Quetiapine extended release: a guide to its use as adjunctive treatment in major depressive disorder
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Quetiapine extended release: a guide to its use as adjunctive treatment in major depressive disorder Gillian M. Keating and Mark Sanford Adis, Auckland, New Zealand
Once-daily oral quetiapine extended release (XR) is effective as an adjunct to antidepressant therapy in the treatment of patients with a major depressive episode and an inadequate response to an antidepressant alone. The tolerability profile of quetiapine XR when administered as adjunctive therapy in patients with major depressive disorder is consistent with that seen in other indications.
What is the rationale for developing the drug? Major depressive disorder (MDD) is a common illness and a leading cause of disability,[1,2] with many patients not experiencing the full benefit of treatment because of inadequate antidepressant dosages, poor treatment adherence, treatment resistance or an incomplete response.[3] Residual depressive symptoms, which are indicative of an incomplete treatment response, are predictive of early relapse, recurrence or a more chronic course.[4] Current treatment guidelines for MDD recommend antidepressants as a first-line treatment option for MDD of moderate severity.[5] For severe MDD, first-line treatment options include electroconvulsive therapy, antidepressants combined with psychotherapy, or an antidepressant combined with an antipsychotic for patients with depression with psychotic features. Antidepressant drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors and newer agents, such as the tetracyclic antidepressants mirtazapine and mianserin.[4] Second-line treatments for patients who have an inadequate response despite optimized dosages of first-line treatments include switching to another antidepressant or combining/augmenting the antidepressant with another drug, such as an antipsychotic.[5] There has been a reemergence of interest in the use of antipsychotics in depression following the observed antidepressant effects of the atypical antipsychotics in major psychoses.[3] One such antipsychotic is quetiapine extended release (quetiapine XR), a once-daily oral sustained-release formulation of the atypical antipsychotic quetiapine.[6] Que-
tiapine XR is marketed under a number of trade names, including Seroquel SR, Seroquel XL, Seroquel XR, Seroquel Prolong and Seroquel Depot.[7-9]
How does the drug work? The antipsychotic effects of quetiapine are thought to be related to antagonism of dopamine D1 and D2 and serotonin 5-HT2A receptors.[8,10] The mechanisms underlying the antidepressant effects of quetiapine are unknown,[9] but may stem from its direct effects on dopamine receptors, increased serotonergic neurotransmission resulting from antagonism and downregulation of cortical 5-HT2A receptors and/or increased prefrontal extracellular dopamine release, as a result of partial agonism of prefrontal 5-HT1A receptors.[11] Norquetiapine, the N-desalkyl metabolite of quetiapine, also
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