Panic disorders

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Panic attacks are commonly experienced across a range of anxiety, mood, and substance-related disorders and require no specific treatment. Panic disorder frequently presents in primary care and can be associated with high service utilisation and costs if left unrecognised and inadequately treated.[11][79] The primary goals of treatment are to reduce the intensity, frequency, and duration of panic episodes, reduce avoidance behaviour, limit over-reliance on safety cues, and improve functional capacity.

General considerations

Owing to limitations in the current evidence base, it is not possible to say whether psychological therapies or pharmacological interventions are more effective for panic disorder overall.[80] When constructing a treatment approach, consider potential adverse effects, past treatment history, patient preference, comorbid disorders, and treatment availability.

Treatment options for panic disorder include:[4]

Cognitive behavioural therapy (CBT)
Medication
The combination of CBT and medication.

Treatment guidelines vary internationally and should be individualised to the patient, but as a general guide, for those with mild panic disorder, consider offering self-help or CBT initially. For those with panic disorder of moderate severity, consider offering CBT, medication (i.e., a selective serotonin-reuptake inhibitor [SSRI] or a serotonin-noradrenaline reuptake inhibitor [SNRI]), or a combination of CBT and medication. For those with severe panic disorder, consider offering both CBT and an SSRI/SNRI from the offset.[4] Note that in some areas, such as the UK, a stepped care model is recommended; psychological treatment is recommended first-line by the National Institute for Health and Care Excellence (NICE) for patients with panic disorder irrespective of severity (unless the disorder is long-standing or the patient has not benefited from or has declined psychological treatment).[69]

A referral to a psychiatrist for additional pharmacotherapy options and a mental health professional with expertise in the cognitive-behavioural management of panic disorder may be required in patients with an inadequate response to initial treatment in primary care.[69] Treatment strategies may also need to involve family members to help maximise the patient's engagement with recommended interventions.[69] Routinely monitor functional status and avoidance behaviour across time to offset relapse.[4]

Collaborative care, involving the integration of evidence-based cognitive behavioural therapy (CBT) and pharmacotherapy within the primary care setting, is an effective approach in treating anxiety disorders. A large-scale, multicentre randomised controlled trial known as the Coordinated Anxiety Learning and Management (CALM) study demonstrated that evidence-based interventions (such as CBT and/or pharmacotherapy) significantly reduce anxiety symptoms and functional impairments, and improve quality of care, in patients with anxiety disorders in primary care.[81][82] CALM has been found to be superior to usual care for panic disorder at 6- and 12-month follow-up intervals.[83] Likewise, studies of collaborative care models using phone-based care co-ordination and computerised CBT with step-care options were found to be superior to usual care.[84][85]

Psychoeducation and lifestyle advice

Offer psychoeducation as soon as a diagnosis has been made.[12] A key part of any treatment approach is information and education about the nature of panic and anxiety.[69] In particular, panic is an understandable reaction to perceived danger (the 'fight or flight' response). Panic attacks, while uncomfortable, are not dangerous. Fear arises from the misinterpretation of normal body sensations. Drawing a simple diagram together with the patient - linking symptoms, interpretation, anxiety with arrows in a 'vicious circle' - can be helpful. It is important for the patient to appreciate that the first goal of treatment is not to remove all anxiety, only to manage it successfully. Attempts by the patient to cope (e.g., by avoidance or safety seeking) are understandable, but inadvertently lead to maintaining the problem.

Advice on lifestyle factors includes:[4]

Good sleep
Regular exercise
Reduced use of caffeine, tobacco, and alcohol
Healthy diet
Staying engaged with meaningful activities and healthy social supports.

For some patients, e.g., those with mild panic disorder without comorbidities, a watchful waiting approach following psychoeducation and lifestyle advice may be suitable, followed by specific treatments if necessary.[4]

Panic attacks without panic disorder

If patients present with an acute panic attack, provide reassurance that the symptoms are not dangerous and that the attack will subside soon. Patients usually hyperventilate as part of the attack but subjectively experience this as shortness of breath; this should be explained to the patient and an emphasis placed on slowing the breathing. Using a quiet room and support from a significant other are useful. In the emergency department setting, benzodiazepines may sometimes be considered to terminate an acute attack, for example if the patient’s agitation or anxiety is particularly severe.[4]

Explain to patients who present with new-onset panic attacks that attacks are common, affecting up to one third of individuals in their lifetime.[2][3] Although the attacks are uncomfortable, they are not dangerous and are time-limited.

No particular treatment is indicated for presentations which do not meet established criteria for panic disorder, e.g., DSM-5-TR. Despite its inherent use in the treatment of panic-related symptoms, placebo-controlled studies have found no evidence for the effectiveness of propranolol.[86] Self-help materials based on principles of CBT are beneficial. The provision of written materials, either used alone or in combination with brief phone contact, may be helpful in reducing panic-related symptoms.[87][88] Bibliotherapy may be particularly helpful when used in combination with a professional who monitors treatment response.[89][90] Self-help interventions yield a strong effect size, although therapist-administered treatment appears to outperform self-help.[91] The advantages of self-help interventions include cost, availability, ease of administration, and convenience. The disadvantages include the generic treatment approach, lack of accountability, and potential difficulties with understanding and properly implementing treatment principles.

Panic attacks are common to other anxiety, mood, and substance use disorders, and thus additional screening for these conditions is recommended.

Encourage patients to monitor the intensity, frequency, and duration of attacks, and whether episodes are expected or unexpected. Schedule a follow-up evaluation or a telephone check within 2 weeks to reassess the patient's symptoms. See below for recommended management of patients who then go on to meet DSM-5-TR criteria for panic disorder.

Panic disorder with no comorbidity

The evidence supports self-help, CBT, and SSRIs/SNRIs as equally valid first-line options according to the severity of the patient’s symptoms and their individual preference.[4][69][92] CBT can be used alone without pharmacotherapy, or may be used as an adjunct to any form of pharmacotherapy.[93]

Tricyclic antidepressants (TCAs) (e.g., imipramine or clomipramine) are regarded as second-line options. Benzodiazepines may be used when specifically indicated for short-term anxiety crisis, or as an adjunct to augment SSRIs, SNRIs, and TCAs in the management of patients with treatment-resistant panic disorder, or at the initiation of antidepressant therapy to prevent worsening of symptoms due to antidepressant side effects.[70] An inadequate response to initial treatment should prompt reconsideration of the diagnosis or comorbidity with other anxiety, mood, or substance-related disorders.

CBT:

CBT is a time-limited, skills-based approach designed to modify thoughts, behaviours, and environmental contingencies that are maintaining or exacerbating symptoms and impairments, and is an effective first-line treatment.[94][95][96][97] [ ] [Evidence C] It may be delivered face-to-face (individual or group) or as digital CBT (dCBT) accessed by computer, tablet or smartphone application. The evidence in favour of dCBT is growing, and it appears to be equally beneficial, compared with face-to-face CBT, for the management of panic disorder, with similar reductions in symptoms and improvements in quality of life.[85][98][99][100][101][102][103][104] Therefore dCBT may be considered as an equal first-line option to face-to-face CBT.[4]
Treatment sessions may continue for 12 to 14 visits, although 6 to 7 sessions have also been found to be effective.[105] A referral to a mental health professional with expertise in CBT is recommended. The referring physician and mental health professional should maintain routine collaboration. Evidence also suggests beneficial effects of collaborative care in primary care settings, including the use of computerised CBT and care co-ordination programmes.[81][84][85][106]
The aim of cognitive behavioural therapy for panic is to enable the person to experience the symptoms of panic without feeling frightened, and also to eliminate reliance on avoidance and safety seeking in order to learn that nothing dangerous is actually going to happen during a panic attack. Temporarily increasing anxiety through facing feared sensations and situations in a predictable, controllable manner may often be necessary in order to learn how to self-manage and overcome panic.
CBT for panic disorder involves a combination of education, self-monitoring, relaxation training (including breathing re-training), challenging negative styles of thinking, situational exposure training, and systematic exposure to uncomfortable physical sensations. The latter involves exposure to both internal body sensations (as 'behavioural experiments') and external triggers (if the individual also has agoraphobia). Exposure to relevant uncomfortable physical sensations (e.g., dizziness, hyperventilation, and tachycardia) in a gradual, repeated, controlled manner can reduce fearful beliefs and increase tolerance for these sensations over time. For example, the individual and the therapist may overbreathe together to demonstrate that this does not lead to loss of consciousness, or they may agree to exercise in a hot room to prove that a racing heart does not lead to a heart attack. External graded exposure involves gradually increasing the patient's tolerance to previously avoided situations (e.g., crowds, shops, queues, public transport) without relying on safety cues (e.g., spouse, medication). Repeated, frequent, controllable, and predictable exposures are associated with optimal outcomes. Although certain activities, such as exercise or drinking coffee, should be avoided during earlier stages of exposure therapy as they may provoke physical sensations similar to those experienced during panic episodes, these can be incorporated into the exposure hierarchy at later stages of treatment.
dCBT courses may be integrated with face-to-face therapy, and may be supervised by a clinician or completed on a self-help basis. Guided dCBT is generally more effective than unguided dCBT; this involves regular help and contact to complete the course, although this does not necessarily have to be from a clinician.[4]
Self-help materials based on principles of CBT are beneficial. Bibliotherapy, either alone or in combination with brief phone contact, may be helpful in reducing panic-related symptoms.[87][88] Self-help interventions yield a strong effect size, although therapist-administered treatment appears to outperform self-help.[91] Therapist-assisted exposure tends to result in greater reductions in agoraphobic avoidance and panic severity in comparison with those doing self-directed exposure without therapist assistance.[107] Bibliotherapy may be particularly helpful when used in combination with a professional who monitors treatment response.[89] The advantages of self-help interventions include cost, availability, ease of administration, and convenience. The disadvantages include the generic treatment approach, lack of accountability, and potential difficulties with understanding and properly implementing treatment principles.
CBT adjunctive to pharmacotherapy may increase medication adherence, improve response rate, and reduce the amount of medication needed to gain symptom control.[95][106][108][109][110][111][112][113] Patients discontinuing benzodiazepines may particularly benefit from adjunctive CBT.[114][115]

SSRIs/SNRIs:

First-line pharmacotherapy for the treatment of panic disorder.[11][25][116][117][118][119][120][121][122]
Also effective in the management of a variety of other symptoms, such as sleep disruption, and other disorders of anxiety and mood that commonly co-occur.[123]
Paroxetine, sertraline, fluoxetine, fluvoxamine, citalopram, escitalopram, and venlafaxine have all demonstrated efficacy and have a delayed onset of efficacy (2 to 12 weeks).[117][124][125][126][127][128][129][130]
The choice of antidepressant depends on availability, adverse effects, risk of withdrawal symptoms (e.g., dizziness, irritability, nausea, rebound anxiety), and ease of titration. Paroxetine and venlafaxine have a higher risk of withdrawal symptoms than fluoxetine.
Patients with anxiety disorders may be more susceptible to medication adverse effects; it is therefore advisable to start at the lowest dose and increase the dose with caution ('start low, go slow').[12]

Benzodiazepines:

There is low-quality evidence suggesting that benzodiazepines are superior to placebo in the short-term management of panic disorder; data on the long term efficacy and risks of treatment are currently lacking, providing limited guidance for clinical practice.[131] Some clinicians consider benzodiazepines to be a useful part of the treatment armamentarium for a subsection of patients with anxiety disorders.[132][133] However, their use within clinical practice is frequently limited due to concern about their associated adverse effects (e.g., cognitive impairment, falls, and sedation), tolerance, dependence, and potential for misuse.[4]
Benzodiazepines are sometimes used for a short-term anxiety crisis, or as an adjunct to augment SSRIs, SNRIs, and TCAs in the management of patients with treatment-resistant panic disorder, or at the initiation of antidepressant therapy to prevent worsening of symptoms due to antidepressant side effects.[70] They are recommended for short-term use only (e.g., 2 to 4 weeks).[134]
UK National Institute for Health and Care Excellence guidelines do not recommend using benzodiazepines for patients with panic disorder, stating that they are associated with less good outcomes in the long term.[69] However, other international practice guidelines recommend that cautious short-term benzodiazepine use may be considered as an alternative option for selected patients with panic disorders, for example for patients whose symptoms have not responded to other treatments or for management of severe agitation or anxiety during initiation of an SSRI.[4][70]
Tolerance, dependence, and misuse potential can be associated with all benzodiazepines. Short-acting agents may warrant special consideration of risks without demonstrating additional benefits.[135][136] If benzodiazepines are indicated, the preference may be for scheduled, longer-acting agents so that medication use is time-dependent rather than response/panic-dependent. 'As needed' use of short-acting benzodiazepines may result in the patient developing psychological dependence on these medications, which could diminish the ability for an individual to develop an internal locus of control over these symptoms, and so, if required, benzodiazepines should be dosed regularly and not 'as needed'.
Avoid prescribing benzodiazepines for patients with a previous or current history of substance misuse.[4]
They have a rapid onset of action and are generally well tolerated. Physiological dependence can occur in as little as 2 to 4 weeks. Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms (e.g., dizziness, irritability, nausea, sweating, tremors, rebound anxiety, and seizure). Longer-acting agents (e.g., clonazepam) may be preferable to minimise interdose rebound anxiety.
Long-term treatment with benzodiazepines should be rare, supervised, made with caution and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long-term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[134][137]
Patients on the highest average daily doses, typically more than recommended guidelines, are more likely to have substance misuse, comorbid diagnoses, and concurrent prescriptions for psychoactive medications, suggestive of a more complex management.[138][139]

TCAs:

TCAs are indicated in patients for whom treatment with one or more SSRI has failed, or in patients with neuropathic pain. Patients with panic disorder with a high likelihood of pain complaints may also benefit from TCA treatment.[140]
Both imipramine and clomipramine have demonstrated efficacy.[95][141] However, they are less favourable with respect to adverse effects and may not be as well tolerated as SSRIs and SNRIs.[123]
For an individual to develop an internal locus of control over these symptoms, and so, if required, benzodiazepines should be dosed regularly and not 'as needed'.

Panic disorder with comorbidity

Anxiety and depressive disorders may pre-date, co-occur with, or post-date the onset of panic disorder. With severe anxiety and depression, referral to a psychiatrist is indicated.

Comorbid depression:

Patients are treated initially with CBT or SSRIs/SNRIs, or with TCAs where treatment with one or more SSRI/SNRI or CBT has failed. Benzodiazepines are relatively contra-indicated for persons with comorbid depression.[123]
Benzodiazepines are sometimes considered to be relatively contraindicated for persons with comorbid depression. However, there is moderate quality evidence that adding a benzodiazepine to an antidepressant regimen may be helpful towards improving depression severity, treatment response, and remission during the early phase of treatment. These benefits are not observed during acute and continuous phases.[142]
Guidelines from the STAR*D study for treatment-resistant comorbid depression recommend dual pharmacotherapy in non-responding patients if they show a partial response (25% improvement in symptoms) with a maximum dose of 1 antidepressant.[143] Combining 2 drugs from groups with different mechanisms of action may be considered, the groups being SSRIs (paroxetine, sertraline, fluoxetine, fluvoxamine, citalopram, escitalopram), SNRIs (venlafaxine), mirtazapine, and TCAs (imipramine, clomipramine). Check carefully for drug interactions should be checked and consider consulting with a psychiatrist before initiating combination therapy.
CBT for panic disorder is effective among patients with severe depression and/or comorbid substance use disorders.[144] Exposure-based CBT for panic disorder is effective in reducing anxiety and comorbid depressive symptoms, irrespective of depression severity.[145] Adjunctive CBT is also recommended for patients receiving pharmacotherapy.

Comorbid anxiety (e.g., agoraphobia, social anxiety disorder, post-traumatic stress disorder):

Treatment can be commenced with pharmacotherapy (i.e., SSRIs, SNRIs, benzodiazepines, TCAs) with or without CBT, or CBT alone. Benzodiazepines and TCAs are considered second-line pharmacotherapy. [ ]
SSRIs can be augmented with higher-potency benzodiazepines for some patients on a short-term basis, especially if intense, persistent anxiety symptoms are interfering with treatment adherence and engagement, and if rapid control over anxiety symptoms is necessary.[70][146]

Treatment duration and cessation

Pharmacotherapy for panic disorder should be continued for at least 1 year from the point of treatment response to help ensure symptom reduction and protection against relapse.[147][148]

If a medication taper is considered, review advantages and disadvantages of current medication response, discuss duration of symptom stability, and anticipate and problem-solve stressors that may impact relapse. Due to a significant rate of relapse, ensure that the patient attains maximal functioning prior to discontinuation of medications.[149][150] There is limited evidence on effect and safety of different medication discontinuation strategies for anxiety disorders, meaning that evidence is lacking on the optimal rate of discontinuation, as well as on the presence of psychological support during discontinuation.[151] [ ] Gradually discontinue the medication over an extended period of time to minimise the risk of withdrawal symptoms, and monitor the patient frequently during this time.[69]

There is evidence to suggest that CBT has an enduring positive effect for at least 12 months after treatment completion compared with control conditions.[152] One large meta-analysis of follow-up studies compared the enduring effects of different treatments for anxiety disorders (including panic disorder) over a 24-month period, once treatment had been discontinued. Patients treated with CBT experienced a significant improvement in symptoms over time, whereas patients in the medication group remained stable in the period following treatment discontinuation. Patients in the placebo group did not experience a worsening of symptoms over time, but did show significantly worse outcomes than those treated with CBT.[153]

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