Hyperactivity and impulsivity

Hyperactivity is excessive motor activity, restlessness or inability to remain still when stillness is expected. Impulsivity is acting, speaking or deciding without forethought and without regard for consequences, with difficulty waiting or inhibiting responses. The two occur together in attention deficit hyperactivity disorder (ADHD) but also in mania, anxiety, substance intoxication, drug adverse effects, thyroid disease, neurological disease and trauma.

Definitions. In ADHD, hyperactivity and impulsivity require 6 or more symptoms (5 or more at 17 years and over) for at least 6 months, onset before age 12 years, in 2 or more settings, with impairment:

• fidgeting
• leaving a seat
• running or climbing in inappropriate settings (inner restlessness in adults)
• inability to play quietly
• being constantly on the go
• excessive talking
• blurting answers
• difficulty waiting a turn
• interrupting or intruding

Akathisia is a subjective inner compulsion to move with an inability to sit still, usually caused by dopamine blocking or serotonergic drugs.

Classification by cause

• Neurodevelopmental: ADHD (hyperactive impulsive or combined presentation), autism spectrum disorder, conduct and oppositional disorders, Tourette syndrome, intellectual disability, foetal alcohol spectrum disorder, genetic syndromes (fragile X, Williams syndrome).
• Psychiatric: mania and hypomania, agitated depression, anxiety and panic, posttraumatic stress disorder, psychotic disorders, borderline and antisocial personality disorder, intermittent explosive disorder, and eating disorders with binge behaviour.
• Substance related: stimulant, cannabinoid, hallucinogen and alcohol intoxication, withdrawal from alcohol, benzodiazepines and opioids, and gambling and other behavioural addictions.
• Drug induced: akathisia from antipsychotics, metoclopramide, prochlorperazine and selective serotonin reuptake inhibitors, corticosteroids, theophylline, salbutamol, levodopa and dopamine agonists (impulse control disorders), levetiracetam, perampanel, antihistamines (paradoxical), caffeine, and serotonin syndrome.
• Neurological: delirium, frontal lobe injury, traumatic brain injury, frontotemporal dementia, epilepsy (postictal, frontal), encephalitis, Huntington disease, Sydenham chorea, stroke and tumour.
• Endocrine and metabolic: hyperthyroidism, hypoglycaemia, hypoxia, hypercalcaemia, phaeochromocytoma, and uraemia.
• Other: sleep deprivation and sleep apnoea in children, iron deficiency and restless legs, lead exposure, pain, hunger, and unrecognised hearing or vision loss.

Epidemiology. ADHD affects about 5% of children (male to female about 2 to 1 in children, closer to 1 to 1 in adults) and about 2.5% of adults. Hyperactivity tends to lessen with age and becomes inner restlessness, while impulsivity and inattention persist. Impulse control disorders occur in up to 15% of patients with Parkinson disease treated with dopamine agonists. Akathisia affects 5% to 30% of patients treated with antipsychotics.

Mechanisms. Dopaminergic and noradrenergic dysfunction in frontostriatal circuits with weak inhibitory control (ADHD), elevated dopamine and reduced judgement (mania), dopamine receptor blockade in the nigrostriatal and mesocortical tracts (akathisia), and loss of frontal inhibition in brain injury.

Key distinctions.

• Lifelong, early onset, multi setting symptoms point to ADHD.
• Episodes lasting at least 4 days with decreased need for sleep, grandiosity and pressured speech point to mania.
• Restlessness beginning days after starting or increasing a dopamine blocking drug points to akathisia.
• Restlessness with tremor, tachycardia, weight loss and heat intolerance points to thyrotoxicosis.
• New disinhibition in midlife with apathy and loss of empathy points to frontotemporal dementia.
• Restlessness with confusion, fever, sweating and clonus points to serotonin syndrome or delirium.

History

• Description: what the patient or carers observe (fidgeting, interrupting, risk taking, spending, aggression, unsafe sex, gambling), timing, triggers and where it occurs (home, school, work).
• Onset: since early childhood, adolescent, or recent; relation to drugs, substance use, illness, head injury or bereavement.
• Developmental and school history, family history of ADHD, bipolar disorder, tics or substance use, and collateral report from parents, teachers or partners.
• Mood: decreased need for sleep, elevated or irritable mood, racing thoughts, grandiosity, increased spending, hypersexuality, and depressive episodes.
• Anxiety, trauma, psychotic symptoms, obsessions, tics, autistic features.
• Substances: stimulants (amphetamine, cocaine, methamphetamine, khat), cannabis, synthetic cannabinoids, alcohol, caffeine, energy drinks, hallucinogens, anabolic steroids; recent stopping of alcohol, benzodiazepines or opioids.
• Drugs: antipsychotics (especially haloperidol, aripiprazole, metoclopramide), antidepressants, steroids, bronchodilators, levodopa, dopamine agonists, antiepileptics, decongestants, thyroxine, and recent dose changes.
• Medical: thyroid disease, seizures, head injury, stroke, infection, diabetes, anaemia, pain, sleep disorder.
• Risk behaviours: dangerous driving, fights, self harm, suicidal thoughts, violence, legal trouble, accidents, unprotected sex, and gambling debts.
• Sleep pattern and snoring (children).
• Cardiac history and family history of sudden death before stimulant treatment.

Examination

• Vital signs including temperature, pulse, blood pressure, respiratory rate, oxygen saturation, glucose, weight and height.
• General: thyroid enlargement, tremor, sweating, tachycardia, eye signs, signs of intoxication or withdrawal, injection marks, dysmorphic features (foetal alcohol spectrum disorder), skin signs of neurofibromatosis.
• Neurological: orientation and attention, tone, tremor, chorea, tics, clonus, hyperreflexia, myoclonus, gait, primitive reflexes, and focal signs.
• Akathisia: observe the patient seated for 2 minutes (shifting weight, crossing and uncrossing legs, rocking, pacing) and standing (marching on the spot). Assess with the Barnes Akathisia Rating Scale. Check for rigidity and dystonia.
• Mental state: mood, speech rate, flight of ideas, grandiosity, psychosis, insight, and suicidal or violent thoughts.
• Rating scales: Adult ADHD Self-Report Scale, Conners scales, Vanderbilt scale (children), Young Mania Rating Scale, and Barratt Impulsiveness Scale.

Red flags

• Agitation with violence, threats or inability to engage (risk of harm to self or others).
• Decreased need for sleep for several days with grandiosity or psychosis (mania).
• Delirium: acute onset, fluctuating attention, disorientation, visual hallucinations.
• Fever, tachycardia, sweating, hyperreflexia, clonus or rigidity (serotonin syndrome, neuroleptic malignant syndrome, thyroid storm, sympathomimetic toxicity).
• Withdrawal from alcohol or benzodiazepines (tremor, sweating, seizures, hallucinations).
• Head injury or new focal neurological signs.
• Severe akathisia with suicidal thoughts or self harm.
• Hypoglycaemia, hypoxia or sepsis.
• New impulsive behaviour in midlife without psychiatric history (frontotemporal dementia, tumour).
• Child with sudden change in behaviour, regression, or choreiform movements after sore throat (Sydenham chorea).
• Cardiac symptoms or family history of sudden death before stimulant treatment.
• Safeguarding concerns: injury, neglect, abuse or exposure to violence.

Special groups

• Children: assess sleep, vision, hearing, language, learning, anxiety, trauma, home environment and teacher reports. Behaviour is age dependent, so judge against peers.
• Adolescents: substance use, mood disorder, conduct disorder, and risk behaviours are common. Keep confidentiality within limits of safety.
• Women: inattentive and internalised presentations are missed. Symptoms vary with the menstrual cycle, pregnancy and perimenopause.
• Older adults: delirium, drug effects, thyroid disease, frontotemporal dementia and akathisia are more likely than new ADHD.
• Pregnancy: avoid starting drugs where possible, and exclude thyroid disease, substance use and pre-eclampsia (eclampsia with agitation).
• Intellectual disability and autism: behaviour may express pain, constipation, infection or distress, so examine fully.
• Parkinson disease: impulse control disorders (gambling, hypersexuality, binge eating, compulsive shopping) with dopamine agonists.

Neurodevelopmental and psychiatric

• ADHD (hyperactive impulsive, combined).
• Autism spectrum disorder with sensory overload or meltdown.
• Oppositional defiant disorder, conduct disorder and intermittent explosive disorder.
• Tourette syndrome and tic disorders.
• Bipolar I and II disorder (mania, hypomania, mixed states); cyclothymia.
• Agitated or mixed depression.
• Generalised anxiety, panic disorder, posttraumatic stress disorder.
• Psychotic disorders with agitation; catatonic excitement.
• Borderline, antisocial and other personality disorders.
• Intellectual disability and foetal alcohol spectrum disorder.
• Gambling disorder and other behavioural addictions.

Substance related and drug induced

• Stimulant, cannabinoid, hallucinogen and alcohol intoxication.
• Alcohol, benzodiazepine and opioid withdrawal.
• Akathisia (antipsychotic, metoclopramide, prochlorperazine, antidepressants).
• Serotonin syndrome and neuroleptic malignant syndrome.
• Corticosteroid, theophylline, salbutamol, levodopa and dopamine agonist effects.
• Caffeine and energy drink excess.
• Anticholinergic toxicity.
• Paradoxical reaction to benzodiazepines, antihistamines or alcohol.

Neurological

• Delirium of any cause.
• Traumatic brain injury and frontal lobe syndromes.
• Frontotemporal dementia and other dementias with behavioural change.
• Epilepsy (frontal lobe, postictal) and nonconvulsive status epilepticus.
• Encephalitis (infectious, autoimmune).
• Sydenham chorea and Huntington disease.
• Brain tumour and stroke.
• Restless legs syndrome and sleep apnoea.

Medical and metabolic

• Hyperthyroidism and thyroid storm.
• Hypoglycaemia, hyponatraemia and hypercalcaemia.
• Hypoxia and sepsis.
• Phaeochromocytoma.
• Pain, urinary retention, constipation and hunger as causes of restlessness.
• Iron deficiency and lead poisoning.
• Uraemia and hepatic encephalopathy.

Step 1. Exclude emergencies. Check airway, vital signs, glucose and oxygen saturation. Treat hypoglycaemia, hypoxia and sepsis. Recognise delirium, withdrawal, toxicity and serotonin syndrome. Ensure safety of the patient and staff.

Step 2. Characterise the behaviour. Determine onset, course, setting and function. Obtain collateral history. Review all drugs and substances. Use the Adult ADHD Self-Report Scale or Vanderbilt scale, Young Mania Rating Scale, and Barnes Akathisia Rating Scale as relevant.

Step 3. First line tests

• Capillary glucose, full blood count, ferritin, urea, creatinine, electrolytes, calcium, magnesium, liver tests, thyroid stimulating hormone and free thyroxine.
• Urine or serum toxicology (amphetamines, cocaine, cannabinoids, benzodiazepines, opioids) and blood alcohol.
• Pregnancy test in women of reproductive age.
• 12 lead ECG (QTc before antipsychotics, and before stimulants).
• Creatine kinase if rigidity, fever or agitation with possible muscle injury.

Step 4. Targeted tests

• Delirium workup: urine analysis, chest radiograph, cultures, C-reactive protein, B12, ammonia, and CT head when focal signs, trauma or new neurological change.
• Electroencephalogram if altered consciousness or suspected seizure.
• MRI brain and lumbar puncture when encephalitis, tumour or frontotemporal dementia is suspected.
• HIV and syphilis serology; copper and caeruloplasmin in young adults with movement disorder.
• Antistreptolysin O titre and throat swab for suspected Sydenham chorea; echocardiogram.
• 24 hour urine or plasma metanephrines for episodic hypertension, sweating and palpitations.
• Polysomnography in children with snoring or sleep disruption.
• Neuropsychological testing and structured diagnostic interview (DIVA-5) for ADHD.
• Lead level in children with exposure risk.
• Genetic testing (fragile X, microarray) in children with developmental delay or dysmorphism.

Step 5. Interpretation. Diagnose ADHD only when symptoms are lifelong, multi setting and impairing, and not better explained by mania, substance use, anxiety, trauma, drug effects or medical illness. Bipolar disorder must be excluded before stimulants or antidepressants. New onset impulsivity or hyperactivity in an adult without developmental history is not ADHD until other causes are excluded. Limits. Rating scales support but do not diagnose.

Behaviour varies with setting, so a clinic observation may be normal. Akathisia is often misread as agitation, and an increase in the offending drug worsens it.

Immediate

• Ensure safety. Use verbal de-escalation first: calm voice, low stimulation, clear choices, personal space, and removal of weapons or hazards.
• Treat reversible causes: glucose for hypoglycaemia (50 mL of 50% dextrose or 150 to 200 mL of 10% dextrose intravenously), oxygen for hypoxia, and antimicrobials for sepsis.
• Acute severe agitation when de-escalation fails (adult, oral preferred): lorazepam 1 to 2 mg orally, repeated once after 1 hour if needed (maximum 4 mg in 24 hours), or olanzapine 5 to 10 mg orally (maximum 20 mg in 24 hours).
• Intramuscular: lorazepam 1 to 2 mg, or olanzapine 5 to 10 mg (do not give intramuscular olanzapine within 1 hour of a parenteral benzodiazepine), or haloperidol 5 mg intramuscularly (maximum 12 mg in 24 hours) with promethazine 25 to 50 mg intramuscularly to reduce dystonia, after ECG when feasible.
• Avoid antipsychotics in suspected neuroleptic malignant syndrome, seizures from alcohol withdrawal, and prolonged QTc (over 500 ms).
• Monitor pulse, blood pressure, oxygen saturation and level of consciousness every 15 minutes for 1 hour, then hourly.
• Alcohol or benzodiazepine withdrawal: chlordiazepoxide 15 to 30 mg orally every 6 hours reducing over 5 to 7 days, with thiamine 200 to 500 mg intravenously three times daily for 3 days if Wernicke encephalopathy is suspected.
• Stimulant intoxication: benzodiazepines (diazepam 5 to 10 mg intravenously or lorazepam 1 to 2 mg, repeated every 5 to 10 minutes to effect), cooling, intravenous fluids, and treatment of hypertension and hyperthermia.
• Serotonin syndrome: stop serotonergic drugs, give diazepam 5 to 10 mg intravenously, fluids and cooling, and cyproheptadine 12 mg orally then 2 mg every 2 hours while symptoms continue, then 8 mg every 6 hours for maintenance (maximum 32 mg daily).
• Thyroid storm: propranolol 60 to 80 mg orally every 4 hours (or 1 to 2 mg intravenously slowly), carbimazole 20 mg every 6 hours or propylthiouracil 200 mg every 4 hours, hydrocortisone 100 mg intravenously every 8 hours, and fluids and cooling.

Treatment by cause

• Akathisia: reduce the dose or change the drug (for example to aripiprazole at lower dose, quetiapine or clozapine). Propranolol 10 to 20 mg orally two or three times daily, increased to 40 to 80 mg daily in divided doses, is first line (avoid in asthma and bradycardia).
• Akathisia alternatives: mirtazapine 15 mg at night, benzodiazepine (lorazepam 0.5 to 1 mg twice daily short term), or cyproheptadine 4 mg three times daily. Anticholinergics such as procyclidine 5 mg daily have little effect on akathisia. Review at 1 to 2 weeks.
• Mania: stop antidepressants and stimulants.
• Mania drug treatment: start olanzapine 10 mg daily (maximum 20 mg), or quetiapine 50 mg at night increased over 4 days to 400 to 800 mg daily, or risperidone 2 mg increased to 4 to 6 mg daily, or aripiprazole 15 mg (maximum 30 mg).
• Mania maintenance: lithium (0.8 to 1.2 mmol/L for acute mania) or valproate 20 to 30 mg/kg daily. Valproate is avoided in women who can become pregnant. Admission is often needed.
• ADHD in adults: methylphenidate immediate release 5 mg two to three times daily titrated weekly by 5 to 10 mg daily to 30 to 60 mg daily in divided doses (maximum 100 mg under specialist direction).
• Other options in adults with ADHD: lisdexamfetamine 30 mg in the morning increased by 20 mg weekly to 50 to 70 mg (maximum 70 mg), or atomoxetine 40 mg daily for 7 days then 80 mg (maximum 100 mg).
• Before starting, measure blood pressure, pulse, weight and ECG if cardiac history. Contraindications are uncontrolled hypertension, arrhythmia, hyperthyroidism, glaucoma, mania, psychosis, and monoamine oxidase inhibitor use in the past 14 days. Review at 1 to 2 weeks after each change and every 3 to 6 months.
• ADHD in children (6 years and over): methylphenidate immediate release 5 mg once or twice daily, increased weekly by 5 to 10 mg daily to a maximum of 60 mg daily in divided doses.
• Methylphenidate modified release for children: 18 mg each morning increased to a maximum of 54 mg (some formulations 72 mg).
• Other options in children: lisdexamfetamine 30 mg each morning increased weekly by 10 to 20 mg to 70 mg.
• Atomoxetine 0.5 mg/kg daily for 7 days then 1.2 mg/kg daily (maximum 1.8 mg/kg or 100 mg daily).
• Guanfacine extended release 1 mg daily increased weekly by 1 mg to 0.05 to 0.12 mg/kg (maximum 7 mg).
• Monitor height, weight, blood pressure and pulse every 6 months. Behavioural parent training is the first treatment under 6 years and alongside drugs in older children.
• Tourette syndrome with ADHD: behavioural therapy for tics (habit reversal), clonidine 25 micrograms at night increased to 100 micrograms three times daily, or aripiprazole 2 to 5 mg daily for severe tics.
• Anxiety, depression or trauma: psychological therapy and an SSRI such as sertraline 25 to 50 mg daily increasing to 50 to 200 mg.
• Impulse control disorder from dopamine agonists: reduce or stop the agonist gradually, with neurological review.
• Substance use disorder: brief intervention, addiction services, and treatment of withdrawal.
• Epilepsy or encephalitis: antiepileptic drugs, aciclovir 10 mg/kg intravenously every 8 hours for suspected herpes encephalitis, and neurological care.
• Frontotemporal dementia: behavioural management, environmental safety, and sertraline or trazodone 25 to 50 mg at night; avoid anticholinesterase inhibitors.
• Restless legs or iron deficiency: ferrous sulphate 200 mg orally once daily or on alternate days, and sleep treatment.
• Sleep apnoea in children: adenotonsillectomy.
• Psychological and social measures: structured routines, clear rules, praise, physical activity, reduced screen time, school accommodations, and parent skills programmes.

Special populations

• Pregnancy and breastfeeding: avoid stimulants where possible. Use behavioural measures and specialist advice.
• Children: weigh risk and benefit of drugs, monitor growth, and review need yearly with a short break from treatment if suitable.
• Older adults: use lower doses, avoid anticholinergics and benzodiazepines when possible, and treat delirium by cause.
• Kidney and liver impairment: lowest effective dose; avoid atomoxetine in severe hepatic impairment (halve the dose in moderate impairment).

Monitoring. Behaviour and function, rating scales, blood pressure, pulse, weight and height, sleep, appetite, mood, tics, suicidal thoughts, substance use, adherence, QTc with antipsychotics, and lithium levels (every 3 months).

Referral and escalation. Psychiatry for mania, psychosis, severe agitation, and complex ADHD. Paediatric or neurodevelopmental services for children. Neurology for seizures, chorea and suspected frontotemporal dementia. Addiction services, endocrinology, cardiology and social services as needed. Admission criteria. Severe agitation or violence not controlled, mania with risk, psychosis, delirium, withdrawal needing inpatient care, serotonin syndrome or neuroleptic malignant syndrome, thyroid storm, and risk of suicide or harm to others.

Discharge and follow up. Written plan and information for patient and carers, safe drug use and storage (stimulants are controlled drugs), driving advice, review in 1 to 2 weeks, then every 3 to 6 months. Safety net advice: return for violence, suicidal thoughts, severe sleeplessness with elation, fever with rigidity or confusion, chest pain or palpitations, or fainting.