Randomized, Placebo-Controlled Effectiveness Study of Quetiapine XR in Comorbid Depressive and Anxiety Disorders

Nisha Ravindran, MD; Martha McKay, PhD; Angela Paric, PhD; Sunny Johnson, MD; Ranjith Chandrasena, MD; Gaby Abraham, MD; Arun V. Ravindran, MD, PhD

J Clin Psychiatry 2022;83(3):21m14096

ABSTRACT

Objective: Quetiapine is approved as an adjunctive treatment for major depressive disorder (MDD) and as monotherapy for bipolar depression. It is often used off-label for treating anxiety conditions and as an augmentation agent for treatment-resistant depression. However, its benefit in depression with comorbid anxiety disorders has not been systematically evaluated. The current study evaluated the benefit and tolerability of quetiapine as augmentation to first-line antidepressants for MDD comorbid with anxiety disorders.

Methods: In this multicenter trial (June 2008–June 2013), 76 adults (aged 18–65 years) with a primary diagnosis of unipolar depression comorbid with at least 1 anxiety disorder (per DSM-IV-TR criteria) received flexible-dose quetiapine extended-release (XR) 50–300 mg/d or placebo as add-on for 12 weeks in a 2:1 ratio. Depression, anxiety, life satisfaction, and adverse events were assessed.

Results: Depression, anxiety, and function improved significantly in both groups. On primary outcome measures, quetiapine was superior to placebo in improving depression (17-item Hamilton Depression Rating Scale score: mean difference = −3.64; 95% CI, −7.01 to –0.27) and anxiety symptoms (Hamilton Anxiety Rating Scale score: mean difference = –4.02; 95% CI, −7.41 to –0.64), as well as Clinical Global Impressions–Severity of Illness scale score (mean difference = –0.64; 95% CI, −1.13 to –0.15). On secondary measures including the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Penn State Worry Questionnaire, and Quality of Life Satisfaction and Enjoyment Questionnaire, quetiapine produced a greater degree of improvement compared to placebo, but group differences were not statistically significant. Quetiapine was well tolerated, with mostly minor and no serious adverse effects.

Conclusions: Quetiapine augmentation may be a useful intervention for MDD with comorbid anxiety.

Trial Registration: ClinicalTrials.gov Identifier: NCT00688818

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