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Zinc sulphate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial

Akhondzadeh, S., Mohammadi, M-R, Khademi, M. (2004) BMC Psychiatry 4:9  

Web URL: View this and related abstracts via PubMed here. Free full text of this article is available from th


Background: Attention-deficit hyperactivity disorder is an early-onset, clinically heterogenous disorder of inattention, hyperactivity, and impulsiveness. The diagnosis and treatment of attention-deficit hyperactivity disorder continues to raise controversy, and, there is also an increase in treatment options. In this 6-week double blind, placebo controlled-trial, we assessed the effects of zinc plus methylphenidate in the treatment of children with attention deficit hyperactivity disorder. To the best of our knowledge, this study is the first double blind and placebo controlled clinical trial assessing the adjunctive role of zinc in ADHD.

Methods: Our subjects were 44 outpatient children (26 boys and 18 girls) between the ages of 5-11 (mean +/- SD was 7.88 +/- 1.67) who clearly met the DSM IV diagnostic criteria for attention-deficit hyperactivity disorder and they were randomized to methylphenidate 1 mg/kg/day + zinc sulfate 55 mg/day (with approximately 15 mg zinc element) (group 1) and methylphenidate 1 mg/kg/day + placebo (sucrose 55 mg) (group 2) for a 6 week double blind clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 14, 28 and 42 days after the medication started.

Results: The present study shows the Parent and Teacher Rating Scale scores improved with zinc sulfate over this 6-week, double blind and placebo controlled trial. The behavior of the two treatments was not homogeneous across the time. The difference between the two protocols was significant as indicated by the effect on the group, the between-subjects factor (F = 4.15, d.f.=1, P = 0.04; F = 4.50, d.f.=1, P = 0.04 respectively). The difference between the two groups in the frequency of side effects was not significant.

Conclusions:This double-blind, placebo-controlled study demonstrated that zinc as a supplementary medication might be beneficial in the treatment of children with attention-deficit hyperactivity disorder. However, further investigations and different doses of zinc are required to replicate these findings in children with ADHD.


See also the controlled trial by Bilici et al 2004, in which zinc sulphate as a sole therapy also reduced ADHD symptoms.

These results add weight to those of previous experimental studies in supporting the proposal made many years ago by the UK Hyperactive Children’s Support Group - that zinc deficiency and/or its effects on fatty acid metabolism could play a causal role in ADHD. (See Colquhoun and Bunday,1981.)

Considerable evidence now supports the idea that zinc deficiency is often associated with ADHD, but further controlled trials are still needed to establish any firm causal link. For a review of this area see:

A key issue that complicates research in this area is that the 'ADHD' diagnosis is purely descriptive, with many possible causes that can vary between individuals. It is therefore unreasonable to expect that any one treatment will help all individuals with this condition - but as zinc deficiency is relatively simple and cheap to remedy, it is a possibility worth considering, particularly as there are suggestions that zinc status may help to moderate the effects of other treatment. See