Quetiapine for Mania

By: Flavio Guzman, MD.


Quetiapine immediate release (IR) was approved in 2003 for the treatment of manic episodes in patients diagnosed with bipolar disorder.

In 2008, the extended release formulation – quetiapine ER (Seroquel XR) – was also approved for the same indication.

Reviews

Quetiapine in the treatment of acute mania: target dose for efficacious treatment.

Journal of affective disorders
Vieta E, Goldberg JF, Mullen J, Vågerö M, Paulsson B,
Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain. evieta@clinic.ub.es
Published:  2007

Abstract:

Objective
To analyze the available evidence from randomized clinical trials regarding the effective dose range and optimal dose of quetiapine when treating bipolar I disorder patients with acute mania.

Methods

Patients with acute mania were treated with quetiapine as monotherapy (for 12 weeks) or in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 69.5 microg/mL) (Li/DVP) (for 3-6 weeks) in four double-blind, placebo-controlled studies according to a predetermined dosing schedule. Guidance for the dosing of quetiapine involved increasing the first day’s dose (100 mg/day) by 100 mg on a daily basis until Day 4 (400 mg/day), then adjusting the dose up to 600 mg/day at Day 5, and up to 800 mg/day thereafter. Pooled data from the two monotherapy studies and the two combination therapy studies have been used to evaluate the effective quetiapine dose range. As the dose was flexible, effective dose was estimated by the mean last-week dose among responders. The mean last-week dose was defined as the median dose during the 7 days before the last available Young Mania Rating Scale (YMRS) assessment. Patients who achieved a > or = 50% decrease in the YMRS total score from baseline to end of treatment with quetiapine were considered responders. Tolerability was assessed from direct patient reports.

Results

According to randomized clinical trials, administration of quetiapine compared with placebo achieved a statistically significant improvement in change from baseline YMRS score within the first week and onward, as monotherapy or in combination with Li/DVP. The average quetiapine dose (+/-SD) in responders during the last week of treatment was 575 (+/-175) at Day 21 and 598 (+/-198) mg/day at Day 84 for monotherapy, and 584+/-208 mg/day at Day 21 for combination therapy, with most responders receiving doses within the range of 400-800 mg/day. Dose escalation was rapid, with 92% of patients treated with monotherapy and 80% of patients treated with combination therapy reaching doses of 400 mg/day by Day 4, in accordance with protocol-defined dosing guidance. This dose administration schedule was generally well tolerated.

Conclusions

The mean last-week median dose among responders suggests that 600 mg/day of quetiapine is an effective target dose in acute mania.

Quetiapine for the treatment of acute bipolar mania, mixed episodes and maintenance therapy.

Expert opinion on pharmacotherapy
Janicak PG, Rado JT,
Rush University Medical Center, Psychiatric Research Clinical Center, 2150 West Harrison, Chicago, IL 60612, USA. p_janicak@rush.edu
Published: Aug 2012

Abstract:

INTRODUCTION: Bipolar disorder is characterized by mood instability, which can be challenging to manage. First-line pharmacological approaches usually involve lithium, anticonvulsants and antipsychotics. Over the past fifteen years, several second-generation antipsychotics have demonstrated benefits for various phases of this disorder.

AREAS COVERED: This article examines the pharmacodynamics and pharmacokinetics of quetiapine ; its evidence base as an acute and maintenance monotherapy or adjunctive therapy for bipolar manic or mixed episodes is also discussed, along with the related issues of its safety and tolerability.

EXPERT OPINION: In the context of bipolar disorder, quetiapine is the only agent approved as a monotherapy or adjunct therapy for acute manic/mixed episodes in adults and adolescents; as a monotherapy for acute depressive episodes in adults; and as an adjunctive maintenance therapy for bipolar I and II disorder in adults. In addition to its antipsychotic properties, this broad mood-stabilizing potential may simplify the management of select patients.

Quetiapine for acute mania in bipolar disorder.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
Brahm NC, Gutierres SL, Carnahan RM,
Department of Pharmacy Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy (UOCP), Tulsa, OK 74135-2512, USA. nancy-brahm@ouhsc.edu
Published: May 2007

Abstract:

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 in the treatment of acute bipolar mania: efficacy across a broad range of symptoms.

Journal of affective disorders
McIntyre RS, Konarski JZ, Jones M, Paulsson B,
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada. roger.mcintyre@uhn.on.ca
Published:  2007

Abstract:

Objective
An ideal antimanic therapy is well tolerated and offers full multidimensional symptom relief. The efficacy of quetiapine in the treatment of acute bipolar mania has previously been established. This post-hoc analysis aims to extend our understanding of quetiapine’s antimanic efficacy by evaluating its therapeutic effect across the full spectrum of manic symptoms.

Methods

Patient-level data from four similar, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of quetiapine in bipolar disorder patients with DSM-IV acute mania were combined. Two trials investigated quetiapine as monotherapy (twice daily) and two trials assessed the combination of quetiapine with either lithium (Li) or divalproex (DVP). Changes in scores on the total Young Mania Rating Scale (YMRS), and on each of the 11 items comprising the YMRS, were the primary measures of interest in this analysis. Changes in the Supplemental Aggression and Agitation subscales of the Positive and Negative Syndrome Scale (PANSS) were secondary measures analyzed.

Results

Quetiapine as monotherapy, or in combination with Li or DVP, was a highly effective treatment for acute mania, as shown by overall change scores in the total YMRS. Patients treated with quetiapine monotherapy exhibited a significantly greater reduction (versus placebo) in YMRS total scores at Day 4 (-3.5 versus -2.2; p=0.021), with an increasing between-group difference reported throughout the duration of the trials at Day 21 (-13.6 versus -7.8; p<0.001) and at study endpoint on Day 84 (-19.0 versus -9.6; p<0.001). Quetiapine was also superior in efficacy to placebo on all categorical (i.e., response and remission rates) and secondary outcome parameters. On each of the 11 YMRS items, including the double-weighted core manic items, quetiapine was significantly superior to placebo (p<0.05). Effect sizes at Day 84 ranged from 0.37 to 0.61. Quetiapine in combination with Li/DVP offered a significant benefit over Li/DVP monotherapy, starting at Day 7 (p<0.05) and continuing to the primary study endpoint on Day 21 (p=0.01). Four of 11 YMRS items improved significantly more on quetiapine combination therapy than on Li/DVP monotherapy.

The efficacy of quetiapine in these trials appeared independent of baseline disease severity, the presence of psychosis, and treatment-emergent sedation/somnolence. Quetiapine monotherapy produced significantly greater improvement than placebo on the PANSS Activation and the PANSS Supplemental Aggression Risk subscale scores. Similar findings were obtained with quetiapine combined with Li or DVP.

Conclusions

Patients with bipolar disorder may report severe and complex manic symptoms. The results herein indicate that quetiapine is efficacious across the multiple dimensions of mania, including medically serious symptoms commonly encountered in practice.

 

Quetiapine for the treatment of bipolar mania in older adults.

Bipolar disorders
Sajatovic M, Calabrese JR, Mullen J,
Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, OH 44106, USA. martha.sajatovic@uhhs.com
Published: Sep 2008

Abstract:

Objectives:
A post hoc analysis of pooled data from two quetiapine monotherapy clinical trials was conducted to evaluate the efficacy and tolerability of quetiapine therapy (twice daily, 400-800 mg/day) among bipolar manic adults aged 55 years and older. The primary efficacy endpoint was the change from baseline in Young Mania Rating Scale (YMRS) total score at Day 21. A secondary endpoint was change from baseline in YMRS score at Day 84.

Methods

A total of 407 patients made up the safety population, consisting of 59 older adults (aged >or=55 years) and 348 younger adults. A total of 403 patients made up the efficacy population, consisting of 59 older adults and 344 younger adults. Efficacy outcomes were analyzed using covariance models (ANCOVA); descriptive statistics are presented for safety outcomes.

Results

Both older and younger individuals treated with quetiapine had significant improvement from baseline on YMRS scores compared with placebo-treated patients. The older adult group demonstrated a sustained reduction in YMRS score compared with placebo that was apparent by Day 4 of treatment. For the quetiapine treatment groups, the most common adverse effects (at a frequency >or=10%) were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness in older adults, and dry mouth, somnolence, and insomnia in younger adults. For the placebo treatment groups, insomnia was the most common adverse event in both older and younger adults.

Conclusions

This secondary analysis suggests that quetiapine represents a potentially useful treatment option among older adults with bipolar I mania. Studies with a primary focus of geriatric bipolar mania, and including larger patient numbers, are needed to confirm these findings.

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