Antidepressant treatment effects and country income: meta-regression analysis of individual participant data from duloxetine trials

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Thomas Klein - , Center for Evidence-Based Healthcare, Ulm University (Author)
  • Stefan Weinmann - , Rudolf-Sophien-Stift, University of Basel (Author)
  • Thomas Becker - , Ulm University (Author)
  • Markus Koesters - , Ulm University (Author)

Abstract

Objective: In recent decades, significant numbers of pharmaceutical trials have gradually been relocated to low- and middle-income countries. However, there is little evidence regarding the transferability of trial outcomes across countries. Analysing duloxetine randomised controlled trials (RCTs) conducted in different countries, we investigated whether per capita gross national income (GNI) and healthcare expenditure (HE) are associated with pre-post mean changes of depression severity and differences in duloxetine-placebo effect sizes. Method: Meta-analyses included RCTs investigating duloxetine efficacy in patients with depression. Individual participant data (IPD) from multi-centre duloxetine trials were provided by the manufacturer. Data extracted from published reports also entered analyses in case of trials conducted in only one country. A meta-regression approach was applied to analyse associations of GNI and HE with standardised pre-post mean change using raw score standardisation (SMCR) and comparative effect size, that is, the mean differences (MD) in pre-post effect size between duloxetine and placebo treatment. Results: 23 trials with 8417 randomised participants entered analyses. Regression coefficients indicated a negative linear relationship of SMCR with GNI (z-standardised β = −3.61, R2 = 14.8%, p < 0.001) and HE (β = −4.72, R2 = 24.8%, p < 0.001) for participants treated with duloxetine. Similar associations were found for placebo treatment (GNI: β = −3.52, R2 = 23.8%, p < 0.001; β = −3.34, R2 = 21.0% p < 0.001). Neither GNI nor HE was associated with the MD between duloxetine and placebo pre-post differences. Conclusions: Findings challenge the idea of the universal transferability of antidepressant trial outcomes across countries. Understanding the results of antidepressant RCTs demands more sophisticated clarification of context factors involved in determining effectiveness of antidepressant medication and should be discussed with a view to socio-economic context in their countries of origin.

Details

Original languageEnglish
Pages (from-to)277-287
Number of pages11
JournalActa psychiatrica Scandinavica
Volume144
Issue number3
Publication statusPublished - Sept 2021
Peer-reviewedYes

External IDs

PubMed 34139020
ORCID /0000-0001-7018-6021/work/168207928

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • duloxetine hydrochloride, global health, major depressive disorder, meta-analysis