Clinical Review: Anxiety disorders

Section 1: Aetiology and epidemiology
Anxiety is a normal response to danger, but it can become out of proportion to the threat posed and disable patients affected.

The most striking features of anxiety disorders are the mental and physical symptoms of anxiety occurring in the absence of organic brain disease or another psychiatric disorder. Co-morbidity is common and the disorder is chronic, with treatment providing only partial success.

Epidemiology
Estimates of incidence vary due to differing diagnostic criteria in the US and Europe. The one-year rate is approximately 3 per cent and lifetime rates 4-5 per cent, with women more affected than men.

Aetiology
The familial distribution of anxiety disorders suggests a pivotal importance of genetic factors. Generalised anxiety disorders (GAD) occur more often in first-degree relatives with the disorder than in controls. Twin studies have shown a higher concordance for anxiety disorders between monozygotic than dizygotic pairs.

Heritability seems to be shared with mood disorders, suggesting environment is key to the subsequent expression of either disease.

There is a link between anxiety disorders and specific areas of the brain, such as the cortex and limbic system. The serotonergic systems are involved in controlling anxiety and are almost certainly involved in the pathogenesis of anxiety disorders. Other neurotransmitters implicated include GABA and noradrenaline.

Early separation or loss in childhood is a proposed mechanism for development of generalised anxiety. In normal development, children overcome anxiety through secure relationships with parents. Failure to achieve this renders them vulnerable to anxiety when experiencing separation in later life.1

Objective studies have shown increased reporting of early adverse life events and increased rates of anxiety disorders.2

Cognitive theory suggests that people with anxiety disorders are prone to overestimate danger. This leads to avoidance of situations that might expose them to what they fear.

Behavioural theory proposes that people learn to associate the fear felt during a stressful event with certain cues such as a place or a sound. When the cues reoccur, the fear is re-experienced. Once learnt, the association is out of conscious control.

Twin studies have shown overlap between genetic factors related to neuroticism and those found in GAD.

Classification of anxiety disorders (ICD10)
F40 Phobic anxiety disorder:

  • Agoraphobia: with or without panic disorder.
  • Social phobia.
  • Specific phobia.

F41 Other anxiety disorders:

  • Panic disorder.
  • Generalised anxiety disorder.
  • Mixed anxiety and depressive disorder.


Section 2: Making the diagnosis
Anxiety that occurs in a predictable setting is classed as a phobic disorder, while constant anxiety is labelled as a GAD. Panic disorders occur in unpredictable situations.

Symptoms of anxiety can affect most systems of the body.

Psychological arousal results in irritability, restlessness and poor concentration.

It may also cause worrying thoughts, sensitivity to noise and fearful anticipation.

Autonomic arousal leads to widespread manifestations: dry mouth, difficulty swallowing and epigastric discomfort may be accompanied by flatulence and frequent, loose motions.

Trouble inhaling due to a constricted chest can affect breathing, while palpitations and an awareness of missed beats are cardiovascular manifestations.

There are further important autonomic effects such as erectile dysfunction, menstrual discomfort or amenorrhoea.

Muscle tension causes tremor, headache and aching, while dizziness, breathlessness and tingling in the extremities can result from hyperventilation.

Sufferers may also experience insomnia and night terrors.

GAD
Symptoms of anxiety occur in all situations with a GAD. No particular set of circumstances should exacerbate symptoms.

Patients suffering from this disorder will often have a furrowed brow, tense posture and a pale, strained face.

Phobic disorder
Phobic anxiety is defined as a persistent, irrational fear of a specific object or situation, resulting in a compelling desire to avoid. Social phobias are particular fears of humiliating oneself in front of others.

Specific phobias are the fear of dire consequences resulting from contact with feared object or situation. Anxiety caused by being in crowds or places that are hard to exit is agoraphobia.

Panic disorder
Discrete periods of intense fear (panic attacks) are associated with panic disorder. Symptoms reach a peak in about 10 minutes, are severe and the patient fears catastrophic outcome. Hyperventilation is common.

Blood-gas analysis shortly after attack may aid diagnosis if uncertain.

Differential diagnoses for GAD
Physical illness

  • Thyrotoxicosis
  • Phaechromocytoma
  • Hypoglycaemia

Psychiatric illness
Depressive disorder:
severity and chronology of symptoms should differentiate. Depressive symptoms usually worse in the morning. Morning anxiety suggests a depressive disorder. Check for suicidal ideation.
Schizophrenia: check for abnormal thoughts.

Substance misuse
Withdrawal from alcohol or prescribed or illicit substances.

Dementia
Check cognition in patients aged 50 or over.

Social phobia differentials
Differential diagnoses:

Agoraphobia and panic disorder
Use severity and chronology of symptoms.

Schizophrenia
Paranoid delusions.

Avoidant personality disorder
Lifelong time course compared to specific onset. Difficult to distinguish.

Normal shyness
Functioning unimpaired.

Differential diagnoses
Agoraphobia

  • Other anxiety disorders.
  • Depressive disorder.
  • Schizophrenia.

Panic disorder

  • Anxiety disorders.
  • Thyroid disease.
  • Mitral valve prolapse.
  • Cocaine use, alcohol withdrawal.

Section 3: Managing the condition
Psychological treatments are more effective than pharmacological treatment and should be used first line wherever possible. They include self-help based on cognitive behavioural therapy (CBT) principles, CBT (seven sessions are recommended for panic disorder and eight to 10 for GAD and social phobia) and exposure therapy, which is useful in social phobia.

Patients with anxiety symptoms are often sensitive to the side-effects of medication, especially SSRIs and tricyclic antidepressants.

It is advisable to discuss side-effects, start with a low dose and titrate slowly. Benzodiazepines may be used in the short term but should not be used for panic disorder.

New developments
Unfortunately, the evidence for the efficacy of CBT in the treatment of panic disorder and GAD has not been coupled with improved access to this therapy.

Many patients either cannot access psychological treatment or have a long waiting time for therapy.

The government commissioned a report by the health economist, Lord Richard Layard and the London School of Economics looking at the provision of CBT in depression and anxiety disorders.3

One of the drives behind this was to reduce the number of people claiming incapacity benefit (1.3 million) for mental health problems.

The report recommends 10,000 new NHS psychological therapists to deliver the CBT. There are currently two pilot projects, in Lewisham and Dagenham (www.csip.org.uk).

Computer-aided treatment
In recent years there has been developments and subsequent research into computer-aided psychotherapy. Treatment tasks are delegated to the computer and the patient is involved in treatment decisions.

Computer-aided CBT (CCBT) has been recommended for the treatment of panic and phobic disorders.

The DoH has issued guidance prompting trusts in England and Wales to buy licences for unlimited password-protected use of CCBT by patients in their area.

They are also required to train staff to supervise the delivery of the CCBT.

Pharmacological treatments
Panic disorder

  • First line: SSRIs
  • Second line: TCAs, e.g. imipramine, clomipramine
  • Benzodiazepines are not recommended.

Gad

  • First line: SSRIs for initial exacerbation of symptoms; venlafaxine; TCAs (imipramine, clomipramine).
  • Second line: buspirone; hydroxyzine; beta-blockers.
  • Benzodiazepines should not be used beyond 2-4 weeks.

Phobic disorders

  • First line: SSRIs, MAOIs
  • Second line: moclobemide; clonazepam; propanolol (performance anxiety only).

Section 4: Prognosis and follow-up
GAD

GAD is chronic with few periods of remission. Only a quarter of patients have a good outcome, with many misusing alcohol and benzodiazepines.

There is a poorer outcome when associated with depression. GAD tends to persist into old age and often accompanied with co-morbid physical illness.

Social phobia
Social phobia runs a chronic course from pre-adolescence throughout adulthood, with half the patients experiencing illness duration of 25 years followed by remission.

Predictors of poorer outcome include onset before the age of 8-11 years; co-morbid psychiatric and physical disorder; and lower educational status.

Panic disorder
Panic disorder has a fluctuating course with spontaneous remission from months to years, followed by relapse.

It is not possible to predict which patients will develop agoraphobia. At the extreme end of the spectrum, patients can be housebound for years.

The goal of treatment is to abolish the panic attacks before the emergence of entrenched, phobic avoidance.

Generally, a third of patients fully recover, half of patients have continued minimal impairment and a sixth have moderate-to-severe impairment.

Predictors of poorer outcome include more severe panic attacks; more severe agoraphobia; longer duration of illness; co-morbid depression and anxious personality type.

There has been much research but as yet no evidence that patients with pure panic disorder have an increased risk of suicide.

Panic disorder tends to decline with old age.

Resources
For clinicians

  • NICE www.nice.org.uk
  • Taylor D, Paton C, Kerwin R. The Maudsley prescribing guidelines (9th edition). London: Informa Healthcare, 2007.

For patients and carers

  • NICE guidance on treatment of anxiety disorders - www.nice.org.uk
  • The mental health charity, MIND, provide information, evening groups, literature, and carers' support - www.mind.org.uk

References

  1. Bowlby J. Attachment and loss: Attachment (Vol 1). New York: Basic, 1969.
  2. Brown G, Harris T. Aetiology of anxiety and depressive disorders in an inner-city population 1: Early adversity. Psychol Med 1993; 23: 143-54.
  3. The Centre for Economic Performance's Mental Health Policy Group. The Depression Report: A New Deal for Depression and Anxiety Disorders. www.cep.lse.ac.uk/research/mentalhealth/

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