Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct 27;52(4):8-30.
doi: 10.64719/pb.4448.

Adjunctive Pimavanserin in Patients with Major Depressive Disorder: Combined Results from Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies

Bryan Dirks  1 , Maurizio Fava  2 , Sarah D Atkinson  3 , Mark Joyce  4 , Michael E Thase  5 , Becky Howell  6 , Tim Lin  7 , Serge Stankovic  8
Affiliations

Adjunctive Pimavanserin in Patients with Major Depressive Disorder: Combined Results from Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies

Bryan Dirks et al. Psychopharmacol Bull. .

Abstract

Objective: In a phase 2 study, pimavanserin demonstrated efficacy as adjunctive treatment for major depressive disorder (MDD). Subsequently, two phase 3 studies (NCT03968159 in the US; NCT03999918 in Europe) were initiated to examine the efficacy and safety of adjunctive pimavanserin in subjects with MDD and inadequate response to antidepressant treatment. Studies were combined with a prespecified statistical analysis plan owing to recruitment challenges related to the COVID-19 pandemic.

Experimental design: The randomized, double-blind studies enrolled 298 patients with MDD and inadequate response to current antidepressants. Patients were randomly assigned 1:1 to pimavanserin or placebo added to current antidepressant for 6 weeks. Primary endpoint was change from baseline to week 5 in the Hamilton Rating Scale for Depression, 17-item version (HAM-D-17).

Principal observations: There was no effect of pimavanserin in change from baseline to week 5 in the HAM-D-17 (pimavanserin [n = 138]: least-squares mean [LSM] [standard error {SE}], -9.0 [0.58]; placebo [n = 135]: -8.1 [0.58]; mixed-effects model for repeated measures LSM [SE] difference, -0.9 [0.82], P = 0.2956). Nominal improvement with pimavanserin was observed on 2 secondary endpoints: Clinical Global Impressions-Severity scale, Karolinska Sleepiness Scale. Treatment-emergent adverse events occurred in 58.1% of pimavanserin-treated and 54.7% of placebo-treated patients.

Conclusions: Adjunctive pimavanserin did not significantly improve depressive symptoms, although pimavanserin was well tolerated.

Keywords: MDD; antidepressant agents; anxious depression; controlled study; pharmacotherapy; pimavanserin; randomized.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Change from Baseline to Week 5 in the HAM-D-17 Total Score (LSM ± SE)
Figure 2
Figure 2
Treatment Differences in LSM Change from Baseline to Week 5 in HAM-D-17 Total Score in Prespecified Subgroups
Figure 3
Figure 3
Change from Baseline by Visit (LSM ± SE) in CGI-S (A), KSS (B), CSFQ-14 (C), and SDS (D)
Figure S1
Figure S1
Patient Disposition
See this image and copyright information in PMC

References

    1. Global Burden of Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet . 2018;392(10159):1789–1858. doi: 10.1016/S0140-6736(18)32279-7. doi: - DOI - PMC - PubMed
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders . (5th Edition) 2013 American Psychiatric Association.
    1. Otte C, Gold SM, Penninx BW et al. Major depressive disorder. Nat Rev Dis Primers . 2016;2:16065. doi: 10.1038/nrdp.2016.65. doi: - DOI - PubMed
    1. Forte A, Baldessarini RJ, Tondo L, Vazquez GH, Pompili M, Girardi P. Long-term morbidity in bipolar-I, bipolar-II, and unipolar major depressive disorders. J Affect Disord . 2015;178:71–78. doi: 10.1016/j.jad.2015.02.011. doi: - DOI - PubMed
    1. Kessler RC, Berglund P, Demler O et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) JAMA . 2003;289(23):3095–3105. doi: 10.1001/jama.289.23.3095. doi: - DOI - PubMed