(270) Indirect treatment comparison of somnolence or sedation with dopamine partial agonists versus D2 receptor antagonists in major depressive disorder and schizophrenia

Background: : Major depressive disorder (MDD) and schizophrenia (SCZ) are often treated with atypical antipsychotics (AAs). AAs can be categorized as dopamine D2 receptor partial agonists (eg, cariprazine) or dopamine D2 receptor antagonists (eg, quetiapine). Some AAs are associated with somnolence and sedation; these side effects can cause desire for sleep, slower reaction times, and impaired performance.

Objective: : Evaluate somnolence/sedation rates associated with dopamine D2 receptor partial agonists vs D2 receptor antagonists in the adjunctive treatment of MDD and the treatment of acute SCZ.

Methods: : Two systematic literature reviews identified relevant clinical trials in MDD and SCZ. The MDD analysis included randomized, double-blind, placebo-controlled, phase II/III trials ≥6wks long evaluating AAs approved by the US FDA for the adjunctive treatment of MDD in adults; somnolence was a required outcome. The SCZ analysis included double-blind, randomized controlled trials with a randomized phase ≥4wks long evaluating AAs for the treatment of acute SCZ in adults (excluding patients with first episode SCZ, predominantly negative symptoms or refractory disease); somnolence/sedation was a required outcome. A Bayesian network meta-analysis evaluated the absolute effect of each treatment on somnolence (MDD) and somnolence/sedation (SCZ) and conducted an indirect treatment comparison of dopamine D2 receptor partial agonists vs antagonists. Relative treatment effects of dopamine D2 receptor partial agonists vs antagonists on somnolence or somnolence/sedation rates were estimated using a binomial likelihood model with a logit link function, with relative effects expressed as Odds ratios (OR) with 95% credible intervals (CrI).

Results: : 10 studies were included in the MDD analysis (8 evaluating partial agonists, 2 evaluating antagonists). The odds of experiencing somnolence were 72% less for patients taking dopamine D2 receptor partial agonists compared with those taking D2 receptor antagonists (OR[95% CrI]: 0.28[0.13, 0.59]). In the SCZ analysis, 50 studies were included (5 studies of partial agonists, 43 of antagonists, 2 of partial agonists vs antagonists vs placebo). The odds of somnolence/sedation were 56% less for patients taking dopamine D2 receptor partial agonists compared with those taking antagonists (OR[95% CrI]: 0.44[0.27,0.77]). Limitations include a disparity in dopamine D2 receptor partial agonist vs antagonist studies in the MDD analysis.

Conclusions: : Dopamine D2 receptor partial agonists may be less likely to cause somnolence (MDD) or somnolence/sedation (SCZ) relative to D2 receptor antagonists.

Sponsorship:: AbbVie