Quetiapine extended release for the treatment of bipolar disorder

Abstract

Management of bipolar disorder (BD) requires a complex combination of pharmacological and psychosocial interventions. Over recent decades the therapeutic arsenal for BD has expanded to include lithium, anticonvulsants and second-generation antipsychotics (SGAs). Immediate release (IR) quetiapine fumarate is a SGA approved in several countries for the treatment of patients with schizophrenia and BD or as an add-on treatment for major depressive disorders. Extended release (XR) quetiapine fumarate was developed more recently. There is interest in a once-daily formulation which may improve patient compliance but there may be some differences between quetiapine IR and XR in terms of safety and efficacy. This article provides an update of recent data on the efficacy and safety of quetiapine XR for the treatment of BD.

Keywords::

• bipolar disorder
• depression
• extended release
• immediate release
• mania
• number need to harm
• number need to treat
• quetiapine
• second-generation antipsychotic

Financial & competing interests disclosure

L Samalin has received honoraria for conferences and consulting from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Lundbeck and Otsuka. P-M Llorca declares grants, consulting, expertise and conferences from Astra-Zeneca, Eli Lilly, Lundbeck and Otsuka. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The precise mechanism of action on depression is not well understood. Quetiapine and its active metabolite, norquetiapine, interact with a broad range of neurotransmitter receptors; in particular, they are partial 5-HT1A and 5-HT1C receptor agonists and norepinephrine reuptake inhibitors, and these actions contribute to their antidepressant properties.

• As quetiapine immediate release (IR), the extended release (XR) formulation demonstrated efficacy as monotherapy for the treatment of acute manic and depressive episodes in adult patients with bipolar disorder (BD) in several studies with high standards of evidence.

• To date there has been no trial of the XR formulation as maintenance treatment. Most national and European regulatory agencies have extrapolated from the results of studies with quetiapine IR to approve the use of the XR formulation as a maintenance treatment of BD.

• In bipolar patients with a co-occurring panic disorder or generalized anxiety disorder, quetiapine XR was found to be effective in reducing anxiety symptoms.

• The overall tolerability of quetiapine XR is comparable to that of quetiapine IR, but it produces lower immediate postdose sedation (1–3 h).

• Quetiapine XR is a once-a-day formulation and may therefore result in better adherence to treatment in bipolar patients than drugs that have to be administered several times a day.

• All second-generation antipsychotics have different pharmacodynamic profiles and a new compound may hold particular interest, in terms of either efficacy or tolerance, as a treatment for patients with BD. Second-generation antipsychotics cannot be considered as a homogeneous group, and the current classification of these drugs should probably be revised.

• Quetiapine XR (and IR) could be considered as a ‘prototype’ in drug development for BD since it is effective in mania, depression and as a maintenance treatment.