Evidence map›Paper›PMID 30678686›Full record

Trial reportBMC medicine2019

A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo.

Michael Berk, Alyna Turner, Gin S Malhi, Chee H Ng, Susan M Cotton, Seetal Dodd, Yuval Samuni, Michelle Tanious, Claire McAulay, Nathan Dowling and 5 more

Erratum issuedOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 7 pooled it
10.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 7 syntheses or guidelines pooled it, 97 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. A Systematic Review of Nutraceuticals for the Treatment of Bipolar Disorder.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2021
    Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Trial
  10. Trial
  11. Review
  12. Article
  13. Review
  14. Mitochondrial dysfunction: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2024
    Review
  15. Review
  16. Article
  17. Article
  18. Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2023
    Article
  19. Review
  20. The Impact ofClinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 9 institutions in 2 countries.

Michael BerkIMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia. mikebe@barwonhealth.org.au.
Alyna TurnerIMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.
Gin S MalhiCADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.
Chee H NgDepartment of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.
Susan M CottonOrygen, The National Centre of Excellence in Youth Mental Health, 35 Poplar Rd, Parkville, VIC, Australia.
Seetal DoddIMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.
Yuval SamuniIMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.
Michelle TaniousCADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.
Claire McAulayCADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.
Nathan DowlingDepartment of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.
Jerome SarrisDepartment of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.
Lauren OwenSchool of Psychology, University of Central Lancashire, Preston, UK.
Astrid WaterdrinkerMelbourne Health, 300 Grattan St, Melbourne, VIC, Australia.
Deidre SmithDepartment of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.
Olivia M DeanIMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.
University of Melbourne · AUDeakin University · AURoyal North Shore Hospital · AUMelbourne Clinic · AUMelbourne Health · AUNorthern Sydney Local Health District · AUOrygen Youth Health · AUThe Royal Melbourne Hospital · AUUniversity of Central Lancashire · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis.

methodsA three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes.

resultsOne hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group.

conclusionsThese overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction.

trial registrationANZCTR ( ACTRN12612000830897 ).

Indexed as

Dietary SupplementsAcetylcysteineAdultBipolar DisorderCombined Modality TherapyDouble-Blind MethodFemaleHumansMaleMiddle AgedMitochondriaTreatment OutcomeAcetylcysteineAdjunctiveBipolar disorderDepressionMitochondriaNutraceuticalOxidative stress

Identifiers

PMID30678686
PMCPMC6346513
OpenAlexW2918722353

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.