Clinical Review - Anxiety disorders

Contributed by Professor Femi Oyebode, consultant psychiatrist and professor of psychiatry, and Dr Abhinav Rastogi, ST5 psychiatry, Barberry National Centre for Mental Health, Birmingham.

Psychological treatments, such as CBT, have been shown to be efficacious in the treatment of GAD (Photograph: JH Lancy)
Psychological treatments, such as CBT, have been shown to be efficacious in the treatment of GAD (Photograph: JH Lancy)

Section 1: Epidemiology and aetiology
Anxiety is a normal physiological and psychological reaction to stress or imminent danger. Anxiety can be beneficial as it enables us to stay focused and motivated to deal with the stressors that cause it.

In 1908, Yerkes and Dodson suggested that anxiety can be healthy and boosts performance. However, as the anxiety or arousal levels continue to increase beyond the realms of one's endurance, performance invariably diminishes.

Anxiety becomes pathological when it presents frequently in the absence of a real threat and is disproportionately severe in intensity to a degree that it impairs a person's life.

Anxiety disorders can be broadly classified into phobic anxiety disorder (social phobia, agoraphobia and specific phobias) and other anxiety disorders, including panic disorder and generalised anxiety disorder (GAD).

Anxiety disorders are one of the most common psychiatric disorders. The worldwide lifetime prevalence of all anxiety disorders is 16.6 per cent.1 The 12-month prevalence of GAD, agoraphobia (plus panic disorder), social phobia and specific phobia is 1.5 per cent, 2 per cent, 2 per cent and 7.6 per cent, respectively.2

Females are twice as likely to have an anxiety disorder as males, with the exception of social phobia, where the ratio is 1:1.


Females are twice as likely as males to have an anxiety disorder (Photograph: SPL)

Genetic contribution
All anxiety disorders, and panic disorder in particular, are more common in first degree relatives of affected patients. This is supported by a higher concordance for GAD in twin studies.

However, the genetic contribution to the aetiology of anxiety disorders is poorly understood due to the complexity of interaction between environmental and genetic factors, as well as the lack of adoption studies.

Neurotransmitters and hormones
The three main putative neurotransmitters associated with anxiety disorders are gamma-amino-butyric acid, serotonin and noradrenaline.

The efficacy of benzodiazepines, SSRIs and tricyclic antidepressants in managing anxiety symptoms is regarded as confirmatory evidence of the involvement of these neurotransmitters in the pathophysiology of anxiety disorders.

Stress also causes increased release of corticotropin-releasing hormone, which in turn increases the level of cortisol. Increased cortisol level causes heightened arousal and when chronically secreted also has a contributory role in medical conditions, including hypertension and osteoporosis.

Patients with panic disorder may have heightened autonomic arousal even in the absence of threatening situations.

Life events
Adverse life events and early life experiences also have aetiological significance in the development of anxiety disorders.

Another proposed theory is the manifestation of anxiety symptoms through classical conditioning in response to environmental stimuli.

Psychoanalytical theories propose that anxiety is a result of a weakened ego that is in conflict with the Id, super-ego or the outside world.

Section 2: Making the diagnosis
The primary pathophysiology in all anxiety disorders is autonomic overactivity along with psychological arousal. Peripheral symptoms include palpitations, tachycardia, dizziness, shortness of breath and hyperventilation, sweating, tremors, restlessness and GI upset.

A range of other symptoms secondary to autonomic arousal may be present, such as urinary frequency and headaches.

The psychological arousal can present as impaired concentration, distorted perception of time and space, irritability and selective attention on environmental cues that exacerbate anxiety symptoms.

Many symptoms of anxiety are similar in all disorders, however other clinical features are exclusive to particular types of anxiety disorders (see box).

Comorbidity
Anxiety disorders seldom present as an isolated diagnosis.4 The most common comorbidity is another anxiety disorder.

In a 32-year prospective cohort study, 72 per cent of lifetime anxiety patients had a history of depression and 48 per cent had a history of anxiety disorders.5

Patients with comorbid anxiety and mood disorder are more disabled than patients with pure anxiety or mood disorder.6

Differential diagnosis
Differential diagnosis includes other anxiety disorders, mood disorders, personality disorder, including anxious-avoidant personality disorder, and illicit substance misuse.

Patients with schizophrenia may present in a prodromal phase with vague anxiety symptoms before the onset of full-blown illness.

Anxiety symptoms in schizophrenia can be vague, ill-defined and bizarre. The insight into the irrationality of anxiety symptoms that is so well preserved in anxiety disorders is also lacking in schizophrenia.

Panic attacks can be the only presenting complaint in a range of medical disorders, including endocrine disorders, such as thyroid dysfunction (both hypoand hyper-), hyperparathyroidism, episodic hypoglycaemia, cardiovascular causes including MI and angina, and neurological disorders.

This list is not exhaustive and appropriate investigations should be performed if there is suspicion of an underlying medical disorder.

Investigations
Psychiatric symptoms are often non-specific and can belie an underlying medical disorder.

Careful attention should be paid to other associated symptoms, pre-existing risk factors and atypical presentations.

The initial investigations should include FBC, LFT, U&Es, TFT, blood glucose and urine drug screen. Cardiac and CNS causes should be ruled out with appropriate investigations.

Symptoms of some common anxiety disorders3

Panic disorder

Recurrent, unpredictable and severe anxiety (panic) attacks, which are not restricted to any particular situation. Sudden onset of palpitations, chest pain, choking sensations, dizziness and feelings of unreality. Fear of dying, losing control, or going mad.

Panic disorder should not be given as the main diagnosis if the patient has a depressive disorder at the start of panic attacks.

Generalised anxiety disorder

Generalised and persistent anxiety, which is not restricted to, or strongly predominating in, any particular environmental circumstances.

Symptoms include complaints of persistent nervousness, trembling, muscular tensions, sweating, light-headedness, palpitations, dizziness and epigastric discomfort.

Fears that the patient or a relative will shortly become ill or have an accident are often present.

Agoraphobia

Well-defined fears of leaving home, crowds and public places, or travelling alone on trains, buses or planes.

Panic disorder is a frequent feature. Depressive, obsessional symptoms, social phobias and avoidance of the phobic situation are common.

Social phobia

Fear of scrutiny by other people leading to avoidance of social situations. Associated with low self-esteem and fear of criticism.

Patient may present with complaint of blushing, hand tremor, nausea or urgency of micturition. Symptoms may progress to panic attacks.

Section 3: Managing the condition
NICE guidelines recommend psychological treatment as the first-line treatment.

A Cochrane review of psychological treatments concluded that cognitive behavioural therapy (CBT) has strong evidence supporting its efficacy in alleviating symptoms of GAD.7

A total of 46 per cent of patients post-CBT showed clinical response, compared with 14 per cent of patients on waiting lists. CBT was shown to improve both anxiety and depressive symptoms.

Conclusive evidence for long-term efficacy of CBT in GAD is lacking. There is evidence to support the use of CBT in social phobia and other specific phobias, including agoraphobia.

Exposure treatments, such as systematic desensitisation, are effective treatments for resolving avoidance behaviours which are critical in the maintenance of phobic illnesses.

Exposure treatments do not have a role in the treatment of GAD as triggers in GAD are nonspecific. On their own, relaxation treatments are generally ineffective.

Benzodiazepines
Benzodiazepines are the most rapid and effective treatment of anxiety disorders and can be useful in facilitating commencement of other treatments. However, their long-term efficacy is poor. Benzodiazepines are well known to cause dependence.

There is already a high prevalence of alcohol and drug misuse in patients with anxiety disorder, therefore warranting extra caution when prescribing benzodiazepines.

Antidepressants
SSRIs are the first choice medications for anxiety disorders and have extensive evidence to support their superior effect compared with placebo.

They are generally well tolerated, cause better symptom control of anxiety and comorbid depressive symptoms, and are associated with longer remission periods.

In order to maximise compliance, patients should be advised that there is a two to four-week latency period in the therapeutic effects of SSRIs.

Tricyclic antidepressants are as efficacious as SSRIs, however due to a higher incidence of anticholinergic side-effects they are generally not used as first-line medications.

Other antidepressants that can be considered are selective serotonin and noradrenaline reuptake inhibitors, such as venlafaxine and duloxetine.

Other medications
Buspirone is a 5-HT1a receptor partial agonist anxiolytic drug.

It has a slower onset of action and, unlike benzodiazepines, lacks euphoric effect and has a low potential for dependence.

It is best used as an adjunct with pre-existing treatment for GAD. It is not an effective treatment for panic disorder. Beta-blockers may help with short-term symptomatic relief in performance-related anxiety, such as social phobia.

Monoamine oxidase inhibitors are the most effective treatment for social phobia but they are rarely used due to diet-related restrictions and their pharmacological interactions.

Recommended approaches to managing GAD
Psychological Pharmacological Self-help
CBT sessions of one or two hours, completed within four months, are suitable for most patients. Consider age, tolerability, patient preference, risks of overdose and previous treatment response before prescribing. Consider group CBT or support groups.
The optimal amount of CBT is 16-20 hours. Offer an SSRI unless otherwise indicated. Discuss the benefits of exercise as part of good general health.
Briefer CBT should be designed to integrate with structured self-help materials. Written information should be made available. Consider suggesting reading materials based on CBT principles.
Those delivering CBT should be trained and supervised and closely follow treatment protocols. Start at a low dose and increase slowly to minimise side-effects on initiation.  
  Inform patients about potential side-effects, time course of the treatment and delay in onset of effects.  


Exercise can be beneficial as part of a self-help programme and to maintain good general health (Photograph: SPL)

Section 4: Prognosis
There are only a handful of prospective studies which ascertain the natural progression of anxiety disorders.

In a 12-year follow-up study with more than 700 participants, the authors found that social phobia has the most chronic progression and the least likelihood of recovery with a probability of 0.37 by year 12.

However, patients who did recover from social phobia had less likelihood of having a recurrence compared with other anxiety disorders.

Panic disorder without agoraphobia had the best chance of recovery with a probability of 0.82.8 The presence of comorbidities, such as depression, substance misuse and other anxiety disorders are associated with poor prognosis.

Only half of patients with social phobia and specific phobia will make treatment contact.

Most patients with panic disorder will make contact but even then only a third make contact in the year of onset.9

In a five-year prospective naturalistic study of panic disorder, the authors found that the duration of illness before treatment showed a strict relationship with long-term outcome, with patients having a lesser duration of illness at the moment of the index episode showing a better outcome.10

Section 5: Case study
Mr P was a 34-year-old IT professional who presented with anxiety symptoms. On evaluation, Mr P said that his job involved making public presentations and interacting with other professionals.

Increasingly anxious
Over the years, he had been becoming increasingly anxious about giving presentations, due to fear of embarrassing himself by saying 'stupid things'.

He would start worrying excessively days before a presentation. He would experience palpitations and tremors.

He had been able to cope by drinking small amounts of alcohol prior to his presentations.

However, his symptoms had been increasing and he resorted to avoiding these interactions as much as possible.

It had affected his career progression and his employers were concerned.

He described himself as shy and introvert but denied having difficulties in interacting with his family or close friends.

He also denied being anxious in other situations that did not involve interaction with others or worrying excessively in general.

A diagnosis of social phobia was made. He was referred for CBT and commenced on SSRIs.

A follow-up appointment was offered for two weeks' time.

Section 6: Evidence base
Guidelines

BAP's guidelines are a valuable source of information and give a good outline of management of specific anxiety disorders both in primary and secondary care.

They also suggest a scheme for exploration of anxiety disorders.

  • NICE. Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. CG22. NICE, 2004, London.

Key texts

  • Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock's Comprehensive Textbook of Psychiatry. 9th edition. Lippincott Williams and Wilkins, 2009.
  • Semple D, Smyth R. Oxford Handbook of Psychiatry. 2nd edition. OUP, 2009, Oxford. This book has relevant information on psychiatric disorders, ideal for quick reference.

Curriculum
The RCGP covers this topic in statement 13 of the GP curriculum 'Care of people with mental health problems'.

Online

  • Royal College of Psychiatrists

http://rcpsych.ac.uk/mentalhealthinfoforall/problems/anxietyphobias.aspx

There is a dedicated section on patient information, self-help tips and leaflets on anxiety disorders.

  • Anxiety Care

www.anxietycare.org.uk

A London-based organisation that provides help and support through an online community, as well as a helpline. They also run a mutual support and recovery group.

References
1. Somers JM, Goldner EM, Waraich P et al. Prevalence and incidence studies of anxiety disorders: A systematic review of the literature. Can J Psychiatry 2006; 51: 100-13.

2. Wittchen H U, Jacobi F. Size and burden of mental disorder in Europe: a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005; 15: 357-76.

3. WHO. ICD-10 classification of mental and behavioural disorders. WHO, Geneva, 1992.

4. Goldenberg IM, White K, Yonkers K et al. The infrequency of "pure culture" diagnoses among the anxiety disorders. J Clin Psychiatry 1996; 57 (11): 528-33.

5. Moffitt TE, Harrington H, Caspi A et al. Depression and generalized anxiety disorder: cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years. Arch Gen Psychiatry 2007; 64: 651-60.

6. Grant BF, Hasin DS, Stinson FS et al. Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychol Med 2005. 35, 12; 1747-59.

7. Hunot V, Churchill R, Teixeira V et al. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev 2007; 1. Art. No: CD001848.

8. Bruce SE, Yonkers KA, Otto MW et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: A 12-Year prospective study. Am J Psychiatry 2005; 162: 1179-87.

9. Wang PS, Berglund P, Olfson M et al. Failure and delay in initial treatment contact after first onset of mental disorders in the national comorbidity survey replication. Arch Gen Psychiatry 2005; 62: 603-13.

10. Faravelli C, Paterniti, Scarpato A. 5-Year prospective, naturalistic follow-up study of panic disorder. Compr Psychiatry 1995; 36: 271-7.

CPD IMPACT: Earn more credits

These further impact points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Perform a search of your patients with anxiety. Look at the proportion that have had their baseline blood tests. Consider performing these tests in patients who have no results documented.
  • Ensure none of your patients with anxiety have benzodiazepines prescribed as a repeat prescription.
  • Consider having a meeting with your local mental health team to discuss the availability of psychological treatments, including CBT, for the management of patients with anxiety.

Record all your learning with your free online CPD Organiser


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