123 Adjunctive Brexpiprazole in Patients With MDD and Symptoms of Anxiety: Results From Post-Hoc Analyses of Three Placebo-Controlled Studies

Abstract

Study objectives: Symptoms of anxiety areprevalent in Major Depressive Disorder (MDD) and areassociated with greater illness severity, suicidality,impaired functioning and poor response to antidepressant treatment (ADT). In MDD, anxiety symptoms can beassessed as 'anxious distress' (new DSM‐5 specifier) or'anxious depression' (score =7 on the HAM‐D anxiety/somatization factor). Brexpiprazole is a serotonin‐dopamine activity modulator that is a partial agonist at5‐HT1A and dopamine D2 receptors, and an antagonistat 5‐HT2A and noradrenaline alpha1B/2C receptors‐allat similar potency. Brexpiprazole is approved in the USfor treatment ofschizophrenia, and as adjunctive treatment in MDD. The objective of this post‐hoc analysis wasto assess the efficacy of brexpiprazole as adjunct to ADTin patients with MDDand anxiety symptoms, using thesetwo definitions of anxiety.METHODS: Data were pooled from three randomized,double‐blind, placebo‐controlled studies with similardesigns (Pyxis‐NCT01360645; Polaris‐NCT01360632; Sirius‐NCT02196506). In each study,patients with MDD and an inadequate response to 1‐3ADTs received single‐blind ADT for 8 weeks. Patientswith inadequate response throughout this prospectivephase were randomized to receive either ADT+brexpiprazole (2mg in Pyxis and Sirius; 1mg or 3 mg in Polaris)or ADT+placebo for 6 weeks. Proxies used to categorizepatients as having 'anxious distress' included a score of=2 on the following symptoms at randomization: tension(MADRS item 3 score =3); restlessness (IDS item 24score =2); concentration (MADRS item 6 score =3); orapprehension (HAM‐D item 10 score =3). Scores on theitems of the HAM‐D anxiety/somatization factor atrandomization (baseline) were used to identify patientswith 'anxious depression'. Efficacy was assessed as thechange in MADRS total score from baseline to Week 6.Statistical analysis used a Mixed Model RepeatedMeasure approach using pooled brexpiprazole doses.RESULTS: After 8 weeks of prospective ADT monotherapy, 57.6% (n = 797/1,383) of patients met the criteriafor anxious distress, and 48.5% (n = 671/1,383) foranxious depression. The mean MADRS total score was29.0 for patients with anxious distress in the adjunctivebrexpiprazole (n = 462) group and 29.1 in the placebo(n = 327) group; while those with anxious depressionwere 28.9 (brexpiprazole; n = 384) and 28.6 (placebo;n = 282). Compared to those receiving placebo, patientswith both anxious distress and anxious depression whoreceived adjunctive brexpiprazole showed a greaterimprovement in MADRS total score (LS mean difference‐2.38, p = 0.0001 and‐1.68, p = 0.012, respectively).These improvements, compared to placebo, were similarto those in patients who had not met the criteria foranxious distress (‐1.40, p = 0.023) or anxious depression(‐2.17, p < 0.001).CONCLUSION: Adjunctive brexpiprazole may be efficacious in reducing depressive symptoms both in patientswith or without symptoms of anxiety.