The rating scheme for the strength of the recommendations (I, II, III) is repeated at the end of the "Major Recommendations" field.
Panic disorder is a common and often disabling mental disorder. Treatment is indicated when symptoms of the disorder interfere with functioning or cause significant distress [I]. Effective treatment for panic disorder should lead not only to reduction in frequency and intensity of panic attacks, but also reductions in anticipatory anxiety and agoraphobic avoidance, optimally with full remission of symptoms and return to a premorbid level of functioning [I]. Psychiatric management consists of a comprehensive array of activities and interventions that should be instituted for all patients with panic disorder, in combination with specific modalities that have demonstrated efficacy [I].
Establishing a Therapeutic Alliance
Psychiatrists should work to establish and maintain a therapeutic alliance so that the patient's care is a collaborative endeavor [I]. Careful attention to the patient's preferences and concerns with regard to treatment is essential to fostering a strong alliance [I]. In addition, education about panic disorder and its treatment should be provided in language that is readily understandable to the patient [I]. Many patients with panic disorder are fearful of certain aspects of treatment (e.g., medication side effects, confronting agoraphobic situations). A strong therapeutic alliance is important in supporting the patient through phases of treatment that may be anxiety provoking [I].
Performing the Psychiatric Assessment
Patients should receive a thorough diagnostic evaluation both to establish the diagnosis of panic disorder and to identify other psychiatric or general medical conditions [I]. This evaluation generally includes a history of the present illness and current symptoms; past psychiatric history; general medical history; history of substance use; personal history (e.g., major life events); social, occupational, and family history; review of the patient's medications; previous treatments; review of systems; mental status examination; physical examination; and appropriate diagnostic tests (to rule out possible medical causes of panic symptoms) as indicated [I]. Assessment of substance use should include illicit drugs, prescribed and over-the-counter medications, and other substances (e.g., caffeine) that may produce physiological effects that can trigger or exacerbate panic symptoms [I].
Delineating the specific features of panic disorder that characterize a given patient is an essential element of assessment and treatment planning [I]. It is crucial to determine if agoraphobia is present and to establish the extent of situational fear and avoidance [I]. The psychiatrist also should evaluate other psychiatric disorders, as co-occurring conditions may affect the course, treatment, and prognosis of panic disorder [I]. It must be determined that panic attacks do not occur solely as a result of a general medical condition or substance use and that they are not better conceptualized as a feature of another diagnosis [I]. The presence of medical disorders, substance use, and other psychiatric disorders does not preclude a concomitant diagnosis of panic disorder. If the symptoms of panic disorder are not deemed solely attributable to these factors, then diagnosing (and treating) both panic disorder and another condition may be warranted [I].
Tailoring the Treatment Plan for the Individual Patient
Tailoring the treatment plan to match the needs of the particular patient requires a careful assessment of the frequency and nature of the patient's symptoms [I]. It may be helpful, in some circumstances, for patients to monitor their panic symptoms using techniques such as keeping a daily diary [I]. Such monitoring can aid in identification of triggers for panic symptoms, which may become a focus of subsequent intervention.
Continuing evaluation and management of co-occurring psychiatric and/or medical conditions is also essential to developing a treatment plan for an individual patient [I]. Co-occurring conditions may influence both selection and implementation of pharmacological and psychosocial treatments for panic disorder [I].
Evaluating the Safety of the Patient
A careful assessment of suicide risk is necessary for all patients with panic disorder [I]. Panic disorder has been shown to be associated with an elevated risk of suicidal ideation and behavior, even in the absence of co-occurring conditions such as major depression. An assessment of suicidality includes identification of specific psychiatric symptoms known to be associated with suicide attempts or suicide; assessment of past suicidal behavior, family history of suicide and mental illness, current stressors, and potential protective factors such as positive reasons for living; and specific inquiry about suicidal thoughts, intent, plans, means, and behaviors [I].
Evaluating Types and Severity of Functional Impairment
Panic disorder can impact numerous spheres of life including work, school, family, social relationships, and leisure activities. The psychiatrist should develop an understanding of how panic disorder affects the patient's functioning in these domains [I] with the aim of developing a treatment plan intended to minimize impairment [I].
Establishing Goals for Treatment
All treatments for panic disorder aim to reduce the frequency and intensity of panic attacks, anticipatory anxiety, and agoraphobic avoidance, optimally with full remission of symptoms and return to a premorbid level of functioning [I]. Treatment of co-occurring psychiatric disorders when they are present is an additional goal [I]. The intermediate objectives that will help achieve these goals will depend on the chosen modality or modalities [I].
Monitoring the Patient's Psychiatric Status
The different elements of panic disorder may resolve at different points during the course of treatment (e.g., panic attacks may remit before agoraphobic avoidance is eliminated). The psychiatrist should continue to monitor the status of all symptoms originally presented by the patient [I]. Psychiatrists may consider using rating scales to help monitor the patient's status at each session [I]. Patients also can be asked to keep a daily diary of panic symptoms to aid in ongoing assessment [I].
Providing Education to the Patient and, When Appropriate, to the Family
Education alone may relieve some of the symptoms of panic disorder by helping the patient realize that his or her symptoms are neither life-threatening nor uncommon. Thus, once a diagnosis of panic disorder is made, the patient should be informed of the diagnosis and educated about panic disorder and treatment options [I]. Regardless of the treatment modality selected, it is important to inform the patient that in almost all cases the physical sensations that characterize panic attacks are not acutely dangerous and will abate [I]. Educational tools such as books, pamphlets, and trusted web sites can augment the face-to-face education provided by the psychiatrist [I].
Providing the family with accurate information about panic disorder and its treatment is also important for many patients [I]. Education sometimes includes discussion of how changes in the patient's status affect the family system and of how responses of family members can help or hinder treatment of the patient's panic disorder [II].
Patient education also includes general promotion of healthy behaviors such as exercise, good sleep hygiene, and decreased use of caffeine, tobacco, alcohol, and other potentially deleterious substances [I].
Coordinating the Patient's Care with Other Clinicians
Many patients with panic disorder will be evaluated by or receive treatment from other health care professionals in addition to the psychiatrist. Under such circumstances, the clinicians should communicate periodically to ensure that care is coordinated and that treatments are working in synchrony [I].
It is important to ensure that a general medical evaluation has been done (either by the psychiatrist or by another health care professional) to rule out medical causes of panic symptoms [I]. Extensive or specialized testing for medical causes of panic symptoms is usually not indicated but may be conducted based on individual characteristics of the patient [III].
Enhancing Treatment Adherence
Problems with treatment adherence can result from a variety of factors (e.g., avoidance that is a manifestation of panic disorder, logistical barriers, cultural or language barriers, problems in the therapeutic relationship). Whenever possible, the psychiatrist should assess and acknowledge potential barriers to treatment adherence and should work collaboratively with the patient to minimize their influence [I].
Many standard pharmacological and psychosocial treatments for panic disorder can be associated with short-term intensification of anxiety (e.g., because of medication side effects or exposure to fear cues during therapy). These temporary increases in anxiety may contribute to decreased treatment adherence. The psychiatrist should adopt a stance that encourages patients to articulate their fears about treatment and should provide patients with a realistic notion of what they can expect at different points in treatment [I]. In particular, patients should be informed about when a positive response to treatment can be expected so that they do not prematurely abandon treatment due to misconceptions about the time frame for response [I]. Patients should also be encouraged to contact the psychiatrist (e.g., by telephone if between visits) if they have concerns or questions, as these can often be readily addressed and lead to enhanced treatment adherence [I].
Working with the Patient to Address Early Signs of Relapse
Although standard treatments effectively reduce the burden of panic disorder for the majority of patients, even some patients with a good treatment response may continue to have lingering symptoms (e.g., occasional panic attacks) or have a recurrence of symptoms after remission. Patients should be reassured that fluctuations in symptoms can occur during the course of treatment before an acceptable level of remission is reached [I]. Patients should also be informed that symptoms of panic disorder may recur even after remission and be provided with a plan for how to respond [I].
Formulation and Implementation of a Treatment Plan
Choosing a Treatment Setting
The treatment of panic disorder is generally conducted entirely on an outpatient basis, as the condition by itself rarely warrants hospitalization [I]. However, it may be necessary to hospitalize a patient with panic disorder because of symptoms of co-occurring disorders (e.g., when acute suicidality associated with a mood disorder is present or when inpatient detoxification is required for a substance use disorder) [I]. Under such circumstances, the treatment of panic disorder can be initiated in the hospital along with treatment of the disorder that prompted hospitalization [I]. Rarely, hospitalization or partial hospitalization is required in very severe cases of panic disorder with agoraphobia when administration of outpatient treatment has been ineffective or is impractical [I]. Home visits are another treatment option for patients with severe agoraphobia who are limited in their ability to travel or leave the house [II]. When accessibility to mental health care is limited (e.g., in remote or underserved areas), telephone- or Internet-based treatments may be considered [II].
Choosing an Initial Treatment Modality
A range of specific psychosocial and pharmacological interventions have proven benefits in treating panic disorder. The use of a selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), benzodiazepine (appropriate as monotherapy only in the absence of a co-occurring mood disorder), or cognitive-behavioral therapy (CBT) as the initial treatment for panic disorder is strongly supported by demonstrated efficacy in numerous randomized controlled trials [I]. A particular form of psychodynamic psychotherapy, panic-focused psychodynamic psychotherapy (PFPP), was effective in one randomized controlled trial and could be offered as an initial treatment under certain circumstances [II].
There is insufficient evidence to recommend any of these pharmacological or psychosocial interventions as superior to the others, or to routinely recommend a combination of treatments over monotherapy [II]. Although combination treatment does not appear to be significantly superior to standard monotherapy as initial treatment for most individuals with panic disorder, psychiatrists and patients may choose this option based on individual circumstances (e.g., patient preference) [II].
Considerations that guide the choice of an initial treatment modality include patient preference, the risks and benefits for the particular patient, the patient's past treatment history, the presence of co-occurring general medical and other psychiatric conditions, cost, and treatment availability [I]. Psychosocial treatment (with the strongest evidence available for CBT) is recommended for patients who prefer nonmedication treatment and can invest the time and effort required to attend weekly sessions and complete between-session practices [I]. One caveat is that CBT and other specialized psychosocial treatments are not readily available in some geographic areas. Pharmacotherapy (usually with an SSRI or serotonin-norepinephrine reuptake inhibitor [SNRI]) is recommended for patients who prefer this modality or who do not have sufficient time or other resources to engage in psychosocial treatment [I]. Combined treatment should be considered for patients who have failed to respond to standard monotherapies and may also be used under certain clinical circumstances (e.g., using pharmacotherapy for temporary control of severe symptoms that are impeding the patient's ability to engage in psychosocial treatment) [II]. Adding psychosocial treatment to pharmacotherapy either from the start, or at some later point in treatment, may enhance long-term outcomes by reducing the likelihood of relapse when pharmacological treatment is stopped [II].
Evaluating Whether the Treatment Is Working
After treatment is initiated, it is important to monitor change in key symptoms such as frequency and intensity of panic attacks, level of anticipatory anxiety, degree of agoraphobic avoidance, and severity of interference and distress related to panic disorder [I]. Effective treatment should produce a decrease in each of these domains, although some may change more quickly than others. The severity of co-occurring conditions also should be assessed at regular intervals, as treatment of panic disorder can influence co-occurring conditions (e.g., major depression; other anxiety disorders) [I]. Rating scales are a useful adjunct to ongoing clinical assessment for the purpose of evaluating treatment outcome [I].
Determining If and When to Change Treatment
Some individuals do not respond, or respond incompletely, to first-line treatments for panic disorder. Whenever treatment response is unsatisfactory, the psychiatrist should first consider the possible contribution of fundamental clinical factors such as an underlying untreated medical illness that accounts for the symptoms, interference by co-occurring general medical or psychiatric conditions (including depression and substance use), inadequate treatment adherence, problems in the therapeutic alliance, the presence of psychosocial stressors, motivational factors, and inability to tolerate a particular treatment [I]. These potential impediments to successful treatment should be addressed as early as possible in treatment [I]. In addition, if panic-related concerns are leading the patient to minimize the impact of avoidance or accept functional limitations, the patient should be encouraged to think through the costs and benefits of accepting versus treating functional limitations [I]. Clinicians should be reluctant to accept partial improvement as a satisfactory outcome and should aim for remission whenever feasible [I].
If response to treatment remains unsatisfactory, and if an adequate trial has been attempted, it is appropriate for the psychiatrist and the patient to consider a change [I]. Decisions about whether and how to make changes will depend on the level of response to the initial treatment (i.e., none versus partial), the palatability and feasibility of other treatment options for a given patient, and the level of symptoms and impairment that remain [I]. Persistent significant symptoms of panic disorder despite a lengthy course of a particular treatment should trigger a reassessment of the treatment plan, including possible consultation with another qualified professional [I].
Approaches to Try When a First-Line Treatment Is Unsuccessful
If fundamental clinical issues have been addressed and it is determined that a change is desirable, the psychiatrist and patient can either augment the current treatment by adding another agent (in the case of pharmacotherapy) or another modality (i.e., add CBT if the patient is already receiving pharmacotherapy, or add pharmacotherapy if the patient is already receiving CBT) [I], or they can decide to switch to a different medication or therapeutic modality [I]. Decisions about how to address treatment resistance are usually highly individualized and based on clinical judgment, since few studies have tested the effects of specific switching or augmentation strategies. However, augmentation is generally a reasonable approach if some significant benefits were observed with the original treatment [II]. On the other hand, if the original treatment failed to provide any significant alleviation of the patient's symptoms, a switch in treatment may be more useful [II].
If one first-line treatment (e.g., CBT, an SSRI, an SNRI) has failed, adding or switching to another first-line treatment is recommended [I]. Adding a benzodiazepine to an antidepressant is a common augmentation strategy to target residual symptoms [II]. If the treatment options with the most robust evidence have been unsuccessful, other options with some empirical support can be considered (e.g., a monoamine oxidase inhibitor [MAOI], panic-focused psychodynamic psychotherapy) [II]. After first- and second-line treatments and augmentation strategies have been exhausted (either due to lack of efficacy or intolerance of the treatment by the patient), less well-supported treatment strategies may be considered [III]. These include monotherapy or augmentation with gabapentin or a second-generation antipsychotic or with a psychotherapeutic intervention other than CBT or panic-focused psychodynamic psychotherapy [III]. Psychiatrists are encouraged to seek consultation from experienced colleagues when developing treatment plans for patients whose symptoms have been resistant to standard treatments for panic disorder [I].
Specific Psychosocial Interventions
Psychosocial treatments for panic disorder should be conducted by professionals with an appropriate level of training and experience in the relevant approach [I]. Based on the current available evidence, CBT is the psychosocial treatment that would be indicated most often for patients presenting with panic disorder [I]. Cognitive-behavioral therapy is a time-limited treatment (generally 10–15 weekly sessions) with durable effects. It can be successfully administered individually or in a group format [I]. Self-directed forms of CBT may be useful for patients who do not have ready access to a trained CBT therapist [II]. Cognitive-behavioral therapy for panic disorder generally includes psychoeducation, self-monitoring, countering anxious beliefs, exposure to fear cues, modification of anxiety-maintaining behaviors, and relapse prevention [I]. Exposure therapy, which focuses almost exclusively on systematic exposure to fear cues, is also effective [I].
Panic-focused psychodynamic psychotherapy also has demonstrated efficacy for panic disorder, although its evidence base is more limited. Panic-focused psychodynamic psychotherapy may be indicated as an initial psychosocial treatment in some cases (e.g., patient preference) [II]. Panic-focused psychodynamic psychotherapy is a time-limited treatment (twice weekly for 12 weeks) that is administered on an individual basis. Panic-focused psychodynamic psychotherapy utilizes the general principles of psychodynamic psychotherapy, with special focus on the transference as the therapeutic agent promoting change, and encourages patients to confront the emotional significance of their panic symptoms with the aim of promoting greater autonomy, symptom relief, and improved functioning. Although psychodynamic psychotherapies (other than panic-focused psychodynamic psychotherapy) that focus more broadly on emotional and interpersonal issues have not been formally tested for panic disorder, some case report data and clinical experience suggest this approach may be useful for some patients [III].
Other psychosocial treatments have not been formally tested for panic disorder or have proven ineffective (e.g., eye movement desensitization and reprocessing [EMDR]) or inferior to standard treatments such as CBT (e.g., supportive psychotherapy).
Group CBT is effective and can be recommended for treatment of panic disorder [I]. Other group therapies (including patient support groups) are not recommended as monotherapies for panic disorder, although they may be useful adjuncts to other effective treatments for some patients [III].
Couples or family therapy alone is not recommended as a treatment for panic disorder, although it may be helpful in addressing co-occurring relationship dysfunction [III]. It can be beneficial to include significant others in CBT (e.g., partner-assisted exposure therapy for agoraphobia), especially if they are educated in the cognitive-behavioral model of panic disorder and enlisted to help with between-session practices [II]. When pursuing other treatments for panic disorder (e.g., pharmacotherapy), education of significant others about the nature of the disorder and enlisting significant others to improve treatment adherence may also be helpful [III].
Specific Pharmacological Interventions
Selective serotonin reuptake inhibitors, SNRIs, tricyclic antidepressants (TCAs), and benzodiazepines have demonstrated efficacy in numerous controlled trials and are recommended for treatment of panic disorder [I]. Monoamine oxidase inhibitors appear effective for panic disorder but, because of their safety profile, they are generally reserved for patients who have failed to respond to several first-line treatments [II]. Other medications with less empirical support (e.g., mirtazapine, anticonvulsants such as gabapentin) may be considered as monotherapies or adjunctive treatments for panic disorder when patients have failed to respond to several standard treatments or based on other individual circumstances [III].
Because SSRIs, SNRIs, TCAs, and benzodiazepines appear roughly comparable in their efficacy for panic disorder, selecting a medication for a particular patient mainly involves considerations of side effects (including any applicable warnings from the U.S. Food and Drug Administration [FDA]), cost, pharmacological properties, potential drug interactions, prior treatment history, co-occurring general medical and psychiatric conditions, and the strength of the evidence base for the particular medication in treatment of panic disorder [I]. The relatively favorable safety and side effect profile of SSRIs and SNRIs makes them the best initial choice for many patients with panic disorder [I]. Although TCAs are effective, the side effects and greater toxicity in overdose associated with them often limit their acceptability to patients and their clinical utility. Selective serotonin reuptake inhibitors, SNRIs, and TCAs are all preferable to benzodiazepines as monotherapies for patients with co-occurring depression or substance use disorders [I]. Benzodiazepines may be especially useful adjunctively with antidepressants to treat residual anxiety symptoms [II]. Benzodiazepines may be preferred (as monotherapies or in combination with antidepressants) for patients with very distressing or impairing symptoms in whom rapid symptom control is critical [II]. The benefit of more rapid response to benzodiazepines must be balanced against the possibilities of troublesome side effects (e.g., sedation) and physiological dependence that may lead to difficulty discontinuing the medication [I].
Patients should be educated about the likely time course of treatment effects associated with a particular medication [I]. Because patients with panic disorder can be sensitive to medication side effects, low starting doses of SSRIs, SNRIs, and TCAs (approximately half of the starting doses given to depressed patients) are recommended [I]. The low dose is maintained for several days then gradually increased to a full therapeutic dose over subsequent days and as tolerated by the patient [I]. Underdosing of antidepressants (i.e., starting low and then not increasing gradually to full therapeutic dosages as needed) is common in treatment of panic disorder and is a frequent source of partial response or nonresponse [II]. A regular dosing schedule rather than a p.r.n. ("as needed") schedule is preferred for patients with panic disorder who are taking benzodiazepines [II], where the goal is to prevent panic attacks rather than reduce symptoms once an attack has already occurred.
Once an initial pharmacotherapy has been selected, patients are typically seen every 1–2 weeks when first starting a new medication, then every 2–4 weeks until the dose is stabilized [I]. After the dose is stabilized and symptoms have decreased, patients will most likely require less frequent visits [I].
When considering any specific medication, the psychiatrist must balance the risks associated with the medication against the clinical need for pharmacotherapy [I]. The Food and Drug Administration has warned of the possibility that antidepressants may increase the risk of suicidal ideation and behavior in patients age 25 years and younger; this is an important factor to consider before using an SSRI, an SNRI, or a TCA for panic disorder. Other important safety considerations for SSRIs include possible increased likelihood of upper gastrointestinal bleeding (particularly when taken in combination with non-steroidal anti-inflammatory drugs [NSAIDs] or with aspirin) and increased risk of falls and osteoporotic fractures in patients age 50 years and older. With venlafaxine extended release (ER), a small proportion of patients may develop sustained hypertension. It is recommended that psychiatrists assess blood pressure during treatment, particularly when venlafaxine extended release is titrated to higher doses [I].
Tricyclic antidepressants should not be prescribed for patients with panic disorder who also have acute narrow-angle glaucoma or clinically significant prostatic hypertrophy. Tricyclic antidepressants may increase the likelihood of falls, particularly among elderly patients. A baseline electrocardiogram should be considered before initiating a TCA, because patients with preexisting cardiac conduction abnormalities may experience significant or fatal arrhythmia with TCA treatment. Overdoses with TCAs can lead to significant cardiac toxicity and fatality, and therefore TCAs should be used judiciously in suicidal patients.
Benzodiazepines may produce sedation, fatigue, ataxia, slurred speech, memory impairment, and weakness. Geriatric patients taking benzodiazepines may be at higher risk for falls and fractures. Because of an increased risk of motor vehicle accidents with benzodiazepine use, patients should be warned about driving or operating heavy machinery while taking benzodiazepines [I]. Patients should also be advised about the additive effects of benzodiazepines and alcohol [I]. Caution and careful monitoring is indicated when prescribing benzodiazepines to elderly patients, those with preexisting cognitive impairment, or those with a history of substance use disorder [I].
For women with panic disorder who are pregnant, nursing, or planning to become pregnant, psychosocial interventions should be considered in lieu of pharmacotherapy [II]. Pharmacotherapy may also be indicated [III] but requires weighing and discussion of the potential benefits and risks with the patient, her obstetrician, and, whenever possible, her partner [I]. Such discussions should also consider the potential risks to the patient and the child of untreated psychiatric illness, including panic disorder and any co-occurring psychiatric conditions [I].
Maintaining or Discontinuing Treatment After Response
Pharmacotherapy should generally be continued for 1 year or more after acute response to promote further symptom reduction and decrease risk of recurrence [I]. Incorporating maintenance treatment (e.g., monthly "booster" sessions focused on relapse prevention) into psychosocial treatments for panic disorder also may help maintain positive response [II], although more systematic investigation of this issue is needed.
Before advising a taper of effective pharmacotherapy, the psychiatrist should consider several factors, including the duration of the patient's symptom stability, the presence of current or impending psychosocial stressors in the patient's life, and the extent to which the patient is motivated to discontinue the medication [II]. Discussion of medication taper should also include the possible outcomes of taper, which could include discontinuation symptoms and recurrence of panic symptoms [I]. If medication is tapered, it should be done in a collaborative manner with continual assessment of the effects of the taper and the patient's responses to any changes that emerge [I].
If a decision is made to discontinue successful treatment with an SSRI, an SNRI, or a TCA, the medication should be gradually tapered (e.g., one dosage step down every month or two), thereby providing the opportunity to watch for recurrence and, if desired, to reinitiate treatment at a previously effective dose [II]. However, under more urgent conditions (e.g., the patient is pregnant and the decision is made to discontinue medications immediately), these medications can be discontinued much more quickly [I].
The approach to benzodiazepine discontinuation also involves a slow and gradual tapering of dose [I]. Withdrawal symptoms and symptomatic rebound are commonly seen with benzodiazepine discontinuation, can occur throughout the taper, and may be especially severe toward the end of the taper. This argues for tapering benzodiazepines very slowly for patients with panic disorder, probably over 2–4 months and at rates no higher than 10% of the dose per week [I]. Cognitive-behavioral therapy may be added to facilitate withdrawal from benzodiazepines [I].
Grading of Recommendations
[I] Recommended with substantial clinical confidence
[II] Recommended with moderate clinical confidence
[III] May be recommended on the basis of individual circumstances