Panic disorder

Synonym: panic attacks (recurrent)

What is panic disorder?

Panic disorder is characterised by recurrent unexpected panic attacks that are not situational.¹ It 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 of its symptoms may also be experienced with physical illness. Those who experience panic disorder 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. Panic disorder is often classified into panic disorder with, or without, agoraphobia. Social anxiety disorder can often co-exist 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 which relapses and can lead to much distress and social dysfunction.²

Definition^{3 4}

To satisfy the DSM-5 diagnostic criteria:

• Panic attacks are recurrent and unexpected.

• At least two unexpected attacks are necessary for the diagnosis.

• At least one attack must be followed by at least one month of persistent concern about additional attacks or their consequences, or by significant maladaptive behavioural changes related to the attacks.

• Panic attacks must not arise as a result of alcohol or substance misuse, medical conditions or other psychiatric disorders.

A panic attack is defined as a discrete episode of intense subjective fear or discomfort, where at least four of the characteristic symptoms, listed below, surge abruptly and peak within minutes of the onset of the attack. Attacks usually last at least 10 minutes but their duration is variable.

Characteristic symptoms experienced during panic attacks

Panic disorder manifests as the sudden, spontaneous and unanticipated occurrence of panic attacks, with variable frequency, from several in a day to just a few per year:

• Palpitations, pounding heart or accelerated heart rate.

• Sweating.

• Trembling or shaking.

• Dry mouth.

• Feeling short of breath, or a sensation of smothering.

• Feeling of choking.

• Chest pain or discomfort.

• Nausea or abdominal distress.

• Feeling dizzy, unsteady, light-headed or faint.

• Derealisation or depersonalisation (feeling detached from oneself).

• Fear of losing control or 'going crazy'.

• Fear of dying.

• Numbness or tingling sensations.

• Chills or heat sensations.

How common is panic disorder and what causes it? (Epidemiology and aetiology)

Panic disorder is a common problem. The prevalence of panic disorder with or without agoraphobia in one UK study was 1.70%.⁵ In the USA, the lifetime prevalence of panic disorder in adults is estimated at 7% for women and 3.3% for men.³ Psychiatric case-finding studies of patients presenting with chest pain to emergency departments found that up to 25% satisfied criteria for panic disorder.

The aetiology of panic disorder is not well understood and likely rests on an interplay between genetic and environmental factors. These include adverse childhood events, major negative life events, irregularities in specific brain structures, hyperexcitable neuronal circuitry, neurochemical imbalances (in particular, GABA, cortisol and serotonin), and dysfunctional corticolimbic interaction during emotional processing.^{3 6}

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.

Presentation

Panic disorder symptoms

Anxiety disorders often go unrecognised, partly because patients frequently complain of pain, sleep disturbances, or other somatic problems as their main symptom, rather than of the underlying anxiety.⁷

Most patients are seen in general practice, although patients may present to the Emergency Department with somatic symptoms such as chest pain. As attention is given to the physical symptoms, the diagnosis of panic attacks may not be made. Therefore, a high index of suspicion is needed. Although screening tools such as GAD-7, PRIME-MD and the Panic Disorder Severity Scale (PDSS) exist, the National Institute for Health and Care Excellence (NICE) in the UK states there is insufficient evidence to recommend any, and that the diagnosis should be based on careful history-taking.²

As detailed above, the patient will describe a history of sudden onset of episodes of panic, featuring four or more of the characteristic symptoms. These will usually peak within minutes and can last for 20-30 minutes but they will rarely persist beyond one hour. There is marked individual variation in the length of attacks. 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.

One cross-sectional study of older patients with persistent dizziness found that anxiety and/or a depressive disorder were present in 22% and this could be a presentation for conditions such as panic disorder.⁸

Signs of panic disorder

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. Examination of mental status 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.

Diseases associated with panic disorder

Mental health disorders

Panic disorder is frequently associated with agoraphobia and/or social phobia. 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. One study found that 98% of panic disorder patients had at least one comorbid disorder.⁹ Major depressive disorder and other anxiety disorders were the most common. The other anxiety disorders tended to be persistent, although other depressive disorders and alcohol use disorders had high remission rates.⁹ Alcohol and substance misuse can complicate the picture and these can be used in some cases to self-medicate.

Physical health conditions

These may co-exist but one would not generally use the term panic disorder if the symptoms arise directly from the physical illness. Cardiovascular conditions 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 disorders such as irritable bowel syndrome and tension-type headache. A link with joint hypermobility disorder has been elucidated.¹⁰ There is a growing body of evidence linking the COVID-19 pandemic to mental ill health, including anxiety, although robust associations with panic disorder are not yet defined.¹¹

Differential diagnosis

Although a good description of the episode may help diagnose a panic attack, it is important to exclude other conditions. For example, there is a rare case report of a cingulate ganglioma presenting as panic attacks in a teenager.¹² More typical alternatives include:

Mental health conditions

• Agoraphobia (often co-exists).

• Social anxiety disorder (often co-exists).

• Anxiety disorders, including generalised anxiety disorder (may co-exist).

• Adjustment disorders.

• Bipolar disorder.

• Depression.

• Dissociative disorders.

• Factitious illness.

• Somatisation disorder.

• Mental symptoms arising as a result of physical illness.

• Obsessive-compulsive disorder.

• Specific phobic disorders.

• Post-traumatic stress disorder.

• Stimulant-drug misuse (including caffeine-related illness).

Physical health 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 - eg, Ménière's disease.

Investigations

There are no specific investigations to diagnose the condition but clinicians may wish to refer the patient, or carry out tests to exclude underlying physical causes for the symptoms. Whilst it is important not to miss likely or serious physical causes or comorbidities, one should not endlessly or excessively investigate these patients. Such a course of action can leave them with the impression that there is a physical problem which their doctor(s) just can't find.

After initially excluding major physical causes and confirming the characteristic clinical features of panic disorder, you can explain the diagnosis to the patient in terms that they will understand, recognising the complex interactions and interdependencies between mind and body and taking into account the patient's health beliefs.

Panic disorder treatment and management

Psychological therapy, medication, and self-help have all been shown to be effective in the treatment of panic disorder.² There is no high-quality, unequivocal evidence to support one psychological therapy over another.¹³ There is also no strong evidence regarding the relative effectiveness of psychological therapies and pharmacological treatment.¹⁴

NICE recommends a stepped care approach.²

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

For people with mild to moderate panic disorder, offer or refer for one of the following low-intensity interventions:

• Individual non-facilitated self-help.

• Individual facilitated self-help.

Self-help

• Offer information about the condition, and about support groups or other help where available.

• Give the patient details of books based on CBT principles, and contact details of any available support groups. There is evidence that self-help interventions are an effective option for people with panic disorder.¹⁵

• Advise on the benefits of exercise for general good health. There is some evidence that exercise reduces anxiety symptoms. A systematic review suggested that the effect is not as great as antidepressants but it could be a useful adjunct.¹⁶

• Advise avoiding anxiety-producing substances - eg, caffeine.¹⁷

• Patients may benefit from advice on how they can control some of their symptoms by using abdominal/diaphragmatic breathing.

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.

Monitor the patient on a regular basis, usually every 4-8 weeks, preferably using a self-completed questionnaire.

Step 3: review and offer alternative treatment if appropriate

For people with moderate to severe panic disorder (with or without agoraphobia), consider referral for:

• CBT; or

• An antidepressant if the disorder is long-standing or the person has not benefited from, or has declined, psychological intervention.

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, for a total of 7-14 hours to be completed within four months from starting.

• Briefer CBT of about seven 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.

• Overall, there is evidence of a moderate treatment effect with psychological treatments in primary care.

Antidepressant 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.

• The classes of antidepressants that have an evidence base for effectiveness are the selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). One systematic review found that SSRIs are effective in the treatment of panic disorder, with relatively few adverse events.¹⁸

• 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 four, six and 12 weeks.

• If there has been an improvement after 12 weeks, continue for six 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 after a 12-week course, offer an antidepressant from the alternative class (if appropriate) or another form of therapy.

Step 4: review and offer referral from primary care if appropriate

If two interventions (including self-help, psychological therapy, and medication) 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. In one study, panic disorder had a long course lasting several years.⁹ In another study in primary care, only a quarter of patients with panic disorder and agoraphobia had remission in a three-year follow up. Yet, three quarters of those with just panic disorder improved.¹⁹ There is an increased risk of attempted suicide in people with panic disorder.²⁰

Those who have recovered should be made aware that the condition may relapse and that they should seek early help for further treatment if panic attacks return. They can be helped to recognise and ameliorate triggers to panic.