long-term maintenance antipsychotic treatment. In total 131 outpatients meeting the DSM IV criteria for schizophrenia or schizoaffective disorder and receiving maintenance therapy with haloperidol, fluphenazine, zuclopethixole or risperidone were genotyped for 14 polymorphic CYP2D6 alleles. Psychopathological symptoms were assessed with the Positive and Negative Symptom Scale for Schizophrenia (PANSS). EPS were assessed with the Simpson Angus Scale (SAS), the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale (AIMS). Six patients (4.6%) were genotyped as poor metabolizers (PMs). PMs scored significantly higher on the negative subscale for PANSS. There were no statistically significant differences between the group of PMs and the group of patients with at least one functional CYP2D6 allele in view of patient's characteristics or any of the items of the AIMS, the SAS or the Barnes Akathisia Scale. CYP2D6 genotype may not be the major factor that determines the susceptibility to antipsychotic-induced EPS in Slovenian patients in stable remission and on maintenance therapy with antipsychotics that are mainly CYP2D6 substrates. However, CYP2D6 genotype might be a factor contributing to the persistent negative symptoms of schizophrenia.     

Effects of quetiapine and haloperidol on body mass index and glycaemic control: a long-term, randomized, controlled trial

The topic of antipsychotic-induced weight-gain and its relationship to glucose metabolism is under-studied. We evaluated the long-term effects of a new-generation antipsychotic, quetiapine and a conventional antipsychotic, haloperidol on body mass index (BMI) and glycaemic control in patients with schizophrenia previously treated with conventional antipsychotics. Forty-five clinically stable patients with schizophrenia participated in this randomized, investigator-blinded, parallel-group comparison of flexible doses of quetiapine and haloperidol treatment over 52 wk. Primary outcome measures were change from baseline in BMI and glycosylated haemoglobin (HBA1c) levels. There were no between-group differences at any of the time-points for BMI (F = 1.90, p = 0.1) and HBA1c (F = 1.17, p = 0.3) values, and there were no significant changes in BMI from baseline for either group. HBA1c levels decreased significantly at end-point for the haloperidol group (-1.5%, p = 0.04), but not for the quetiapine group (-0.3%, p = 0.5). Although the sample was not generally obese (mean baseline BMI 25.5 +/- 6.3 kg/m2), a large proportion exhibited evidence of abnormal glycaemic control prior to randomization (mean HBA1c 6.7 +/- 1.9%), with 48% having values that were at least mildly elevated (HBA1c > 6.1%) and 19% markedly elevated (HBA1c > 7%). The number of subjects with elevated HBA1c values decreased from baseline in both the haloperidol and quetiapine treatment groups. These findings suggest that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycaemic control, even in the long term. The study also highlights the high incidence of unrecognized glucose dysregulation in patients with schizophrenia receiving conventional antipsychotic treatment.     

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.     

Review of quetiapine and its clinical applications in schizophrenia

Preclinical studies have shown that quetiapine (Seroquel, AstraZeneca) is an atypical antipsychotic with many similarities to clozapine. Both placebo-controlled and comparative studies in patients with schizophrenia have demonstrated that quetiapine has long-term efficacy in both positive and negative domains, as well as beneficial effects on affective and cognitive symptoms. Comparative clinical studies confirm that quetiapine is at least as effective as the standard antipsychotics, chlorpromazine and haloperidol and response rates with quetiapine are similar to those reported with other atypical antipychotics. Quetiapine has also demonstrated superior efficacy to haloperidol in partially responsive patients, who can be particularly difficult to treat. Quetiapine has a wide clinical dosing range (150-750 mg/day), although doses of 400 mg or above should be used in patients who do not fully respond to lower doses of the drug. Quetiapine is generally well tolerated with no requirement for routine ECG or blood monitoring and it has minimal effects on weight. Uniquely among other first-line atypical antipsychotics, quetiapine is associated with a placebo-level incidence of EPS and an indistinguishable effect from placebo on plasma prolactin at all doses. Thus, clinicians can confidently increase the dose of quetiapine, without increasing the risk of EPS or hyperprolactinaemia. A number of studies have also shown that quetiapine is well-tolerated and effective in patients who are particularly susceptible to EPS, including elderly and adolescent patients and those with pre-existing dopaminergic pathology, such as Alzheimer's disease and Parkinson's disease. The consistent efficacy in treating all schizophrenic domains and good tolerability, particularly placebo-level EPS, make quetiapine acceptable to patients, as demonstrated in a survey of patient satisfaction. Thus quetiapine is a suitable first-line therapy for the treatment of schizophrenia and psychosis.     

3种抗精神病药物对首发精神分裂症患者血清泌乳素的影响

目的　探讨不同抗精神病药物对首发精神分裂症患者血清泌乳素PRL水平的影响。方法　 6 2例患者随机分为 3组 ,分别采用奎的平、氯丙嗪、利培酮治疗 4周 ,治疗前、后分别评定精神症状并测定PRL水平。结果　治疗前、后精神症状及不良反应在各组间无差异 ,但是治疗后氯丙嗪及利培酮组的PRL水平显著高于奎的平组。治疗前 3组患者的精神症状及不良反应量表分与PRL水平的相关无统计学意义 ,治疗后氯丙嗪组及利培酮组的多项精神症状量表分与PRL水平的负相关有统计学意义 (P <0 .0 5 )。结论　氯丙嗪及利培酮在改善精神症状的同时伴有PRL增高 ,而奎的平无PRL增高。     

Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol

RATIONALE: Extrapyramidal symptoms (EPS) are common with conventional antipsychotics. Clozapine and other novel antipsychotic substances with lower in vitro affinity for dopamine-2 (D(2)) receptors have a lower propensity to induce EPS. OBJECTIVE: We investigated whether striatal D(2) receptor occupancy predicted the occurrence of EPS with atypical antipsychotics and the typical neuroleptic haloperidol. METHODS: [(123)I]Iodobenzamide (IBZM) and single photon emission tomography (SPECT) were used to quantify receptor occupancy in 71 patients treated with antipsychotics. EPS were rated according to the Simpson-Angus scale (SAS). EPS were deemed clinically relevant, if the SAS score was > or = 5 and/or anticholinergic medication was required. Patients received atypical antipsychotic monotherapy for at least 14 days with amisulpride ( n=2), clozapine ( n=6), haloperidol ( n=10), olanzapine ( n=6), quetiapine ( n=4), risperidone ( n=14), sertindole ( n=13), or zotepine ( n=16). RESULTS: The striatal D(2) receptor occupancy ranged from < 20% to almost saturation. The lowest occupancy was seen with quetiapine and clozapine, the highest with haloperidol. Twenty-two of 71 patients (29%) experienced clinically relevant EPS. These patients displayed significantly higher mean striatal D(2) receptor occupancy (77%) than those without EPS (61%; P=0.002). We found a positive correlation between the percentage of striatal D(2) receptor occupancy and the SAS score ( r=0.28; P=0.02), despite 18 of these patients receiving anticholinergics, thus lowering their SAS score. CONCLUSIONS: Striatal D(2) receptor occupancy as measured with [(123)I]IBZM and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. In vivo imaging of brain receptors with SPECT may provide a useful clinical tool to titrate doses individually and avoid motor side effects in patients treated with novel antipsychotics.     

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.     

Review of quetiapine and its clinical applications in schizophrenia

Preclinical studies have shown that quetiapine (Seroquel?, AstraZeneca) is an atypical antipsychotic with many similarities to clozapine. Both placebo-controlled and comparative studies in patients with schizophrenia have demonstrated that quetiapine has long-term efficacy in both positive and negative domains, as well as beneficial effects on affective and cognitive symptoms. Comparative clinical studies confirm that quetiapine is at least as effective as the standard antipsychotics, chlorpromazine and haloperidol and response rates with quetiapine are similar to those reported with other atypical antipychotics. Quetiapine has also demonstrated superior efficacy to haloperidol in partially responsive patients, who can be particularly difficult to treat. Quetiapine has a wide clinical dosing range (150 - 750 mg/day), although doses of 400 mg or above should be used in patients who do not fully respond to lower doses of the drug. Quetiapine is generally well tolerated with no requirement for routine ECG or blood monitoring and it has minimal effects on weight. Uniquely among other first-line atypical antipsychotics, quetiapine is associated with a placebo-level incidence of extrapyramidal side-effects (EPS) and an indistinguishable effect from placebo on plasma prolactin at all doses. Thus, clinicians can confidently increase the dose of quetiapine, without increasing the risk of EPS or hyperprolactinaemia. A number of studies have also shown that quetiapine is well-tolerated and effective in patients who are particularly susceptible to EPS, including elderly and adolescent patients and those with pre-existing dopaminergic pathology, such as Alzheimer’s disease and Parkinson’s disease. The consistent efficacy in treating all schizophrenic domains and good tolerability, particularly placebo-level EPS, make quetiapine acceptable to patients, as demonstrated in a survey of patient satisfaction. Thus quetiapine is a suitable first-line therapy for the treatment of schizophrenia and psychosis.     

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.     

DRD2 Taq1A polymorphism modulates prolactin secretion induced by atypical antipsychotics in healthy volunteers

Hyperprolactinemia mediated by antagonism of dopaminergic neurotransmission in the pituitary gland is a common adverse effect of antipsychotics. Recent studies have suggested that polymorphisms of dopamine receptors can affect the therapeutic response to antipsychotics. Thus, our aim was to evaluate whether 2 such polymorphisms (DRD2 Taq1A and DRD3 Ser9Gly) modulate prolactin release in healthy volunteers (n = 119) receiving a single dose of quetiapine (25 mg, n = 26), olanzapine (5 mg, n = 57), or risperidone (1 mg, n = 36). The increases in maximum concentration and in area under the curve were calculated from plasma prolactin levels after subtraction of pretreatment levels. Multiple regression analyses revealed that prolactin increases in maximum concentration and in area under the curve depended on drug (quetiapine < olanzapine < risperidone; P < 0.001), sex (women > men; P < 0.001), and Taq1A polymorphism (A1? > A2/A2; P < 0.05). Analysis of the individual drugs revealed that prolactin secretion was modulated by sex and Taq1A polymorphism in olanzapine and risperidone (P < 0.05); however, these factors were not linked to prolactin secretion in quetiapine.     

Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics

Long-acting injectable risperidone was assessed in schizophrenia patients who were symptomatically stable on conventional depot antipsychotics and who were then switched to long-acting risperidone. Participants in this open-label, multicentre, 12-week trial had received flupenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, or zuclopenthixol decanoate for 4 months or longer. Each was considered symptomatically stable by investigators. After receiving two cycles of their conventional depot antipsychotic during the run-in period, patients were switched to receive long-acting risperidone every 2 weeks for 12 weeks at an initial dose of 25 mg. This dose could be increased in 12.5-mg increments at 4-week intervals. Ninety-two percent of the patients received all six injections; 62% received the 25-mg dose throughout the treatment period. Adverse events related to movement disorders were reported in 3%. Severity of movement disorders decreased during long-acting risperidone treatment. Positive and Negative Syndrome Scale (PANSS) total and factor scores and scores on the Clinical Global Impressions severity scale were significantly reduced during treatment; 48% of these stable patients showed further symptom improvement (> or =20% decrease in PANSS score at endpoint). The results indicate that patients with schizophrenia who are symptomatically stable during treatment with a conventional depot antipsychotic can be safely and effectively switched to long-acting injectable risperidone without a prior transition to oral risperidone.     

Antipsychotic-induced type 2 diabetes: evidence from a large health plan database

Case evidence suggests that some of the atypical antipsychotics may induce type 2 diabetes. The objective of this study was to evaluate the association of antipsychotic treatment with type 2 diabetes in a large health plan database. Claims data for patients with psychosis within a health plan of nearly 2 million members were analyzed using logistic regression. Frequencies of newly treated type 2 diabetes in patients untreated with antipsychotics and among patients treated with quetiapine, risperidone, olanzapine, and conventional antipsychotics were compared. Based on exposure measured in months of antipsychotic treatment, quetiapine and risperidone patients had estimated odds of receiving treatment for type 2 diabetes that were lower than those of patients untreated with antipsychotics (not statistically significant); patients treated with conventional antipsychotics had estimated odds that were virtually equivalent to those of patients untreated with antipsychotics; olanzapine alone had odds that were significantly greater than those of patients untreated with antipsychotics (P = 0.0247). Odds ratios based on 8 months of screening for pre-existing type 2 diabetes and assuming 12 months of antipsychotic treatment were: risperidone = 0.660 (95% CI 0.311-1.408); olanzapine = 1.426 (95% CI 1.046-1.955); quetiapine = 0.976 (95% CI 0.422-2.271); and conventional antipsychotics = 1.049 (95% CI 0.688-1.613). Case reports, prospective trials, and other retrospective studies have increasingly implicated olanzapine and clozapine as causing or exacerbating type 2 diabetes. Few have implicated risperidone while evidence on quetiapine has been limited. This study supports earlier findings on risperidone versus olanzapine and builds evidence on quetiapine. Additional studies are needed to evaluate the association of antipsychotic treatment with type 2 diabetes.     

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.