Generalised anxiety disorder: clinical review

An overview of the diagnosis and management of generalised anxiety disorder (GAD), including identifying organic causes co-morbidities, environmental triggers and remission rates.

Women are twice as likely as men to develop anxiety disorders (Photo: SPL)
Women are twice as likely as men to develop anxiety disorders (Photo: SPL)

Section 1: Epidemiology and aetiology
Section 2: Making the diagnosis
Section 3: Managing the condition
Section 4: Prognosis
Section 5: Case study
Section 6: Evidence base


Section 1: Epidemiology and aetiology

Anxiety as an emotion from an evolutionary perspective usually has an obvious cause and also a goal (safety, and the avoidance of danger). Anxiety is related partly to social situations but also to non-social dangers.

Anxiety is classically thought to be concerned with the real or perceived threat of danger. However, it stops being helpful and starts being pathological when it starts to impede an individual's normal baseline functioning.

Generalised anxiety disorder (GAD) is characterised by excessive and inappropriate worrying that is persistent and not restricted to particular circumstances.

Patients have physical anxiety symptoms (such as tachycardia and tremor) and key psychological symptoms, including restlessness, fatigue, and difficulty in concentrating, irritability, and disturbed sleep.

Despite anxiety disorders being common, they are often underdiagnosed and subsequently left untreated.

The estimated proportion of generalised anxiety disorder (GAD) in England is 4.4%.1 A review of epidemiological studies in Europe found a 12-month prevalence of 1.7% to 3.4%,and a lifetime prevalence of 4.3% to 5.9%.3

Women are twice as likely as men to develop an anxiety disorder,4 other than social anxiety disorder, for which there is equal prevalence. GAD is probably the most common anxiety disorder among the elderly population.2

Aetiology
Several aetiological factors contribute to the development of anxiety disorders; the main theories include genetics, neurotransmitters and life events. GAD is thought to be caused by environmental stressors, such as stressful life events, acting on a personality that has a predisposition to anxiety through genetic factors.

There is a higher concordance between monozygotic twins than dizygotic twins for anxiety disorders, suggesting a significant genetic association.3 The risk in first-degree relatives of patients with GAD is five times greater than in controls.4-6

Neuroanatomically, it is the amygdala that is believed to play a key part in co-ordination of the anxiety response, along with various neurotransmitters, including noradrenaline, serotonin and gamma-aminobutyric acid.5-7

Management of anxiety with agents such as SSRIs and SNRIs provides evidence for this neurobiological basis. Corticotropin-releasing hormone has also been implicated in the regulation of anxiety. The personality trait of "neuroticism" (or negative affectivity) is associated with comorbid GAD and major depression.8


Blood test
Blood tests could help to identify a possible organic cause

Section 2: Making the diagnosis

Diagnosis is made mainly on clinical symptoms. In GAD, these symptoms are persistent, regardless of the environment and situation. According to the DSM-IV classification system, a GAD diagnosis should include two major symptoms, excessive anxiety and worry about a number of events and activities, and difficulty controlling the worry for at least six months, and three or more additional symptoms (see box). In this way, GAD can be differentiated from phobic disorders. There are many symptoms associated with anxiety disorders.

Organic causes, for example, hyperthyroidism, hypoglycaemia, tachycardia or temporal lobe epilepsy, or comorbidities of anxiety should always be considered and may require further investigation, depending on the clinical picture (for example, patients with late-onset anxiety, with weight loss, or with cognitive impairment).

Blood tests, including FBC, U&Es, LFTs, TFTs and blood glucose, should be considered, as well as urine drug screening as a basis for investigation.

Symptoms associated with GAD
  • Free-floating worry, not associated with any specific problem.
  • Autonomic overactivity (sweating, palpatations, dry mouth, epigastric discomfort and dizziness).
  • Increased motor tension and inability to relax.
  • Psychological arousal and poor concentration.
  • Sleep disturbance, not including early morning wakening.

Section 3: Managing the condition

Check for comorbidities
Comorbidities, such as depression, substance misuse or physical conditions such as thyroid disorders, are common. Treating these will have an impact on symptoms of anxiety.6-7

Environmental triggers
Social circumstances and interpersonal conflicts7 act as triggers for patients who present with GAD. It is important to identify these early and consider ways in which to modify them.

Treatments
The choice between medication and CBT for GAD can be made on the basis of treatment availability and/or patient preference. Studies have shown them to be similarly effective.16

Psychological treatments
Psychological therapies are first-line for the active management of anxiety. CBT has been found to be significantly superior in trials with placebo and has been shown to be as effective as medications for treatment of GAD.7-9 In less severe cases, relaxation therapy has been found to be effective.

Pharmacological treatment
Selective serotonin reuptake inhibitors (SSRI) antidepressants are the first line treatment for GAD. No individual SSRI has been shown to have superior efficacy over another in GAD.

If there is no clinical benefit after 4-6 weeks, the SSRI should be weaned off and another SSRI could be tried. In our clinical experience, an inadequate response to one SSRI does not predict failure of a second SSRI in GAD. There is no optimal duration of treatment identified but it should be at least one year.

Benzodiazepines should be used only for short term management of severe anxiety. They have poor long term efficacy in GAD and can cause dependence. They can also be used as an adjunct to SSRI to manage SSRI-induced agitation and insomnia, in patients without a history of substance misuse, as a short term option (for example, lorazepam 0.5 mg BD for two-three weeks whilst waiting for an SSRI’s clinical response).

If patients do not respond to SSRI treatment 13-14, consider referral for psychiatric opinion for second-line options such as pregabalin or quetiapine.

Working with patients
Consider referral to specialist services if functional or social impairment is severe or there is a significant risk of suicide.8-10

NICE guidelines on GAD recommend that healthcare professionals need to provide for patients, their families and covers information and support about the nature of GAD and the range of treatments available.

Table 1: Summary of factors to consider in the management of GAD

Comorbidities

  • Depression
  • Substance misuse
  • Physical conditions

Environmental

  • Social circumstances
  • Interpersonal conflicts

Psychological

  • CBT
  • Relaxation techniques

Medication

  • SSRIs
  • Benzodiazepines

Specialist

  • Secondary psychiatric service


Section 4: Prognosis

GAD is a chronic and recurring condition and as such, to make a diagnosis, DSM-IV requires that the patient must experience symptoms for at least six months. NICE recommends a stepped-care model (1-4) that offers the most intensive and effective intervention first.

Remission rates
The future course of the GAD is best predicted by the past course,11,12 although studies have had mixed outcomes, with some showing prognosis for patients with GAD is poor, with low rates of remission demonstrated in secondary services.13

Patients with GAD have a higher risk of developing a major depressive disorder.14 However, there is no similar increased risk for schizophrenia or bipolar affective disorder.15

GAD is associated with a significant degree of functional impairment, poor cardiovascular health and coronary artery disease.

It tends to run either a chronic course, fluctuating in severity over time, or an episodic course with some intervening periods of relative wellbeing. Patients with marked functional impairment, for example, self-neglect or a high risk of self-harm, should receive input from multi-agency teams or crisis services.


Section 5: Case study

Jane is a 47-year-old part-time medical secretary who cares for her father, who has lived with her at home since he was diagnosed with dementia six months ago. She has no past medical or psychiatric history, but frequently attends her GP with headaches and nausea, for which there is no clear medical cause.

Jane describes feeling constantly worried about 'things', but when you try to find out what these are, she has trouble giving you a specific cause and just says 'everything'. She says she would describe herself as a nervous person, but feels she worries more now she is caring for her father.

Jane explains she has been finding it difficult to look after him recently because she often has episodes when she feels dizzy and notices her heart beating very fast.

She finds it difficult to relax and says she regularly needs a couple glasses of wine in the evening to wind down, which she has never needed before. She describes frequent waking in the middle of the night, but says she eventually goes back to sleep and wakes at her usual time of 7am to get her father up and ready for the day.

She is given self-help resources and asked to return in two weeks. When she returns, her symptoms are no better, so she is referred for CBT and started on an antidepressant.


Section 6: Evidence base

Clinical trials

This study, led by the University of Melbourne, found that kava (a medicinal South Pacific plant) could be an alternative treatment to pharmaceutical products for the treatment of GAD.

In this mixed treatment meta-analysis, fluoxetine was ranked first for response and remission and sertraline was ranked first for tolerability. Among treatments licensed specifically for GAD in the UK, duloxetine, escitalopram and pregabalin might offer some advantages over venlafaxine and paroxetine.

The efficacy of CBT for GAD was investigated and compared with the efficacy of pharmacological therapy using meta-analytical techniques.

A total of 65 CBT studies and pharmacological studies were included. CBT was found to be more effective than control conditions.

Guidelines

NICE. Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults. CG113. London, NICE, January 2011.

British Association of Psychopharmacology guidelines on management of anxiety disorder. Sec 12 for pharmacological treatment options. www.bap.org.uk/pdfs/AnxietyGuidelines2014.pdf

Self-help resources

Dr Reshad Malik is core trainee in psychiatry and Dr Muffazal Rawala is consultant psychiatrist, Camden and Islington NHS Foundation Trust

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This is an updated version of an article that was first published in June 2014.

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