Akathisia is a common adverse effect associated with use of dopamine receptor blocking agents.1,2 Symptoms of akathisia, in severe cases, may lead to discontinuation of treatment. Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist approved to treat schizophrenia and acute manic, mixed, and depressive episodes of bipolar 1 disorder. Cariprazine is well tolerated in patients across its indications, but is associated with a higher incidence of akathisia compared with placebo.3,4 This pooled post hoc analysis of data from phase 3 clinical trials of adjunctive cariprazine aimed to characterize the incidence, severity, and management of akathisia and other extrapyramidal symptoms (EPS) in adult patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to cariprazine 1.5 mg/d + ADT, cariprazine 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analysis evaluated incidence, severity, and time to resolution of akathisia, restlessness, and other EPS; use of rescue medications; and the rate of discontinuation due to these treatment-emergent adverse events (TEAEs).

A total of 1508 patients (cariprazine + ADT: 1.5 mg/d, n=502, 3 mg/d, n=503; placebo + ADT, n=503) were included in these 2 studies. The incidence of akathisia was greater with cariprazine 3 mg/d + ADT (9.7%) than with cariprazine 1.5 mg/d + ADT (6.4%) and placebo + ADT (2.0%). Most patients treated with cariprazine + ADT (94%) experienced only mild or moderate akathisia. The incidence of restlessness was 3.8% for patients treated with cariprazine 3 mg/d + ADT, 3.6% for cariprazine 1.5 mg/d + ADT, and 1.8% for placebo + ADT. The incidence of EPS excluding akathisia and restlessness was 4.4% for patients treated with cariprazine 3 mg/d + ADT, 4.6% for cariprazine 1.5 mg/d + ADT, and 3.2% for placebo + ADT. For patients treated with cariprazine + ADT and placebo + ADT, respectively, EPS-related study discontinuations were 1.4% and 0.4% due to akathisia, 0.2% and 0.0% due to restlessness, and 0.1% and 0.4% due to EPS excluding akathisia and restlessness. Rescue medications were used to treat EPS-related TEAEs during the double-blind treatment period in 3% of cariprazine-treated patients and 0.4% of placebo-treated patients. The mean time to resolution of akathisia during treatment was slightly shorter in cariprazine-treated patients (15.6 days) versus placebo-treated patients (19.5 days).

Incidence of akathisia was higher for cariprazine than placebo, with a lower incidence observed for patients treated with cariprazine 1.5 + ADT than with cariprazine 3 mg/d + ADT, suggestive of a dose related effect. Most patients experienced mild or moderate akathisia. Rates of study discontinuation and rescue medication use due to akathisia were low, suggesting that akathisia was tolerated by most patients.

This data was previously presented at the CINP World Congress; Montreal, Canada; May 7-10, 2023.

AbbVie

Anhedonia, a multidimensional domain including the reduced ability to experience pleasure, is a core diagnostic symptom of major depressive disorder (MDD) and a common residual symptom. In patients with MDD, anhedonia has been associated with poor treatment outcomes, suicide and reduced functioning and quality of life. This post-hoc analysis of data from a phase 3 trial (NCT03738215) evaluated the efficacy of adjunctive cariprazine (CAR) treatment on anhedonia symptoms in patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to CAR 1.5 mg/d + ADT, CAR 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analyses evaluated the change from baseline to Week 6 in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, MADRS anhedonia subscale score (items: 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]), and MADRS anhedonia item 8 in the overall modified intent-to-treat (mITT) population and in subgroups of patients with baseline MADRS anhedonia item 8 score of ≥4 or baseline anhedonia subscale score of ≥18. Least square (LS) mean change from baseline to Week 6 was analyzed using a mixed-effects model for repeated measures.

There were 751 patients in the mITT population (CAR + ADT: 1.5 mg/d=250, 3 mg/d=252; placebo + ADT=249). At baseline, 508 (67.6%) patients had MADRS anhedonia item 8 scores ≥4, and 584 (77.8%) had MADRS anhedonia subscale scores ≥18. In the overall mITT population, LS mean change from baseline to Week 6 in anhedonia subscale score was significantly greater for CAR 1.5 mg/d + ADT (-8.4) and CAR 3 mg/d + ADT (-7.9) than for placebo + ADT (-6.8; both P<.05). The LS mean change from baseline in MADRS individual item 8 was also significantly greater for CAR 1.5 mg/d + ADT (-1.7) vs placebo + ADT (-1.3; P=.0085). In both subgroups of patients with baseline anhedonia, CAR 1.5 mg/d + ADT was associated with significantly greater reduction in MADRS total score, MADRS anhedonia subscale score, and MADRS item 8 score compared with placebo + ADT (all P<.05). In the CAR 3 mg/d + ADT group, significantly greater reductions vs placebo + ADT were observed for MADRS total score and MADRS anhedonia subscale score in the subgroup of patients with baseline anhedonia subscale scores ≥18 (both P<.05).

Adjunctive treatment with CAR was associated with a reduction in symptoms of anhedonia relative to adjunctive placebo in patients with MDD and inadequate response to ADT alone. In subgroups of patients with moderate-to-severe anhedonia at baseline, CAR + ADT demonstrated greater improvements than placebo + ADT in overall depressive symptoms and symptoms of anhedonia. These results suggest that adjunctive CAR treatment may be effective for improving symptoms of anhedonia in patients with MDD who have symptoms of anhedonia.

AbbVie

‘DASH for Asthma’ (n 90) was a 6-month randomized controlled trial that demonstrated potential benefits of a DASH (Dietary Approaches to Stop Hypertension) behavioural intervention for improving diet quality and asthma control by comparing intervention to usual care in adults with uncontrolled asthma. The present study examined acceptability and feasibility of the intervention from the perspective of intervention participants and lifestyle coaches.

Grounded in Social Cognitive Theory, the 3-month intensive stage, including three individual and eight group sessions, focused on diet modifications and behavioural self-regulation. The 3-month maintenance stage contained telephone consultations. Participants and lifestyle coaches completed surveys including 5-point Likert scales and open-ended questions. We analysed data using descriptive and inductive content analyses.

Forty-six intervention participants (survey response rate was 65–72 %) and two lifestyle coaches.

Participants and lifestyle coaches were highly satisfied (all mean ratings >4) with individual and group sessions. Participants identified mastery of knowledge and skills (awareness, goal setting, self-monitoring, problem solving), social learning (class members sharing experiences and ideas) and good coaching skills (reflective listening, empathy, motivational counselling) as important contributors to self-efficacy and programme satisfaction. Participants also valued personalized feedback received in individual sessions. Lifestyle coaches viewed participant engagement as a facilitator to effective sessions. Finally, participants and lifestyle coaches identified food tasting as beneficial for observational learning and facilitation of participant engagement. High class attendance and self-monitoring rate also reflected the high engagement among participants.

The DASH behavioural intervention was feasible and highly acceptable to participants with uncontrolled asthma and lifestyle coaches.