Attention Deficit Hyperactivity Disorder
Attention deficit hyperactivity disorder (ADHD) is characterized by persistent inattentiveness, impulsivity, and/or hyperactivity that interfere with functioning and are present in 2 or more settings. The disorder affects an estimated 11% of US children aged 4-17, with increased prevalence in teen years, and more than 4% of American adults., It can affect cognitive, academic, behavioral, emotional, and social functioning, and may be associated with comorbid psychiatric conditions. These include oppositional-defiant and conduct disorders, learning disabilities, anxiety, depression, and, later in life, substance-use disorders.
This neurobehavioral disorder is probably caused by a combination of genetic and environmental factors. Neurotransmitter abnormalities have been postulated, focusing on catecholamine metabolism in the cerebral cortex and basal ganglia. An imbalance between norepinephrine and dopamine in the prefrontal cortex is suspected. Methylphenidate, a stimulant that is effective in treating ADHD symptoms, is known to increase synaptic dopamine concentrations.
Inattention may present as disorganization, forgetfulness, frequent misplacing of things, inability to follow instructions, academic underachievement, distractibility, inability to finish tasks, poor concentration, careless mistakes, or poor attention to detail. Hyperactivity is identified by fidgeting, restlessness, difficulty remaining seated, talking excessively, or inability to remain quiet when appropriate.
Impulsivity is noted by difficulty waiting turns, disruptive classroom behavior, interrupting others, peer rejection, and attempting risky activities without considering consequences. Affected adults may show inattention and impulsivity, rather than hyperactivity, and may have difficulty keeping a schedule, managing money, maintaining steady employment, or maintaining relationships
Male gender. ADHD is identified 2-3 times more frequently in boys than in girls. Boys are more likely to experience hyperactivity symptoms, which makes the illness easier to recognize, and are also more likely to engage in disruptive behavior, calling attention to themselves and making a diagnosis more likely.
Age. The average age of diagnosis is 7 years. Although some cases remit by adolescence, others persist into adulthood. ADHD has been historically considered a disorder that develops in childhood; however, new evidence is beginning to suggest that some cases may be late-onset or adult-onset. Relative age, compared to other children within a classroom, also has an effect. The age at which a child starts school is based on the month of his or her birthday, and ages within a classroom can vary by up to 12 months. In a large study in Iceland, investigators found that between the ages of 7 and 14, children in the youngest third of the class were 50% more likely to be prescribed stimulant medication for ADHD.
Genetics. Siblings of an individual with ADHD are at increased risk of the disorder, and there is a 90% concordance in monozygotic twins. Several genes have been identified as possible candidates, notably dopamine receptor and transporter genes.
For a diagnosis of ADHD, the American Psychiatric Association requires at least 6 symptoms of inattention or at least 6 symptoms of hyperactivity and impulsivity, as outlined in the DSM-5. Symptoms must have lasted for at least 6 months and must have onset before age 12. Prior to 2013, when the latest diagnostic manual was released, the age of onset was 7. A growing body of evidence suggests that the age of onset does not appear to affect a patient’s neuropsychological profile or response to treatment, suggesting that ADHD can be appropriately diagnosed in those with a later onset. Symptoms must be present in at least 2 settings (e.g., school and home). There must also be clear evidence of clinically significant impairment in social, academic, or occupational functioning. Symptoms must be considered excessive for the developmental level of the child, and other possible causative mental disorders must be ruled out. A medical, neurological, psychological, and cognitive evaluation should be performed to rule out underlying medical contributors, cognitive deficiencies, and mimicking disorders.
Diagnosis of adult ADHD is similar to that in children but may be complicated by a more subtle presentation, usually lacking the hyperactivity component. Adults may develop compensatory mechanisms that mask the symptoms. For example, rather than displaying forgetfulness in daily activities, an adult with ADHD may rely on extensive smart phone calendar alarms to manage his or her schedule. Investigation into possible compensatory mechanisms should be included in a diagnostic evaluation.
A thorough history and physical exam, focusing particularly on cardiovascular stability as well as potential for substance abuse, should be performed prior to initiation of pharmacologic therapy for ADHD. The presence of a substance use disorder will complicate the treatment; however, it should not be viewed as an absolute contraindication to the use of medications with abuse potential, such as psychostimulants. Effective treatment of ADHD can actually reduce the risk for a substance use disorder by as much as 85%.,
Methylphenidate and dextroamphetamine are effective in 60-70% of children with ADHD. They increase catecholamine release from presynaptic neurons. Sustained-release preparations and longer-acting medications, such as lisdexamfetamine, minimize rebound symptoms and irritability, as well as minimize disruptions in the school day caused by twice-daily or three-times-daily dosing schedules. Sustained-release preparations also produce less euphoria, reducing the risk of abuse and diversion. Side effects may include decreased appetite, insomnia, anxiety, irritability, or headache. These often resolve on their own as the patient adjusts to the medication. More long-term effects include elevated blood pressure and heart rate, potentially contributing to risk of sudden cardiac death in individuals with preexisting risk factors. Stimulants may inhibit childhood growth patterns, reducing height potential up to 2 cm.
Nonstimulants. Several classes of nonstimulant medications may be effective, although controlled studies are limited.
Atomoxetine is a selective norepinephrine reuptake inhibitor. It may be most appropriate for patients with a history of medication abuse or family members who may abuse medication. The Food and Drug Administration has warned that this medication may cause hepatotoxicity, suicidal thinking, and serotonin syndrome (when used along with fluoxetine). It should be discontinued in patients who develop jaundice or laboratory evidence of hepatotoxicity. Most patients find it less effective than stimulants however, it is a first line treatment for adults, followed by antidepressants.
Among the antidepressant medications, small studies have demonstrated that bupropion and desipramine have potential benefit for ADHD.
Clonidine and guanfacine are alpha-2 adrenergic agonists that may be useful in children but have not been well studied in adults. Side effects may include hypotension, sedation, fatigue, headache, and urinary changes. In addition, several drugs may interact with clonidine, including alcohol, barbiturates, beta-blockers, digoxin, and cold medicines. Combined use with methylphenidate requires monitoring of blood pressure and heart rate. When an alpha-2 agonist is discontinued, it must be tapered slowly to avoid potentially dangerous rebound hypertension.
Behavioral interventions are recommended as initial treatment for preschool-aged children with ADHD and may help to augment pharmacotherapy for school-aged children. Behavioral interventions include parent-child therapy as well as school-based interventions, such as seating near the teacher, daily report card with home reinforcement, and extended time to complete tasks.
Physical activity in children plays a critical role in their growth and development. Research suggests physical activity may help to reduce the symptoms of ADHD in children. Sports and other social activities help children learn appropriate social skills.
Biofeedback. Electroencephalographic (EEG) biofeedback training may be a promising investigational treatment. Research studies have demonstrated that some individuals who have ADHD have excess slow-wave activity and reduced fast-wave activity compared with matched peers. Using video and auditory feedback, individuals can learn to reduce their slow-wave activity and/or increase their fast-wave activity. Case series report that approximately 75% of patients have a positive clinical response.
The role of diet in ADHD has been controversial ever since it was first proposed by pediatrician Ben Feingold in the book Why Your Child Is Hyperactive. Dr. Feingold demonstrated that the removal of synthetic colorings, flavorings, and preservatives from the diet led to a marked improvement in many children. Feingold suspected a much wider array of dietary sensitivities, but those three were the most accessible for study. Later research suggested that these sensitivities were relevant in only relatively few ADHD cases. However, subsequent studies have supported a causal role of diet. They suggest that unhealthy Western dietary patterns, including dairy products, sugar, salt, and fat, and minimal consumption of whole grains, fruits, vegetables, and fish are associated with increased risk of ADHD., This association may be stronger in boys than girls.
The following nutritional factors are under study for their effect on ADHD:
Diets free of artificial food colorings and common allergens.
Artificial food colorings do not appear to cause ADHD but may exacerbate symptoms in some ADHD patients. An elimination diet is a valuable tool to identify problematic foods. At least 8 controlled studies have demonstrated either significant behavioral improvement on oligoantigenic (elimination) diets compared with regular diets, or behavioral deterioration on a placebo-controlled challenge with foods suspected of aggravating symptoms. In one of these studies, parental reports indicated that more than half the subjects exhibited a reliable improvement in behavior on an oligoantigenic diet. A 2017 review of double-blind, placebo-controlled trials concluded that elimination diets, referenced as “few-foods diets,” may be a beneficial short-term diagnostic treatment for ADHD, although likely dependent upon families who are highly motivated and supportive, given the time and effort required to find the offending foods. A study looking at 35 years of elimination diets found that > 70% of children responded positively.
Some children with ADHD may also be sensitive to foods other than artificial colorings, such as milk, chocolate, soy, eggs, wheat, corn, and legumes, as well as salicylate-containing foods (e.g., grapes, tomatoes, and oranges).
Aspartame or sucrose restriction. Controlled trials of sugar-restricted diets found no effect on behavioral symptoms in ADHD, even in children thought to be sugar-sensitive. Similarly, studies have not supported a causal role for aspartame in ADHD.
Adequate vitamin and mineral intake or supplementation. Deficiency of several minerals (iron, copper, zinc, magnesium, calcium) is common in ADHD patients, and theoretically may influence neurotransmission in the central nervous system., Some studies have suggested a contributory role of nutrient-poor meals and snacks. Controlled studies have not established a clear benefit of supplementation, though research on multinutrient supplementation looks promising.,,,
Zinc. As a cofactor for neurotransmitters, zinc influences regulation of γ-aminobutyric acid (GABA), serotonin, and dopamine, all of which may play roles in ADHD. Poor zinc status is common and can delay cognitive development; it has been found with greater frequency in hyperactive children compared with controls. A small study in Canada found ADHD children were 8 times more likely to have zinc deficiency compared with age-matched population data. Zinc status has been reported in a small sample to correlate with response to amphetamine treatment, and controlled clinical trials in the Middle East, an area of zinc deficiency, support the possibility that supplemental zinc (55-150 mg ZnSO4/day) may improve response to methylphenidate or improve symptoms of hyperactivity and impulsiveness when used as monotherapy.,, However, these reports leave questions about sample retention and data analysis, and further controlled clinical trials are required.
Iron. A 2017 meta-analysis found low serum ferritin levels to be more prevalent in patients with ADHD than in healthy controls. Iron deficiency is associated with decreased dopamine transporter density and activity, causing increased extracellular dopamine. Deficiency may also result in dysfunction in the basal ganglia. Iron supplementation may therefore improve symptoms in ADHD patients with low serum ferritin.,
Polyunsaturated fatty acids. ADHD patients may have lower levels of omega-3 fatty acids, higher levels of omega-6 and a higher n6:n3 ratio., A 2016 meta-analysis supports these findings and suggests this leads to an overproduction of pro-inflammatory cytokines that alters neurotransmitter systems. The efficacy of supplementation continues to be evaluated.,
Oxidative stress. Markers of inflammation may be higher in ADHD patients, suggesting insufficient responses to oxidative stress., This could be exacerbated by nutrient-poor diets. Some have hypothesized that antioxidant-rich plant compounds such as Ginkgo biloba, ginseng, and pycnogenol (pine bark extract) may help reduce oxidative stress.
A diet based on whole grains, beans, fruits, and vegetables could supply these nutrients as well as antioxidants to reduce inflammation, although the direct benefit of this on ADHD symptoms has not been evaluated through clinical trials.
See Basic Diet Orders chapter and Nutritional Requirements Throughout the Life Cycle chapter.
What to Tell the Family
ADHD can impair learning, work performance, and social relationships; however, several effective treatments are available. Although many parents have understandable concerns about drug therapy, medications are highly effective, generally provide significant relief, and, in some cases, reduce the risk of developing a substance use disorder. Other options—behavioral treatment, special educational programming, and for some, an oligoantigenic diet—may be tried separately or in combination with medication.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). 5 th ed. Arlington, VA: American Psychiatric Publishing; 2013.
- Visser SN, Danielson ML, Bitsko RH, et al. Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003-2011. J Am Acad Child Adolesc Psychiatry. 2014;53(1):34-46.e2. [PMID:24342384]
- Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163(4):716-23. [PMID:16585449]
- Quinn PO. Treating adolescent girls and women with ADHD: gender-specific issues. J Clin Psychol. 2005;61(5):579-87. [PMID:15723425]
- Moffitt TE, Houts R, Asherson P, et al. Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four-Decade Longitudinal Cohort Study. Am J Psychiatry. 2015;172(10):967-77. [PMID:25998281]
- Zoëga H, Valdimarsdóttir UA, Hernández-Díaz S. Age, academic performance, and stimulant prescribing for ADHD: a nationwide cohort study. Pediatrics. 2012;130(6):1012-8. [PMID:23166340]
- Franke B, Faraone SV, Asherson P, et al. The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry. 2012;17(10):960-87. [PMID:22105624]
- Nilsen FM, Tulve NS. A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD. Environ Res. 2020;180:108884. [PMID:31706600]
- Narad ME, Kennelly M, Zhang N, et al. Secondary Attention-Deficit/Hyperactivity Disorder in Children and Adolescents 5 to 10 Years After Traumatic Brain Injury. JAMA Pediatr. 2018;172(5):437-443. [PMID:29554197]
- Stojanovski S, Felsky D, Viviano JD, et al. Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury. Biol Psychiatry. 2019;85(5):408-416. [PMID:30119875]
- Froehlich TE, Lanphear BP, Epstein JN, et al. Prevalence, recognition, and treatment of attention-deficit/hyperactivity disorder in a national sample of US children. Arch Pediatr Adolesc Med. 2007;161(9):857-64. [PMID:17768285]
- Biederman J, Faraone SV, Mick E, et al. Clinical correlates of ADHD in females: findings from a large group of girls ascertained from pediatric and psychiatric referral sources. J Am Acad Child Adolesc Psychiatry. 1999;38(8):966-75. [PMID:10434488]
- Kieling C, Kieling RR, Rohde LA, et al. The age at onset of attention deficit hyperactivity disorder. Am J Psychiatry. 2010;167(1):14-6. [PMID:20068122]
- Wasserstein J. Diagnostic issues for adolescents and adults with ADHD. J Clin Psychol. 2005;61(5):535-47. [PMID:15723419]
- American Academy of Child and Adolescent Psychiatry. Practice parameter on the use of psychotropic medication in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2009;48(9):961-73. [PMID:19692857]
- Biederman J, Wilens T, Mick E, et al. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics. 1999;104(2):e20. [PMID:10429138]
- Quinn PD, Chang Z, Hur K, et al. ADHD Medication and Substance-Related Problems. Am J Psychiatry. 2017;174(9):877-885. [PMID:28659039]
- Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921. [PMID:17581453]
- Faraone SV, Upadhyaya HP. The effect of stimulant treatment for ADHD on later substance abuse and the potential for medication misuse, abuse, and diversion. J Clin Psychiatry. 2007;68(11):e28. [PMID:18052554]
- Nissen SE. ADHD drugs and cardiovascular risk. N Engl J Med. 2006;354(14):1445-8. [PMID:16549404]
- Wetterer L. Attention-deficit/hyperactivity disorder: AAP updates guideline for diagnosis and management. Am Fam Physician. 2020;102(1):58-60.
- Hanwella R, Senanayake M, de Silva V. Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis. BMC Psychiatry. 2011;11:176. [PMID:22074258]
- Post RE, Kurlansik SL. Diagnosis and management of adult attention-deficit/hyperactivity disorder. Am Fam Physician. 2012;85(9):890-6. [PMID:22612184]
- Yang MT, Lee WT, Liang JS, et al. Hyperactivity and impulsivity in children with untreated allergic rhinitis: corroborated by rating scale and continuous performance test. Pediatr Neonatol. 2014;55(3):168-74. [PMID:24211085]
- Yang MT, Chen CC, Lee WT, et al. Attention-deficit/hyperactivity disorder-related symptoms improved with allergic rhinitis treatment in children. Am J Rhinol Allergy. 2016;30(3):209-14. [PMID:27216352]
- Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee on Quality Improvement and Management, Wolraich M, et al. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011;128(5):1007-22. [PMID:22003063]
- Cooper DM, Nemet D, Galassetti P. Exercise, stress, and inflammation in the growing child: from the bench to the playground. Curr Opin Pediatr. 2004;16(3):286-92. [PMID:15167015]
- Gapin JI, Labban JD, Etnier JL. The effects of physical activity on attention deficit hyperactivity disorder symptoms: the evidence. Prev Med. 2011;52 Suppl 1:S70-4. [PMID:21281664]
- Butnik SM. Neurofeedback in adolescents and adults with attention deficit hyperactivity disorder. J Clin Psychol. 2005;61(5):621-5. [PMID:15723361]
- Monastra VJ. Electroencephalographic biofeedback (neurotherapy) as a treatment for attention deficit hyperactivity disorder: rationale and empirical foundation. Child Adolesc Psychiatr Clin N Am. 2005;14(1):55-82, vi. [PMID:15564052]
- Feingold BF. Why Your Child Is Hyperactive: The Bestselling Book on How ADHD is caused by Artificial Food Flavors and Colors . New York, NY: Random House; 1985.
- Howard AL, Robinson M, Smith GJ, et al. ADHD is associated with a "Western" dietary pattern in adolescents. J Atten Disord. 2011;15(5):403-11. [PMID:20631199]
- Woo HD, Kim DW, Hong YS, et al. Dietary patterns in children with attention deficit/hyperactivity disorder (ADHD). Nutrients. 2014;6(4):1539-53. [PMID:24736898]
- Wu X, Ohinmaa A, Veugelers PJ. The Influence of Health Behaviours in Childhood on Attention Deficit and Hyperactivity Disorder in Adolescence. Nutrients. 2016;8(12). [PMID:27918425]
- Arnold LE, Lofthouse N, Hurt E. Artificial food colors and attention-deficit/hyperactivity symptoms: conclusions to dye for. Neurotherapeutics. 2012;9(3):599-609. [PMID:22864801]
- Pelsser LM, Frankena K, Toorman J, et al. Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. Lancet. 2011;377(9764):494-503. [PMID:21296237]
- Kaplan BJ, McNicol J, Conte RA, et al. Overall nutrient intake of preschool hyperactive and normal boys. J Abnorm Child Psychol. 1989;17(2):127-32. [PMID:2745894]
- Pelsser LM, Frankena K, Toorman J, et al. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PLoS One. 2017;12(1):e0169277. [PMID:28121994]
- Stevens LJ, Kuczek T, Burgess JR, et al. Dietary sensitivities and ADHD symptoms: thirty-five years of research. Clin Pediatr (Phila). 2011;50(4):279-93. [PMID:21127082]
- Wolraich ML, Lindgren SD, Stumbo PJ, et al. Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children. N Engl J Med. 1994;330(5):301-7. [PMID:8277950]
- Fitch C, Keim KS, Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet. 2012;112(5):739-58. [PMID:22709780]
- Villagomez A, Ramtekkar U. Iron, Magnesium, Vitamin D, and Zinc Deficiencies in Children Presenting with Symptoms of Attention-Deficit/Hyperactivity Disorder. Children (Basel). 2014;1(3):261-79. [PMID:27417479]
- Daley KC. Update on attention-deficit/hyperactivity disorder. Curr Opin Pediatr. 2004;16(2):217-26. [PMID:15021207]
- Rucklidge JJ, Johnstone J, Kaplan BJ. Nutrient supplementation approaches in the treatment of ADHD. Expert Rev Neurother. 2009;9(4):461-76. [PMID:19344299]
- Hariri M, Azadbakht L. Magnesium, Iron, and Zinc Supplementation for the Treatment of Attention Deficit Hyperactivity Disorder: A Systematic Review on the Recent Literature. Int J Prev Med. 2015;6:83. [PMID:26445630]
- Rucklidge JJ, Kaplan BJ. Broad-spectrum micronutrient treatment for attention-deficit/hyperactivity disorder: rationale and evidence to date. CNS Drugs. 2014;28(9):775-85. [PMID:25056569]
- Gordon HA, Rucklidge JJ, Blampied NM, et al. Clinically Significant Symptom Reduction in Children with Attention-Deficit/Hyperactivity Disorder Treated with Micronutrients: An Open-Label Reversal Design Study. J Child Adolesc Psychopharmacol. 2015;25(10):783-98. [PMID:26682999]
- Kiddie JY, Weiss MD, Kitts DD, et al. Nutritional status of children with attention deficit hyperactivity disorder: a pilot study. Int J Pediatr. 2010;2010:767318. [PMID:20652039]
- Akhondzadeh S, Mohammadi MR, Khademi M. Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial [ISRCTN64132371]. BMC Psychiatry. 2004;4:9. [PMID:15070418]
- Bilici M, Yildirim F, Kandil S, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(1):181-90. [PMID:14687872]
- Arnold LE, Disilvestro RA, Bozzolo D, et al. Zinc for attention-deficit/hyperactivity disorder: placebo-controlled double-blind pilot trial alone and combined with amphetamine. J Child Adolesc Psychopharmacol. 2011;21(1):1-19. [PMID:21309695]
- Wang Y, Huang L, Zhang L, et al. Iron Status in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis. PLoS ONE. 2017;12(1):e0169145. [PMID:28046016]
- Konofal E, Lecendreux M, Deron J, et al. Effects of iron supplementation on attention deficit hyperactivity disorder in children. Pediatr Neurol. 2008;38(1):20-6. [PMID:18054688]
- Cortese S, Angriman M, Lecendreux M, et al. Iron and attention deficit/hyperactivity disorder: What is the empirical evidence so far? A systematic review of the literature. Expert Rev Neurother. 2012;12(10):1227-40. [PMID:23082739]
- Hawkey E, Nigg JT. Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev. 2014;34(6):496-505. [PMID:25181335]
- Colter AL, Cutler C, Meckling KA. Fatty acid status and behavioural symptoms of attention deficit hyperactivity disorder in adolescents: a case-control study. Nutr J. 2008;7:8. [PMID:18275609]
- LaChance L, McKenzie K, Taylor VH, et al. Omega-6 to Omega-3 Fatty Acid Ratio in Patients with ADHD: A Meta-Analysis. J Can Acad Child Adolesc Psychiatry. 2016;25(2):87-96. [PMID:27274744]
- Gillies D, Sinn JKh, Lad SS, et al. Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2012. [PMID:22786509]
- Königs A, Kiliaan AJ. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment. Neuropsychiatr Dis Treat. 2016;12:1869-82. [PMID:27555775]
- Mitchell RH, Goldstein BI. Inflammation in children and adolescents with neuropsychiatric disorders: a systematic review. J Am Acad Child Adolesc Psychiatry. 2014;53(3):274-96. [PMID:24565356]
- Joseph N, Zhang-James Y, Perl A, et al. Oxidative Stress and ADHD: A Meta-Analysis. J Atten Disord. 2015;19(11):915-24. [PMID:24232168]
- Ahn J, Ahn HS, Cheong JH, et al. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy. Neural Plast. 2016;2016:1320423. [PMID:26966583]