Effectiveness of Extended-release Formulation of Quetiapine as Monotherapy for the Treatment of Acute Bipolar Mania (Trial D144CC00004)

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
C. Datto ◽  
A. Nordenhem ◽  
M. Minkwitz ◽  
B. Dettore ◽  
L. Acevedo ◽  
...  
Keyword(s):  
Extended Release ◽  
Rating Scale ◽  
Analysis Of Covariance ◽  
Secondary Outcome ◽  
Double Blind Study ◽  
Double Blind ◽  
Once Daily ◽  
Bipolar I Disorder ◽  
Manic Symptoms ◽  
Quetiapine Xr

Objectives:To evaluate the effectiveness of extended release quetiapine fumarate (quetiapine XR) as once-daily monotherapy for manic symptoms in bipolar I disorder.Methods:In this 3-week, randomized, parallel-group, double-blind study, adults with bipolar I disorder (most recent episode manic or mixed; with or without rapid cycling) were randomized to once-daily treatment with either quetiapine XR (n=149; Day 1, 300 mg; Day 2, 600 mg; Day 3 through Week 3, 400-800 mg flexibly dosed) or placebo (n=159). Primary outcome measure was change from baseline to Week 3 in Young Mania Rating Scale (YMRS) total score. Secondary outcome measures included YMRS response and remission and change in Clinical Global Impression-Bipolar (CGI-BP)-Severity of Illness and -Change scales. Change from baseline was compared between groups with analysis of covariance, using the last observation carried forward approach for missing data.Results:Once-daily quetiapine XR was associated with significant, sustained improvement in manic symptoms compared with placebo, beginning on Day 4 (P< 0.001) and continuing through Week 3 (mean change: -14.34 versus -10.52; P< 0.001). At Week 3, quetiapine XR-treated patients showed significantly greater response (P< 0.01) and remission (P< 0.01) rates and improvement in CGI-BP-associated scores than placebo-treated patients. Adverse events were mild to moderate in intensity, the most common being sedation, dry mouth, and somnolence for quetiapine XR.Conclusions:Once-daily quetiapine XR monotherapy (400-800 mg) was efficacious (from Day 4 through Week 3) and generally well tolerated in the treatment of manic episodes associated with bipolar I disorder.Supported by funding from AstraZeneca Pharmaceuticals LP.

Effectiveness of the New Extended-release Formulation of Quetiapine as Monotherapy for the Treatment of Acute Bipolar Depression (Trial D144CC00002)

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
C. Datto ◽  
M. Minkwitz ◽  
A. Nordenhem ◽  
C. Walker ◽  
D. Darko ◽  
...  
Keyword(s):  
Extended Release ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Analysis Of Covariance ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Madrs Total Score ◽  
Once Daily ◽  
Quetiapine Xr ◽  
Item Scores

Objectives:To evaluate the effectiveness of extended-release quetiapine fumarate (quetiapine XR) as once-daily monotherapy for bipolar depression.Method:Patients in this double-blind, placebo-controlled study were acutely depressed adults with bipolar I or II disorder (with or without rapid cycling), and were randomized to 8 weeks of once-daily treatment with quetiapine XR 300 mg (n=133) or placebo (n=137). The primary outcome measure was change from baseline to endpoint (Week 8) in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcome measures included response (MADRS total score reduction ≥50%) and remission (MADRS total score ≤12) rates at endpoint, changes from baseline to endpoint in MADRS item scores, and Clinical Global Impressions-Bipolar (CGI-BP) severity of illness and change. Change from baseline was compared between groups with analysis of covariance using last observation carried forward approach.Results:Quetiapine XR 300 mg/d was significantly more effective than placebo in improving depressive symptoms, from first assessment (Week 1; P< 0.001) to endpoint (P< 0.001). Compared with placebo, quetiapine XR was associated with higher response (P< 0.001) and remission (P< 0.05) rates and greater improvements from baseline to endpoint in MADRS total score (-17.43 vs -11.92; P< 0.001), MADRS item scores for core symptoms of depression, and CGI-BP-related outcomes at Week 8. Most common adverse events with quetiapine XR were dry mouth, somnolence, and sedation.Conclusions:Quetiapine XR (300 mg) once-daily monotherapy was efficacious (from Weeks 1 through 8) compared with placebo and generally well tolerated in bipolar depression.Supported by funding from AstraZeneca Pharmaceuticals LP.

A 6-months, randomised, placebo-controlled evaluation of efficacy and tolerability of a low-dose 7-day buprenorphine transdermal patch in osteoarthritis patients naïve to potent opioids

2010 ◽  
Vol 1 (3) ◽  
pp. 122-141 ◽  
Author(s):  
Harald Breivik ◽  
Tone Marte Ljosaa ◽  
Kristian Stengaard-Pedersen ◽  
Jan Persson ◽  
Hannu Aro ◽  
...  
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Low Dose ◽  
Rating Scale ◽  
Secondary Outcome ◽  
Double Blind Study ◽  
Double Blind ◽  
Skin Reactions ◽  
Local Skin

AbstractObjectivePatients with osteoarthritis (OA) pain often have insufficient pain relief from non-opioid analgesics. The aim of this trial was to study efficacy and tolerability of a low dose 7-day buprenorphine transdermal delivery system, added to a NSAID or coxib regimen, in opioid-naïve patients with moderate to severe OA pain.MethodsA 6 months randomised, double-blind, parallel-group study at 19 centres in Denmark, Finland, Norway, and Sweden, in which OA patients (>40 years) with at least moderate radiographic OA changes and at least moderate pain in a hip and/or knee while on a NSAID or a coxib were randomised to a 7-day buprenorphine patch (n = 100) or an identical placebo patch (n = 99). The initial patch delivered buprenorphine 5 μg/h. This was titrated to 10 or 20 μg/h, as needed. Rescue analgesic was paracetamol 0.5–4 g daily. Statistical analysis of outcome data was mainly with a general linear model, with treatment as factor, the primary joint of osteoarthritis, baseline scores, and season as covariates.ResultsMost patients had OA-radiographic grade II (moderate) or grade III (severe), only 8 in each group had very severe OA (grade IV). The median buprenorphine dose was 10 μg/h. 31 buprenorphine-treated patients and 2 placebo-treated patients withdrew because of side effects. Lack of effect caused 12 placebo-treated and 7 buprenorphine-treated patients to withdraw. The differences in effects between treatments: Daytime pain on movement, recorded every evening on a 0–10 numeric rating scale decreased significantly more (P = 0.029) in the buprenorphine group. Patients’ Global Impression of Change at the end of the double blind period was significantly improved in the buprenorphine group (P = 0.017). The chosen primary effect outcome measure, the Western Ontario and McMaster Universities (WOMAC) OA Index for Pain (P = 0.061), and secondary outcome measures, the WOMAC OA score for functional abilities (P = 0.055), and the WOMAC total score (P = 0.059) indicated more effects from buprenorphine than placebo, but these differences were not statistically significant. In a post-hoc, subgroup analysis with the 16 patients with radiographic grad IV (very severe) excluded, WOMAC OA Index for Pain was significantly (P = 0.039) reduced by buprenorphine, compared with placebo. WOMAC OA score for stiffness and the amount of rescue medication taken did not differ. Sleep disturbance, quality of sleep, and quality of life improved in both groups. Side effects: Typical opioid side effects caused withdrawal at a median of 11 days before completing the 168 days double blind trial in 1/3 of the buprenorphine group. Mostly mild local skin reactions occurred equally often (1/3) in both groups.ConclusionsAlthough the 24 hours WOMAC OsteoArthritis Index of pain was not statistically significantly superior to placebo, day-time movement-related pain and patients’ global impression of improvement at the end of the 6-months double blind treatment period were significantly better in patients treated with buprenorphine compared with placebo. Opioid side effects caused 1/3 of the buprenorphine-patients to withdraw before the end of the 6-months double blind study period.ImplicationsA low dose 7-days buprenorphine patch at 5–20 μg/h is a possible means of pain relief in about 2/3 of elderly osteoarthritis patients, in whom pain is opioid-sensitive, surgery is not possible, NSAIDs and coxibs are not recommended, and paracetamol in tolerable doses is not effective enough. Vigilant focus on and management of opioid side effects are essential.

scholarly journals Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: Randomised double-blind placebo-controlled study

2006 ◽  
Vol 188 (1) ◽  
pp. 46-50 ◽  
Author(s):  
Sophia Frangou ◽  
Michael Lewis ◽  
Paul McCrone
Keyword(s):  
Eicosapentaenoic Acid ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Unipolar Depression ◽  
Adjunctive Treatment ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Double Blind Study ◽  
Young Mania ◽  
Double Blind

BackgroundEpidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid (EPA) alleviates unipolar depression.AimsTo examine the efficacy of EPA in treating depression in bipolar disorder.MethodIn a 12-week, double-blind study individuals with bipolar depression were randomly assigned to adjunctive treatment with placebo (n=26) or with 1g/day (n=24) or 2 g/day (n=25) of ethyl-EPA. Primary efficacy was assessed by the Hamilton Rating Scale for Depression (HRSD), with changes in the Young Mania Rating Scale and Clinical Global Impression Scale (CGI) as secondary outcome measures.ResultsThere was no apparent benefit of 2g over 1g ethyl-EPA daily. Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD (P=0.04) and the CGI (P=0.004) scores. Both doses were well tolerated.ConclusionsAdjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression.

Efficacy and tolerability of quetiapine XR 400/600/800mg/day in acute schizophrenia: a post-hoc analysis of data from two pooled randomised studies

2011 ◽  
Vol 26 (S2) ◽  
pp. 1411-1411
Author(s):  
R. Kahn ◽  
A. Kalali ◽  
U. Gustafsson ◽  
S. Nyberg
Keyword(s):  
Dose Response ◽  
Extended Release ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Once Daily ◽  
Quetiapine Fumarate ◽  
Post Hoc Analysis ◽  
Response Efficacy ◽  
Quetiapine Xr ◽  
Post Hoc

IntroductionData from two, identically designed, placebo-controlled, randomised, double-blind clinical trials (D1444C00132+D1444C00133) for once-daily extended-release quetiapine fumarate (QTP-XR) were pooled and analysed.ObjectiveEvaluate dose response, efficacy and safety for QTP-XR in schizophrenia.MethodsPost-hoc analysis of data from patients receiving QTP-XR 400, 600, 800 mg/day or placebo. Endpoints: least squares means (LSM) change from baseline to Day 42 in PANSS total and positive and negative subscale scores. No corrections for multiplicity were performed. Adverse events (AEs) were recorded.Results914 patients were included; PANSS scores were assessed in the MITT population (n = 889). LSM change from baseline in PANSS total score diverged significantly from placebo at: Day 14 for QTP-XR 800 mg/day (-15.3 vs -12.1 for placebo; p = 0.018); Day 21 for 600 mg/day (-17.3 vs -14.2; p = 0.039); Day 42 for 400 mg/day (-19.2 vs -15.4; p = 0.033).Jonckheere-Terpstra analysis of change in PANSS total score at Day 42 showed a significant QTP-XR dose response (p = 0.0196; p < 0.001 with placebo). PANSS positive scores diverged by Day 21 for both QTP-XR 800 (-5.7 vs -4.8; p = 0.049) and 600 mg/day (-5.8 vs -4.8; p = 0.046). PANSS negative scores diverged by Day 21 (-4.0 vs -3.2; p = 0.040) and 42 (-4.8 vs -3.6; p = 0.009) for QTP-XR 800 and 600 mg/day, respectively. AEs occurred in 59.4%, 66.5%, 62.1% and 56.2% of patients in the QTP-XR 800, 600, 400 mg/day and placebo groups, respectively. Most common AEs were somnolence, dry mouth, sedation, insomnia, dizziness, headache, constipation and nausea.ConclusionsQTP-XR was generally well tolerated and demonstrated efficacy that increased with dose in schizophrenia.Financial support: AstraZeneca.

scholarly journals Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia

CNS Spectrums ◽  
2013 ◽  
Vol 19 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Antony D. Loebel ◽  
Cynthia O. Siu ◽  
Josephine B. Cucchiaro ◽  
Andrei A. Pikalov ◽  
Philip D. Harvey
Keyword(s):  
Functional Capacity ◽  
Daytime Sleepiness ◽  
Controlled Trial ◽  
Antipsychotic Agents ◽  
Placebo Treatment ◽  
Double Blind Study ◽  
Double Blind ◽  
Once Daily ◽  
Quetiapine Xr ◽  
Atypical Antipsychotic Agents

ObjectiveThe aim of this analysis was to compare the effects of 2 atypical antipsychotic agents, lurasidone (80 mg/d or 160 mg/d) and quetiapine XR (600 mg/d), on daytime alertness, and to evaluate the effects of daytime sleepiness on treatment outcomes in patients with an acute exacerbation of schizophrenia.MethodsPatients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for schizophrenia were randomized to 6 weeks of double-blind treatment with fixed doses of lurasidone 80 mg/d (n = 125), lurasidone 160 mg/d (n = 121), quetiapine XR 600 mg/d (n = 119), or placebo (n = 121), all dosed once daily in the evening, with food. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS).ResultsDaytime sleepiness improved in the lurasidone and placebo-treated groups but worsened in the quetiapine XR treatment group when compared to placebo (p = 0.001) and to either dose of lurasidone (both p < 0.01). Sedation associated with quetiapine XR treatment mediated an improvement in agitation [assessed by the Positive and Negative Syndrome Scale—Excitement (PANSS-EC) subscale] and a worsening in functional capacity [assessed by the University of California–San Diego (UCSD) Performance-Based Skills Assessment—Brief Version (UPSA-B) total score]; these mediating relationships were not observed for the lurasidone or placebo treatment groups.ConclusionIn this 6-week double-blind study, treatment with lurasidone 80 mg or 160 mg, administered once daily in the evening, was associated with a reduction in daytime sleepiness similar in magnitude to placebo, while quetiapine XR 600 mg/d was associated with a significant increase in daytime sleepiness, compared to both lurasidone dose groups and placebo. Daytime sleepiness was associated with improvement in agitation and worsening in functional capacity for quetiapine XR, but not lurasidone or placebo-treated patients.

Analysis of Pooled Data: Once-daily Extended Release Quetiapine Fumarate (Quetiapine XR) Monotherapy in Patients with Major Depressive Disorder (MDD)

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
S. Montgomery ◽  
R. Weisler ◽  
W. Earley ◽  
M. Åstrom ◽  
A. Lazarus
Keyword(s):  
Extended Release ◽  
Primary Outcome ◽  
Individual Item ◽  
Major Depressive ◽  
Double Blind ◽  
Once Daily ◽  
Quetiapine Fumarate ◽  
Pooled Data ◽  
Quetiapine Xr ◽  
Item Scores

Aim:To evaluate efficacy and tolerability of quetiapine XR monotherapy in patients with MDD.Methods:Data were analysed from two 6-week, multicentre, double-blind, placebo-controlled studies (D1448C00001, D1448C00002), prospectively designed to be pooled. Outpatients received quetiapine XR 150mg/day (n=315), 300mg/day (n=323), placebo (n=330). Primary outcome: change at Week 6 in MADRS total scores. Other assessments: MADRS individual item scores, HAM-A total scores, MADRS response and remission; AE reporting.Results:Quetiapine XR 150mg/day and 300mg/day reduced MADRS total scores at Week 6 (-14.7 and -14.7; p< 0.001) versus placebo (-11.1); significant reductions were also seen at Week 1 (p< 0.001).Subgroup analyses showed the therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as gender, age or depression severity.Quetiapine XR demonstrated consistent improvements in MADRS items: both doses significantly improved 8/10 items at Week 6 versus placebo. At Week 6, MADRS response (≥50% decrease in total score) was 52.7% (p< 0.001), 49.5% (p< 0.001) versus 33.0%; MADRS remission (total score ≤10) was 33.7% (p< 0.01), 34.7% (p< 0.01) versus 24.2% for quetiapine XR 150mg/day and 300mg/day and placebo, respectively. Quetiapine XR 150mg/day and 300mg/day improved HAM-A total scores versus placebo at Week 1 (-4.6 [p< 0.01], -4.7 [p< 0.01], -3.6) and Week 6 (-8.1 [p< 0.001], -7.9 [p< 0.001], -6.2). Common AEs (≥10%) were dry mouth, sedation, somnolence, dizziness, headache and nausea with quetiapine XR.Conclusion:In patients with MDD, quetiapine XR monotherapy improved a broad range of depressive symptoms, with improvements seen from Week 1. Quetiapine XR was generally well tolerated.

Sign in / Sign up

Export Citation Format

Share Document