Efficacy of quetiapine for the treatment of schizophrenia: a combined analysis of three placebo-controlled trials

SUMMARY

Objective: To determine the effectiveness of quetiapine (Seroquel*) against specific aspects of schizophrenic symptomatology.

Research design and methods: Combined data from three placebo-controlled, double-blind, randomised trials that had previously demonstrated quetiapine’s overall clinical effectiveness and tolerability were analysed. Efficacy assessments evaluated were the Clinical Global Impression (CGI) Severity of Illness score, Brief Psychiatric Rating Scale (BPRS) factors I–V, BPRS positive symptom cluster score and 18 individual BPRS items. The Simpson–Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), changes in weight and prolactin concentrations and the recording of adverse events comprised the main tolerability measures.

Results: Efficacy assessments were available for a total of 426 quetiapine patients (mean age 36.9 years) with a DSM-IIIR diagnosis of schizophrenia; 502 patients were included in the tolerability analyses. The mean quetiapine dose was 300.5?mg/day with a mean maximum dose of 686.0?mg/day. Quetiapine was efficacious across a broad range of symptoms, including depression, anxiety and hostility. Significant improvements compared with placebo were noted for CGI Severity of Illness (?p < 0.001) and in 14 of the 18 individual BPRS items (?p < 0.001). Positive symptoms also improved (?p < 0.01 at Week 2 and p < 0.001 from Week 3); greater improvements were observed in patients who received at least 400?mg/day quetiapine. Quetiapine was generally well tolerated: 4.0% of patients withdrew from treatment due to adverse events compared with 3.0% of placebo patients. Akathisia occurred in 2.0% and 2.5% of quetiapine and placebo patients, respectively. Similar decreases in prolactin levels for quetiapine (–10.0?µg/L) and placebo (–10.9?µg/L) were noted from baseline to end of treatment. Agitation and headache, the most common adverse events, were comparable in the quetiapine and placebo groups (agitation: 19.3% vs. 20.3%, respectively; headache: 19.1% vs. 17.3%, respectively).

Conclusions: The results of this combined analysis confirm the individual findings of the three pivotal studies to demonstrate that quetiapine is effective across several domains of schizophrenia, improving positive, negative and depressive symptoms and reducing agitation, aggression and hostility. Similarly, the analysis reiterated the good tolerability profile of quetiapine, particularly in terms of its placebo-like effects on prolactin levels and incidence of extrapyramidal symptoms (EPS).     

Quetiapine in schizophrenia: onset of action within the first week of treatment

OBJECTIVE: Three placebo-controlled clinical trials have established the efficacy of the atypical antipsychotic quetiapine (Seroquel) in schizophrenia. These trials were designed and powered to detect a treatment difference in the primary endpoint at Week 6. The objective of the current analysis was to investigate the effect of quetiapine at earlier timepoints. RESEARCH DESIGN AND METHODS: A combined analysis of data from three acute, double-blind, placebo-controlled, randomised trials was carried out. The trials comprised hospitalised patients with an acute exacerbation of chronic or subchronic schizophrenia who were randomised to receive quetiapine 150-750 mg/day (n = 422) or placebo (n = 198). Symptoms were assessed using changes from baseline to Week 1 in the Brief Psychiatric Rating Scale (BPRS) total score, BPRS positive symptom cluster score and the individual BPRS items of excitement, tension and depression. Changes from baseline to Weeks 1-6 were calculated for BPRS Factor 1 scores (which measures mood symptoms) and Scale for Assessment of Negative Symptoms (SANS) summary scores. RESULTS: Within 1 week, overall symptom improvement (BPRS total score) was significantly (p < 0.05) greater with quetiapine than with placebo; improvement also occurred in individual BPRS items of excitement, tension and depression. Improvement in negative symptoms was significantly (p < 0.05) greater with quetiapine than with placebo from Week 1, as was the BPRS Factor I score from Week 2. More quetiapine- than placebo-treated patients showed a response of positive symptoms to treatment within 1 week (p < 0.05). CONCLUSIONS: The beneficial effects of quetiapine are observed within 1 week across a broad spectrum of symptoms.     

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.     

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

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

Extended Release Quetiapine Fumarate (Quetiapine XR) as Adjunct Therapy in Patients with Generalized Anxiety Disorder and a History of Inadequate Treatment Response: A Randomized,Double-Blind Study

Objective

To evaluate the efficacy and tolerability of adjunct extended release quetiapine fumarate (quetiapine XR) in patients with generalized anxiety disorder (GAD) and inadequate response to selective serotonin reuptake inhibitors/ serotonin norepinephrine reuptake inhibitors (SSRI/SNRIs).

Methods

11-week (1-week single-blind placebo run-in; 8-week randomized treatment; 2-week post-treatment period), double-blind, placebo-controlled study. Patients were randomized to quetiapine XR or placebo adjunct to SSRI/SNRI. 50 mg initial dose; 150 mg/day, Day 3; 300 mg/day, Weeks × and 4 if indicated (Clinical Global Impressions-Severity of Illness [CGI-S] ≥ 4; 150 mg/day tolerated). Primary endpoint: change from randomization to Week 8 in HAM-A total score. Secondary variables: Hamilton Rating Scale for Anxiety (HAM-A) psychic/somatic clusters, response and remission; and CGI-S.

Results

409 patients were randomized to quetiapine XR (n = 209) or placebo (n = 200); 41% and 55% of patients, respectively, had dose increases (300 mg/day). Week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (–10.74; p = 0.079) versus placebo (–9.61). Secondary variables were generally consistent with the primary analysis, except a significant reduction in HAM-A total score at Week 1 (–6.45, quetiapine XR versus –4.47, placebo; p < 0.001); significant improvements in HAM-A psychic cluster (p < 0.05) and CGI-S total (p < 0.05) scores at Week 8. Adverse events (.10% either group) were dry mouth, somnolence, sedation, headache, and dizziness.

Conclusions

In patients with GAD and inadequate response to SSRI/SNRI, adjunct quetiapine XR did not show a statistically significant effect for the primary endpoint at Week 8, although some secondary endpoints were statistically significant versus placebo. Quetiapine XR was generally well tolerated.     

Quetiapine in schizophrenia: onset of action within the first week of treatment

SUMMARY

Objective: Three placebo-controlled clinical trials have established the efficacy of the atypical antipsychotic quetiapine (Seroquel*) in schizophrenia. These trials were designed and powered to detect a treatment difference in the primary endpoint at Week 6. The objective of the current analysis was to investigate the effect of quetiapine at earlier timepoints.

Research design and methods: A combined analysis of data from three acute, double-blind, placebo-controlled, randomised trials was carried out. The trials comprised hospitalised patients with an acute exacerbation of chronic or subchronic schizophrenia who were randomised to receive quetiapine 150–750?mg/day (n = 422) or placebo (n = 198). Symptoms were assessed using changes from baseline to Week 1 in the Brief Psychiatric Rating Scale (BPRS) total score, BPRS positive symptom cluster score and the individual BPRS items of excitement, tension and depression. Changes from baseline to Weeks 1–6 were calculated for BPRS Factor 1 scores (which measures mood symptoms) and Scale for Assessment of Negative Symptoms (SANS) summary scores.

Results: Within 1?week, overall symptom improvement (BPRS total score) was significantly (?p < 0.05) greater with quetiapine than with placebo; improvement also occurred in individual BPRS items of excitement, tension and depression. Improvement in negative symptoms was significantly (?p < 0.05) greater with quetiapine than with placebo from Week 1, as was the BPRS Factor I score from Week 2. More quetiapine- than placebo-treated patients showed a response of positive symptoms to treatment within 1?week (?p < 0.05).

Conclusions: The beneficial effects of quetiapine are observed within 1?week across a broad spectrum of symptoms.     

Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial

The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy for patients with generalized anxiety disorder (GAD). Time-to-event (anxiety symptom recurrence; maximum 52 weeks) multicenter, randomized-withdrawal, parallel-group, double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) following open-label run-in (4-8 weeks) and open-label stabilization (≥ 12 weeks). Primary variable: time from randomization to anxiety event. Secondary variables included: Hamilton Anxiety Rating Scale (HAM-A) total, HAM-A psychic/somatic anxiety factors, Clinical Global Impression-Severity of Illness (CGI-S), and Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores; adverse events (AE) reporting. Four hundred and thirty-two patients, stabilized on quetiapine XR, were randomized to continue quetiapine XR (N=216) or switch to placebo (N=216). Risk of anxiety symptom recurrence was significantly reduced by 81% for quetiapine XR versus placebo: hazard ratio=0.19 (95% confidence interval 0.12-0.31; P<0.001). Fewer patients receiving quetiapine XR (N=22, 10.2%) than placebo (N=84, 38.9%) experienced anxiety symptom recurrence. Significant differences were observed between quetiapine XR and placebo in: HAM-A total, psychic/somatic, CGI-S (all P<0.001) and Q-LES-Q (P<0.05) scores. AEs (>10%) during open-label treatment were dry mouth, sedation, somnolence, dizziness, fatigue, and constipation. During randomized treatment, the most common AEs for quetiapine XR were headache and nasopharyngitis. Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR, with tolerability results consistent with the known profile of quetiapine.     

Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study)

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P 相似文献   

A Randomized,Double-blind Study of the Efficacy and Tolerability of Extended Release Quetiapine Fumarate (Quetiapine XR) Monotherapy in Patients with Major Depressive Disorder

Objectives

Evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD).

Methods

10-week (8-week active-treatment/2-week post-treatment), randomized, double-blind, placebo- and active-controlled study (D1448C00004). Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in MADRS total score) at Week 2 received double-treatment dose. Primary endpoint: Week 8 change from randomization in MADRS total score. Secondary endpoints included: MADRS response (≥50% improvement) and remission (score ≤8), HAM-D total and Item 1, HAM-A total, psychic and somatic, CGI-S total, PSQI global, and Q-LES-Q-SF% maximum total scores; tolerability was assessed throughout.

Results

471 patients were randomized. No significant improvements in MADRS total score were observed at Week 8 (LOCF) with either active treatment (quetiapine XR, −17.21 [p=0.174]; escitalopram, −16.73 [p=0.346]) versus placebo (−15.61). There were no significant differences in secondary endpoints versus placebo, with the exception of Week 8 change in PSQI global score (quetiapine XR, −4.96 [p < 0.01] versus placebo, −3.37). MMRM analysis of observed cases data suggested that the primary analysis may not be robust. Most commonly reported AEs included: dry mouth, somnolence, and dizziness for quetiapine XR; headache and nausea for escitalopram.

Conclusions

In this study, neither quetiapine XR (150/300 mg/day) nor escitalopram (10/20 mg/day) showed significant separation from placebo. Both compounds have been shown previously to be effective in the treatment of MDD; possible reasons for this failed study are discussed. Quetiapine XR was generally well tolerated with a profile similar to that reported previously.     

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     

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.     

A randomized, double-blind, and placebo-controlled trial of quetiapine augmentation of fluoxetine in major depressive disorder

The objective of this study was to investigate whether quetiapine, when compared with placebo, can speed the onset of action and improve the quality of response to fluoxetine treatment in patients suffering from major depressive disorder. A total of 114 patients with major depressive disorder were enrolled in an 8-week treatment study. Patients were initiated on a course of fluoxetine treatment and randomized to quetiapine or placebo. Quetiapine was flexibly dosed starting at 25 mg to a maximum of 100 mg daily. Mixed-effects regression showed that quetiapine plus fluoxetine did not achieve 50% reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale, Clinical Global Improvement (CGI)-Severity, and CGI-Improvement scores sooner than the fluoxetine plus placebo group; however both groups improved in all scores over time. Mixed-effects linear regression of insomnia scores showed that the quetiapine plus fluoxetine group improved significantly more rapidly compared with the fluoxetine plus placebo group. The study indicates that quetiapine plus fluoxetine did not achieve a reduction in the Montgomery-Asberg Depression Rating Scale score or improvement in Hamilton Anxiety Scale or CGI scores from baseline sooner than the fluoxetine plus placebo group. The combination of quetiapine and fluoxetine, however, improved sleep over fluoxetine alone over the first few weeks of treatment.     

Quetiapine for acute mania in bipolar disorder.

PURPOSE: The efficacy and tolerability of quetiapine in the treatment of acute mania were reviewed. SUMMARY: Five randomized, placebo-controlled trials involving quetiapine as monotherapy or adjunct therapy in combination with either divalproex or lithium in the treatment of bipolar mania in either adolescents or adults were identified and reviewed. The primary outcome measure used in the trials was a change in Young Mania Rating Scale total scores. Monotherapy trials evaluated quetiapine, lithium, haloperidol, and placebo. Quetiapine was superior to placebo in both trials. Quetiapine and lithium showed comparable efficacy in one study, though lithium serum concentrations may have been suboptimal. Haloperidol was superior to quetiapine in efficacy at day 21 but similar at day 84. In the two trials evaluating quetiapine or placebo as adjunct therapy to lithium or divalproex, quetiapine was significantly more efficacious than placebo in one trial. In adolescents, quetiapine was more effective than placebo as an adjunct to divalproex. The most common adverse effects clearly attributable to quetiapine in these trials were somnolence and dry mouth. Quetiapine did not induce extrapyramidal effects, but weight gain was notable with the drug. CONCLUSION: While quetiapine treatment demonstrated efficacy in the majority of the studies, the robustness of its efficacy is questionable. The use of quetiapine as first-line therapy for acute mania is not recommended based on the available results and cost considerations. However, it may be a useful second-line agent, particularly when sensitivity to extrapyramidal symptoms limits treatment options.     

Quetiapine or haloperidol as monotherapy for bipolar mania--a 12-week, double-blind, randomised, parallel-group, placebo-controlled trial.

METHODS: Patients (n=302) with bipolar I disorder (manic episode) were randomised to 12 weeks' double-blind treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or haloperidol (up to 8 mg/day). The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale (YMRS) score. RESULTS: YMRS score improved with quetiapine at Day 21 (-12.29 versus -8.32 for placebo; P<0.01). The difference in favor of quetiapine increased by Day 84 (-17.52 versus -9.48; P<0.001). Haloperidol also showed an advantage over placebo at Days 21 and 84 (P<0.001). There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21. The only common adverse event with quetiapine was somnolence (12.7%). Extrapyramidal symptoms (EPS), including akathisia, occurred at 59.6% with haloperidol, 12.7% with quetiapine, 15.8% with placebo. Most quetiapine responders (84%) received a dose of 400-800 mg/day. CONCLUSIONS: Quetiapine was effective and well tolerated. The efficacy and tolerability profile of haloperidol (including its propensity for EPS) supported study validity.     

Once-daily controlled release remoxipride is equieffective with twice-daily immediate release remoxipride in the treatment of schizophrenia

A controlled release (CR) formulation of remoxipride (Roxiam(?), Astra) given once-daily was compared to immediate release (IR) remoxipride given twice-daily, with respect to efficacy and tolerability, in a 4-week multicentre parallel-group dose titration (200-600 mg/day) study with acutely ill schizophrenic patients. Forty- three patients received remoxipride CR (mean dose 344 mg/day) and 49 patients received remoxipride IR (mean dose 346 mg/day). Efficacy was assessed using the Kolakowska version of the Brief Psychiatric Rating Scale (BPRS score of ≥ 18 points at entry) and the Clinical Global Impression scale (CGI), while extrapyramidal symptoms were rated using the Simpson and Angus scale. Both formulations of remoxipride produced clinical improvement, with the BPRS median total score falling from 35 at baseline to 16 at last rating in the remoxipride CR group, and from 33 to 12.5 in the remoxipride IR group. More than 70% of the patients in both groups were assessed as 'much improved' or 'very much improved' according to the CGI scale. Both formulations of remoxipride were well-tolerated, with a low incidence of treatment-emergent adverse symptoms, including extrapyramidal side effects. No statistically significant differences were detected between the treatment groups with regard to efficacy, safety or tolerability.     

Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder.

The augmentation of serotonin reuptake inhibitors (SRIs) with atypical antipsychotics for the management of treatment-resistant obsessive-compulsive disorder (OCD) is gaining increasing acceptance. Quetiapine is a novel antipsychotic which is well tolerated, and which may therefore be particularly useful in this context. Charts of all patients treated in our OCD clinic with the combination of an SRI and quetiapine were reviewed. Demographic details and clinical symptoms on the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (CGI) were tabulated before and after augmentation. Eight OCD patients who had proven resistance to treatment with SRIs had received quetiapine augmentation. Four of these eight patients were responders (CGI of 1 or 2) within 4 weeks. In the treatment-responders, the medication was well tolerated. Although limited by the retrospective design and lack of controls, these data are consistent with the growing literature suggesting that approximately one-half of OCD patients resistant to treatment with SRIs may respond to augmentation with an atypical antipsychotic. Quetiapine, a relatively well tolerated agent, deserves further controlled study in this context.     

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

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

Safety and efficacy of rapid dose administration of quetiapine in bipolar mania

In this open-label pilot study, 20 adult patients hospitalized for acute bipolar mania received oral quetiapine as a single evening dose of 200 mg on day 1, increased by 200 mg/day on days 2, 3, and 4 until 800 mg/day taken in 2 divided doses on day 4. From day 5 onward, patients received a flexible total dose of 400-800 mg/day until completion of 3 weeks of treatment. Safety and tolerability were assessed by adverse-event (AE)-related dropouts in week 1, incidence of AEs including EPS, changes in electrocardiogram, and vital signs. Efficacy was assessed using the YMRS, PANSS, and CGI scales. Nineteen of 20 patients (95%) completed the quetiapine rapid titration during week 1. Significant improvement was observed in YMRS, PANSS, and CGI Severity of Illness scores by day 5, and was maintained throughout the study. A reduction of > or = 50% in YMRS score was achieved by 75% of patients by day 7, and maintained to day 21. Overall, 20% of patients discontinued due to AEs. Agitation was the most common cause of AE-related study discontinuation. Thirty-five per cent of patients required dose adjustment due to AEs after rapid dose administration was completed. Most patients tolerated rapid titration of quetiapine to 800 mg/day by day 4 of therapy, with a significant improvement in manic symptoms by day 7 of treatment.     

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.