A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study. Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study [ISRCTN83050762]. Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study. A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Comparison of quetiapine and risperidone in the treatment of schizophrenia: A randomized, double-blind, flexible-dose, 8-week study. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. 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. Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study. Quetiapine augmentation in patients with treatment resistant obsessive-compulsive disorder: a single-blind, placebo-controlled study. Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study. Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophrenia. Quetiapine has equivalent efficacy and superior tolerability to risperidone in the treatment of schizophrenia with predominantly negative symptoms. Effectiveness of long-term aripiprazole therapy in patients with acutely relapsing or chronic, stable schizophrenia: a 52-week, open-label comparison with olanzapine. Adding quetiapine to SRI in treatment-resistant obsessive-compulsive disorder: a randomized controlled treatment study. Cognition, functioning and quality of life in schizophrenia treatment: results of a one-year randomized controlled trial of olanzapine and quetiapine. Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning. Comparative effectiveness of second-generation antipsychotics and haloperidol in acute schizophrenia. Randomized, double-blind, placebo-controlled study of paliperidone extended-release and quetiapine in inpatients with recently exacerbated schizophrenia. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder.
The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice.
                The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms.
                This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D).
                A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028).
                The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability. Although serotonin reuptake inhibitors are effective in the treatment of OCD, many patients fail to respond to these agents. Growing evidence from open-label and placebo-controlled trials suggests a role for augmentation of SRIs with atypical antipsychotics in OCD. Quetiapine is generally well tolerated and previous open-label data has produced mixed results in OCD and additional controlled data is needed.
                We undertook a double-blind, randomised, parallel-group, flexible-dose, placebo-controlled study of quetiapine augmentation in subjects who had responded inadequately to open-label treatment with an SRI for 12 weeks. Following informed consent and screening, forty-two subjects were randomised to either placebo or quetiapine for six weeks.
                There was significant improvement from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale in both the quetiapine and placebo groups (quetiapine, n = 20, p < 0.0001; placebo, n = 21, p = 0.001) with 40% (n = 8) of quetiapine and 47.6% (n = 10) of placebo treated subjects being classified as responders. Quetiapine did not demonstrate a significant benefit over placebo at the end of the six-week treatment period (p = .636). Similarly quetiapine failed to separate from placebo in the subgroup of subjects (n = 10) with co-morbid tics. Quetiapine was generally well tolerated.
                In this study, quetiapine augmentation was no more effective than placebo augmentation of SRIs. A number of limitations in study design make comparisons with previous studies in this area difficult and probably contributed to our negative findings. Future work in this important clinical area should address these limitations. Schizophrenia is a devastating psychiatric disorder. Clozapine has long been the gold standard for treatment of patients with treatment-resistant schizophrenia; however, some patients are only partially responsive to clozapine treatment. Augmentation of clozapine treatment might enhance its effectiveness in partial responders, but only a few studies have investigated possible augmentation strategies. This study compared the effectiveness and tolerability of the combination of amisulpride and clozapine with the combination of quetiapine and clozapine in patients who were only partially responsive to clozapine monotherapy. Fifty-six treatment-resistant patients who were partially responsive to clozapine were randomly assigned to receive amisulpride or quetiapine along with an ongoing stable dose of clozapine. Fifty patients completed the study. Patients were evaluated at baseline and at the first, third, sixth, and eighth weeks. Efficacy measures consisted of the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression (CGI) scale. Tolerability and adverse effects were assessed with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and the Simpson Angus Scale (SAS). A substantial improvement occurred in both groups by the end of the eighth week; however, the improvement associated with amisulpride was significantly greater than that seen with quetiapine. This difference was noted as early as the third week of follow-up in terms of CGI scores, and by the sixth week with regard to BPRS, SANS, and SAPS scores. Both drugs were well tolerated, as measured by UKU and SAS. Improvement favoring clozapine+amisulpride could be attributed to the selective D2/D3 binding property of amisulpride, which had an additional effect in improving symptoms of schizophrenia. The authors concluded that amisulpride seems to be effective and well tolerated for augmentation purposes in clozapine-resistant patients. This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.
                This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.
                Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.
                While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings. In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic.
                Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason.
                The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168).
                Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason. When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.
                Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).
                Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.
                For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects. To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.
                In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.
                Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).
                Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone. This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.
                Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.
                A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).
                Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation. 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 beneficial effect of sulpiride augmentation of clozapine therapy for treatment-resistant schizophrenia patients is enhanced by its antisalivatory effect on clozapine-induced hypersalivation (CIH). Amisulpride, similar to sulpiride, is a substitute benzamide derivative with higher selective binding to the D2/D3 dopamine receptor. We hypothesized that add-on amisulpride would also be beneficial in controlling CIH. In a randomized, double-blind, placebo-controlled cross-over study, 20 clozapine-treated schizophrenia (DSM-IV criteria) inpatients with CIH were randomly initially assigned to add-on amisulpride (nine patients; 400 mg/day up-titrated from 100 mg/day over 1 week) or placebo (11 patients). Primary outcome was change in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Other measures included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale (CGI) and Simpson-Angus Scale (SAS). Mean NHRS indices were considerably lower with amisulpride (1.79 +/- 1.25) than with placebo (2.63 +/- 1.33) [F(1,38) = 5.36, P < 0.05]. With amisulpride treatment, there was a significant improvement on the negative symptoms subscale of the PANSS [F(3,57) = 3.76, P < 0.05], but not on the SAS, CGI or other subscales of the PANSS (all F < 1). Short-term amisulpride augmentation has a strong ameliorating effect on CIH. A long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time. Recently, atypical antipsychotics have been used for the management of the patients with refractory obsessive-compulsive disorder (OCD). The aim of the present study was to evaluate the results of quetiapine augmentation to a serotonin reuptake inhibitor (SRI) in the patients with refractory OCD. Fifty-two patients with OCD according to DSM-IV entered 3 months of an open-label phase treatment with a SRI with or without concomitant adjunctive treatment regimen. Of them, 27 patients were refractory OCD. These patients were randomly divided into two groups, SRI plus quetiapine and SRI plus placebo, for an 8-week single-blind phase. The course of OCD was evaluated by Yale-Brown Obsession-Compulsion (Y-BOCS) and Clinical Global Impression-Severity of Illness and Improvement (CGI-SI and I) Scales every other week for 8 weeks. Of the 14 patients in group I, nine (64.4%) showed significant improvement with 60% or greater improvement on the Y-BOCS and one (7.1%) partial improvement with 30% or greater improvement on the Y-BOCS, whereas no improvement was observed in group II. The addition of quetiapine to ongoing SRI therapy has been found to be effective and well-tolerated approach in patients with refractory OCD. This study evaluated once-daily extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressant treatment. In this 8-wk (6-wk active treatment/2-wk post-treatment drug-discontinuation/follow-up), multicentre, double-blind, placebo-controlled, Phase III study, 446 patients were randomized to quetiapine XR 150 mg/d, 300 mg/d, or placebo adjunct to ongoing antidepressant treatment. The primary endpoint was the change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. At week 6, MADRS total scores significantly improved with quetiapine XR 300 mg/d vs. placebo (-14.7 vs. -11.7, p<0.01). Quetiapine XR 300 mg/d showed significant improvements vs. placebo for: MADRS total score from week 1 onwards; MADRS response [(> or = 50% total score reduction) 58.9% vs. 46.2%, p<0.05] and remission [(total score < or = 8) 42.5% vs. 24.5%, p<0.01] rates; Hamilton Depression Rating Scale (HAMD) (-13.53 vs. -10.80, p<0.01) and Clinical Global Impression-Severity of illness (CGI-S) change (-1.52 vs. -1.23, p<0.05) at week 6. For quetiapine XR 150 mg/d, improvements were not significantly different vs. placebo, except for MADRS (weeks 1 and 2) and HAMD (week 6) total scores. Withdrawal rates due to adverse events (AEs) were: quetiapine XR 150 mg/d 11.5%, 300 mg/d 19.5%, and placebo 0.7%. The most common AEs (>10%) with quetiapine XR were dry mouth, somnolence, sedation, dizziness, constipation, nausea, insomnia, headache, and fatigue. In this study, quetiapine XR 300 mg/d as adjunctive therapy in patients with MDD with an inadequate response to ongoing antidepressant treatment was effective at week 6. However, the difference from placebo for quetiapine XR 150 mg/d at week 6 was not statistically significant. Both doses studied (150 and 300 mg/d) were effective at week 1 and generally well tolerated. Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637 mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16 mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (> or =7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia.
                Copyright 2006 John Wiley & Sons, Ltd. Atypical antipsychotics are generally thought to be more effective than conventional agents in treating the negative symptoms of schizophrenia; however, there have been few direct comparisons among atypicals. We therefore investigated risperidone and quetiapine with respect to their efficacy against negative symptoms in a 12-week,double-blind, comparative pilot study involving 44 patients with schizophrenia with predominantly negative symptoms, as defined by Positive and Negative Syndrome Scale (PANSS) scores. Other efficacy measures included the Scale for the Assessment of Negative Symptoms (SANS) and the Clinical Global Impression (CGI) rating scale. Antipsychotic tolerability was assessed using the Simpson-Angus Scale (SAS) and various laboratory measures. Mean doses were 589.7 mg/ day quetiapine and 4.9 mg/day risperidone (observed cases). Both antipsychotics produced significant decreases in PANSS total, positive and negative scores, and SANS scores. Patients receiving risperidone were significantly more likely to experience extrapyramidal symptoms (EPS) [p <0.05], or to require anticholinergic medication (p <0.05), and had significantly higher prolactin levels (p <0.001) than quetiapine-treated patients. In conclusion, there is no significant difference in efficacy between quetiapine and risperidone in alleviating the negative symptoms of schizophrenia. Quetiapine is also well tolerated, with a lower incidence of EPS and prolactin increase than risperidone. To compare the long-term efficacy and safety of aripiprazole with olanzapine in patients with either acute relapsing or chronic, stable schizophrenia.
                A 52-week, open-label extension to a 26-week, multicenter, randomized, double-blind, placebo-controlled trial in patients with chronic schizophrenia. Patients who completed the initial treatment or who met the protocol definition of relapse after > or =2 weeks of double-blind treatment were randomized to aripiprazole (15-30 mg/day, n = 104) or olanzapine (10-20 mg/day, n = 110) for 52 weeks.
                Sixty-nine percent of patients completed the study. Efficacy improvements were similar between groups at endpoint, mean reductions in Positive and Negative Syndrome Scale (PANSS) Total scores from baseline for patients completing the study (observed cases) were similar in chronic stable patients (aripiprazole, -7.94; olanzapine, -7.36) and in patients with acute relapse (aripiprazole, -31.19; olanzapine, -29.55). Olanzapine-treated patients reported more extrapyramidal symptoms (EPS)-related adverse events (18%) than aripiprazole-treated patients (10%). No significant differences in EPS were seen between treatments at endpoint. Olanzapine was associated with significantly greater weight gain than aripiprazole at all time points (week 52 [LOCF]: +2.54 vs +0.04 kg; p < 0.001). Changes in fasting glucose and lipid levels at endpoint favored aripiprazole over olanzapine, with significant differences observed for total cholesterol, low- and high-density lipoprotein. While differences observed for changes in fasting glucose and triglycerides favored aripiprazole, they were not statistically significant.
                Aripiprazole showed similar efficacy to olanzapine for long-term treatment of acutely psychotic and chronic, stable schizophrenia patients, with a lower liability for weight gain or increased lipid levels. This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive-compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n = 11) or placebo (n = 10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale-Brown Obsessive-Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD. Cognitive deficits are recognized as a critical determinant of functional outcomes in schizophrenia; and second generation antipsychotic drugs have been touted for their potential to enhance cognitive functioning and community tenure.
                The study examined the relative merits of olanzapine and quetiapine in improving cognitive deficits and enhancing psychosocial functioning in a sample of community dwelling adults previously treated with first generation antipsychotic drugs for schizophrenia.
                In a prospective, rater-blinded study, 86 participants were randomized to receive either olanzapine or quetiapine, and assessed at baseline and after 3, 6, 9 and 12 months. Outcome measures included, besides symptoms and side effects rating scales, the subjective scale to investigate cognition in schizophrenia (SSTICS), a computer-assisted cognitive test battery (COGLAB), the sickness impact profile (SIP), the global assessment of functioning (GAF) scale, and the drug attitude inventory (DAI).
                Both olanzapine and quetiapine were equally effective in improving symptom severity and decreasing the neurological side effects. Quetiapine was significantly better tolerated (p=0.002), improved self-rated cognitive dysfunction (p=0.002) and subjects' performance on selected neurocognitive tasks (p=0.01). Olanzapine use was associated with greater symptom stability, fewer drop outs (p=0.01) and frequent metabolic aberrations (p=0.001). The accrued benefits of drug therapy, however, were not reflected as significant gains in daily functioning and quality of life.
                Quetiapine is noted to have specific cognition enhancing properties in schizophrenia that warrants further exploration. The observed clinical and cognitive benefits associated with quetiapine may likely be attributable to its loose binding to, and fast dissociation from the dopamine receptors. Olanzapine has proved to be a reliable antipsychotic drug with a greater liability to cause metabolic abnormalities. This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy. There is little information on the comparative effectiveness of second-generation antipsychotic agents.
                To determine if any of five second-generation antipsychotics or haloperidol is more effective in treating acutely ill patients with schizophrenia, schizoaffective disorder or schizophreniform disorder.
                A sample of 327 newly admitted patients were randomised to open-label treatment with aripiprazole, haloperidol, olanzapine, quetiapine, risperidone or ziprasidone for a minimum of 3 weeks. Measures of effectiveness were improvement in mental status so that the patient no longer required acute in-patient care, and changes in Brief Psychiatric Rating Scale (BPRS) scores.
                By the first measure, haloperidol (89%), olanzapine (92%) and risperidone (88%) were significantly more effective than aripiprazole (64%), quetiapine (64%) and ziprasidone (64%). Changes in BPRS ratings were not significant among treatments.
                Haloperidol, olanzapine and risperidone are superior to aripiprazole, quetiapine and ziprasidone for the acute treatment of psychosis in hospitalised patients with schizophrenia, schizoaffective disorder or schizophreniform disorder. The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization.
                In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint.
                Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups.
                Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings. Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder.
                In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval.
                Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone. Mean change in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar low incidence of clinically significant weight gain.
                Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder. It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders.
Quetiapine was more effective than placebo treatment. Aripiprazole and quetiapine and partly also olanzapine and risperidone augmentation showed beneficial effects compared to placebo. Some evidence indicated beneficial effects of low-dose amisulpride for dysthymic people. Most SGAs showed worse tolerability.