Differential diagnosis
The DSM provides differential diagnoses – potential alternate explanations for specific symptoms. Assessment and investigation of clinical history determines which is the most appropriate diagnosis. The DSM-5 suggests ODD, intermittent explosive disorder, and other neurodevelopmental disorders (such as stereotypic movement disorder and Tourette's disorder), in addition to specific learning disorder, intellectual developmental disorder, ASD, reactive attachment disorder, anxiety disorders, depressive disorders, bipolar disorder, disruptive mood dysregulation disorder, substance use disorder, personality disorders, psychotic disorders, medication-induced symptoms, and neurocognitive disorders. Many but not all of these are also common comorbidities of ADHD.[3] The DSM-5-TR also suggests post-traumatic stress disorder.[4]
Symptoms of ADHD, such as low mood and poor self-image, mood swings, and irritability, can be confused with dysthymia, cyclothymia or bipolar disorder as well as with borderline personality disorder.[55]: 10 Some symptoms that are due to anxiety disorders, personality disorder, developmental disabilities or intellectual disability or the effects of substance abuse such as intoxication and withdrawal can overlap with ADHD. These disorders can also sometimes occur along with ADHD. Medical conditions which can cause ADHD-type symptoms include: hyperthyroidism, seizure disorder, lead toxicity, hearing deficits, hepatic disease, sleep apnea, drug interactions, untreated celiac disease, and head injury.[218][214][better source needed]
Primary sleep disorders may affect attention and behaviour and the symptoms of ADHD may affect sleep.[219] It is thus recommended that children with ADHD be regularly assessed for sleep problems.[220] Sleepiness in children may result in symptoms ranging from the classic ones of yawning and rubbing the eyes, to hyperactivity and inattentiveness. Obstructive sleep apnea can also cause ADHD-type symptoms.[221]
Management
Main article: Attention deficit hyperactivity disorder management
The management of ADHD typically involves counseling or medications, either alone or in combination. While there are various options of treatment to improve ADHD symptoms, medication therapies substantially improves long-term outcomes, and while completely eliminating some elevated risks such as obesity,[7] they do come with some risks of adverse events.[222] Medications used include stimulants, atomoxetine, alpha-2 adrenergic receptor agonists, and sometimes antidepressants.[77][189] In those who have trouble focusing on long-term rewards, a large amount of positive reinforcement improves task performance.[193] Medications are the most effective treatment,[7][223] and any side effects are typically mild and easy to resolve[7] although any improvements will be reverted if medication is ceased.[224] ADHD stimulants also improve persistence and task performance in children with ADHD.[178][193] To quote one systematic review, "recent evidence from observational and registry studies indicates that pharmacological treatment of ADHD is associated with increased achievement and decreased absenteeism at school, a reduced risk of trauma-related emergency hospital visits, reduced risks of suicide and attempted suicide, and decreased rates of substance abuse and criminality".[225] Data also suggest that combining medication with CBT is a good idea: although CBT is substantially less effective, it can help address problems that reside after medication has been optimised.[7] The nature and range of desirable endpoints of ADHD treatment vary among diagnostic standards for ADHD.[226] In most studies, the efficacy of treatment is determined by reductions in symptoms.[227] However, some studies have included subjective ratings from teachers and parents as part of their assessment of treatment efficacies.[228]
Behavioural therapies
There is good evidence for the use of behavioural therapies in ADHD. They are the recommended first-line treatment in those who have mild symptoms or who are preschool-aged.[229][230] Psychological therapies used include: psychoeducational input, behavior therapy, cognitive behavioral therapy,[231] interpersonal psychotherapy, family therapy, school-based interventions, social skills training, behavioural peer intervention, organization training,[232] and parent management training.[177] Neurofeedback has greater treatment effects than non-active controls for up to 6 months and possibly a year following treatment, and may have treatment effects comparable to active controls (controls proven to have a clinical effect) over that time period.[233] Despite efficacy in research, there is insufficient regulation of neurofeedback practice, leading to ineffective applications and false claims regarding innovations.[234] Parent training may improve a number of behavioural problems including oppositional and non-compliant behaviours.[235]
There is little high-quality research on the effectiveness of family therapy for ADHD—but the existing evidence shows that it is similar to community care, and better than placebo.[236] ADHD-specific support groups can provide information and may help families cope with ADHD.[237]
Social skills training, behavioural modification, and medication may have some limited beneficial effects in peer relationships. Stable, high-quality friendships with non-deviant peers protect against later psychological problems.[238]
Digital interventions
Several clinical trials have investigated the efficacy of digital therapeutics, particularly Akili Interactive Labs's video game-based digital therapeutic AKL-T01, marketed as EndeavourRx. The pediatric STARS-ADHD randomized, double-blind, parallel-group, controlled trial demonstrated that AKL-T01 significantly improved performance on the Test of Variables of Attention, an objective measure of attention and inhibitory control, compared to a control group after four weeks of at-home use.[239] A subsequent pediatric open-label study, STARS-Adjunct, published in Nature Portfolio's npj Digital Medicine evaluated AKL-T01 as an adjunctive treatment for children with ADHD who were either on stimulant medication or not on stimulant pharmacotherapy. Results showed improvements in ADHD-related impairment (measured by the Impairment Rating Scale) and ADHD symptoms after 4 weeks of treatment, with effects persisting during a 4-week pause and further improving with an additional treatment period.[240] Notably, the magnitude of the measured improvement was similar for children both on and off stimulants.[240] In 2020, AKL-T01 received marketing authorization for pediatric ADHD from the FDA, becoming "the first game-based therapeutic granted marketing authorization by the FDA for any type of condition."[241]
In addition to pediatric populations, a 2023 study in the Journal of the American Academy of Child & Adolescent Psychiatry investigated the efficacy and safety of AKL-T01 in adults with ADHD. After six weeks of at-home treatment with AKL-T01, participants showed significant improvements in objective measures of attention (TOVA - Attention Comparison Score), reported ADHD symptoms (ADHD-RS-IV inattention subscale and total score), and reported quality of life (AAQoL).[242] The magnitude of improvement in attention was nearly seven times greater than that reported in pediatric trials.[242] The treatment was well-tolerated, with high compliance and no serious adverse events.[242]
Medication
The medications for ADHD appear to alleviate symptoms via their effects on the pre-frontal executive, striatal and related regions and networks in the brain; usually by increasing neurotransmission of norepinephrine and dopamine.[243][244][245]
Stimulants
Methylphenidate and amphetamine or its derivatives are often first-line treatments for ADHD.[246][247] About 70 per cent respond to the first stimulant tried and as few as 10 per cent respond to neither amphetamines nor methylphenidate.[223] Stimulants may also reduce the risk of unintentional injuries in children with ADHD.[248] Magnetic resonance imaging studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD.[249][250][251] A 2018 review found the greatest short-term benefit with methylphenidate in children, and amphetamines in adults.[228] Studies and meta-analyses show that amphetamine is slightly-to-modestly more effective than methylphenidate at reducing symptoms,[252][253] and they are more effective pharmacotherapy for ADHD than α2-agonists[254] but methylphenidate has comparable efficacy to non-stimulants such as atomoxetine. In a Cochrane clinical synopsis, Dr Storebø and colleagues[255] summarised their meta-review[256] on methylphenidate for ADHD in children and adolescents. The meta-analysis raised substantial doubts about the drug's efficacy relative to a placebo. This led to a strong critical reaction from the European ADHD Guidelines Group and individuals in the scientific community, who identified a number of flaws in the review.[257][258][259][260][261][262] Since at least September 2021, there is a unanimous and global scientific consensus that methylphenidate is safe and highly effective for treating ADHD.[7][263] The same journal released a subsequent systematic review (2022) of extended-release methylphenidate for adults, concluding similar doubts about the certainty of evidence.[264] Other recent systematic reviews and meta-analyses, however, find certainty in the safety and high efficacy of methylphenidate for reducing ADHD symptoms,[265][266][267] for alleviating the underlying executive functioning deficits,[268] and for substantially reducing the adverse consequences of untreated ADHD with continuous treatment.[7] Clinical guidelines internationally are also consistent in approving the safety and efficacy of methylphenidate and recommending it as a first-line treatment for the disorder.[7]
Safety and efficacy data have been reviewed extensively by medical regulators (e.g., the US Food and Drug Administration and the European Medicines Agency), the developers of evidence-based international guidelines (e.g., the UK National Institute for Health and Care Excellence and the American Academy of Pediatrics), and government agencies who have endorsed these guidelines (e.g., the Australian National Health and Medical Research Council). These professional groups unanimously conclude, based on the scientific evidence, that methylphenidate is safe and effective and should be considered as a first-line treatment for ADHD.[7] The likelihood of developing insomnia for ADHD patients taking stimulants has been measured at between 11 and 45 per cent for different medications,[269] and may be a main reason for discontinuation. Other side effects, such as tics, decreased appetite and weight loss, or emotional lability, may also lead to discontinuation.[223] Stimulant psychosis and mania are rare at therapeutic doses, appearing to occur in approximately 0.1% of individuals, within the first several weeks after starting amphetamine therapy.[270][271][272] The safety of these medications in pregnancy is unclear.[273] Symptom improvement is not sustained if medication is ceased.[274][224][275]
The long-term effects of ADHD medication have yet to be fully determined,[276][277] although stimulants are generally beneficial and safe for up to two years for children and adolescents.[278] A 2022 meta-analysis found no statistically significant association between ADHD medications and the risk of cardiovascular disease (CVD) across age groups, although the study suggests further investigation is warranted for patients with preexisting CVD as well as long-term medication use.[279] Regular monitoring has been recommended in those on long-term treatment.[280] There are indications suggesting that stimulant therapy for children and adolescents should be stopped periodically to assess continuing need for medication, decrease possible growth delay, and reduce tolerance.[281][282] Although potentially addictive at high doses,[283][284] stimulants used to treat ADHD have low potential for abuse.[246] Treatment with stimulants is either protective against substance abuse or has no effect.[55]: 12 [276][283]
The majority of studies on nicotine and other nicotinic agonists as treatments for ADHD have shown favorable results; however, no nicotinic drug has been approved for ADHD treatment.[285] Caffeine was formerly used as a second-line treatment for ADHD but research indicates it has no significant effects in reducing ADHD symptoms. Caffeine appears to help with alertness, arousal and reaction time but not the type of inattention implicated in ADHD (sustained attention/persistence).[286] Pseudoephedrine and ephedrine do not affect ADHD symptoms.[246]
Modafinil has shown some efficacy in reducing the severity of ADHD in children and adolescents.[287] It may be prescribed off-label to treat ADHD.
Non-stimulants
Two non-stimulant medications, atomoxetine and viloxazine, are approved by the FDA and in other countries for the treatment of ADHD.
Atomoxetine, due to its lack of addiction liability, may be preferred in those who are at risk of recreational or compulsive stimulant use, although evidence is lacking to support its use over stimulants for this reason.[55]: 13 Atomoxetine alleviates ADHD symptoms through norepinephrine reuptake and by indirectly increasing dopamine in the pre-frontal cortex,[245] sharing 70-80% of the brain regions with stimulants in their produced effects.[244] Atomoxetine has been shown to significantly improve academic performance.[288][289] Meta-analyses and systematic reviews have found that atomoxetine has comparable efficacy, equal tolerability and response rate (75%) to methylphenidate in children and adolescents. In adults, efficacy and discontinuation rates are equivalent.[290][291][292][293]
Analyses of clinical trial data suggests that viloxazine is about as effective as atomoxetine and methylphenidate but with fewer side effects.[294]
Amantadine was shown to induce similar improvements in children treated with methylphenidate, with less frequent side effects.[295] A 2021 retrospective study showed showed that amantadine may serve as an effective adjunct to stimulants for ADHD–related symptoms and appears to be a safer alternative to second- or third-generation antipsychotics.[296]
Bupropion is also used off-label by some clinicians due to research findings. It is effective, but modestly less than atomoxetine and methylphenidate.[297]
There is little evidence on the effects of medication on social behaviours.[298] Antipsychotics may also be used to treat aggression in ADHD.[299]
Alpha-2a agonists
Two alpha-2a agonists, extended-release formulations of guanfacine and clonidine, are approved by the FDA and in other countries for the treatment of ADHD (effective in children and adolescents but effectiveness has still not been shown for adults).[300][301] They appear to be modestly less effective than the stimulants (amphetamine and methylphenidate) and non-stimulants (atomoxetine and viloxazine) at reducing symptoms,[302][303] but can be useful alternatives or used in conjunction with a stimulant. These medications act by adjusting the alpha-2a ports on the outside of noradrenergic nerve cells in the pre-frontal executive networks, so the information (electrical signal) is less confounded by noise.[304]
Guidelines
Guidelines on when to use medications vary by country. The United Kingdom's National Institute for Health and Care Excellence recommends use for children only in severe cases, though for adults medication is a first-line treatment.[305] Conversely, most United States guidelines recommend medications in most age groups.[306] Medications are especially not recommended for preschool children.[305][177] Underdosing of stimulants can occur, and can result in a lack of response or later loss of effectiveness.[307] This is particularly common in adolescents and adults as approved dosing is based on school-aged children, causing some practitioners to use weight-based or benefit-based off-label dosing instead.[308][309][310]
Exercise
Exercise does not reduce the symptoms of ADHD.[7] The conclusion by the International Consensus Statement is based on two meta-analyses: one of 10 studies with 300 children and the other of 15 studies and 668 participants, which showed that exercise yields no statistically significant reductions on ADHD symptoms. A 2024 systematic review and meta analysis commissioned by the Patient-Centered Outcomes Research Institute (PCORI) identified seven studies on the effectiveness of physical exercise for treating ADHD symptoms.[198] The type and amount of exercise varied widely across studies from martial arts interventions to treadmill training, to table tennis or aerobic exercise. Effects reported were not replicated, causing the authors to conclude that there is insufficient evidence that exercise intervention is an effective form of treatment for ADHD symptoms.[198]
Diet
Dietary modifications are not recommended as of 2019 by the American Academy of Pediatrics, the National Institute for Health and Care Excellence, or the Agency for Healthcare Research and Quality due to insufficient evidence.[311][305] A 2013 meta-analysis found less than a third of children with ADHD see some improvement in symptoms with free fatty acid supplementation or decreased consumption of artificial food colouring.[160] These benefits may be limited to children with food sensitivities or those who are simultaneously being treated with ADHD medications.[160] This review also found that evidence does not support removing other foods from the diet to treat ADHD.[160] A 2014 review found that an elimination diet results in a small overall benefit in a minority of children, such as those with allergies.[175] A 2016 review stated that the use of a gluten-free diet as standard ADHD treatment is not advised.[218] A 2017 review showed that a few-foods elimination diet may help children too young to be medicated or not responding to medication, while free fatty acid supplementation or decreased eating of artificial food colouring as standard ADHD treatment is not advised.[312] Chronic deficiencies of iron, magnesium and iodine may have a negative impact on ADHD symptoms.[313] There is a small amount of evidence that lower tissue zinc levels may be associated with ADHD.[314] In the absence of a demonstrated zinc deficiency (which is rare outside of developing countries), zinc supplementation is not recommended as treatment for ADHD.[315] However, zinc supplementation may reduce the minimum effective dose of amphetamine when it is used with amphetamine for the treatment of ADHD.[316]
Prognosis
ADHD persists into adulthood in about 30–50% of cases.[317] Those affected are likely to develop coping mechanisms as they mature, thus compensating to some extent for their previous symptoms.[214] Children with ADHD have a higher risk of unintentional injuries.[248] Effects of medication on functional impairment and quality of life (e.g. reduced risk of accidents) have been found across multiple domains.[318] Rates of smoking among those with ADHD are higher than in the general population at about 40%.[319] About 30–50% of people diagnosed in childhood continue to have ADHD in adulthood, with 2.58% of adults estimated to have ADHD which began in childhood.[212][320][text–source integrity?] In adults, hyperactivity is usually replaced by inner restlessness, and adults often develop coping skills to compensate for their impairments. The condition can be difficult to tell apart from other conditions, as well as from high levels of activity within the range of normal behaviour. ADHD has a negative impact on patient health-related quality of life that may be further exacerbated by, or may increase the risk of, other psychiatric conditions such as anxiety and depression.[225] Individuals with ADHD may also face misconceptions and stigma.[7]
Individuals with ADHD are significantly overrepresented in prison populations. Although there is no generally accepted estimate of ADHD prevalence among inmates, a 2015 meta-analysis estimated a prevalence of 25.5%, and a larger 2018 meta-analysis estimated the frequency to be 26.2%.[321]
Epidemiology
Main article: Epidemiology of attention deficit hyperactive disorder
Percentage of people 4–17 ever diagnosed in the US as of 2011[322]
ADHD is estimated to affect about 6–7% of people aged 18 and under when diagnosed via the DSM-IV criteria.[323] When diagnosed via the ICD-10 criteria, rates in this age group are estimated around 1–2%.[324] Rates are similar between countries and differences in rates depend mostly on how it is diagnosed.[325] Children in North America appear to have a higher rate of ADHD than children in Africa and the Middle East; this is believed to be due to differing methods of diagnosis rather than a difference in underlying frequency. (The same publication which describes this difference also notes that the difference may be rooted in the available studies from these respective regions, as far more studies were from North America than from Africa and the Middle East.)[326] As of 2019, it was estimated to affect 84.7 million people globally.[2]
ADHD is diagnosed approximately twice as often in boys as in girls,[4][323] and 1.6 times more often in men than in women,[4] although the disorder is overlooked in girls or diagnosed in later life because their symptoms sometimes differ from diagnostic criteria.[330][331] In 2014, Keith Conners, one of the early advocates for recognition of the disorder, spoke out against overdiagnosis in a New York Times article.[332] In contrast, a 2014 peer-reviewed medical literature review indicated that ADHD is underdiagnosed in adults.[320]
Studies from multiple countries have reported that children born closer to the start of the school year are more frequently diagnosed with and medicated for ADHD than their older classmates.[333] Boys who were born in December where the school age cut-off was 31 December were shown to be 30% more likely to be diagnosed and 41% more likely to be treated than those born in January. Girls born in December had a diagnosis and treatment percentage increase of 70% and 77% respectively compared to those born in January. Children who were born at the last three days of a calendar year were reported to have significantly higher levels of diagnosis and treatment for ADHD than children born at the first three days of a calendar year. The studies suggest that ADHD diagnosis is prone to subjective analysis.[334]
Rates of diagnosis and treatment have increased in both the United Kingdom and the United States since the 1970s. Prior to 1970, it was rare for children to be diagnosed with ADHD, while in the 1970s rates were about 1%.[335] This is believed to be primarily due to changes in how the condition is diagnosed[336] and how readily people are willing to treat it with medications rather than a true change in incidence.[324] With widely differing rates of diagnosis across countries, states within countries, races, and ethnicities, some suspect factors other than symptoms of ADHD are playing a role in diagnosis, such as cultural norms.[337][334]
Despite showing a higher frequency of symptoms associated with ADHD, non-White children in the US are less likely than White children to be diagnosed or treated for ADHD, a finding that is often explained by bias among health professionals, as well as parents who may be reluctant to acknowledge that their child has ADHD.[338] Crosscultural differences in diagnosis of ADHD can also be attributed to the long-lasting effects of harmful, racially targeted medical practices. Medical pseudosciences, particularly those that targeted Black populations during the period of slavery in the US, lead to a distrust of medical practices within certain communities. The combination of ADHD symptoms often being regarded as misbehaviour rather than as a psychiatric condition, and the use of drugs to regulate ADHD, result in a hesitancy to trust a diagnosis of ADHD. Cases of misdiagnosis in ADHD can also occur due to stereotyping of people of color. Due to ADHD's subjectively determined symptoms, medical professionals may diagnose individuals based on stereotyped behaviour or misdiagnose due to cultural differences in symptom presentation.[339]
History
Timeline of ADHD diagnostic criteria, prevalence, and treatment
Main article: History of attention deficit hyperactivity disorder
ADHD was officially known as attention deficit disorder (ADD) from 1980 to 1987; prior to the 1980s, it was known as hyperkinetic reaction of childhood. Symptoms similar to those of ADHD have been described in medical literature dating back to the 18th century. Sir Alexander Crichton describes "mental restlessness" in his book An inquiry into the nature and origin of mental derangement written in 1798.[340][341] He made observations about children showing signs of being inattentive and having the "fidgets". The first clear description of ADHD is credited to George Still in 1902 during a series of lectures he gave to the Royal College of Physicians of London.[342][336]
The terminology used to describe the condition has changed over time and has included: minimal brain dysfunction in the DSM-I (1952), hyperkinetic reaction of childhood in the DSM-II (1968), and attention-deficit disorder with or without hyperactivity in the DSM-III (1980).[336] In 1987, this was changed to ADHD in the DSM-III-R, and in 1994 the DSM-IV in split the diagnosis into three subtypes: ADHD inattentive type, ADHD hyperactive-impulsive type, and ADHD combined type.[343] These terms were kept in the DSM-5 in 2013 and in the DSM-5-TR in 2022.[3][4] Prior to the DSM, terms included minimal brain damage in the 1930s.[344]
ADHD, its diagnosis, and its treatment have been controversial since the 1970s.[224][6] Positions range from the view that ADHD is within the normal range of behaviour[88][345] to the hypothesis that ADHD is a genetic condition.[346] Other areas of controversy include the use of stimulant medications in children,[224] the method of diagnosis, and the possibility of overdiagnosis.[347] In 2009, the National Institute for Health and Care Excellence states that the current treatments and methods of diagnosis are based on the dominant view of the academic literature.[348]
Once neuroimaging studies were possible, studies in the 1990s provided support for the pre-existing theory that neurological differences (particularly in the frontal lobes) were involved in ADHD. A genetic component was identified and ADHD was acknowledged to be a persistent, long-term disorder which lasted from childhood into adulthood.[349][350] ADHD was split into the current three sub-types because of a field trial completed by Lahey and colleagues and published in 1994.[351] In 2021, global teams of scientists curated the International Consensus Statement compiling evidence-based findings about the disorder.[7]
In 1934, Benzedrine became the first amphetamine medication approved for use in the United States.[352] Methylphenidate was introduced in the 1950s, and enantiopure dextroamphetamine in the 1970s.[336] The use of stimulants to treat ADHD was first described in 1937.[353] Charles Bradley gave the children with behavioural disorders Benzedrine and found it improved academic performance and behaviour.[354][355]
Research directions
Possible positive traits
Possible positive traits of ADHD are a new avenue of research, and therefore limited.
A 2020 review found that creativity may be associated with ADHD symptoms, particularly divergent thinking and quantity of creative achievements, but not with the disorder of ADHD itself – i.e. it has not been found to be increased in people diagnosed with the disorder, only in people with subclinical symptoms or those that possess traits associated with the disorder. Divergent thinking is the ability to produce creative solutions which differ significantly from each other and consider the issue from multiple perspectives. Those with ADHD symptoms could be advantaged in this form of creativity as they tend to have diffuse attention, allowing rapid switching between aspects of the task under consideration; flexible associative memory, allowing them to remember and use more distantly-related ideas which is associated with creativity; and impulsivity, allowing them to consider ideas which others may not have.[356]
Possible biomarkers for diagnosis
Reviews of ADHD biomarkers have noted that platelet monoamine oxidase expression, urinary norepinephrine, urinary MHPG, and urinary phenethylamine levels consistently differ between ADHD individuals and non-ADHD controls. These measurements could serve as diagnostic biomarkers for ADHD, but more research is needed to establish their diagnostic utility. Urinary and blood plasma phenethylamine concentrations are lower in ADHD individuals relative to controls. The two most commonly prescribed drugs for ADHD, amphetamine and methylphenidate, increase phenethylamine biosynthesis in treatment-responsive individuals with ADHD.[154] Lower urinary phenethylamine concentrations are associated with symptoms of inattentiveness in ADHD individuals.[357]