The efficacy of adjunctive Garcinia mangostana Linn. (mangosteen) pericarp extract for bipolar depression: 24-week randomised controlled trial

Olivia M Dean; Susan M Cotton; Melanie M Ashton; Alyna Turner; Lucy Saunders; Chee H Ng; Malcolm Hopwood; Seetal Dodd; Jon-Paul Khoo; Adam J Walker; Mary Lou Chatterton; Bianca E Kavanagh; Sarah E Nadjidai; Samantha L Lo Monaco; Brian H Harvey; Gin S Malhi; Ellie Brown; David R Skvarc; Danica Diao; Felice N Jacka; Jerome Sarris; Nathan L Dowling; Michael Berk

doi:10.1192/bjp.2025.108

The efficacy of adjunctive Garcinia mangostana Linn. (mangosteen) pericarp extract for bipolar depression: 24-week randomised controlled trial

Br J Psychiatry. 2025 Jul 10:1-10. doi: 10.1192/bjp.2025.108. Online ahead of print.

Authors

Olivia M Dean^{1

2}, Susan M Cotton^{3

4

5

6}, Melanie M Ashton¹, Alyna Turner¹, Lucy Saunders¹, Chee H Ng^{5

7}, Malcolm Hopwood⁸, Seetal Dodd^{1

4}, Jon-Paul Khoo^{1

9}, Adam J Walker¹, Mary Lou Chatterton¹⁰, Bianca E Kavanagh¹¹, Sarah E Nadjidai⁷, Samantha L Lo Monaco¹, Brian H Harvey^{1

12

13}, Gin S Malhi^{14

15

16}, Ellie Brown^{3

4}, David R Skvarc¹, Danica Diao¹, Felice N Jacka¹, Jerome Sarris^{2

17

18}, Nathan L Dowling⁷, Michael Berk^{1

2

4

7}

Affiliations

¹ IMPACT Strategic Research Centre, School of Medicine, Deakin University, Barwon Health, Geelong, Australia.
² Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
³ Orygen Ltd, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.
⁴ Centre of Youth Mental Health, The University of Melbourne, Parkville, Australia.
⁵ School of Psychological Sciences, Monash University, Clayton, Australia.
⁶ Turner Institute for Brain and Mind, Clayton, Australia.
⁷ Department of Psychiatry University of Melbourne, The Melbourne Clinic, Professorial Unit, Richmond, Australia.
⁸ Department of Psychiatry University of Melbourne, Albert Road Clinic, Melbourne, Australia.
⁹ Faculty of Medicine, The University of Queensland, Brisbane, Australia.
¹⁰ Deakin University, Institute for Health Transformation, Geelong, Australia.
¹¹ Deakin Rural Health, School of Medicine, Deakin University, Warrnambool, Australia.
¹² Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Potchefstroom, South Africa.
¹³ MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁴ Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia.
¹⁵ CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St. Leonards, Australia.
¹⁶ Department of Psychiatry, University of Oxford, Oxford, UK.
¹⁷ NICM Health Research Institute, Western Sydney University, Westmead, Australia.
¹⁸ Centre for Mental Health, Swinburne University, Melbourne, Australia.

PMID: 40637133
DOI: 10.1192/bjp.2025.108

Abstract

Background: Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

Aims: The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

Method: This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results: Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Conclusions: Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

Keywords: Garcinia mangostana; bipolar disorder; clinical trial; depression; mangosteen pericarp extract.