Anxiety disorders: agoraphobia, social phobia (social anxiety disorder), specific phobias, panic disorder, and generalized anxiety disorder. Epidemiology, etiology, clinical features, course, and treatment

01Definition and overview

Anxiety is a normal response to threat: it sharpens attention and readies the body to act. Anxiety disorders are diagnosed when the fear or worry is out of proportion to the danger, persists, causes marked distress or impairs daily life, and is not better explained by another disorder, a drug or a physical illness. Fear is the response to a threat that is present; anxiety is apprehension about one that might come.

ICD-10 splits them into phobic anxiety disorders (F40: agoraphobia, social and specific phobias) and other anxiety disorders (F41: panic disorder, GAD, mixed anxiety and depressive disorder). ICD-11 calls them anxiety or fear-related disorders and DSM-5 anxiety disorders; both add separation anxiety disorder and selective mutism, and give obsessive-compulsive disorder and PTSD blocks of their own.

A panic attack is an abrupt surge of intense fear that peaks within minutes, with at least four physical or mental symptoms. Attacks can occur in any anxiety disorder, in depression and with drugs; panic disorder needs attacks that are recurrent and at least partly unexpected.

02Etiology and pathophysiology

The anxiety disorders share most of their causes, which act together:

• Genes: heritability is about 30 to 50 per cent, highest for panic disorder, and shared across the anxiety disorders and with depression; many genes of small effect are involved.
• Temperament: behavioural inhibition in toddlers (withdrawal from the unfamiliar) predicts social anxiety, and high neuroticism predicts all of them.
• Upbringing and life events: overprotective or critical parenting, anxious parents as models, childhood adversity, and recent losses, threats and transitions.
• Substances: caffeine, cannabis and stimulants provoke attacks, and withdrawal from alcohol or benzodiazepines causes rebound anxiety.

The fear circuit

Threat is detected by the amygdala, which drives the autonomic and hormonal response through the hypothalamus, the noradrenaline cells of the locus coeruleus and the hypothalamic-pituitary-adrenal axis; the hippocampus places the threat in context, and the prefrontal cortex damps the response once the danger has passed. In anxiety disorders the amygdala and insula over-respond and prefrontal control is weaker. The drugs that work act on serotonin, noradrenaline and GABA, but no single transmitter fault explains the disorders.

People with panic disorder are unusually sensitive to carbon dioxide, lactate and cholecystokinin, which can provoke attacks in them. Hyperventilation lowers the arterial carbon dioxide, and the respiratory alkalosis brings dizziness, tingling round the mouth and fingers, and sometimes carpopedal spasm, sensations that are then read as danger.

What keeps anxiety going

Fear is learnt by association (classical conditioning), and avoidance is kept up because it brings relief (negative reinforcement), so the person never learns that the feared outcome would not have happened. Each disorder adds a pattern of its own:

The cognitive model of panic shows how an attack builds:

1. 1

   Trigger

   A bodily sensation (palpitations after coffee, dizziness on standing) or a place linked with past attacks.
2. 2

   Arousal

   The sensation feels dangerous, and apprehension releases adrenaline: the heart races, the breath quickens, the hands tingle.
3. 3

   Catastrophe

   The stronger sensations are misread as proof of disaster ("I am dying"), driving the anxiety higher in a vicious circle.
4. 4

   Escape

   Fleeing or calling an ambulance ends the attack and is credited with preventing the disaster, so the belief survives.

Blood-injection-injury phobia is the exception in its physiology: after a brief rise, the heart rate and blood pressure fall sharply, a vasovagal response, so these patients faint rather than flee.

03Clinical features

Anxiety has psychological symptoms (apprehension, irritability, poor concentration, restlessness, a sense of dread, depersonalisation and derealisation) and physical ones from autonomic arousal and muscle tension: palpitations, chest tightness, breathlessness, dry mouth, nausea, diarrhoea, frequency of urination, sweating, tremor, dizziness, headache and aching muscles. Many patients present with the physical symptoms alone, to primary care, cardiology or the emergency department.

Panic disorder

Attacks start suddenly, peak within about 10 minutes and rarely last beyond 30, with palpitations, sweating, trembling, breathlessness, choking, chest pain, nausea, dizziness, tingling, depersonalisation, and fear of losing control or of dying; some wake the patient from sleep. Between attacks the patient fears the next one, watches the body for signs, and avoids exercise, caffeine and places linked with attacks. Many present repeatedly with chest pain or breathlessness; suicidal thoughts are more common than in the general population, especially with comorbid depression or alcohol misuse, and should be asked about.

Agoraphobia

The fear is of situations where escape might be difficult or help unavailable: public transport, shops and queues, crowds, bridges, open spaces or being far from home alone. The patient avoids them, goes only with a trusted companion, or endures them with intense fear. At its worst the patient becomes housebound. Most cases seen in clinics begin with panic attacks; in older people, a fear of falling can lead to the same avoidance.

Social anxiety disorder

The fear is of being watched and judged in social or performance situations: speaking in a meeting, eating or writing in front of others, talking to strangers, parties, using public toilets. Blushing, trembling, sweating, a shaking voice and a fear of vomiting are common, and the person fears that others will notice them. It may be limited to performance (public speaking) or spread across most social contact. Onset is usually in the early teens. Sufferers underachieve at school and work, have fewer relationships, and some drink to cope. Anxious (avoidant) personality disorder overlaps heavily with its generalised form.

Specific phobias

The fear is immediate and intense on meeting, or expecting to meet, the feared thing, and adults recognise it as excessive. DSM-5 lists five types: animal (spiders, dogs, snakes), natural environment (heights, storms, water), blood-injection-injury, situational (flying, lifts, enclosed spaces, driving) and other (choking, vomiting). Most begin in childhood. A phobia matters clinically when it restricts life or, as with blood, needle or dental phobias, stops a person getting healthcare.

Generalised anxiety disorder

The core is excessive, hard-to-control worry about several everyday matters, on most days for months, out of proportion to their likelihood. With it come restlessness or feeling keyed up, fatigue, poor concentration, irritability, muscle tension and aches, poor sleep (difficulty falling asleep for worrying), and autonomic symptoms such as palpitations, sweating and a dry mouth. Patients often present with insomnia, headache or bodily symptoms rather than worry, and many have depression as well.

The GAD-7 questionnaire measures severity: scores of 5, 10 and 15 mark mild, moderate and severe anxiety, and 10 or more warrants assessment for an anxiety disorder.

04Diagnosis and management

Making the diagnosis

The diagnosis is clinical: what is feared, when, how the body responds and what is avoided, with a mental state examination. The assessment covers depression, alcohol, drugs and caffeine, suicide risk and how far life is restricted. An examination and a few tests (full blood count, glucose, thyroid function, and an ECG for palpitations or chest pain) look for the mimics.

The psychiatric differentials are depression (anxiety is common within it, and it is treated first), the other anxiety disorders, obsessive-compulsive disorder, PTSD, health anxiety, early dementia, and psychosis, where avoidance follows a delusion of persecution.

Stepped care

UK practice, set out in NICE's guidelines on GAD and panic disorder and on social anxiety disorder, offers the least intensive treatment that is likely to work and steps up if it does not. For GAD:

1. 1

   Step 1, all presentations

   Assessment, explanation of the disorder and its treatments, and active monitoring.
2. 2

   Step 2, not improved

   Low-intensity treatment based on CBT: self-help, guided self-help (five to seven short sessions), or psychoeducational groups.
3. 3

   Step 3, marked impairment or no response

   CBT or applied relaxation (usually 12 to 15 weekly hour-long sessions), or a drug, as the patient prefers, since neither is better.
4. 4

   Step 4, complex or refractory

   Specialist care: combined drug and psychological treatment, crisis, day or inpatient services, especially with self-neglect or a high risk of self-harm.

Panic disorder follows a similar ladder, from recognition and treatment in primary care to specialist services.

Psychological treatment

Cognitive behavioural therapy is the first-line psychological treatment for every anxiety disorder, adapted to each. Its common ground is explaining the anxiety, testing feared predictions in behavioural experiments, dropping safety behaviours, and exposure: facing the feared situation, step by step and for long enough, until the fear falls and the expected disaster fails to happen.

Drugs

SSRIs are the first-line drugs for panic disorder, social anxiety disorder and GAD, with SNRIs as the alternative; drugs have little place in specific phobias. The detail of each drug is in anxiolytics.

Buspirone is licensed in the UK for the short-term management of anxiety disorders, and hydroxyzine for anxiety in adults, though hydroxyzine can prolong the QT interval. Quetiapine has trial evidence in GAD but is not licensed for it in the UK, and NICE advises against starting antipsychotics for GAD in primary care.

05Epidemiology

Anxiety disorders are the commonest mental disorders. In the European Union, Switzerland, Iceland and Norway about 14 per cent of people, over 60 million, have one in a year, and worldwide about 300 million people, around 4 per cent, were living with one in 2019, a number thought to have risen by about a quarter in 2020 during the COVID-19 pandemic. Over a lifetime, between about one person in seven (in European surveys) and more than one in four (in American ones) has one. Women are affected about twice as often as men.

Comorbidity is the rule: most patients with one anxiety disorder have another at some time, about half develop depression, and alcohol and sedative misuse are common. Panic disorder is far commoner in cardiology, emergency and dizziness clinics than in the community. Fewer than half of those affected are treated.

06Prognosis

Without treatment, most anxiety disorders that start in adolescence or adulthood run a chronic, fluctuating course, worse at times of stress. Childhood fears and many childhood phobias fade, but phobias that last into adult life rarely go without treatment. Social anxiety disorder can last for life untreated. GAD is the most persistent, with remission in only about a third over the first few years. Many patients with panic disorder have had symptoms for years before diagnosis.

Treatment helps most patients. Exposure cures most specific phobias, often in a few sessions. CBT and SSRIs each bring response in about half to two-thirds of patients with panic disorder, social anxiety disorder or GAD. Relapse after stopping a drug is common, while the gains of CBT tend to last.

Outcomes are worse with severe symptoms at the start, agoraphobia, comorbid depression, substance misuse, personality disorder, a long duration before treatment and little social support. The complications are depression, alcohol and benzodiazepine dependence, lost work and education, and a raised risk of suicidal thoughts and attempts. Follow-up reviews any drug every 2 to 4 weeks for the first 3 months and plans its slow withdrawal once the patient is well.