Seroquel XR For Depression? Two Recent Studies Weigh In.
Suddenly, psychopharmacology has apparently become “all Seroquel, all the time.” AstraZeneca’s atypical antipsychotic (generic name, extended release quetiapine), which already had FDA approval for schizophrenia and bipolar mania, recently won approval for bipolar depression, and is now pushing for indications in depression and generalized anxiety disorder (GAD). Just prior to this newsletter’s publication, the FDA’s psychopharmacology advisory committee recommended against approving the drug for GAD or depression monotherapy, but recommended approval for adjunctive use in depression. In this article, we review the clinical trial evidence for Seroquel XR in depression.
Seroquel XR for monotherapy of major depression. AstraZeneca sponsored a study in which 612 patients with major depression were randomly assigned to 150 mg Seroquel XR, 300 mg Seroquel XR, 60 mg duloxetine (Cymbalta), or placebo for six weeks of active treatment followed by a two-week discontinuation period. Improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) was greater for all three medication groups than for placebo, with no differences between treatment groups. Response rates were significantly higher (50%-55% across the three treatment groups) for participants receiving medication than for placebo (36%). Remission rates for the 300 mg Seroquel XR and Cymbalta groups (32% in each) were statistically significantly higher than placebo (20%), while the small advantage for 150 mg Seroquel XR was not significant (27%) (Cutler AJ et al., J Clin Psychiatry 2009;70:526-539).
Seroquel XR for augmentation of antidepressants. In the treatment augmentation trial, 493 patients who had not responded to at least 6 weeks of antidepressant treatment were randomly assigned to receive either 150 mg Seroquel XR, 300 mg Seroquel XR, or placebo in addition to their current antidepressant for 6 weeks. The response rate for 300 mg Seroquel XR (58%) was significantly higher than placebo (46%), while 150 mg Seroquel XR (55%) did not significantly differ from placebo. Remission rates were 36% for 150 mg Seroquel XR, 31% for 300 mg Seroquel XR, and 24% for placebo; only the advantage for 150 mg Seroquel XR was significant (Bauer M et al., J Clin Psychiatry 2009;70:540-549).
Seroquel XR Side Effects. Sedation was prominent in the monotherapy trial, and was reported by 39% of patients taking 150 mg Seroquel XR, 37% of patients taking 300 mg Seroquel XR, 16% of patients taking Cymbalta, and 5% of placebo patients. This side effect was less pronounced in the augmentation trial (13% of patients on 300 mg Seroquel XR, 10% of patients on 150 mg Seroquel XR, and 4% of patients on placebo). Surprisingly, Seroquel XR did not lead to much more weight gain than placebo. For example, in the monotherapy trial, increases in body weight of > 7% occurred in only 3% of 300 mg Seroquel XR patients, 2% of 150 mg Seroquel XR patients, 1% of Cymbalta patients and no placebo patients, though the trial was only 6 weeks long, probably too short to properly assess this side effect. Rates of clinically elevated glucose levels were 6%- 7% on 300 mg Seroquel XR across studies, which was higher than placebo (1%-3%, depending on the trial). Triglycerides also tended to increase in the Seroquel XR groups relative to placebo. Rates of extrapyramidal symptoms did not appear higher on Seroquel XR in either study.
TCPR’s Take: Seroquel XR appears to be a moderately effective antidepressant, whether used as monotherapy or as adjunctive therapy. As is true for most large studies of antidepressants, the actual clinical magnitude of the benefit over placebo was small-to-modest. For example, looking at the MADRS scores in the monotherapy study, patients on placebo improved 75% as much as patients on 150 mg Seroquel XR and 73% as much as patients on 300 mg Seroquel XR. This is similar to the contribution of placebo to antidepressant response for most other approved antidepressants, according to a wellknown meta-analysis (Khan A. et al. Arch Gen Psychiatry 2000;57:311-317). A similar picture emerged in the augmentation study, with placebo patients improving 80% as much as patients taking 150 mg Seroquel XR and 82% as much as those taking 300 mg Seroquel XR.
While sedation was a troublesome side effect in these studies, Seroquel XR led to relatively little weight gain or metabolic abnormalities, presumably a reflection of the short time periods of the studies. Patients are typically kept on antidepressants for at least a year after an episode, and using Seroquel XR when equally effective but more tolerable antidepressants are available seems unwise in this context. At this point, the FDA has not yet announced its final decision regarding Seroquel XR, so any use in unipolar depression or anxiety is off-label.
The bottom line is that Seroquel XR is effective for depression, but the side effect burden should make it a third or fourth line choice for our patients.