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J Affect Disord. 2010 Nov;126(3):447-52. doi: 10.1016/j.jad.2010.04.024. Epub 2010 May 20.

Serum zinc level in depressed patients during zinc supplementation of imipramine treatment.

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Department of Psychiatry, Jagiellonian University, Collegium Medicum, Kraków, Poland.



Recurrent major depression is associated with decreased blood zinc concentrations that may be increased by effective antidepressant therapy. Some clinical investigations point to alterations of the zinc level in blood as a potential marker of depression.


A placebo-controlled, double blind study of zinc supplementation to imipramine therapy was conducted on sixty patients fulfilling the DSM-IV criteria for major depression (18-55 years old, 40 females, 20 males). Moreover, a group of 25 healthy volunteers was recruited (16 females, 9 males). Blood samples were drawn for the assay of serum zinc once from the control subjects and four times (before, and then 2, 6 and 12 weeks after the beginning of treatment) from the depressed subjects.


We report that: 1) the serum zinc level was significantly lower (by 22%) in depressed patients than in healthy volunteers, 2) all groups demonstrated a gradual increase in zinc concentrations over the period of imipramine treatment with or without zinc supplementation, 3) treatment-resistant patients demonstrated lower concentrations of zinc (by 14%) than treatment-non-resistant patients, 4) zinc concentrations were higher in zinc-supplemented patients than in placebo-supplemented patients, 5) zinc supplementation increased zinc concentrations over the period of treatment, and 6) at a 12-week imipramine treatment, a significant negative correlation was demonstrated between the Montgomery-Asberg Depression Rating Scale and the serum zinc level together with a concomitant increase in serum zinc in patients in remission.


Serum zinc is a state marker of depression.

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