Progress in Neuro-Psychopharmacology and Biological Psychiatry
Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder
Introduction
Attention deficit hyperactivity disorder (ADHD) is a serious, high-incidence disorder that impairs academic learning, disrupts social and peer relations, and can greatly disturb functioning within the home and at school. ADHD is characterized by symptoms of inappropriate inattention, impulsivity, and overactivity, according to DSM criteria (American Psychiatric Association, 1994). Although many studies have been carried out regarding the aetiology of ADHD, no definite cause of the illness has yet been determined.
In the recent years, some research into the role of trace elements in enlightening the aetiology of ADHD had been conducted. Most notable among the studies are the ones particularly examining the relationship between zinc and ADHD. Both animal and human study suggest that involvement of zinc deficiency plays a major role in hyperactivity (Golub et al., 1996). Human zinc deficiency syndrome leads to concentration impairment and jitters (Agget and Harries, 1979), and can delay cognitive development (Black, 1998). Some investigators have reported that zinc was found to be significantly deficient in ADHD compared to controls Bekaroglu et al., 1996, Kozielec et al., 1994; and we concluded that zinc deficiency might play a role in the aetiopathogenesis of ADHD (Bekaroglu et al., 1996). In addition we reported previously a significant correlation between serum zinc and serum free fatty acid (FFA) levels in patients with ADHD, who had significantly lower FFA and zinc than those of healthy controls (Bekaroglu et al., 1996). With those findings, it may suggest that zinc and fatty acids may be used in ADHD treatment.
In spite of the good response of many patients with ADHD to stimulant drugs, a substantial percent do not respond to or develop significant side effects from stimulants. For this reason, new investigations have been initiated for ADHD treatment. As an example, it has been shown in some research that if ephamol is given to children with ADHD having a lack of essential fatty acids, a rise is observed in the plasma levels of dihomo-δ-linolenic acid, while some patients recover from hyperactivity (Mitchell et al., 1987). Similarly, zinc treatment has been considered to show positive results on various symptoms in ADHD patients with zinc deficiency. Zinc supplementation is hypothetically supported by systematic case-control data, but no systematic clinical trial. If it is not to consider the coadministration of zinc with other medication in the treatment of ADHD (Arnold et al., 2000), as far as we know, there is no double-blind placebo-controlled study on the effect of the administration of zinc in the treatment of ADHD.
Using that study, the authors undertook a confirmatory, randomised, placebo-controlled, parallel-group study to more definitively address the issue of efficacy of zinc for ADHD symptoms. Our primary hypothesis was that zinc administration would lead to significantly greater reduction in ADHD symptoms than would placebo, as determined by using the Attention Deficit Hyperactivity Disorder Scale (ADHDS). Secondary aims were addressed to possible patterns of response, safety and tolerability.
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Study design
This study was conducted in the Department of Psychiatry, Karadeniz Technical University (KTU), Trabzon, Turkey. During the school year from 1996–1997, a two-phase surveillance was conducted on a total of 21979 primary school children throughout the primary schools from Trabzon province (10 805 girls and 11 174 boys) between the ages of 6 and 14 (the mean 9.05±1.9 years) in the first five grades.
Demographic characteristics
Of the 618 patients screened for study inclusion, 400 were randomly assigned to receive zinc (n=202) or placebo (n=198). Data from all 400 patients were used in the evaluation of the safety of zinc, and data from 95 and 98 patients in the respective treatment groups were used in the evaluation of efficacy (Fig. 1). Some sociodemographic and baseline clinical and laboratory characteristics of the patients are given in Table 1. At baseline, all patients had an ADHDS total score ≥65, and there
Discussion
The most widely used medications for ADHD are the psychostimulants methylphenidate and amphetamine (Popper, 2000). There is, however, considerable interest in alternative, nonstimulant therapies, because some patients respond inadequately to stimulants or are unable to tolerate them. In addition, some physicians are unenthusiastic to use stimulants because of concerns about misuse in a population at increased risk for substance abuse (Wilens and Biederman, 1992).
In this study, zinc was
Conclusion
In conclusion, this double-blind, placebo-controlled study demonstrated that zinc is effective and well tolerated in patients with ADHD. In the treatment of ADHD zinc sulfate displayed positive effects on the symptoms of ADHD, although these were somewhat limited. For this reason, it is suggested that the treatment of zinc in ADHD would be more beneficial as a supplementary medication rather than by itself. The response of zinc treatment would be augmented in cases that have low pretreatment
Acknowledgements
This study was supported in part by the Research Foundation of Karadeniz Technical University, and Karadeniz Mental Health Foundation, Trabzon, Turkey.
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