Management of Adverse Events

Abstract

Adverse effects of stimulant medications include decreased appetite, sleep disturbance, headaches, irritability, nervousness, stomach upset, abdominal pain, nausea, abdominal discomfort, weight loss, tearfulness, stuttering, dizziness, increased heart rate and blood pressure.

Alternative Approaches from Scottish Guidelines

The following is directly from the Scottish Guidelines; please refer to the permission listing at the beginning of the book.

Nutrition and Complementary and alternative Therapies

Nutrition

This section examines the evidence base for dietary manipulation and supplementation as an alternative or complementary intervention in the treatment of core ADHD/HKD symptoms. Investigation of the role of dietary factors in the causation of ADHD/HKD was outside the guideline remit.

8.1.1 food additives

There is evidence from well controlled studies that some food colourants and preservatives can have adverse behavioural effects on children both in the general population and in those diagnosed with ADHD/HKD. ^134,135

In two studies in non-clinical populations of children aged three years and eight/nine years, mixed artificial colourants (sunset yellow, tartrazine, carmoisine and ponceau 4R) or the preservative sodium benzoate, or both, exacerbated hyperactive behaviours as rated by parents.

The nature of the response is individual and appears to have a pharmacological rather than an allergic mechanism. ^136,137

A meta-analysis of additive-free diets followed by food challenges in children with hyperactive disorders showed that pathological responses to foods were multiple and idiosyncratic although the most common responses were to the artificial colourant tartrazine and the preservative sodium benzoate. ¹³⁸

Avoiding foods and drinks that contain certain artificial colours and/or preservatives may help some children with ADHD/HKD. Parents should be advised to take reasonable steps to limit the number and variety of these in their children’s diets, excluding any item that seems to provoke an extreme physical or behavioural reaction.

8.1.2 omega-3 and omega-6 fatty acid supplementation

Three systematic reviews of studies of the effectiveness of fatty acid supplementation in children with ADHD/HKD reported a range of methodological difficulties in the trials included. ^134,138,139

No consistent evidence was identified and meta-analysis of study results was not possible.

8.1.3 iron supplementation

In a small (n = 23) well conducted, placebo controlled RCT of ferrous sulphate supplementation in French school children with ADHD/HKD who had low ferritin stores but were not clinically anaemic, there were significant decreases in symptom scores over 12 weeks (ADHD/HKD Rating Scale, p < 0.008; Clinical Global Impression Scale, p < 0.01). ¹⁴⁰

Clinicians should consider iron status when taking a history, with measurement of serum iron and ferritin, and treatment, where appropriate.

8.1.4 zinc supplementation

A single RCT on zinc sulphate monotherapy as a treatment for ADHD/HKD found a significant therapeutic response but the validity of these findings was compromised by a high drop-out rate. ¹⁴¹

A small study (n = 44) examining the effect of zinc supplementation on the response to methylphenidate in medication-naive children with ADHD/HKD, found that the group taking methylphenidate and zinc improved significantly more than those on methylphenidate and placebo as judged by Du Paul scale parent ratings (p < 0.048) and teacher ratings (p = 0.04). ¹⁴²

There is insufficient evidence on which to base a recommendation.

8.1.5 antioxidants

One controlled study was identified using the antioxidant Pycnogenol®, derived from maritime pine bark, in children diagnosed with a hyperkinetic disorder or attention deficit disorder. A significant effect on hyperactivity scores compared with the baseline and a placebo was seen after one month on treatment. The effects disappeared after a further month without treatment. ¹⁴³

This trial has not been replicated.

8.2 complementary and alternative therapies

There is insufficient evidence on which to base any recommendations for complementary or alternative therapies in the treatment of ADHD.

8.2.1 bach flower remedies

One small placebo controlled RCT found no effect for Bach flower remedies (five flower essences) in the treatment of children with ADHD/HKD. ¹⁴⁴

8.2.2 homeopathy

A well conducted Cochrane meta-analysis identified four small trials of homeopathic treatments.

The study concluded that there is little evidence of efficacy. ¹⁴⁵

8.2.3 massage therapy

One small, short term RCT study found that twice weekly massage therapy improved short term mood state and classroom behaviour in young people with ADHD/HKD. ¹⁴⁶

8.2.4 neurofeedback

Neurofeedback is presently considered to be an experimental intervention in children and young people with ADHD/HKD. There are no standardised interventions. ^147,148

Related references from Scottish Guidelines

134. Rojas NL, Chan E. Old and new controversies in the alternative treatment of attention-deficit hyperactivity disorder. Mental Retardation & Developmental Disabilities Research Reviews 2005;11(2):116–30.

135. Schab DW, Trinh NH. Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A metaanalysis of double-blind placebo-controlled trials. Journal of Developmental & Behavioral Pediatrics 2004;25(6):423–34.

136. Bateman B, Warner JO, Hutchinson E, Dean T, Rowlandson P, Grant C, et al. The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children. Archives of Disease in Childhood 2004;89(6):506–11.

137. McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 2007;370(9598):1560–7.

138. Benton D. The impact of diet on anti-social, violent and criminal behaviour. Neuroscience and Biobehavioral Reviews 2007;31(5):752–74.

139. Clayton EH, Hanstock TL, Garg ML, Hazell PL. Long chain omega-3 polyunsaturated fatty acids in the treatment of psychiatric illnesses in children and adolescents. Acta Neuropsychiatrica 2007;19(2):92–103.

140. Konofal E, Lecendreux M, Deron J, Marchand M, Cortese S, Zaim M, et al. Effects of iron supplementation on attention deficit hyperactivity disorder in children. Pediatr Neurol 2008;38(1):20–6.

141. Bilici M, Yildirim F, Kandil S, Bekarolu M, Yildirmi S, Deer O, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2004;28(1):181–90.

142. Akhondzadeh S MM, Khademi M. Zinc sulphate as an adjunct to methylphenidate for the treatment of attentiondeficit hyperactivity disorder in children: a double blind and randomised trail. BMC Psychiatry 2004;4:9.

143. Trebaticka J, Kopasova S, Hradecna Z, Cinovsky K, Skodacek I, Suba J, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry 2006;15(6):329–35.

144. Pintov S, Hochman M, Livne A, Heyman E, Lahat E. Bach flower remedies used for attention deficit hyperactivity disorder in children - a prospective double blind controlled study. European Journal of Paediatric Neurology 2005;9(6):395–8.

145. Coulter MK, Dean ME. Homeopathy for attention deficit/hyperactivity disorder or hyperkinetic disorder. Cochrane Database of Systematic Reviews. 2007(4):(CD005648).

146. Khilnani S, Field T, Hernandez-Reif M, Schanberg S. Massage therapy improves mood and behavior of students with attentiondeficit/hyperactivity disorder. Adolescence 2003;38(152):623

147. Beauregard M, Levesque J. Functional magnetic resonance imaging investigation of the effects of neurofeedback training on the neural bases of selective attention and response inhibition in children with attention-deficit/hyperactivity disorder. Ap1plied Psychophysiology & Biofeedback 2006;31(1):3–20.

148. Baydala L, Wikman E. The efficacy of neurofeedback in the management of children with attention deficit/hyperactivity disorder. Paediatrics and Child Health 2001;6(7):451–5.