Naturalistic follow-up of a micronutrient intervention for children with ADHD : effects on social skills, psychiatric, and executive functioning over 52 weeks.

Type of content
Theses / Dissertations
Publisher's DOI/URI
Thesis discipline
Degree name
Doctor of Philosophy
University of Canterbury
Journal Title
Journal ISSN
Volume Title
Darling, Kathryn Ann

Background: ADHD is a common and chronic neurodevelopmental disorder of childhood, with far-reaching implications throughout the life course. Social skills and executive function are commonly impaired in children with ADHD and are associated with additional functional impairment. There is increasing interest from the public in nutritional approaches to treating a range of psychiatric conditions including ADHD, and a growing body of research showing promise in this area. It is of utmost importance that long-term outcomes are evaluated as well as the short-term efficacy of emerging nutritional treatments. This thesis presents the first study to report naturalistic outcomes after a randomised controlled trial followed by open-label extension using micronutrients to treat ADHD in children. It also investigated the effects of the micronutrient treatment on participants’ social skills and executive function, and used mediation analyses to examine relationships between these variables.

Methods: Ninety-three children aged 7-12, who were diagnosed with ADHD, took part in a 10-week randomised, double-blinded, placebo-controlled trial (RCT) followed by 10-week open label extension. During RCT, participants were randomly allocated in a 1:1 ratio to receive either a broad- spectrum micronutrient (vitamins and minerals) formula or identical placebo. After 10 weeks of RCT, there was an additional 10-week open label phase during which all participants received micronutrients. Follow-up assessments were conducted approximately seven months after participants completed the open label trial. Measures included the Social Skills Improvement System questionnaires (SSIS), Behavioral Rating Inventory of Executive Function (BRIEF), neuropsychological assessments, ADHD rating scales (Conner’s Parent and Teacher Rating Scales and ADHD-RS-IV for clinicians), Strengths and Difficulties Questionnaire (SDQ), Child Mania Rating Scale (CMRS), Screen for Child Anxiety Related Emotional Disorders (SCARED), Child Depression Rating Scale (CDRS), Clinical Global Impressions - Improvement (CGI-I) scale, and the Children’s Global Assessment Scale (CGAS).

Results: Intent-To-Treat (ITT) analyses utilising ANCOVA (n = 93) did not identify any statistically significant differences between groups in amount of change from baseline to 10 weeks (end of RCT) for any measures of social skills or executive function, or for neurocognitive assessments. Re-analysis with the sample of participants who were compliant with trial protocol (‘per-protocol’, n = 75) revealed that the micronutrient group showed greater improvement in problematic social behaviours over 10 weeks than the placebo group, F(1, 72) = 4.12, p = 0.046, d = 0.49. Per-protocol analyses also identified a non-significant trend for the micronutrient group to improve more over 10 weeks than the placebo group on parent-rated global executive function, F(1, 72) = 3.385, p = 0.070, d = 0.43. Consistent with these results, Modified Brinley plots revealed greater improvement for those on micronutrients than placebo on parent-rated problematic social behaviours (d = 0.88 and d = 0.45 respectively) and global executive function (d = 1.02 for micronutrients and d = 0.60 for placebo).

Based on dominant treatment used during the follow-up period, more of those who continued to take the trial micronutrients (84%) were identified as “Much” or “Very Much” improved relative to baseline functioning, compared to 50% of those who switched to psychiatric medications and only 21% of those who discontinued treatment [ꭓ2(2) = 19.5, p < 0.001]. Fifteen (79%) of those still taking micronutrients, 8 (42%) of those using medications, and 7 (23%) of those who discontinued treatment were considered remitters based on parent-reported ADHD [ꭓ2(2) = 15.3, p < 0.001]. Those who stayed on micronutrients were more likely to have failed medication treatment in the past. The micronutrient group also displayed better outcomes on measures of parent-rated hyperactivity and anxiety, and clinician-rated general function and mood, with moderate to large between-group effect sizes (micronutrients vs. medication: ES = 0.73-1.01; micronutrients vs. no treatment: ES = 0.65-1.01). Most common reasons for stopping trial micronutrients were cost and number of pills to swallow. No ongoing side effects were associated with micronutrients.

At one-year follow-up, those who continued trial micronutrients showed more improved social skills, F(2, 58) = 4.222, p = 0.019, and overall executive function, F(2, 57) = 4.170, p = 0.020, than those who discontinued treatment (but not those who switched to psychiatric medication). Within-group effect sizes for change in social skills from 10 to 52 weeks were moderate for the micronutrient group, d = 0.47, large for those who changed to psychiatric medication, d = 0.96, and there was no reliable change for those who discontinued treatment. There were no reliable effects during this time for change in problematic social behaviours or overall executive function for any group.

Mediation analyses suggested that global change in executive function may have mediated the relationship between treatment used during follow up and problematic social behaviours at 52 weeks (continued micronutrients relative to stopping treatment: indirect coefficient = 8.10, SE = 4.15, 95% CI [1.87, 17.59], micronutrients relative to psychiatric medication: indirect coefficient = 5.89, SE = 3.45, 95% CI [0.18, 13.39]).

Conclusions: This research demonstrated that children who stayed on micronutrients longer- term maintained short-term benefits alongside a very favourable side-effect profile. A minority of children who were exposed to micronutrients maintained changes even after stopping them; however, most showed regression in symptoms over the longer period of time. Benefits were observed not only in the core ADHD symptoms, but also across anxiety, mood, and some domains of social and executive function as well. Compared with those who switched to medications or stopped treatment, outcomes overall were more favourable for those on micronutrients.

Ngā upoko tukutuku/Māori subject headings
ANZSRC fields of research
All Rights Reserved