Generalised Anxiety Disorder

Introduction

Generalised anxiety disorder (GAD) is characterised by persistent, excessive worry about a range of everyday events and activities - health, finances, work, relationships - that is out of proportion to any actual threat and difficult for the person to control.¹

It is common, with a UK prevalence of around 4-6% at any time, and around twice as common in women as men. It is frequently under-recognised because patients present to primary care with somatic symptoms - palpitations, headache, gastrointestinal upset, muscle tension - rather than describing worry directly, and it commonly coexists with depression.²

The defining feature that separates GAD from other anxiety disorders is that the anxiety is generalised and free-floating rather than tied to a specific object, situation, or discrete attack. A phobia is anxiety about one thing; panic disorder is anxiety about having panic attacks; GAD is anxiety about almost everything.

Aetiology

As with most psychiatric disorders, GAD arises from an interaction between genetic vulnerability, neurobiological factors and environmental experience. Understanding the maintaining mechanisms matters clinically, because they are what CBT targets - and because they explain the otherwise puzzling observation that reassurance does not help.

• Genetics: moderate heritability of around 30%, with shared genetic vulnerability across anxiety and depressive disorders - which is part of why the two coexist so frequently
• Neurobiology: dysregulation of GABAergic, serotonergic and noradrenergic systems, and heightened amygdala reactivity to perceived threat with reduced prefrontal regulation of that response
• Early environment: overprotective or inconsistent parenting, childhood adversity and insecure attachment, all of which reduce the developing tolerance of uncertainty
• Temperament: trait anxiety and behavioural inhibition in childhood are predictive of later GAD
• Chronic stress: ongoing financial, occupational or relationship strain, which both precipitates and maintains symptoms

Why the worry persists

Three cognitive models explain the self-sustaining nature of GAD, and each points to a specific treatment target.

Risk factors

• Female sex
• Family history of anxiety or depression
• Childhood adversity, including abuse, neglect or parental separation
• Chronic physical illness
• Comorbid depression or another anxiety disorder
• Substance misuse, including alcohol and caffeine
• Ongoing social or financial stressors
• Personality traits of neuroticism and perfectionism

Clinical features

ICD-11 requires marked symptoms of anxiety, persisting for at least several months, with anxiety and worry present on most days, more days than not, and general in nature (not restricted to particular circumstances). Symptoms typically fall into psychological, physical (autonomic) and behavioural clusters.¹

Psychological symptoms

• Excessive, difficult-to-control worry about multiple everyday matters
• Restlessness or feeling on edge
• Poor concentration, or the mind going blank
• Irritability
• Sleep disturbance - typically difficulty falling asleep because of worry, rather than early waking
• Anticipating the worst in ambiguous situations (catastrophising)

Physical symptoms

• Muscle tension, aches and headache
• Fatigue
• Palpitations and chest tightness
• Gastrointestinal symptoms - nausea, diarrhoea, a sensation of a lump in the throat
• Sweating, tremor and dry mouth
• Dizziness or light-headedness

Because somatic symptoms dominate the presentation, GAD is a common cause of extensive, ultimately negative, physical investigation before the underlying anxiety is recognised.

Screening and severity

The GAD-2 (two questions on frequency of feeling nervous/anxious and of being unable to stop worrying) is a quick case-finding tool. A positive screen is followed by the GAD-7, a seven-item questionnaire that also guides monitoring of treatment response.

A GAD-7 of 10 or more is the usual threshold prompting consideration of active treatment, and the score should be repeated during treatment rather than only at diagnosis - a falling score is the most practical objective evidence that an intervention is working.

Points to cover in the history

• The content and breadth of the worry - how many separate domains, and whether it shifts from one topic to another as each is resolved, which is characteristic
• Controllability - can the person set the worry aside and return to a task? Uncontrollability is the diagnostic core, more than the worry itself
• Duration and course - at least several months, most days; a shorter history suggests adjustment disorder
• Functional impact in concrete terms - work absence, avoiding social events, tasks delegated to others, decisions postponed
• Reassurance-seeking and checking - how often, from whom, and how long relief lasts
• Sleep - specifically difficulty falling asleep with a racing mind, which contrasts with the early morning waking of depression
• Caffeine, alcohol and drug intake quantified - number of coffees and energy drinks daily, units of alcohol weekly, and whether alcohol is used specifically to settle anxiety
• Screen for depression and suicidal ideation in every case, given the high comorbidity
• Past treatment - which drugs, at what dose, for how long, and why they were stopped, since 'SSRIs didn't work' frequently means two weeks at a subtherapeutic dose

Clinical examination

Examination in GAD is usually normal, and its purpose is to identify organic mimics and to demonstrate to the patient that their physical symptoms have been taken seriously - which is itself therapeutically useful before offering a psychological explanation.

• General: tremor, sweating, weight change, agitation or restlessness during the consultation
• Thyroid: goitre, fine tremor, lid lag, warm peripheries and tachycardia - thyrotoxicosis is the organic mimic most often missed
• Cardiovascular: pulse rate and rhythm (irregularly irregular suggests atrial fibrillation), blood pressure, and auscultation for murmurs
• Respiratory: to exclude asthma, which can both mimic and coexist with anxiety
• Neurological: a brief screen where dizziness or paraesthesiae are prominent
• Signs of alcohol excess: palmar erythema, spider naevi, hepatomegaly - relevant given the frequency of self-medication

Mental state examination

Differential diagnosis

• Depression: anxiety symptoms are extremely common in depression - assess for the core depressive triad and treat the dominant syndrome
• Panic disorder: anxiety occurs in discrete, unexpected attacks rather than as constant background worry
• Specific phobia or social anxiety disorder: anxiety is restricted to a specific trigger or social situations
• Obsessive-compulsive disorder: worry takes the form of intrusive, ego-dystonic obsessions with associated compulsions, not free-floating worry
• Adjustment disorder: anxiety directly related to an identifiable recent stressor, expected to resolve as the stressor resolves
• Thyrotoxicosis: tremor, tachycardia, weight loss and heat intolerance can mimic anxiety closely - always check TFTs
• Substance or caffeine-related: excess caffeine, stimulant use, or alcohol/benzodiazepine withdrawal
• Cardiac arrhythmia or phaeochromocytoma: rare organic causes of episodic autonomic symptoms
• Medication side effects: salbutamol, theophylline, corticosteroids, levothyroxine over-replacement, and some antidepressants early in treatment

Investigations

GAD is a clinical diagnosis. Investigations are used to exclude organic mimics, particularly at first presentation or when physical symptoms are prominent.

• TFTs - to exclude thyrotoxicosis
• FBC, U&Es, glucose - general screen and baseline
• ECG - if palpitations are prominent, to exclude arrhythmia
• Caffeine, alcohol and recreational drug history - a common and easily missed contributor
• GAD-7 at diagnosis and at intervals to track response to treatment

Management

NICE recommends a stepped-care approach, moving to the next step if a person does not improve, and starting at the step appropriate to symptom severity and impairment.³

1. Step 1: identification, education about GAD, and active monitoring for mild symptoms with little functional impairment
2. Step 2: low-intensity psychological intervention - individual non-facilitated or facilitated self-help, or psychoeducational groups
3. Step 3: for marked functional impairment, or no response to step 2 - a choice between high-intensity psychological therapy (individual CBT or applied relaxation) or drug treatment
4. Step 4: referral to specialist mental health services for very marked functional impairment, high risk, or no response to step 3 interventions

An important principle running through all four steps is that treatment is offered alongside, not instead of, addressing the person's actual circumstances. Debt advice, occupational health involvement or resolution of a housing problem frequently does more than either therapy or medication, and asking what is driving the worry rather than only measuring it is part of good management.

Psychological therapy

CBT is the best-evidenced psychological treatment and typically runs to 12-15 sessions. It is worth knowing what it actually contains, because describing it accurately improves uptake:

• Psychoeducation about the anxiety response, explaining that the physical symptoms are a normal fight-or-flight response and are not dangerous
• Worry monitoring - recording worries to distinguish those about solvable current problems from hypothetical 'what if' worries, which need different handling
• Problem-solving for actionable worries, and worry postponement for hypothetical ones
• Cognitive restructuring - testing catastrophic predictions against what actually happens
• Behavioural experiments - deliberately dropping a safety behaviour (not checking, not seeking reassurance) to test whether the feared outcome occurs
• Exposure to uncertainty, deliberately leaving small things unresolved to build tolerance

Applied relaxation is an equally recommended alternative, teaching progressive muscle relaxation until it can be deployed rapidly in an anxiety-provoking situation. Physical activity has a reasonable evidence base and should be encouraged. Mindfulness-based approaches are widely used, though the evidence base in GAD specifically is less strong than for CBT.

Drug treatment

An SSRI is first-line - sertraline is usually chosen first on cost and tolerability grounds. Start at a low dose, warn about transient early worsening, and titrate upwards after 1-2 weeks. Response should be assessed at an adequate dose after at least 4-6 weeks before concluding a drug has failed; premature switching is one of the commonest prescribing errors in anxiety.

Review within 1 week of starting in anyone under 25 because of the small increased risk of suicidal thoughts in that group, and within 2 weeks otherwise. Do not offer an antidepressant to a person under 18 without specialist assessment.

Effective treatment - whether psychological or pharmacological - is usually continued for at least a year, given the high rate of relapse if treatment is stopped early. When stopping, taper gradually over at least four weeks and warn about discontinuation symptoms, which are otherwise easily misinterpreted by the patient as the anxiety returning.

Particular groups

• Older adults: watch for hyponatraemia with SSRIs, which presents as confusion, drowsiness or falls; start lower and check sodium if the patient becomes unwell
• Pregnancy and breastfeeding: do not stop an effective antidepressant reflexively on discovering pregnancy - the risk of relapse is substantial. Discuss with specialist perinatal services; sertraline is commonly used.
• Comorbid alcohol misuse: anxiety is frequently driven or worsened by alcohol, and by the mini-withdrawals between drinks. Address the alcohol first, since anxiety often improves markedly with abstinence and treatment otherwise appears to fail.
• Cardiac or respiratory disease: avoid propranolol in asthma; take new or changed physical symptoms seriously rather than attributing them to known anxiety
• Children and young people: refer rather than prescribe; psychological therapy is first-line

Complications

The most immediate consequence is functional: GAD causes significant impairment at work, in relationships and socially, with high rates of absenteeism and of presenteeism, where the person attends but functions poorly. Decisions are postponed, opportunities declined, and responsibilities gradually transferred to others, which erodes confidence further.

It generates substantial healthcare use through repeated presentation with somatic symptoms, and the resulting investigations carry their own risks - incidental findings, radiation exposure and the reinforcement of illness beliefs described earlier. Comorbid depression develops in a large proportion and worsens prognosis, raising suicide risk. Self-medication with alcohol is common and can progress to dependence, and benzodiazepine dependence remains a genuine iatrogenic risk where prescribing is not time-limited.

There is also a physical health cost. Chronic sympathetic activation and raised cortisol are associated with an increased incidence of cardiovascular disease, and the sleep disruption that accompanies persistent worry contributes independently to metabolic and cardiovascular risk.

Red flags

Prognosis

GAD tends to run a chronic, fluctuating course, with symptoms waxing and waning in relation to life stress rather than resolving completely. Onset is often insidious, and many patients describe having been 'a worrier' for as long as they can remember, which means the therapeutic goal is usually a substantial reduction in worry and its functional consequences rather than its complete elimination. Framing this honestly at the outset prevents patients concluding that partial improvement means failure.

Most patients respond well to CBT, medication, or the combination, with meaningful improvement in the majority. Relapse is common where treatment is withdrawn early, which is the rationale for continuing an effective drug for at least a year, and the skills learned in CBT appear to protect against relapse more durably than medication alone once it is stopped.

Poorer outcome is associated with comorbid depression, personality difficulty, harmful alcohol use, longer duration of untreated illness, and ongoing social adversity - the last of which is frequently the least medical and the most decisive. Better outcome is associated with earlier treatment, good engagement with therapy, an adequate drug trial at an adequate dose, and resolution of the underlying stressor. With sustained treatment most patients achieve good symptom control and function well, even if some background trait anxiety persists.