Synonym: panic attacks (recurrent)

Panic disorder can be a severe and disabling illness and is common in primary care. It can be difficult to assess when it presents acutely, as many symptoms may also be experienced with physical illness. Sufferers often present repeatedly to their GP or local emergency department with worrying episodes of multiple symptoms that the patient may ascribe to life-threatening illness.

This condition often co-exists with agoraphobia - the avoidance of exposed situations for fear of panic or inability to escape. Agoraphobia is not a stand-alone diagnosis and occurs very rarely without panic disorder. Panic disorder is often classified into panic disorder with, or without, agoraphobia. Social phobia also often co-exists and is diagnosed where the situations avoided are predominantly social and interactive in nature.

The first panic attack may be associated with a stressful episode but gradually the attacks become dissociated and occur 'out of the blue'. It is a chronic condition with relapses and leads to much distress and social dysfunction.¹ Gamma-aminobutyric acid (GABA) receptor dysfunction is thought to play an important role in panic disorder pathophysiology.

Aetiology²

There are many aetiological theories, none of which are proven in isolation. Several aetiological factors may contribute to its occurrence in a given individual. The postsynaptic serotonergic/adrenergic hypersensitivity hypotheses are probably the most biologically plausible and relevant to treatment response but there are also important genetic and environmental factors involved.

Panic disorder can also be associated with the use of certain medications: selective serotonin reuptake inhibitors (SSRIs), benzodiazepine withdrawal and withdrawal from zopiclone. These should be considered in assessing any patient who presents with panic disorder.

Epidemiology

A common problem. The prevalence of panic disorder with or without agoraphobia in one UK study was 1.70%.³ In the USA, lifetime prevalence is estimated at 3-5.6% for panic attacks and 1.5-5% for panic disorder.² Psychiatric case-finding studies of patients presenting to emergency departments with chest pain found that up to 25% satisfied criteria for panic disorder.⁴

There is a familial tendency and a bimodal peak in age of onset - late adolescence and mid-thirties.²

Presentation

Symptoms

The condition is commonly unrecognised and untreated. Most patients are seen in general practice, although patients may present to A&E with somatic symptoms, e.g. chest pain. Due to the physical symptoms, the diagnosis of panic attacks may not be made. Therefore, a high index of suspicion is needed. Screening tools are available.^5,6

Classically, the patient will describe a history of sudden onset of episodes of panic featuring 4 or more of the characteristic symptoms listed above. The symptoms will reach their peak of intensity within ten minutes. Attacks usually last for 20-30 minutes and rarely persist beyond 1 hour. There is marked individual variation in the length of attacks. To be classified as panic disorder, the attacks should cause subsequent anxiety about their recurring or their effects, or bring about significant behavioural change in the patient. It is worth asking about any triggering caused by alcohol or drugs (including legal drugs such as caffeine, nicotine, complementary remedies or over-the-counter (OTC) preparations). Enquiry about other triggers for the attacks helps in constructing the differential diagnosis:

• Those that arise unexpectedly and without any obvious triggering situation or event are characteristic of panic disorder without agoraphobia.
• Those that arise in a predictable way as a follow-on to a given anxiety-provoking situation or event usually reflect a specific phobia-type diagnosis, or panic disorder with social phobia if the precipitant is a social phenomenon.
• Those that arise in an inconsistent or unpredictable way following exposure to a given anxiety-provoking situation or event suggest panic disorder with agoraphobia.

Signs

There are no specific physical signs associated with the condition, unless the patient is seen during a panic attack, when increased sympathetic outflow may manifest as tachycardia, hypertension, tremors, sweating, etc. During the panic attack the patient may be extremely preoccupied about suffering death or a severe, life-threatening physical illness. The Mental Status Examination reveals no specific findings other than a reflection of anxiety and/or urgency in their appearance, speech or mood (this is not necessary to make the diagnosis). The patient's affect should be congruent with their mental state. Thought processes should be normal and thought content should be essentially normal but may be preoccupied with death or illness. Thought content should be assessed for suicidal or homicidal ideation, or thoughts of self-harm. Judgement and insight are normally preserved. Abnormalities in thought processes or content (other than impulsive thoughts of suicide or self-harm) suggest alternative psychiatric diagnoses. The presence of incongruent affect should raise concerns that panic disorder is the wrong diagnosis.

Associated diseases

Psychiatric disorders

Panic disorder is frequently associated with agoraphobia (affecting about 26% of sufferers) and/or social phobia (affecting about 33% of sufferers). There is a significant association with mood disorders, particularly depression, with lifetime prevalence rates as high as 50-60%. There appears to be a higher risk of suicide attempts than in the general population. Alcohol/substance misuse can complicate the picture, although the overall prevalence of alcohol and drug misuse is not thought to be higher than in the general population.⁴

Medical conditions

May co-exist, although strictly speaking this cannot then be termed panic disorder, if the symptoms arise directly from the physical illness. Cardiovascular disease such as mitral valve prolapse, cardiomyopathy and hypertension are associated. Chronic obstructive airways disease and migraine headaches are also present in a larger proportion of sufferers than chance would suggest, as are functional disorders such as irritable bowel syndrome and tension-type headache. A recent link with joint hypermobility disorder has been elucidated, further suggesting a genetic basis for panic disorder.⁷

Differential diagnosis

Although a good description of the episode may suggest a panic attack, it is important to exclude other organic conditions. For example, there is a case report of a cingulate ganglioma presenting as panic attacks in a teenager.⁸

Psychiatric conditions

• Agoraphobia (often co-exists).
• Social phobia (often co-exists).
• Anxiety disorders, including generalised anxiety disorder (may co-exist).
• Adjustment disorders.
• Bipolar affective disorder.
• Depression.
• Dissociative disorders.
• Factitious illness.
• Somatisation syndrome.
• Mental symptoms arising as a result of physical illness.
• Obsessive-compulsive disorder.
• Specific phobic disorders.
• Post-traumatic stress disorder.
• Social phobia.
• Stimulant-drug misuse (including caffeine-related illness).

Physical conditions

• Hyperthyroidism.
• Phaeochromocytoma.
• Carcinoid syndrome.
• Hypoglycaemic episodes (possibly due to insulinoma in those not using insulin/oral hypoglycaemic agents).
• Paroxysmal cardiac dysrhythmia.
• Mitral valve prolapse.
• Myocardial infarction.
• Recurrent small pulmonary emboli.
• Epileptiform disorders, particularly temporal lobe epilepsy.
• Withdrawal from alcohol/sedatives/opiates.
• Paroxysmal vestibular disorders, e.g. Ménière's disease.

Investigations

There are no specific investigations to diagnose the condition but clinicians may feel inclined to refer the patient, or carry out tests to exclude underlying physical causes for the symptoms. Whilst it is important not to miss likely physical causes, one should not endlessly or excessively investigate these patients. Such a course of action can leave them with the impression that there actually is a physical problem, which their doctor(s) just can't find. After initial exclusion of top-ranking physical causes, with the confirmation of characteristic clinical features of panic disorder, the absence of a physical cause should be clearly explained to the patient. Response to treatment will be better in those patients who accept the absence of physical causes for their symptoms and in those who have an understanding of the nature of panic disorder as a primarily mental phenomenon.

Management

The National Institute for Health and Clinical Excellence (NICE) recommends a stepped-care approach.⁹

Step 1: recognition and diagnosis

This has been dealt with in the 'Presentation', 'Differential diagnosis' and 'Investigations' sections, above.

Step 2: treatment in primary care

General

• Try to involve the patient's family or carer if the patient allows this. It is important for them to understand how they can best help the patient during an attack.¹⁰
• Advise avoiding anxiety-producing substances, e.g. caffeine.¹¹
• It is important to exclude alcohol or drug misuse as a factor and to treat these problems if present. Reassessment after successful management of substance-related issues will reveal if this is true panic disorder. Response to pharmacological/psychological therapies is likely to be poor in the face of alcohol/drug misuse or dependence.

Offer the following interventions (listed as per NICE in the order - according to the evidence base - of duration of efficacy):

Cognitive behavioural therapy (CBT)

• Treatment focused on the recognition of factors which trigger the panic and behavioural methods to cope with the symptoms have been found to be very useful.
• Trained and supervised personnel should be involved in the delivery of treatment, working to empirically grounded protocols.
• 1-2 hours a week is suitable for most people over a 4-month period.
• Briefer CBT of about 7 hours may be appropriate for some patients, combined with self-help materials.
• More intensive CBT over a shorter period of time may be suitable for some patients.

Medication

• Antidepressant drugs have been shown to be effective in reducing the amplitude of panic, reducing frequency of, or eliminating, panic attacks and improving quality-of-life measures in this group of patients.
• Offer an SSRI licensed for this indication first-line unless contra-indicated.
• Consider imipramine or clomipramine if there is no improvement after 12 weeks and further medication is indicated (NB: neither is licensed for this indication in the UK, so document informed consent)..
• Review the patient after two weeks to check for side-effects and efficacy, and at 4, 6 and 12 weeks.
• If there has been an improvement after 12 weeks, continue for 6 months after the optimum dose has been reached.
• If medication is used for longer than 12 weeks, review at 8- to 12-weekly intervals.
• Follow the summary of product characteristics of the individual drugs for other monitoring requirements.
• Use self-completed questionnaires to monitor outcomes where possible.
• At the end of treatment, withdraw the SSRI gradually, as dictated by patient preference, and monitor monthly for relapse for as long as appropriate to the individual.
• If there is no improvement and a second intervention has not been tried, go to Step 3 (below).
• If there has been no improvement and a second intervention has been tried, go to Step 4 (below).

Self-help

• Give the patient details of books based on CBT principles, and contact details of any available support groups.
• Promote exercise as part of good general health.
• Monitor the patient on a regular basis, usually every 4-8 weeks, preferably using a self-completed questionnaire.

Step 3

Reassess the condition and consider another intervention.

Step 4

If two interventions have been offered without benefit, consider referral to specialist mental health services. Specialist treatment may include management of comorbid conditions, structured problem solving, other types of medication and treatment at tertiary centres.

Prognosis

The literature is contradictory about prognosis. Some sources say that 20-30% of people with panic disorder have symptoms up to 10 years from the time of initial diagnosis and treatment.¹² Others suggest that the prognosis is excellent if there is adherence to medical management.² The author of this article suggests that this variation in perspective reflects differences in both compliance rates and in the institution of appropriate treatment relative to the onset of symptoms.

Prevention

Those who suffer can help themselves by recognising triggers to panic and ameliorating them through avoidance or CBT-based strategies. Recovered sufferers should be made aware that the condition may relapse and that they should seek early help for further treatment if panic attacks return.

Document references

1. Saeed SA, Bruce TJ; Panic disorder: effective treatment options.; Am Fam Physician. 1998 May 15;57(10):2405-12, 2419-20. [abstract]
2. Daniels C; Panic Disorder, eMedicine, Apr 2010
3. Skapinakis P, Lewis G, Davies S, et al; Panic disorder and subthreshold panic in the UK general population: Epidemiology, Eur Psychiatry. 2010 Aug 31. [abstract]
4. Ham P et al; Treatment of Panic Disorder; Am Fam Phys 2005 Feb 15;71(4):733-739
5. Farvolden P, McBride C, Bagby RM, et al; A Web-based screening instrument for depression and anxiety disorders in primary care.; J Med Internet Res. 2003 Jul-Sep;5(3):e23. Epub 2003 Sep 29. [abstract]
6. Terluin B, Brouwers EP, van Marwijk HW, et al; Detecting depressive and anxiety disorders in distressed patients in primary BMC Fam Pract. 2009 Aug 23;10:58. [abstract]
7. Garcia Campayo J, Asso E, Alda M, et al; Association between joint hypermobility syndrome and panic disorder: a Psychosomatics. 2010 Jan;51(1):55-61. [abstract]
8. Tamburin S, Cacciatori C, Bonato C, et al; Cingulate gyrus tumor presenting as panic attacks. Am J Psychiatry. 2008 May;165(5):651-2.
9. Anxiety (partial update), NICE Clinical Guideline (January 2011); Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults
10. Kelly CM, Jorm AF, Kitchener BA; Development of mental health first aid guidelines for panic attacks: a Delphi BMC Psychiatry. 2009 Aug 10;9:49. [abstract]
11. Nardi AE, Lopes FL, Freire RC, et al; Panic disorder and social anxiety disorder subtypes in a caffeine challenge test. Psychiatry Res. 2009 Sep 30;169(2):149-53. Epub 2009 Aug 20. [abstract]
12. Tefera L et al; Anxiety, eMedicine, May 2010

Internet and further reading

• Gliatto M; Generalized Anxiety Disorder. Am Fam Phys 2000 Oct 1; 62(7):1591-1601. Full Text; Good review article on this related condition
• Depression and anxiety - computerised cognitive behavioural therapy (CCBT), NICE Technology Appraisal (2006)
• Bergstrom J, Andersson G, Ljotsson B, et al; Internet-versus group-administered cognitive behaviour therapy for panic disorder BMC Psychiatry. 2010 Jul 2;10:54. [abstract]

Acknowledgements