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A randomised, placebo-controlled 24-week study evaluating adjunctive brexpiprazole in patients with major depressive disorder

Published online by Cambridge University Press:  18 September 2018

Michael Bauer ,
Nanco Hefting ,
Annika Lindsten ,
Mette Krog Josiassen  and
Mary Hobart
Michael Bauer*
Affiliation:
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
Nanco Hefting
Affiliation:
H. Lundbeck A/S, Valby, Denmark
Annika Lindsten
Affiliation:
H. Lundbeck A/S, Valby, Denmark
Mette Krog Josiassen
Affiliation:
H. Lundbeck A/S, Valby, Denmark
Mary Hobart
Affiliation:
Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA
*
Author for correspondence: Michael Bauer, Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. E-mail: Michael.Bauer@uniklinikum-dresden.de
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Abstract

Objective

To evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.

Methods

The study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation. Patients with early response to open-label ADT were withdrawn at Week 6. Patients fulfilling criteria for inadequate response were randomised to ADT+brexpiprazole 1–3 mg/day, or ADT+placebo. The primary endpoint was full remission: Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.

Results

The primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (−0.4; p=0.3259). The most frequent treatment-emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole group and 3.4% in the ADT+placebo group.

Conclusion

Adjunctive brexpiprazole did not differentiate from ADT+placebo on the primary endpoint of full remission. A number of design elements in this previously untried study design may have contributed to the study result. Brexpiprazole was well tolerated.

Keywords

antipsychoticclinical trialsdepression
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 31 , Issue 1 , February 2019 , pp. 27 - 35
Copyright
© Scandinavian College of Neuropsychopharmacology 2018 

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