Effects of escitalopram on sleep problems in patients with major depression or generalized anxiety disorder

Introduction: Disturbed sleep is a key symptom in major depressive disorder (MDD) and generalized anxiety disorder (GAD). First-line antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs), may have different effects on sleep. Methods: Data from 22 randomized, controlled trials comparing escitalopram with SSRIs, SNRIs, or placebo in the treatment of adult MDD or GAD were included. Both last observation carried forward (LOCF) and repeated measurements (MMRM) were used to analyze the sleep item of the Montgomery Åsberg Depression Rating Scale (MADRS) or Hamilton Anxiety Rating Scale (HAM-A) after 8 weeks of treatment. Sleep-related treatment-emergent adverse events were also compared across groups. Results: For patients with MDD (n=5133), the treatment difference on MADRS item 4 ("reduced sleep") was significantly in favor of escitalopram versus placebo (LOCF [P=0.0017] and MMRM [P=0.0002]), versus SSRIs (LOCF [P=0.0020] and MMRM [P<0.0031]), and versus SNRIs (LOCF [P=0.0002] and MMRM [P=0.0352]). For the 53% of patients with MDD who suffered from sleep problems at baseline (baseline MADRS item 4 score ≥4), the improvement in sleep symptoms was significantly in favor of escitalopram versus placebo (LOCF [P=0.0022] and MMRM [P<0.0005]), versus SSRIs (LOCF [P=0.0001] and MMRM [P=0.0002]), and versus SNRIs (LOCF [P<0.0067] but not MMRM [P>0.0787]). For patients with GAD (n=2052) the treatment difference in sleep symptoms measured by HAM-A item 4 ("insomnia") was significantly in favor of escitalopram versus placebo (LOCF [P=0.0005] and MMRM [P<0.0001]), but not different to paroxetine or venlafaxine. The same pattern was seen for the large proportion (67%-82%) of GAD patients reporting sleep problems at baseline (baseline HAM-A item 4 score ≥2). In MDD, the rate of insomnia as an adverse event after escitalopram was higher than placebo, similar to SSRIs, and lower than SNRIs. Conclusions: Additional research assessing the comparative effects of antidepressants with polysomnography is needed. In the interim, from a clinical perspective, escitalopram appears to be beneficial for the treatment of sleep problems in MDD and GAD.