Seroquel XR Approved as Add-On Treatment for Major Depressive Disorder - after two 6-week, multicentre studies

Seroquel XR Approved as Add-On Treatment for Major Depressive Disorder


March 1, 2011 By marie-catherine.mousseau@mims.ie Leave a Comment

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AstraZeneca announced that once daily Seroquel XR (quetiapine) has been approved for add-on treatment of major depressive episodes in patients with Major Depressive Disorder (MDD) who have had sub-optimal response to antidepressant monotherapy.



MDD is currently treated with antidepressants, such as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin norepinephrine reuptake inhibitors). However, these treatments do not always fully satisfy the needs of patients or physicians. Studies have shown at least one-third of patients fail to achieve a satisfactory response with such antidepressants, even after two to three rounds of therapy,and side effects may interfere with treatment compliance1.To address these issues, other drug classes have been investigated as adjuncts to standard antidepressant therapy, including the antipsychotic drug Seroquel XR.



The new approval follows results from clinical studies showing that treatment with Seroquel XR provides significant symptom relief and is generally well tolerated in patients with MDD who do not respond adequately to current treatments2.



The mode of action of the Seroquel XR has not been fully understood, but both quetiapine and its metabolite norquetiapine have moderate-to-high affinity for serotonin 5-HT2A and dopamine D2 receptors. Norquetiapine is also a potent inhibitor of the norepinephrine transporter, which could account for its antidepressant action2.







Study Design



Two double-blind, randomised, placebo-controlled studies evaluated adjunctive extended release quetiapine fumarate (quetiapine XR) in patients with MDD showing inadequate response to antidepressant treatment. During these two 6-week, multicentre studies, a total of 919 participants received once-daily quetiapine XR 150mg/day, 300mg/day or placebo adjunctive to ongoing antidepressant therapy. The larger sample size obtained from pooling these two studies enabled Bauer and colleagues to conduct sub-group analyses to examine the efficacy of quetiapine XR against specific depressive symptoms including inner tension and pessimistic thoughts. Additionally, a preplanned pooled analysis was conducted to evaluate the influence of demographic and disease related factors on patients responses.



The primary endpoint was change from randomisation to Week 6 in the MontgomeryÅsberg Depression Rating Scale (MADRS) total score. Other assessments included the percentage of MADRS responders (50% decrease in MADRS total score) and change in the scores of the individual MADRS items.







Seroquel XR improved depressive symptoms as early as week 1



Quetiapine XR (150 and 300 mg/day) significantly reduced MADRS total scores vs. placebo as early as week 1, and up to week 6 of the trial (see Figure 1). The percentage of MADRS responders was also significantly greater at Week 1 with both doses of quetiapine XR compared with placebo (Figure 2). At week 6, quetiapine XR 300mg/day (but not 150 mg/day) was associated with significantly greater MADRS response rates than placebo.







Seroquel XR showed efficacy across a broad range of depressive symptoms



Quetiapine XR demonstrated consistent improvements in individual MADRS items observed as early as Week 1 and up to week 6 with both doses of quetiapine XR (Figure 3). In particular, a significant improvement in sleep a core symptom of depression was noted. Beyond sleep, quetiapine XR improved other MADRS items such as apparent and reported sadness, and inability to feel.



These analyses also demonstrated that improvement in depressive symptoms with quetiapine XR was neither limited nor driven by factors such as severity of depression, concomitant antidepressant, gender or age.



The results show that, overall, adjunctive quetiapine XR was generally well tolerated, with safety profile consistent with that documented for its acute use in other psychiatric illnesses. Side-effects included somnolence, sedation and weight gain findings that are consistent with the recommendation to administer quetiapine XR at bedtime at the lowest effective dose (starting with 50mg/day).







Conclusion



This pooled analysis shows adjunct Seroquel XR (150mg/day and 300mg/day) to be significantly more effective then add on placebo at improving a broad range of symptoms associated with major depressive disorder, with improvement seen as early as Week 1. Seroquel XR was also found to be generally well tolerated.



An inadequate response to antidepressant treatment is a well recognised problem in the management of mood disorders. Patients experiencing sub-optimal responses to antidepressant therapy experience greater functional impairment and have an increased risk of depressive relapse said Dr. Robert Daly, Consultant Psychiatrist at St. Itas Hospital, Dublin, Seroquels recent indication as an add-on treatment for major depressive disorder in patients who have had sub-optimal response to antidepressant monotherapy will provide physicians with a helpful management strategy for this common and challenging clinical problem.



Seroquel XR is the first and only atypical antipsychotic to be approved in Europe as an add-on treatment of MDD in patients who have had sub-optimal response to antidepressant monotherapy.



Prior to initiating treatment clinicians should consider the safety profile of Seroquel XR.



References



1- Nemeroff, CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007;68(Suppl 8):17-25.



2- Bauer M, El-Khalili N, Datto C, et al. J Affect Disord. 2010;127:19-30