Zinc as an adjunct to antidepressant medication: a meta-analysis with subgroup analysis for different levels of treatment response to antidepressants

ABSTRACT

Objectives: Depressive disorders are severe mental disorders Here, we perform a meta-analysis of the effect of zinc vs. placebo as an adjunct to conventional antidepressants on the scores in the Hamilton Rating Scale for Depression after 6 and after 12 weeks. A systematic literature search found only three such trials (total n = 124 at baseline, n = 103 at 6 weeks (imputed sample size) and n = 103 at endpoint after 12 weeks).

Results

We performed random effects meta-analysis We computed a weighted effect size (Hedges’ g) for the difference of the absolute scores of the Hamilton Depression Rating Scale between the group given zinc and the group given placebo after 6 and after 12 weeks. We performed subgroup analysis according to whether not it was stated in the original studies that patients in a clinical trial or subgroup within a trial had not reached remission with previous treatment with a standard antidepressant during the same illness episode. After 6 weeks, we obtained the following effect sizes: Overall effect size: Hedges’ g = −0.67, p = 0.03. Subgroup with documented non-remission: Hedges’ g = − 0.97, p = 0.001. Group without documented non-remission −0.35, p = 0.24. After 12 weeks: Overall effect size: Hedges’ g = −1.0, p = 0.03. Subgroup with documented non-remission: Hedges’ g = − 1.46, p < 0.001. Group without documented non-remission: Hedges’ g = − 0.54, p = 0.07.

Conclusions

We provide preliminary evidence for the efficacy of zinc vs. placebo as an adjunct to antidepressant medication.

KEYWORDS:

• Antidepressant
• zinc
• depression
• treatment resistance
• nutrition
• meta-analysis
• mental health
• dietary supplement

Acknowledgements

We wish to thank Dr. Karla Thierer for her support with the review process and with the data analysis. We also wish to thank two anonymous reviewers for helpful comments.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

Most of the data can be taken from the original papers.

Additional information

Notes on contributors

Andreas Donig

Andreas Donig: born June 30, 1979, studied psychology with an emphasis on clinical psychology, psychiatry, educational psychology, experimental neuropsychology at the Eberhard Karls University Tübingen, Germany, Diploma (equivalent to a MSc degree) 2017.

Martin Hautzinger

Martin Hautzinger: born Aug 30, 1950, PhD 1980, Seniorprofessor for Clinical Psychology and Psychotherapy at Eberhard Karls University Tuebingen. Full Professor since 1990. Working at several national and international universities: Berlin, Freiburg i.Br., Eugene (Oregon), Konstanz, Mainz, Bogota, Duhok, Tuebingen. More than 60 funded projects focusing mainly on Mood Disorder (Depression, Bipolar) and psychotherapy research. More than 400 peer-reviewed publication and more than 300 books or book chapters since 1977.