Hyperkinetic syndrome

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous behavioural syndrome characterised by the core symptoms of:

• hyperactivity
• impulsivity
• inattention
  
  
• while these symptoms tend to cluster together, some people are predominantly hyperactive and impulsive, while others are principally inattentive
  
  
• two main diagnostic criteria are in current use
  • the International Classification of Mental and Behavioural Disorders 10th revision (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5)
    • both systems require that symptoms are present in several settings such as school/work, home life and leisure activities
    • symptoms should be evident in early life, if only in retrospect; for ICD-10, by age 7 years and for DSM-5, by age 12 years
    • ADHD may persist into adult life
  • prevalence rates for ICD-10 (identifying hyperkinetic disorder) are 1 to 2% in childhood. Under the previous, less stringent DSM-IV criteria, childhood prevalence rates were 3 to 9% and these may increase under the new DSM-5 criteria
    
    
• causes of ADHD are not fully understood but a number of risk factors are associated with the condition
  • genetic factors can have an influence, with family members frequently affected
  • the diagnosis of ADHD in older family members such as parents may have previously been missed and should be considered
• both the ICD-10 and DSM-5 require the presence of functional impairment due to symptoms of ADHD, with the symptoms adversely affecting psychological, social and/or educational/ occupational functioning
  • the impact of ADHD may vary considerably in its severity, which is best judged by considering the level of impairment, pervasiveness, and familial and social context
    • for some people, symptoms may be limited to certain settings and cause minimal impairment in a limited number of domains (for example, ability to complete schoolwork, work tasks, avoiding common hazards and forming positive interpersonal relationships)
    • in other people, multiple symptom areas (hyperactivity, inattention and impulsivity) are present in multiple settings, and this causes significant impairment across multiple domains
    • symptoms and impact can also change over time. For some people, symptoms and impairment may be reduced through environmental modifications, such as a modified school curriculum or choice of employment
• symptoms of ADHD can overlap with those of other related disorders
  • common coexisting conditions in children include disorders of mood, conduct, learning, motor control, language and communication, and anxiety disorders; in adults, they include personality disorders, bipolar disorder, obsessive-compulsive disorder and substance misuse

Drug treatment for children and young people with ADHD should always form part of a comprehensive treatment plan that includes psychological, behavioural and educational advice and interventions (1). Medication for ADHD should only be prescribed after expert advice:

• when a decision has been made to treat children or young people with ADHD with drugs, healthcare professionals:
  • methylphenidate (either short or long acting) should be offered as the first line pharmacological treatment for children aged 5 years and over and young people with ADHD
    
    
  • consider switching to lisdexamfetamine for children aged 5 years and over and young people who have had a 6-week trial of methylphenidate at an adequate dose and not derived enough benefit in terms of reduced ADHD symptoms and associated impairment
    
    
  • dexamfetamine should be considered for children aged 5 years and over and young people whose ADHD symptoms are responding to lisdexamfetamine but who cannot tolerate the longer effect profile
    
    
  • atomoxetine or guanfacine should be offered to children aged 5 years and over and young people if:
    • they cannot tolerate methylphenidate or lisdexamfetamine or
    • their symptoms have not responded to separate 6-week trials of lisdexamfetamine and methylphenidate, having considered alternative preparations and adequate dose

Drug treatment for adults with ADHD should always form part of a comprehensive treatment programme that addresses psychological, behavioural and educational or occupational needs

• following a decision to start drug treatment in adults with ADHD, lisdexamfetamine or methylphenidate are options as first-line pharmacological treatment
  • enhance focus by modulating dopamine and norepinephrine (2)
• second-line treatments: non-stimulants, including atomoxetine, which are particularly useful for patients who cannot tolerate stimulants or for whom stimulants prove ineffective (2)

Troubleshooting problems in people prescribed ADHD medications

• patients prescribed ADHD medications may present to general practice with various symptoms, regardless of whether formal pathways exist (2)
  • symptoms might or might not be directly related to their medication
  • considerations for specific medications include:
    • methylphenidate
      • common side effects include - reduced appetite, insomnia, headache, increased heart rate
      • practical advice - preparations can be either immediate release (2-3 doses per day) or modified release (once daily in the morning); regularly assess focus, mood, and cardiovascular health
    • lisdexamfetamine
      • common side effects include - decreased appetite, dry mouth, insomnia, weight loss
      • practical advice - preparations can be immediate release (2–4 doses daily, spaced 4–6 hours apart) or modified release (once daily in the morning)
        • for modified release - assess impact on productivity, emotional regulation, and cardiovascular health
        • for immediate release - monitor energy levels, mood stability, and heart rate
    • atomoxetine
      • common side effects include - fatigue, dry mouth, nausea, mood swings
      • practical advice - take once or twice daily; watch for changes in emotional control, focus, and liver health

Primary care clinicians should consider referring patients to secondary care or the treatment-initiating clinic in the following situations (2):

• significant weight loss — unexplained reductions of more than 5% of body weight;
• new cardiac symptoms — if cardiac symptoms resolve after discontinuing the medication, referral to secondary care is recommended to explore alternative treatment options;
• severe psychiatric symptoms — including suicidal ideation or anxiety that cannot be managed in primary care;
• difficulty managing symptoms — despite optimal dosing, symptom control remains inadequate;
• unmanageable side effects — persisting issues that cannot be resolved in primary care; and
• medication concerns — any suspicion of misuse or diversion

A systematic review (3) found:

• very low-certainty evidence that extended-release methylphenidate compared to placebo improved ADHD symptoms (small-to moderate effects) measured on rating scales reported by participants, investigators, and peers such as family members
  • methylphenidate had no effect on 'days missed at work' or serious adverse events, the effect on quality of life was small, and it increased the risk of several
    adverse effects

Notes:

• methylphenidate preparations have different durations of action - can be divided into three groups:
  • immediate release - lasting approximately 4 hours
  • prolonged release - lasting approximately 8 hours
  • 'extended’ release - lasting approximately 12 hours

• confusingly, the abbreviation ‘XL’ is applied to formulations of prolonged-release and extended-release methylphenidate (4)
  • patients can be started on any of the prolonged-release or immediate-release preparations
  • patients stabilised on immediate-release products can change to equivalent doses of prolonged-release products, if appropriate
• immediate-release methylphenidate is rapidly absorbed with clinical effects less than 30 min after ingestion
• food does not reduce bioavailability of methylphenidate, but a high-fat meal may delay its absorption

• lisdexamfetamine (4)
  • is a prodrug
  • has no effect until it has been hydrolysed (in red cells) into dexamfetamine and lysine - this mechanism prolongs the duration of action to approximately 12 hours or more, facilitating once daily dosing
  • less likely to be abused compared with dexamfetamine
    
    
• combination of stimulants and non-stimulants in ADHD
  • combining stimulants with non-stimulants is not generally recommended (4)
    • is limited evidence for adding methylphenidate to those with a partial response to atomoxetine
    • a Canadian Health Technology Review, largely based on a guideline from Australia, suggests ‘..If stimulants are not tolerated or ineffective, non-stimulants, such as atomoxetine or guanfacine, should be offered as a second-line treatment. A combination of stimulants and non-stimulants may be prescribed to increase the benefit of the treatment. Other drugs such as bupropion, clonidine, modafinil, reboxetine and venlafaxine could be offered as third-line treatments..'

Reference:

• (1) NICE (March 2018).Attention defificit hyperactivity disorder: diagnosis and management
• (2) Noden S et al. A guide for primary care clinicians managing ADHD medication side effects. BJGP 2025; 75 (755): 285-286.
• (3) Boesen K et al. Extended-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database of Systematic Reviews 2022, Issue 2. Art. No.: CD012857. DOI: 10.1002/14651858.CD012857
• (4) Leaver L Medical management of ADHD in adults: part 2 Drug and Therapeutics Bulletin 2025;63:85-93.