Effect of Adjunctive Cariprazine Treatment on Anxiety and Somatization Symptoms in Patients with Major Depressive Disorder: A Post Hoc Analysis

Introduction Patients with major depressive disorder (MDD) commonly experience comorbid anxiety and somatization, which can complicate treatment. Adjunctive therapy with atypical antipsychotics can be an effective treatment option for patients with MDD who had inadequate responses to antidepressant therapy (ADT) alone. Cariprazine is a dopamine D 3 -preferring D 3 /D 2 and serotonin 5-HT 1A receptor partial agonist that is approved as an adjunctive treatment for MDD. This post hoc analysis examined the effect of adjunctive cariprazine therapy on anxiety and somatization symptoms in patients with MDD. Methods A post hoc analysis was conducted using data from a phase 3, double-blind, placebo-controlled, fixed-dose study of patients with MDD who had inadequate responses to ADT alone. Patients were randomized (1:1:1) to receive ADT plus cariprazine 1.5 mg/d, 3 mg/d, or placebo for 6 weeks. The least squares (LS) mean change from baseline to week 6 in Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization subscale was measured. The Anxiety/Somatization subscale includes six HAM-D items: anxiety-psychic, anxiety-somatic, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. The modified intent to treat population included 751 patients (placebo=249; cariprazine 1.5 mg/d=250; cariprazine 3 mg/d=252). Results The LS mean change from baseline in HAM-D Anxiety/Somatization subscale at week 6 was significantly greater than placebo + ADT for both cariprazine + ADT dose groups (placebo: -3.22; cariprazine 1.5 mg/d: -4.00, P <.001; 3 mg/d: -3.75, P <.05). LS mean change from baseline in the cariprazine 1.5 mg/d + ADT group was also significantly greater than placebo + ADT on the anxiety-psychic (placebo: -0.88; cariprazine 1.5 mg/d: -1.08, P <.01) and anxiety-somatic (placebo: -0.78; cariprazine 1.5 mg/d: -0.96, P <.05) items. In patients treated with cariprazine 3 mg/d + ADT, LS mean changes from baseline on anxiety-psychic and anxiety-somatic items were numerically larger than placebo + ADT but not statistically significant. Both cariprazine + ADT dose groups had significantly larger LS mean changes compared with placebo + ADT on the gastrointestinal somatic symptoms item (placebo: -0.51; cariprazine 1.5 mg/d: -0.66, P <.01; cariprazine 3 mg/d: -0.68, P <.01). General somatic symptoms, hypochondriasis, and insight items showed no significant difference between placebo + ADT and cariprazine + ADT groups. Conclusions Patients treated with adjunctive cariprazine demonstrated greater improvements than patients treated with adjunctive placebo on HAM-D Anxiety/Somatization subscale scores, as shown by reduced scores on anxiety-psychic, anxiety-somatic, and gastrointestinal items. These findings suggest adjunctive cariprazine therapy may be effective in reducing anxiety and somatization symptoms in patients with MDD. Funding AbbVie Study Registration Number: NCT03738215