- Last edited on April 15, 2024
Attention-Deficit/Hyperactivity Disorder (ADHD)
Primer
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, usually first diagnosed in childhood, characterized by inattention, impulsivity, and/or hyperactivity.
Epidemiology
Prognosis
- Childhood ADHD has been found to be associated with worse educational (lower grades, truancy), occupational economic, social, and health related outcomes.[6]
- ADHD in children is linked to a 2 times greater risk for accidental injuries of all types.[7]
- Adolescents with ADHD have a higher risk of earlier substance use, and greater difficulty with substance use.[8]
- ADHD symptoms can negatively impact the ability to drive safely in both adolescents and adults.[9]
- ADHD is associated with deficits in executive function, including: inhibitory control, working memory, and effortful attention.[10]
Comorbidity
- Between 50 to 90% of school-aged children with ADHD have at least one other comorbid psychiatric disorder, most commonly: anxiety disorders, oppositional defiant disorder, and language disorders.
- In adolescents, tic disorders (50-90%) are highly comorbid.
- Anxiety disorders, obsessive-compulsive disorder are also comorbid.
- 85% of adults with ADHD meet criteria for a comorbid mental disorder,[11] most commonly: mood disorders (both depression and bipolar disorder), and substance use disorders.[12]
Risk Factors
- The heritability of ADHD is about 76% (based on monozygotic twin studies).[13]
- Parents with ADHD have a >50% chance of having a child with ADHD.
- Close to 25% of children with ADHD have parents who meet the formal diagnostic criteria for ADHD.
- First-degree relatives of diagnosed ADHD individuals have a 30 to 40% chance.
- Genes implicated in ADHD include DAT1, DRD4, DRD5, DBH, 5-HTT, HTR1B, and SNAP-25.[14]
- However, due to increasing rates of ADHD diagnoses, non-genetic factors are equally as important and explain the reasons behind rising diagnoses.[15]
- The influence of later birthdate on ADHD diagnoses has also been investigated, suggesting that children may be diagnosed due to their relative age differences within their peer group at a certain grade level.[18]
DSM-5 Diagnostic Criteria
Diagnostic Construct
One thing to consider is that the current binary diagnosis of either someone having ADHD or not having ADHD does not reflect the actual reality of how attention span works, which is that attentional capacity is on a spectrum.[19]
Criterion A
A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development, as characterized by the (1) inattention category and/or (2) hyperactivity and impulsivity category:
Inattention
At least 6
of the following symptoms have persisted for at least 6
months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities:
- Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or during other activities (e.g. - overlooks or misses details, work is inaccurate).
- Often has difficulty sustaining attention in tasks or play activities (e.g. - has difficulty remaining focused during lectures, conversations, or lengthy reading)
- Often does not seem to listen when spoken to directly (e.g. - mind seems else where, even in the absence of any obvious distraction)
- Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g. - starts tasks but quickly loses focus and is easily sidetracked).
- Often has difficulty organizing tasks and activities (e.g. - difficulty managing sequential tasks; difficulty keeping materials and belongings in order; messy, disorganized work; has poor time management; fails to meet deadlines).
- Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g. - schoolwork or homework; for older adolescents and adults, preparing reports, completing forms, reviewing lengthy papers).
- Often loses things necessary for tasks or activities (e.g. - school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones).
- Is often easily distracted by extraneous stimuli (for older adolescents and adults, may include unrelated thoughts).
- Is often forgetful in daily activities (e.g., doing chores, running errands; for older adolescents and adults, returning calls, paying bills, keeping appointments).
5
symptoms are required.
Hyperactivity and Impulsivity
At least 6
of the following symptoms have persisted for at least 6
months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities:
- Often fidgets with or taps hands or feet or squirms in seat.
- Often leaves seat in situations when remaining seated is expected (e.g. - leaves his or her place in the classroom, in the office or other workplace, or in other situations that require remaining in place).
- Often runs about or climbs in situations where it is inappropriate (Note: In adolescents or adults, may be limited to feeling restless.)
- Often unable to play or engage in leisure activities quietly
- Is often “on the go,” acting as if “driven by a motor” (e.g. - is unable to be or uncomfortable being still for extended time, as in restaurants, meetings; may be experienced by others as being restless or difficult to keep up with)
- Often talks excessively
- Often blurts out an answer before a question has been completed (e.g. - completes people’s sentences; cannot wait for turn in conversation).
- Often has difficulty waiting his or her turn (e.g. - while waiting in line)
- Often interrupts or intrudes on others (e.g. - butts into conversations, games, or activities; may start using other people’s things without asking or receiving per mission; for adolescents and adults, may intrude into or take over what others are doing).
5
symptoms are required.
Criterion B
Several inattentive or hyperactive-impulsive symptoms were present prior to age 12
years.
Criterion C
Several inattentive or hyperactive-impulsive symptoms are present in at least 2
settings (e.g. - home, school, work, with friends or relatives, in other activities).
Criterion D
There is clear evidence that the symptoms interfere with, or reduce the quality of, social, academic, or occupational functioning.
Criterion E
The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder and are not better explained by another mental disorder.
Mnemonic
When the child is inattentive, youCALL FOR FRED
, this can be used to remember the inattention criteria. When the child is impulsive and hyperactive, he or she RUNS FASTT
, this can be used to remember the hyperactivity-impulsivity criteria.[20]
Inattention Criteria
C
- Careless mistakesA
- Attention difficultyL
- Listening problemsL
- Loses thingsF
- Fails to finish what he/she startsO
- Organizational skills lackingR
- Reluctance to do tasks that need sustained mental effortFR
- Forgetful in routine activitiesED
- Easily distracted
Hyperactivity-Impulsivity Criteria
R
- Runs or is restlessU
- Unable to wait for his or her turnN
- Not able to play quietlyS
- Slow? – Oh no! He's on the go!F
- Fidgets with hands or feetA
- Answers blurted outS
- Staying seated is difficultT
- Talks excessivelyT
- Tends to interrupt
Assessment and Diagnosis
A review of just the DSM criteria is not enough to justify a diagnosis of ADHD! A formal psychiatric interview, plus a detailed review of the following history also needs to occur:[21]
- Medical history
- Rule out any medical issues that may mimic or aggravate symptoms of ADHD
- Nutrition and lifestyle
- High-risk activities (substance use)
- Sexual activity
- Accidents (e.g. - concussions, traumatic brain injuries)
- Neurological history (e.g. - seizures, in particular absence seizures)
- Complete childhood developmental history (a parent, a teacher, or a close family member who knows the individual’s early history may be helpful for collateral)
- Having an objective third party to provide this history is critical, as the accuracy of self-recall of ADHD symptoms in childhood is not accurate![22]
- Perinatal history (birth weight, complications, maternal alcohol and tobacco usage during pregnancy)
- Developmental milestones
- Intellectual disability, learning disorders
- Psychoeducational assessments, report cards
- Impact of symptoms on learning, socialization and independent functioning
- Temperament
- Symptoms of ADHD prior to the age of 12
- Presence of any life events that were of emotional concern in childhood (e.g. - abuse, bullying, divorce, loss, deaths, attachment issues)
Overdiagnosis
- It is important to be aware of diagnostic creep and overdiagnosis! True ADHD is a debilitating condition that presents largely in childhood and absolutely should be treated.
- However, we are likely in a culture of overdiagnosis right now, especially with the ease of prescribing stimulants and short assessments in primary care settings. A short or incomplete assessment means a thorough differential diagnosis has not been considered.
- Since individuals both with and without ADHD can experience improved attention and decreased restlessness while taking stimulants, medication response alone is not and cannot be the basis for diagnosing the disorder.[31][32][33]
- However, this is often a common diagnostic fallacy that most clinicians make.
- It is also important to note that the increase in ADHD diagnoses is multifactorial.
- Factors such as greater awareness of mental health, ADHD itself, and its treatments are contributors.
- Social factors, cultural factors, and the influence of pharmaceutical marketing also plays a role.
- Finally, insufficient diagnostic training (e.g. - diagnosis in primary care without a detailed psychiatric and developmental history assessment) and lack of resources devoted to non-pharmacological management of childhood behavioural problems may further compound the issue.
Father of Modern Conceptualization of ADHD on Current Diagnosis and Treatment of the Condition
“The numbers make it look like an epidemic. Well, it’s not. It’s preposterous … This is a concoction to justify the giving out of medication at unprecedented and unjustifiable levels.”– Dr. Keith Conners,[34] child psychologist and father of the modern conceptualization of ADHD. (From: New York Times: The Selling of Attention Deficit Disorder)
Prevalence
- Although many ADHD guidelines continue to suggest that prevalence rates are stable, and that overdiagnosis is not occurring, the epidemiological data is increasingly showing the opposite.
- A 2015 systematic review and meta-analysis (the most comprehensive to date) provided a conservative benchmark overall pooled estimate prevalence of 7.2% using 36 years of ADHD studies[35]
- In the United States, from 1997 to 2016, the estimated prevalence of diagnosed attention-deficit/hyperactivity disorder in US children and adolescents increased from 6.1% in 1997 to 10.2% in 2016.[36]
- This far exceeds the baseline estimated prevalence rates from the systematic review, suggesting that overdiagnosis may be occurring.
– Rae Thomas
Adult-onset ADHD
Schools and Birth Month
- Children, in particular boys with summer birthdays (e.g. - August) entering kindergarten with a September 1st cutoff date are more likely to have teachers who perceive them as having more behavioural or academic difficulties.
- As a result, immature but age-normal behaviours may be mistaken for ADHD symptoms.
- These youngest children have a 34% higher chance of an ADHD diagnosis and a 32% higher chance of ADHD treatment than children with a September birthday (i.e - children are 1 year older than them).
Misuse and Diversion
Industry Influence
Technology
Screening and Rating Scales
Attention!
While rating scales are useful to support the clinical assessment and monitor symptoms, they should never be used on their own to make a diagnosis of ADHD.Psychometric Scales for ADHD
Name | Rater | Description | Download |
---|---|---|---|
ADHD Checklist | Clinician/Patient | The ADHD Checklist is a list of the 9 DSM items of attention and the 9 DSM items of hyperactivity/impulsivity. The checklist can also be completed to identify ADHD in adults in childhood, or completed by a collateral informant as well as the patient. | Download |
SNAP-IV 26 | Teacher/Parent | The SNAP-IV is a 26-item rating scale, ranging from a 0 to 3 rating scale. Sub scale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. | Download |
Adult ADHD Self-Report Scale | Patient | The Adult ADHD Self-Report Symptom Checklist is an 18-item scale that contains the 18 DSM-IV-TR ADHD criteria. | Download |
Conners’ Rating Scale-Revised | Clinician/Patient | Scale administered to parents and teachers of children and adolescents age 6-18. Self-report, age 8-18 | Link |
Pathophysiology
- Recent research has shown that there are bilateral amygdala, accumbens, and hippocampus reductions in ADHD.[49] However, these findings have been scrutinized and remain under debate.[50][51] Like all psychiatric disorders, there is no single pathophysiological cause for ADHD and the diagnosis is based on behavioural criteria that are sensitive to subjectivity and cognitive biases.[52]
- Implicated brain regions include the prefrontal cortex, basal ganglia, corpus callosum, and cerebellum .[53]
- Neurotransmitter systems involved include dopamine and norepinephrine.
Differential Diagnosis
Not every inattentive or disruptive youth has ADHD! Even those who do have ADHD are likely to have at least one other comorbid condition. A youth may be inattentive or act out because of normal developmental variation, problems related to sleep (e.g. - obstructive sleep apnea), diet, impaired hearing or vision, learning disabilities, anxiety disorders, depression, and/or substances use. Always consider a psychoeducational assessment, including both cognitive and academic testing, to assess for learning problems.
Psychiatric
-
- Children with ODD have distinct characteristics, including refusal to comply with rules, deliberately annoying others, blaming others for their own mistakes, and/or being spiteful or vindictive. Overlapping symptoms with ADHD include losing temper, anger, resentment, irritability, and argumentative behaviours
-
- The essential characteristic of conduct disorder is repetitive and persistent behavior such as violation of others' fundamental rights or of social rules/norms
-
- A recent drop in mood is different from the lifelong demoralization that may be seen in ADHD. Moderate to severe depression should be treated first and suicide must be assessed in all cases
-
- Until the publication of the DSM-5, ASD was an exclusionary criterion in making the diagnosis of ADHD. Thus its relationship to ADHD remains poorly understood, between 30 to 70% of patients with ASD may meet criteria for ADHD
-
- Many symptoms of bipolar disorder overlap with ADHD symptoms (e.g. - insomnia, impulsive sexual behaviours, impulsivity), which can be diagnosis challenging. Bipolar disorder is distinct in that there is grandiosity, and episodic symptoms (versus chronic in ADHD)
-
-
- The symptoms of impulsivity, mood dysregulation, and poor concentration/focus may be better explained by BPD.
-
Medication-related
- Medication with cognitive dulling side effect
- Think about mood stabilizers and antipsychotics
- Medication with psychomotor activation
- Think about decongestants and beta agonists
Other Factors
- Unsafe or disruptive learning environment
- Family dysfunction or poor parenting
- Child abuse or neglect
- Intellectual giftedness
- Individuals with giftedness may be misdiagnosed with ADHD in two ways. They may have high energy and over-excitability in school contexts (particularly in those with little academic stimulation), or individuals may meet full diagnostic criteria for ADHD but are able to concentrate for long periods of time, thus may not be diagnosed with ADHD.
General Medical Conditions
-
-
- Insomnia in both children and adults can cause decreased attention, difficulties in emotional and behavioural regulation, decreased cognitive functioning (e.g., poor memory), and worse academic performance. Thus, a careful sleep history should be done to rule out the impact of sleep on the individuals symptoms. Additionally, stimulants can worsen sleep, and it is important to monitor for this
-
- Sleep apnea can mimic or aggravate ADHD symptoms, once sleep apnea is properly treated, ADHD symptoms may resolve on their own.[54]
-
-
- Since underlying ADHD can increase risk for head trauma, it is important to look for timing of cognitive symptoms apparition (present before, or appeared or worsened after head trauma).
-
- Absence seizures where an individual appears to lose attention or focus may be misdiagnosed as ADHD.[55]
- Anti-epileptic medications side effects can impair attention and learning, may be confused with ADHD symptoms.
- Hearing impairment or vision impairment
- Order audiology and vision assessment if there are any concerns
-
- Order TSH levels to check for hypothyroidism or hyperthyroidism
- Hypoglycemia
- Check blood glucose levels
- Anemia
- Order CBC
- Lead poisoning
- Order blood lead levels
-
- Molecular genetic testing for the FMR-1 gene confirms the diagnosis of Fragile X.
- Phenylketonuria
- Neurofibromatosis
- Fetal alcohol spectrum disorder (FASD) and Intellectual disability
- Consider the presence of intellectual disability and FASD by observing for growth deficiency and facial features and FASD. Ask a thorough developmental history around prenatal alcohol exposure risk. Further psychoeducational testing may also be helpful.
Investigations
- Laboratory and imaging tests if indicated by the clinical evaluation.
Physical Exam
- Hearing and visual tests if clinically indicated.
Treatment
Never Forget this Principle!
When thinking about treatment of ADHD, always remember this core principle:- Psychoeducation and support for all
- Behavioural treatments for most
- Medications for some
Psychoeducation
Psychoeducation involves discussing the impact of ADHD on day-to-day functioning, treatment options, and strategies for optimizing function. Psychoeducation can help empower patients and families by providing information on ADHD.[56] It has been found to increase knowledge, enhance treatment adherence, and improve attitudes and intended behaviours towards the person with ADHD.[57] Psychoeducation typically involves:
- Explaining the rationale for the diagnosis, referencing examples of symptoms and impairment given by the parents and child/adolescent
- Explaining that although ADHD has a genetic component, environmental interventions can still be immensely helpful
- Reviewing the natural course and prognosis of ADHD and discuss comorbid conditions
- Discussing available treatment options (both pharmacological and non-pharmacological)
- Conveying a message of hope and optimism, telling the patient and family that ADHD tends to improve over time and is among the most treatable of psychiatric disorders
Behavioural and Psychosocial
Planning and organization skills may be suboptimal in individuals with ADHD.[58] Behavioural and sychosocial interventions in various environments (home, social situations, extracurricular activities, workplace, and academic) help improve functioning in these unstructured environments. Additionally, it is important to note that psychosocial treatment is the first line treatment for preschoolers. Even for non-high schoolers, behavioural interventions have strong evidence for throughout the lifespan.[59]
Home Interventions
Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Instructional | • Get eye and/or gentle physical contact before giving one or two clear instructions. • Get the person to repeat the instructions before proceeding. |
---|---|
Behavioural | • Use a positive approach and calm tone of voice. Avoid yelling and arguing. • Encourage calming techniques to de-escalate conflict. Example: Teach “stop and think”. Help them put on their brakes by taking deep breaths. • Use praise, “catch them being good” (doing chores, playing nicely). • Set clear attainable goals and limits (specific homework routine, bedtime routine, chores, etc.) and tie them to earning privileges, special outings, etc. • Use positive incentives and natural consequences; “When you…(do homework ) …then you …(may go play )”; if…then. • Use empathy statements such as “I understand” / “however” can be useful. • Recommend that adults model emotional self-regulation and encourage a balanced lifestyle (nutritious meal planning, exercise, hobbies and sleep hygiene). • Schedule family and partner time. • Keep choices limited to two or three options. • Make rewards meaningful and timed in close proximity to the desired behavior. |
Enivronmental | • Implement structure and routines. • Parents/partners must be united, consistent, firm and fair. Follow through with agreed consequences. • Help them prioritize instead of procrastinating. • Post visual reminders (rules, lists, reminders, sticky notes, calendars) in prominent locations, using different colors to accentuate/prioritize. • Use timers/apps for deadlines (routines, homework, chores, paying bills, limiting electronics). • Keep labeled, different coloured folders or containers in prominent locations for items (keys, electronics, household items). • Find work area best suitable to individual, e.g. dining room table, quiet areas. • Chunk tasks (divide larger tasks into smaller ones) and assign specific deadlines to each step. • Allow planned frequent movement breaks during prolonged tasks. • Allow white noise, a fan or background music during homework, work or at bedtime. |
Workplace Interventions
Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Workplace | • Identify accommodation needs. • Request accommodations supports (Suggest using the CADDRA Template letter and adapting to your patient’s situation). • Suggest regular and frequent meetings with manager and support collaborative approach. • Set goals, learn to prioritize, review progress on a regular basis. • Identify time management techniques that work for individual, i.e. using a planner, apps). • Declutter and create work friendly environment. • Use organizational Apps (i.e. Evernote, Omnifocus, Todoist). • Explore productivity Websites (e.g. 43folders.com, zenhabits.net). • Get assistance from an ADHD Coach. • Review workplace strategies and accommodations at www.caddac.ca. |
---|
School Interventions
Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Instructional | • Give clear and precise directions. • Get the student’s attention before providing instructions. • Check the student’s understanding by having the student repeat instructions and provide clarification as needed. • Use direct requests – “when-then”. |
---|---|
Behavioural | • Provide immediate and frequent feedback. • Provide students with positive feedback and encouragement more frequently than negative feedback. • Provide students with specific feedback – “thank you for putting your hand up to ask a question”. • Use visual cues in the classroom or on the desk for transitions. • Use visual prompts/pictures or lists for task initiation and task completion. • Chunk and break down steps to initiate tasks. • Reduce the amount of work required to show knowledge i.e. rather than asking a child to do 10 addition questions, requiring them to do 5. • Providing clear expectations and structure in the classroom. • Allow for acceptable opportunities for movement: “walking passes”. |
Environmental | • Preferential seating away from distractions. • Proximity to the teacher. • A quiet place in the classroom for calming down or working. • Being seated beside a “more attentive” buddy. • Increase change and introduce novelty. |
Academic | • Actively engage the student by providing work at the appropriate academic level. • Allow extended time (1.5 x) to complete quizzes, tests and exams. • Permit student to write quizzes, tests and exams in a quiet room. • Allow ear-plugs/ head-phones to help reduce external noises during tests • Provide a scribe or note taker or access to assistive technology. • Assign homework as necessary but monitor quantity. |
Executive Function | • Find a tutor or academic coach. • Seek a structured classroom. • Establish a routine. • Keep an assignment notebook. • Develop an organization notebook. • Organize what needs to be taken to school the night before. • Monitor and prompt to get started on tasks. • Teach awareness of time; time management. • Use graphic organizer for long-term projects. |
Post-secondary | • Encouraging students to contact the Accessibility/Disability Centres. • Allow extended time for assignments, especially if numerous assignments are all due at the same time. • Allow extended time on tests/exams. • Organizational apps to keep notes, lists, ideas and more e.g. Evernote and Simplenote, Mind Manager. • Technological support to better organize thinking, taking notes, writing, e.g. Livescribe, AudioNote, One Note, SoundNote, Audiotorium and Screen Record • Concept Mapping can be achieved on the computer by using graphic organizers (e.g., Inspiration, Writers Companion, Draft Builder). • Access to preferential seating in lectures (close to the lecturer, away from visual or auditory distractions such as cycling heating/cooling units). • Access to a scribe or note taker to take notes for those courses where it is necessary to focus on the lecture rather than switching attention between the lecture to ensure lecture notes are adequate and thorough enough to review for tests/exams. • Obtaining advance copies of lecture notes, overheads, etc. so that the student can focus on the lecture rather than read what's on the board, take notes, and listen all at the same time. • Use videotape lectures if granted permission and review them later to reinforce class work. • Devices such as a tablet as well as apps that help with writing such as planning (e.g., Inspiration); drafting (e.g., Dragon Dictation, iPad Dictation); and note-taking (e.g., Notability). • Work with accessibility/disability staff to review and chunk assignments, check details, assist with time management and due dates and review progress. • Access to ‘prompt’ sheets/memory aids with outline of steps, formulas etc. • Coaching to identify strengths, negotiate problems, and work on specific goals. |
Manualized and Other Interventions
Many types of standardized, or structured behavioural interventions have been investigated, including:
- Parent Management Training Models
- For preschool-aged children, parent management training models, such as parent–child interaction therapy (PCIT), the Incredible Years programs, the New Forest Program, Triple P (Positive Parenting Program), and Helping the Noncompliant Child, are effective in decreasing symptoms of ADHD and disruptive behaviour disorders.[60]
- Social Skills Training (SST)
- SST teaches children how to perceive and interpret subtle social cues and problem-solve in social interactions
-
- In CBT targeted for ADHD, time management and organizational skills are addressed.[61]
-
- Can lessen ADHD symptoms such as hyperactivity/impulsivity and attention problems, emotional dysregulation, while increasing self- directedness and self-regulation. Importantly, compared to stimulants, these improvements can be maintained over time.[62]
- Other interventions include: behavioural parent training , behavioural classroom management, behavioural peer intervention , combined behaviour management interventions, organization training
Pharmacotherapy
Stimulants are considered the main treatment in ADHD in adolescents and adults, and there are two main classes of medications: amphetamines and methylphenidate (both classes are available in short, intermediary and long-acting preparations). The average response rate to medications is about 70%.[63] The overall response rate in the short-term (i.e. - 12 months) for stimulants is about 90%. Around 40% of individuals will have equal response to methylphenidate and amphetamine, and another 20% each will respond to only one class of medications. On a population level, there is no difference in the efficacy and tolerability between amphetamines and methylphenidate, but individuals may have a better response on one class compared to another.[64] While there is considerable data support the short-term benefits of ADHD treatment, there is little evidence that it improves long-term functional outcomes.[65][66][67] The general ADHD treatment principles are:[68]
- Long-acting stimulants are preferred as first-line treatment agents.
- There should be an adequate trial of both classes of long-acting stimulants before moving onto a trial of a second-line agent.
- Short- and intermediate-acting stimulants, and non-stimulants (i.e. - guanfacine, atomoxetine) are second-line treatment agents, and can be used for patients who experience significant side effects on first-line agents, have had poor response on first-line, or do not have access to first-line medications[69]
- Second-line stimulants can additionally be used for:
- As a PRN for certain activities, and/or
- To augment long-acting formulations early or late in the day, or early in the evening
- Second-line non-stimulants can also be used:
- In combination with first-line agents as a potential augmentation for first-line treatment suboptimal responders
- In patients where stimulants are contraindicated (e.g. - high risk of stimulant misuse or diversion)
- Third-line treatments include agents such as bupropion, clonidine, imipramine, modafinil, and atypical antipsychotics. These medications are off-label use, and may be used in adjunct with other first or second line agents. These medications have higher risks, higher side-effect profile, or lower efficacy.
- There is no significant difference between picking clonidine and guanfacine in terms of efficacy as an adjunct.
It's Not Just About the Meds!
Pharmacological treatment for ADHD must be integrated in a multimodal approach (i.e. - a biopsychosocial that implements psychoeducation, psychosocial interventions, and manualized interventions), plus a medical evaluation and ongoing follow-up. Comorbid disorders and co-administration of other medications must also be taken into account.How Do I Choose Between Amphetamine vs. Methylphenidate?
- There is no overwhelming evidence to suggest picking one class of medications over another.
- Depends on multiple factors:
- Does the child require coverage in the evenings?
- How concerned is the family regarding potential interference with sleep and appetite?
- Does the family prefer convenience or control/flexibility?
- How would the child feel about taking medication at school?
- Is there a risk of abuse or diversion of the stimulant?
- What is the family’s financial/insurance situation?
1st Line: Long-Acting Stimulants for ADHD
Adapted from: Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Tradename | Active ingredient | Formulations | Starting Dose | Titration (q7 days) | Max Dose (6-12 years) (CADDRA*) | Max Dose (13-17 years) (CADDRA*) | Max Dose (18+) (CADDRA*) |
---|---|---|---|---|---|---|---|
Adderall XR | Amphetamine mixed salts | 5, 10, 15, 20, 25, 30 mg cap | 5-10 mg q AM (adults can start at 10 mg) | ↑ 5 mg | 30 mg (30 mg) | 30 mg (50 mg) | 30 mg (50 mg) |
Biphentin | Methylphenidate | 10, 15, 20, 30, 40, 50, 60, 80 mg cap | 10-20 mg q AM | ↑ 5-10 mg | 60 mg (60 mg) | 60 mg (80 mg) | 80 mg (80 mg) |
Concerta | Methylphenidate | 18, 27, 36, 54 mg tab | 18 mg q AM | ↑ 9-18 mg | 54 mg (72 mg) | 54 mg (90 mg) | 72 mg (108 mg) |
Vyvanse | Lisdexamfetamine | 10, 20, 30, 40, 50, 60, 70 mg cap | 20-30 mg q AM | ↑ 10 mg | 60 mg (60 mg) | 60 mg (70 mg) | 60 mg (70 mg) |
2nd Line: Short- and Intermediate-Acting Stimulants for ADHD
Adapted from: Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Tradename | Active ingredient | Formulations | Starting Dose | Titration (q7 days) | Max Dose (6-12 years) (CADDRA*) | Max Dose (13-17 years) (CADDRA*) | Max Dose (18+) (CADDRA*) |
---|---|---|---|---|---|---|---|
Dexedrine | Dextro-amphetamine | 5 mg tab | 2.5-5 mg BID | ↑ 2.5-5 mg | 40 mg (20 mg) | 40 mg (30 mg) | 40 mg (50 mg) |
Dexedrine Spansule | Dextro-amphetamine | 10, 15 mg cap | 10mg q AM | ↑ 2.5-5 mg | 40 mg (30 mg) | 40 mg (30 mg) | 40 mg (80 mg) |
Ritalin | Methylphenidate | 10, 20 mg tab (5 mg generic only) | 5 mg BID to TID | ↑ 5 mg | 60 mg (60 mg) | 60 mg (60 mg) | 60 mg (100 mg) |
Ritalin SR | Methylphenidate | 20 mg tab | 20 mg q AM | ↑ 20 mg | 60 mg (60 mg) | 60 mg (80 mg) | 60 mg (100 mg) |
2nd Line: Non-Stimulants for ADHD
Adapted from: Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Tradename | Active ingredient | Formulations | Starting Dose | Titration (q7 days) | Max Dose (6-12 years) (CADDRA*) | Max Dose (13-17 years) (CADDRA*) | Max Dose (18+) (CADDRA*) |
---|---|---|---|---|---|---|---|
Intuniv XR | Guanfacine | 1, 2, 3, 4 mg tab | 1 mg | ↑ 1 mg q 7-14 days | 4 mg (4 mg) | 7 mg for monotherapy and 4 mg for adjunctive therapy | Not used in adults |
Strattera | Atomoxetine | 10, 18, 25, 40, 60, 80, 100 mg cap | • Children (6-12 years): 0.5 mg/kg/day • Adolescents (3-17 years): 0.5 mg/kg/day • Adults (18+): 40 mg daily | • Children and Adolescents: ↑ q 7-14 days; first to 0.8 mg/kg/day, then 1.2 mg/kg/day • Adults: ↑ q 7-14 days; to 60 mg then 80 mg/day | Lesser of 1.4 mg/kg/day or 60 mg/day | Lesser of 1.4 mg/kg/day or 100 mg/day | Lesser of 1.4 mg/kg/day or 100 mg/day |
Pharmacotherapy: Monitoring
Having an approach to prescribing can help the clinician assess whether a medication is working, and provides a systematic approach to monitoring prescribing:
- Start the medication on weekend so parents can see how the child responds to the drug throughout the day (not on a school day!)
- Educating parents about the length of action of each medication is very important!
- Children may appear “not be responding” because the effect of the medication has actually worn off by the time they come home from school
- Wait approximately 1 week to see if they are having a good response to the medication before making any changes
- This different than titrating an antidepressant where one might wait longer
- Titrating the medication:
- Start low and titrate the dose by small increments, and monitor closely
- Continue the titration until one of these events happen:
- Optimal response is achieved
- Intolerable adverse effects develop
- Maximum dose is reached
- The trick is finding the “sweet spot” dose – not too low such that there is no effect, and not too high that it causes side effects
- If there is non-response, also consider trying a different formulation in the same class (methylphenidate or amphetamine) before switching to another class.
Stimulant Medication Checklist
- There should be precaution in starting stimulants in individuals with a history of cardiac disease, bipolar disorder, psychosis, and/or pregnancy and lactation.
- Always measure initial weight and height in children and adolescents, with ongoing measurements throughout treatment and referencing percentile charts and growth charts.
- Cardiovascular exam should include blood pressure and heart rate measurement
- On average, stimulants increase heart rate (HR) by 5-10 beats/min, and systolic blood pressure (SBP) by 4-6 mmHg.[70]
- Any history of cardiac disease, physical exam suggestive of cardiac disease, and/or family history of sudden cardiac death should make you consider additional investigations (e.g. - ECG) prior to starting treatment.
- Blood pressure measurement should be taken both when patient is off medication and on medication, in order to assess the contribution by medications.
- Assess for sleep quality at baseline and monitor for tics if present.
Contraindications, Precautions, and Monitoring in ADHD Medications
Adapted from: Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Class | Contraindications | Precautions | Monitoring during Treatment |
---|---|---|---|
Any ADHD medication | Known hypersensitivity or allergy to the products | • Cardiac disease • Bipolar disorder • Psychosis • Pregnancy and lactation | • Height and weight in children • New mood, anxiety, substance use disorder, psychotic or manic symptoms • Suicidal behaviour or ideation‡ • Aggressive behaviour (new or worsening) • Sleep, appetite • Irritability or mood swings |
Stimulants | • Treatment with MAOI or RIMA and for up to 14 days after discontinuation. • Glaucoma (narrow angle) • Untreated hyperthyroidism • Moderate to severe hypertension • Pheochromocytoma • Symptomatic cardiovascular disease • History of mania or psychosis | • History of substance abuse • Anxiety (generally speaking, treatment outweighs risks) • Renal impairment • Tic disorders • Epilepsy • Peripheral vasculopathy including Raynaud’s Phenomenon | • BP, HR (may increase) • Palpitations • Priapism† • Growth retardation • Peripheral vasculopathy including Raynaud’s Phenomenon • Insomnia or sleep disturbance |
Atomoxetine | • Treatment with MAOI or RIMA and for up to 14 days after discontinuation. • Narrow angle glaucoma • Uncontrolled hyperthyroidism • Pheochromocytoma • Moderate to severe hypertension • Symptomatic cardiovascular disease • Severe cardiovascular disorders • Advanced arteriosclerosis | • Asthma* • CYP2D6 poor metabolizers • Peripheral vasculopathy including Raynaud’s Phenomenon | • Priapism† and urinary retention • Signs / symptoms of liver injury • Growth retardation • Peripheral vasculopathy including Raynaud’s Phenomenon |
Alpha-2 Agonists (e.g. - guanfacine, clonidine) | Inability for parents or patients to ensure regular daily dosage (due to the risk of rebound hypertension when stopped abruptly) | • Hepatic impairment • Kidney impairment | • Somnolence and sedation • BP, risk of hypotension • Bradycardia, syncope • Elevated BP and HR upon abrupt discontinuation • QTc interval (to be monitored if underlying conditions or other medication increase the risk of prolonged QTc interval) |
Pharmacotherapy: Side Effects and Adverse Events
Common Side Effects in ADHD Medications
Adapted from: Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018Stimulant | Atomoxetine | Alpha-2 Agonist | |
---|---|---|---|
Hypotension (BP ↓) and Bradycardia (HR ↓) | - | - | ✓ |
Hypertension (BP ↑ 5 mmHg) and Tachycardia (HR ↑ 10bpm) | ✓ | ✓ | When stopped suddenly (rebound hypertension) |
Appetite supression | ✓ | ✓ | Low incidence |
Constipation/diarrhea | ✓ | ✓ | ✓ |
Dry mouth | ✓ | ✓ | ✓ |
GI upset | ✓ | ✓ | Upper abdominal pain |
Nausea/vomitting | ✓ | ✓ | ✓ |
Anxiety | ✓ | ✓ | Low incidence |
Dizziness | ✓ | - | - |
Dysphoria/irritability | ✓ | ✓ | Uncommon |
Headache | ✓ | ✓ | Yes |
Initial insomnia | ✓ | ✓ | Low incidence |
Rebound effect | ✓ | - | - |
Tics | ✓ | Uncommon | - |
Weight loss | ✓ | ✓ | - |
Sexual dysfunction | Uncommon | ✓ | - |
Skin reactions | ✓ | ✓ | Low incidence |
Stimulants and the Risk of Psychosis and Mania
Stimulant prescription and use is not without risks:- In patients with diagnosed bipolar disorder, there is a small risk of switching from euthymia or depression to mania when prescribed a stimulant medication.
- If this occurs, the stimulant should be tapered or discontinued, and treatment of mania and bipolar disorder should be prioritized. Stimulant medication may carefully titrated (start low and go slow) once mood symptoms are stabilized.[73]
- In adolescents and young adults with ADHD, the risk of new-onset psychosis occurs in approximately 1 in 660 patients, and amphetamine use is associated with a two-fold greater risk of psychosis than with methylphenidate.[74]
Stimulants in Tic Disorders and Tourette's
- Stimulant medications are a safe and effective treatment for ADHD in individuals with tic disorders but requires careful monitoring for the potential for worsening of tics.[75] Stimulants do not typically raise the risk of tics but may do so in rare cases.
Pharmacotherapy: Outcomes
What's the Long-term Evidence for Stimulants in ADHD?
The Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder, or MTA, is the largest long-term follow up study on stimulant treatment for ADHD.[76][77] At the 8-year follow up mark, the study drew the following conclusions:- “Although the MTA data provided strong support for the acute reduction of symptoms with intensive medication management, these long-term follow-up data fail to provide support for long-term advantage of medication treatment beyond two years for the majority of children.”
- “Overall, the findings of this 6- and 8-year follow-up of the children in the MTA indicate that […] treatment-related improvements for the children in the MTA are generally maintained, but differential treatment efficacy continues to be lost at and beyond 36-months”
There remains a paradox and debate about why individuals on long-term treatment on stimulants did not fare better than those who did not. Furthermore, the NIMH MTA website and MTA FAQ also acknowledges the modest benefits of long-term treatment. Other population studies have also suggested this finding as well.[78] Finally, at the 16-year follow up of the MTA study, ongoing medication was not associated with reduction of symptom severity, and additionally was associated with height loss of approximately 1-inch.[79]
- ADHD medications have been shown in population registry studies to be associated with reduced mortality from unnatural causes, motor vehicle crashes, and possibly substance use disorders.[80]
- Other analyses using more robust data from the MTA study have shown no difference in the impact on substance use disorder risk.[81]
- Long-term exposure to ADHD medications, in particular stimulant medications is associated with an increased risk of cardiovascular disease, specifically hypertension and arterial disease.
Other Treatments
- There is some evidence that fatty fish high in Omega-3s or commercial preparations containing at least 500 mg of EPA can reduce symptoms.[82]
- Restricting artificial food colours have been found to be potentially effective (but modest) in a meta-analysis.[83]
- Polyunsaturated fatty acids (PUFAs) supplementation may help, due to a though of deficiency of PUFAs in ADHD.[84]
- Animal studies indicates that exercise enhances brain development and overall behavioural functioning. Studies in children with ADHD suggest that both short-term (≥20 minutes) and long-term (≥5 weeks) of moderate-to-vigorous physical activity can improve ADHD symptoms and neuropsychological functioning.[85]
- Trigeminal nerve stimulation has been studied and has an estimated treatment effect size similar to non-stimulants.[86]