Irritability

Irritability is a lowered threshold for anger, annoyance or frustration, with a tendency to react to minor provocation with disproportionate verbal or behavioural outbursts. It is a transdiagnostic symptom and not a disorder. It is among the commonest complaints in primary care, and it signals depression, bipolar disorder, anxiety, trauma, attention deficit disorder, substance use, sleep loss, pain, hormonal change, medical illness, brain injury, dementia or drug effect.

Definition. Irritability has a tonic component (a persistently angry, grumpy or touchy mood between outbursts) and a phasic component (temper outbursts, verbal or physical, out of proportion to the situation and inconsistent with developmental level). Clinical significance is judged by frequency, intensity, duration, and effect on relationships, work, school and safety.

Classification by context

• Psychiatric disorders in which irritability is a diagnostic feature: major depressive disorder (especially in children, adolescents and men), bipolar disorder (manic, hypomanic and mixed episodes), generalised anxiety disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, disruptive mood dysregulation disorder, oppositional defiant disorder, intermittent explosive disorder, and borderline personality disorder.
• Neurodevelopmental conditions: attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, and Tourette syndrome.
• Substance related: alcohol, stimulants, cannabis and nicotine intoxication and withdrawal, caffeine excess, and benzodiazepine or opioid withdrawal.
• Medical and neurological: hyperthyroidism, hypoglycaemia, sleep deprivation and sleep apnoea, chronic pain, traumatic brain injury, frontal lobe disease, dementia, epilepsy, delirium, menopause, hypogonadism, and chronic illness.
• Drug induced: corticosteroids, anabolic steroids, levetiracetam, perampanel, montelukast, efavirenz, isotretinoin, interferon alpha, levothyroxine excess, stimulants, SSRIs at start, benzodiazepine disinhibition, and antiepileptics.

Severity. Mild: noticed by others, no loss of function. Moderate: relationship or work strain, occasional shouting or door slamming. Severe: physical aggression, property damage, threats, loss of job or relationship, or risk to children or vulnerable adults.

Measurement. Affective Reactivity Index (7 items, parent and self report forms, score of 4 or more suggests clinically significant irritability in children and adolescents), Brief Irritability Test (5 items), and Irritability Questionnaire in adults. Use PHQ-9, GAD-7 and Mood Disorder Questionnaire in parallel.

Mechanisms. Amygdala hyperreactivity to threat and frustration with reduced prefrontal regulation, reward processing disturbance, serotonergic and dopaminergic dysfunction, autonomic arousal, sleep loss, hormonal fluctuation (oestrogen and progesterone), and learned coercive patterns within families.

Key distinctions.

• Persistent irritability for 2 weeks or more with anhedonia, sleep and appetite change suggests depression.
• Irritability with decreased need for sleep, pressured speech and increased activity suggests mania or hypomania.
• Irritability that follows trauma with hypervigilance and flashbacks suggests posttraumatic stress disorder.
• Irritability limited to the late luteal phase suggests premenstrual dysphoric disorder.
• A new change in personality with irritability and disinhibition in an adult over 45 years suggests frontotemporal dementia, a frontal lesion or a medical cause.

History

• Pattern: onset, duration, triggers, frequency of outbursts, intensity, context (home, work, driving), build up and recovery, memory of the event, remorse, and change from the person's usual temperament.
• Risk: verbal and physical aggression, threats, harm to partner, children or elders, weapons at home, damage to property, driving behaviour, and suicidal or homicidal thoughts. Ask directly about domestic violence in both directions.
• Mood and anxiety symptoms: low mood, loss of interest, hopelessness, worry, panic, obsessions, trauma, nightmares, hypervigilance, and suicidal ideation.
• Elevated mood symptoms: reduced need for sleep, racing thoughts, increased energy, spending, risk taking, and family history of bipolar disorder.
• Attention and hyperactivity: childhood onset inattention, impulsivity, restlessness, and academic or work problems.
• Psychotic symptoms: paranoia, hallucinations, and delusions.
• Sleep: hours, quality, snoring, witnessed apnoeas, shift work, and insomnia.
• Substances: alcohol (AUDIT-C), caffeine, nicotine, cannabis, stimulants, anabolic steroids, opioids and benzodiazepines, including recent reduction.
• Medical history: thyroid disease, diabetes and hypoglycaemia, head injury (with loss of consciousness), epilepsy, stroke, chronic pain, cardiovascular disease, kidney and liver disease, HIV, menopause and menstrual cycle, testosterone deficiency, and sleep apnoea.
• Drugs: corticosteroids, levetiracetam, montelukast, efavirenz, isotretinoin, interferon, levothyroxine, antiepileptics, SSRIs, stimulants, anabolic agents, and supplements containing caffeine or yohimbine.
• Development and family: childhood adversity, parenting style, school history, learning difficulty, family history of mood disorders, substance misuse and violence.
• Psychosocial stressors: bereavement, relationship strain, work or financial stress, caring duties, housing, discrimination, and chronic illness.

Examination

• Vital signs including temperature, heart rate and rhythm, blood pressure, and weight.
• Appearance and behaviour: tense posture, pressured speech, irritable affect, restlessness, and rapport.
• Mental state: mood, affect, thought form (flight of ideas), content (paranoia, grievance), perception, insight, cognition (orientation and attention), and risk.
• Physical: thyroid size and eye signs, tremor, tachycardia, sweating, hypertension, signs of alcohol use or withdrawal, stigmata of liver disease, cushingoid features, injection marks, and signs of head injury.
• Neurological: focal signs, gait, primitive reflexes (grasp, palmomental), eye movements, and frontal executive tests (verbal fluency, clock drawing).
• Bedside tests: glucose, pulse oximetry, urine drug screen if indicated, pregnancy test, PHQ-9, GAD-7 and a brief cognitive test (Montreal Cognitive Assessment score under 26 suggests impairment).

Red flags

• Threats or acts of violence, weapons, or risk to children or vulnerable people.
• Suicidal ideation or thoughts of harming others.
• Psychotic symptoms, mania, or catatonia.
• Acute confusion, fluctuating alertness or hallucinations (delirium).
• New personality change, disinhibition or cognitive decline after age 45 years.
• Head injury, new severe headache, seizure, focal neurological signs, or vomiting.
• Symptoms of hyperthyroidism, hypoglycaemia, or phaeochromocytoma (sweating, headache, palpitations).
• Alcohol or benzodiazepine withdrawal (tremor, sweating, seizures).
• Irritability in a child with sudden change in behaviour, weight loss, vomiting, headache, or suspected abuse.
• Perinatal onset (postpartum psychosis, depression).
• Use of anabolic steroids, corticosteroids at high doses or new antiepileptic drugs.

Special groups

• Children and adolescents: irritability may be the main presentation of depression and anxiety. Assess for bullying, abuse, learning difficulty, ADHD, autism, sleep loss and substance use. Use age specific doses.
• Pregnancy and postpartum: screen for depression and bipolar disorder (Edinburgh Postnatal Depression Scale, score of 13 or more), assess thyroid function and anaemia, and consider infant safety.
• Older adults: irritability often marks depression, dementia, delirium, pain, polypharmacy or sensory loss. Assess for infection, constipation and urinary retention.
• Men: depression often presents with irritability, anger attacks, risk taking and substance misuse, not sadness. Assess suicide risk.
• Chronic illness and cancer: pain, steroids and illness stress contribute.
• Region specific: culturally shaped expression of distress, conflict and displacement related trauma, domestic violence, and khat and alcohol use.

Mood and anxiety disorders

• Major depressive disorder, including agitated and atypical forms.
• Persistent depressive disorder.
• Bipolar I and II disorder (manic, hypomanic, depressive with mixed features) and cyclothymia.
• Generalised anxiety disorder, panic disorder and social anxiety disorder.
• Posttraumatic stress disorder and acute stress disorder.
• Adjustment disorder with disturbance of conduct.
• Premenstrual dysphoric disorder and premenstrual syndrome.
• Perinatal depression and postpartum psychosis.
• Obsessive compulsive disorder.

Neurodevelopmental, behavioural and personality conditions

• Attention deficit hyperactivity disorder.
• Autism spectrum disorder.
• Oppositional defiant disorder, conduct disorder and intermittent explosive disorder.
• Disruptive mood dysregulation disorder (children aged 6 to 18 years).
• Borderline and antisocial personality disorders.
• Intellectual disability and Tourette syndrome.
• Learning disorders with frustration.

Psychotic and cognitive disorders

• Schizophrenia and delusional disorder (persecutory).
• Delirium.
• Dementia (frontotemporal, Alzheimer, vascular, Lewy body).
• Traumatic brain injury and post concussion syndrome.
• Frontal lobe lesion or tumour.

Substance related

• Alcohol intoxication, hangover and withdrawal.
• Cannabis, stimulant, cocaine, amphetamine and anabolic steroid effects.
• Caffeine excess and nicotine withdrawal.
• Opioid and benzodiazepine withdrawal.
• Drug induced (corticosteroids, levetiracetam, perampanel, montelukast, efavirenz, isotretinoin, interferon, levothyroxine, SSRIs at start, benzodiazepine disinhibition).

Medical causes

• Hyperthyroidism, and less commonly hypothyroidism.
• Hypoglycaemia and diabetes.
• Sleep deprivation, insomnia, obstructive sleep apnoea and restless legs syndrome.
• Chronic pain, migraine, and chronic headache.
• Menopause, hypogonadism, Cushing syndrome and Addison disease.
• Hyponatraemia, hypercalcaemia, anaemia, iron deficiency and vitamin B12 deficiency.
• Epilepsy (interictal irritability) and Wilson disease.
• Chronic kidney and liver disease, hepatic encephalopathy.
• HIV infection and neurosyphilis.
• Heart failure, COPD, and other chronic illness.
• Phaeochromocytoma.
• Constipation, urinary retention and infection (older adults).

Step 1. Safety and risk. Assess immediate risk to self, partner, children and others before any other step. Document threats, weapons, previous violence, intoxication and capacity. Apply local safeguarding procedures for children and vulnerable adults.

Step 2. Characterise the irritability and make a psychiatric diagnosis. Define the tonic and phasic components, the time course (episodic, cyclical or continuous), and the setting.

Screen for depression (PHQ-9), bipolar disorder (Mood Disorder Questionnaire, or direct questions about past elevated episodes), anxiety (GAD-7), trauma (PC-PTSD-5), ADHD (Adult ADHD Self-Report Scale, with childhood history), alcohol (AUDIT-C), drug use, sleep (Insomnia Severity Index, STOP-BANG) and cognition. In children use the Affective Reactivity Index and a parent report.

For premenstrual dysphoric disorder, use 2 months of prospective daily ratings (symptoms in the last week before menses that remit within a few days of menses onset and are absent in the week after).

Step 3. First line tests

• Full blood count, urea, creatinine, electrolytes (sodium), calcium, glucose or HbA1c, liver tests and ferritin.
• Thyroid stimulating hormone, with free thyroxine when abnormal.
• Vitamin B12 and folate.
• Pregnancy test in women of reproductive age.
• Urine or serum drug screen and blood alcohol when substance use is suspected.
• HIV and syphilis serology when risk exists.

Step 4. Targeted tests

• Morning cortisol, short synacthen test or dexamethasone suppression test for suspected Cushing or Addison disease.
• Testosterone (morning, repeated) in men with low libido and fatigue. Luteinising hormone, follicle stimulating hormone and oestradiol in women with suspected perimenopause (clinical diagnosis over age 45 years).
• Overnight oximetry or polysomnography for suspected sleep apnoea.
• Electroencephalogram when episodic behaviour change, amnesia or seizures are suspected.
• MRI brain for focal signs, new personality change, age over 45 years with new behavioural change, cognitive decline, or head injury. CT brain urgently after acute head injury.
• Formal cognitive testing and neuropsychology for suspected dementia or head injury.
• Caeruloplasmin and slit lamp examination in young adults with behaviour change, liver disease or movement disorder (Wilson disease).
• Plasma free metanephrines for episodic sweating, headache and hypertension.
• Drug levels where relevant (lithium, valproate, antiepileptics).

Step 5. Interpretation. Treat medical or drug causes first, but start psychological treatment for the irritability at the same time, since learned patterns persist. A normal screen supports a primary psychiatric or developmental cause. Consider the time course: sudden change points to medical, drug or substance causes, and lifelong traits point to neurodevelopmental or personality causes.

Limits. Irritability scales are not diagnostic. Self report underestimates outbursts, so collateral history from a partner, parent or teacher is needed. Hormone levels fluctuate and single values can mislead.

Immediate

• Make the setting safe, lower stimulation and speak calmly. If the patient is agitated or aggressive during the visit, apply de-escalation and manage it as acute agitation using the emergency doses given for that condition.
• Act on risk: separate people at risk, notify child or adult protection services where there is risk of harm, remove weapons and access to means, and arrange same day mental health assessment for suicidal or homicidal thoughts or psychosis.
• Treat the dangerous medical causes at once: glucose if hypoglycaemia, withdrawal regimen if alcohol or benzodiazepine withdrawal, and evaluation for delirium.

Non pharmacological treatment (first line for most patients)

• Education about the link between sleep, alcohol, caffeine, pain, stress and irritability. Regular sleep, aerobic exercise (30 minutes on most days), reduction of caffeine to under 200 mg daily, and avoidance of alcohol and stimulants.
• Cognitive behavioural therapy for anger (8 to 12 weekly sessions) with arousal control (relaxation, timeouts), cognitive restructuring and problem solving.
• Children and adolescents: parent management training (the first line for oppositional behaviour and disruptive mood dysregulation), cognitive behavioural therapy, school liaison, and treatment of coexisting conditions.
• Dialectical behaviour therapy and mentalisation based therapy for emotional dysregulation and borderline personality disorder.
• Couple and family therapy, and trauma focused therapy for posttraumatic stress disorder.
• Mindfulness based approaches and stress management.

Treatment by cause

• Major depression: sertraline 50 mg orally once daily (25 mg for the first week if anxious), increased by 25 to 50 mg every 1 to 2 weeks to a usual 50 to 200 mg, maximum 200 mg daily. Escitalopram 10 mg daily (maximum 20 mg; 10 mg over 65 years). Review at 2 and 4 to 6 weeks. In young people under 25 years, review weekly in the first month for emerging suicidality or increased irritability.
• Bipolar disorder: stop antidepressants if mixed or manic features are present. For mania with irritability, olanzapine 10 to 15 mg orally once daily at night (maximum 20 mg daily), or quetiapine 50 mg twice daily on day 1 increasing by 100 mg daily to 400 to 800 mg daily in 2 divided doses, or risperidone 2 mg daily increasing to 4 to 6 mg (maximum 6 mg), or lithium 400 mg at night increasing to a serum level of 0.6 to 1.0 mmol/L (12 hours after dose; check kidney function, thyroid function and calcium), or sodium valproate 20 to 30 mg/kg daily in divided doses (avoid in women of childbearing potential because of foetal harm). Use specialist direction.
• Generalised anxiety disorder or panic disorder: SSRI (sertraline 25 mg for 1 week, then 50 mg, titrated to 50 to 150 mg) with cognitive behavioural therapy.
• Posttraumatic stress disorder: trauma focused cognitive behavioural therapy or eye movement desensitisation and reprocessing. Sertraline 50 mg increased to 200 mg daily, or venlafaxine modified release 75 mg increased to 225 mg daily. Prazosin 1 mg at night increased every 3 days to 3 to 15 mg for trauma related nightmares (monitor postural blood pressure).
• Attention deficit hyperactivity disorder in adults: methylphenidate immediate release 5 mg orally 2 to 3 times daily, titrated weekly to a usual 30 to 60 mg daily in divided doses (maximum 100 mg daily in adults under specialist direction), or lisdexamfetamine 30 mg every morning increased by 20 mg weekly to a maximum of 70 mg daily, or atomoxetine 40 mg daily increased after 7 days to 80 mg (maximum 100 mg daily; monitor liver injury). Monitor blood pressure, heart rate, weight, appetite, sleep and misuse. Contraindicated in uncontrolled hypertension, arrhythmia, and with monoamine oxidase inhibitors.
• Children with attention deficit hyperactivity disorder: methylphenidate 5 mg once or twice daily increased weekly to a maximum of 60 mg daily (age 6 years or over), with growth and cardiovascular monitoring.
• Disruptive mood dysregulation disorder and severe aggression in autism: parent training first. Risperidone 0.25 mg orally at night in children weighing under 20 kg (0.5 mg at night if 20 kg or over), increased no faster than every 2 weeks to a usual target of 0.5 mg daily (under 20 kg) or 1 mg daily (20 kg or over), with a maximum of 3 mg daily in larger adolescents, under specialist care, with weight, glucose, lipid, prolactin and movement monitoring. Aripiprazole 2 mg daily increased to 5 to 15 mg daily is an alternative.
• Premenstrual dysphoric disorder: sertraline 50 mg daily continuously, or 50 mg in the luteal phase (days 14 to 28), with doubling of the dose in the luteal phase for continuous users; fluoxetine 20 mg daily; or drospirenone 3 mg with ethinylestradiol 20 micrograms for 24 days and 4 placebo days, continuous. Escitalopram 10 to 20 mg is an alternative.
• Menopause: transdermal estradiol 50 micrograms daily (with micronised progesterone 200 mg at night for 12 to 14 days each month, or continuously 100 mg, when the uterus is present), after assessing contraindications (breast cancer, thromboembolism, stroke).
• Hypogonadism: testosterone replacement under specialist care after confirmed low morning levels on 2 occasions.
• Hyperthyroidism: carbimazole 15 to 40 mg orally once daily, with propranolol 10 to 40 mg three or four times daily until euthyroid.
• Sleep problems: treat insomnia with cognitive behavioural therapy, and sleep apnoea with continuous positive airway pressure.
• Drug induced irritability: reduce the dose, change the drug, or add pyridoxine. For levetiracetam, pyridoxine 100 to 200 mg orally daily may help (evidence limited). Consider switching to lamotrigine or another antiepileptic.
• Dementia and brain injury: remove triggers, treat pain, constipation and infection, use structured routines, and consider sertraline 25 to 100 mg daily. Antipsychotics only for severe distress or danger (risperidone 0.25 mg twice daily, maximum 2 mg daily, for no more than 12 weeks with review, given the stroke and mortality risk).
• Alcohol and substance misuse: brief intervention, specialist addiction treatment, withdrawal management.
• Pain: analgesia by step, avoiding long term benzodiazepines and opioids.

Benzodiazepines. Avoid long term use in irritability because of disinhibition, paradoxical aggression, tolerance and dependence. A single short course (lorazepam 0.5 to 1 mg orally, maximum 2 to 4 weeks) is for crisis only.

Special populations

• Pregnancy and breastfeeding: psychological therapy first. If drugs are needed, sertraline is preferred. Avoid valproate and carbamazepine. Lithium requires specialist care with monitoring.
• Older adults: halve starting doses and monitor sodium, falls and anticholinergic burden. Avoid benzodiazepines.
• Kidney and liver impairment: avoid lithium in kidney impairment, reduce valproate and SSRIs in hepatic impairment, and monitor levels.
• Adolescents: psychological therapy first. Fluoxetine 10 mg daily increased after 1 week to 20 mg is the first drug choice for depression in this group.

Monitoring. Outburst diary (frequency, intensity, triggers), PHQ-9, GAD-7, Affective Reactivity Index in children, risk review at every visit, adherence, adverse effects, weight and metabolic indices on antipsychotics, drug levels for lithium and valproate, and sleep.

Referral and escalation. Psychiatry urgently for risk of violence, suicide, psychosis or mania. Routine psychiatry or psychology referral for diagnostic uncertainty, bipolar disorder, treatment resistance, severe or recurrent outbursts, borderline personality disorder and complex comorbidity. Child and adolescent mental health services for children. Neurology or old age psychiatry for brain injury, epilepsy or dementia. Domestic violence, forensic or social services where there is risk to others. Addiction services for dependence.

Admission criteria. Imminent risk of harm to self or others, mania or psychosis with aggression, severe agitation not controlled in the community, delirium, and withdrawal needing inpatient care.

Discharge and follow up. Review in 1 to 2 weeks after starting treatment, then every 2 to 4 weeks until stable. Safety net advice: return or call urgently for thoughts of harming self or others, violence, new confusion, severe agitation, elevated mood with no sleep, or severe side effects of treatment.