Sections

Treatment

Approach Considerations

All patients with panic disorder should be referred to a psychiatrist, psychologist, or other mental health professional. Psychiatric treatment has a demonstrated effect on decreasing medical costs associated with emergency department and nonpsychiatric outpatient care.^[32]Free information is available to patients and physicians from the National Institute of Mental Health (NIMH) and the National Alliance on Mental Illness (NAMI) (which has a separate section on panic disorder that may be useful for patients and their families).

Pharmacotherapy, cognitive- behavioral therapy (CBT), and other psychological treatment modalities are used to manage panic disorder. The American Psychiatric Association (APA) recommends treating patients with panic disorder when symptoms cause dysfunction (e.g., work, family, social, leisure activities) or significant distress.^[55]Treatment goals include the following^[55]:

Tailoring the treatment plan to each individual
Reducing frequency and intensity of panic attacks
Reducing anticipatory anxiety and agoraphobic avoidance
Treating co-occurring psychiatric disorders
Achieving full symptomatic remission
Returning to premorbid level of function

For more information, see the Medscape Reference topics Anxiety Disorders; Separation Anxiety and School Refusal; and Phobic Disorders.

Cognitive-behavioral therapy

Psychotherapy is recommended for patients with panic disorder who prefer nonpharmacologic management and who are able and willing to take the time and effort to participate in weekly (or sometimes alternate weekly) sessions and between-session practices.^[55]The strongest available evidence is for CBT.^{[55, 56]}

CBT, with or without pharmacotherapy, is the treatment of choice for panic disorder, and it should be considered for all patients.^[33]This therapeutic modality has higher efficacy and lower cost, dropout rates, and relapse rates than do pharmacologic treatments. CBT may include countering anxious beliefs, exposure to fear cues, changing anxiety-maintaining behaviors, and preventing relapse.^[55]

It is important to identify the frequency and nature of the panic disorder symptoms as well as the triggers of panic symptoms for effective management.^[55]The patient’s symptomatic status should be monitored at each session, such as with the use of rating scales, and patients can also self-monitor by keeping a daily diary of panic symptoms.^[55]

Pharmacologic management

Providing a few doses of a benzodiazepine as needed (prn) can enhance patient confidence and compliance. Limit the total tablet dispensation to ensure that patients understand that they have a limited supply of the drug and that this medicine represents a temporary or emergency use option.

Educate the patient regarding the importance of longer-term management with selective serotonin reuptake inhibitor (SSRI) medication and psychotherapeutic techniques (e.g., CBT). Avoid prescribing benzodiazepine in patients with a known history of substance misuse or alcoholism.

Inpatient vs outpatient care

Outpatient care is the general setting for uncomplicated panic disorder. Patients may be hospitalized if they display any evidence of dangerous behavior, have safety concerns, and/or report suicidal or homicidal ideation—as may occur in context of acute anxiety, fear of anxiety, or its consequences.

Considerations for admission include intoxication or withdrawal from sedative/hypnotics such as alcohol or alprazolam, which are sometimes ingested or abused in patients’ attempts to medicate or manage the anxiety. Patients may also be hospitalized if they become so incapacitated by their anxiety that they are unable to adhere to outpatient care. Inpatient treatment is also necessary in patients when the differential diagnosis includes other medical disorders that warrant admission (e.g., unstable angina, acute myocardial ischemia).

The APA recommends clinicians carefully assess the risk for suicide in patients with panic disorder as these individuals have an increased risk of suicidal ideation and behavior, regardless of whether comorbid conditions are present (e.g., major depression).^[55]

In rare cases of severe panic disorder in which outpatient management is ineffective or impractical, hospitalization or partial hospitalization may be necessary.^[55]Transfer to an acute psychiatric facility may be necessary for suicidal or homicidal patients.

Emergency Department Management

Patients with chest pain, dyspnea, palpitations, or near-syncope should be placed on oxygen and in a supine or Fowler position. Monitor the patients with pulse oximetry, electrocardiography (ECG), and frequent determination of vital signs (including one set of orthostatic vital signs, when possible).

A major component of therapy involves educating the patient that their symptoms are neither from a serious medical condition nor from a psychotic disorder, but rather from a chemical imbalance in the fight-or-flight response. This alone may account for the significant placebo response rate noted in clinical trials.^[34]

Patients with panic disorder may require frequent reassurance and explanation. Many may benefit from social service intervention, which may provide supportive discussions and explore resources for outpatient care. The emergency department staff must listen effectively and remain empathic and nonargumentative. Statements made by healthcare staff, such as, "It's nothing serious" and "It's related to stress" are frequently misinterpreted by the patient as implying a lack of understanding and concern.

Instituting treatment for panic disorder in the emergency department is appropriate in a very limited subset of patients who are highly motivated and cooperative, who possess an understanding of the psychological nature of their disorder, and whose symptomatology is elicited as a response to a temporary stress. In such cases, pharmacotherapy with an oral benzodiazepine for a brief duration (approximately 1 wk) may be appropriate.

Intravenous (IV) medication (e.g., lorazepam at 0.5 mg IV q20min) may be necessary in patients with panic disorder who, as a result of subsequent poor impulse control, pose a risk to themselves or to those around them. However, patients with panic disorder are probably best served by referral to a psychiatrist before beginning anxiolytic medications. A psychiatrist can establish a constructive rapport with patients and follow their needs on a long-term basis.

Cognitive-Behavioral Therapy

Cognitive-behavioral therapy (CBT) helps patients to understand how automatic thoughts and false beliefs/distortions lead to exaggerated emotional responses, such as anxiety, and how they can lead to secondary behavioral consequences. CBT can be used alone or in addition to pharmacotherapy. However, the combination approach yields superior results for most patients, compared with results from the use of either modality alone,^{[33, 36]}by enhancing long-term outcomes through reduction in the likelihood of relapse when pharmacologic therapy is stopped.^[55]Combination therapy should be considered for patients in whom standard monotherapies have not been successful.^[55]

CBT is most effective when started early after symptom onset and in patients with few psychological comorbidities.^[38]Therapy is generally limited to 10-15 weekly sessions and can be conducted either individually or in a group.^[55]The National Collaborating Centre for Mental Health recommends CBT take the form of weekly sessions of 1-2 hours and be completed within a maximum of 4 months of commencement.^[56]

Cognitive restructuring involves substituting positive thoughts (e.g., patients can tell themselves that they are only feeling a little uneasiness or that their feelings will soon be gone) for the maladaptive thoughts that accompany panic (e.g., feeling that they are going to die or are having a heart attack).

Behavioral therapy involves sequentially greater exposure of the patient to anxiety-provoking stimuli. Over time, the patient becomes desensitized to the experience. Relaxation techniques also help to control patients' levels of anxiety.^{[37, 38]}

Data from 3 national epidemiologic surveys as well as the Cross-National Collaborative Panic Study suggest the existence of 2 subtypes of panic disorder, respiratory and nonrespiratory.^[58]The nonrespiratory subtype was typified by general somatic symptoms, whereas the respiratory subtype was not only thought to be a more severe form of the disorder but also associated with a significantly greater likelihood of lifetime major depression.^[58]

Respiratory training can help patients to control hyperventilation during panic attacks and to control anxiety with controlled breathing. In addition, capnometry feedback-assisted breathing training can be used to prevent hypocapnia and stabilize the respiratory rate.

Interoceptive exposure involves encouraging patients to induce internal sensations (e.g., dizziness, increased heart rate, lightheadedness) by spinning, exercising, or rapid breathing and to interpret these as normal bodily sensations. Guided imagery and hypnotic suggestion may also be beneficial.

Pharmacotherapy

The American Psychiatric Association (APA) found insufficient evidence to either recommend any pharmacologic intervention as superior to others for panic disorder or to routinely recommend combination therapy over monotherapy.^[55]However, pharmacotherapy is recommended for patients who prefer to be managed with medication or those who don’t have the time or other resources to participate in psychosocial therapy.^[55]Keep in mind that patients with panic disorder are twice as likely as the population to use alternative therapies. The use of dietary supplements (e.g., herbs) should be discussed to avoid drug interactions.

It is important to inform patients of the potential adverse effects of specific pharmacotherapies, as well as a realistic time frame for expecting results and the likely duration of treatment.^{[55, 56]}

SSRIs and TCAs

Selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, escitalopram, fluoxetine, sertraline, paroxetine and paroxetine controlled release, fluvoxamine) are generally used as first-line pharmacologic agents in panic disorder, followed remotely by tricyclic antidepressant agents (TCAs) (e.g., imipramine, desipramine, nortriptyline, clomipramine).^{[55, 56]}

The National Collaborating Centre for Mental Health practice guidelines indicate that TCAs such as imipramine or clomipramine may be considered for the management of panic disorder if an SSRI is not suitable or if there is no improvement after a 12-week course of SSRI treatment.^[56](Prior to the use of SSRIs for panic disorder, the TCAs and the monoamine oxidase inhibitors [MAOIs] were used much more commonly for this condition.) In addition to SSRIs, the APA reported that there is strong support from randomized controlled trials for the effective use of serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., venlafaxine, duloxetine) as the initial treatment of panic disorder.^[55]

Citalopram (Celexa) and escitalopram (Lexapro) are likely to cause fewer hepatic enzyme interactions than other SSRIs and may be appropriate initial choices for patients with complicated medical regimens or for those who are concerned about drug interactions.

However, the FDA issued a Drug Safety Communication in August 2011 stating that citalopram (Celexa) should not be used at doses greater than 40 mg per day, owing to the potential for dangerous abnormalities in cardiac electrical activity.^[57]Citalopram 20 mg per day is the maximum recommended dose in patients with hepatic impairment, who are older than 50 years, who are CYP 2C19 poor metabolizers, or who are taking concomitant cimetidine (Tagamet) or another CYP 2C19 inhibitor. Such individuals can have higher blood levels of citalopram, leading them to have an increased risk of prolonged QT interval and torsade de pointes.^[57]

Additional warnings as of March 2012 discourage the use of citalopram at any dose in patients with certain conditions (congenital long QT syndrome, bradycardia, hypokalemia, hypomagnesemia, recent acute myocardial infarction, uncompensated heart failure) due to potentially dangerous prolongation of the QT interval.^[57]

Escitalopram seems to be well tolerated in preliminary studies, but costs more than citalopram and does not appear to offer any significant advantage. Fluoxetine (Prozac) can be used, especially if panic disorder occurs with depression. Patients may have poor tolerance for it at the start because the drug may initially increase anxiety, except at very low starting doses. Fluoxetine has a long half-life, making it a good choice in marginally compliant patients. However, this agent alters the metabolism of cytochrome P-450 2D6-cleared agents.

Sertraline (Zoloft) represents a similar SSRI option with a slightly different pharmacodynamic profile, including sigma-receptor effects, although it has some P450 3A4 interactions.

Paroxetine (Paxil), mirtazapine, and TCAs are usually prescribed for use before bedtime to help improve sleep. Caution patients to avoid operating a motor vehicle or machinery directly after the dose or if they are feeling sedated.

Paroxetine is also available in a controlled release preparation (Paxil CR), which may improve tolerability, but it still inhibits P450 2D6. Paroxetine is a category D drug during pregnancy (ie, human studies have shown a risk to the fetus, but the drug’s benefits may outweigh the risk in pregnant women). Use of this medication requires patient counseling as well as documentation of the potential risks in women of reproductive age.

Mirtazapine (Remeron), a noradrenergic and specific serotonergic antidepressant (NaSSA), has a much more sedating effect, generally reducing its potential to aggravate initial anxiety.^[35]Mirtazapine acts distinctly as an alpha-2 antagonist, consequently increasing synaptic norepinephrine and serotonin, while it also blocks some postsynaptic serotonergic receptors that conceptually mediate excessive anxiety when stimulated with serotonin. Note that mirtazapine may cause residual morning sedation that often improves with continued therapy, and it may also cause an increase in appetite or weight gain.

Most patients are started on long-term (e.g., 6 mo) therapy with SSRIs, TCAs, or MAOIs only after consultation with their primary physician or psychiatrist.

Benzodiazepines

Benzodiazepines (e.g., alprazolam, clonazepam, lorazepam) can achieve long-term control of panic disorder, but these agents should be reserved for patients with refractory panic disorder. Patients started on benzodiazepines for panic disorder should receive a psychiatric referral for review of pharmacologic management and, potentially, a psychotherapist for any additional nonpharmacologic treatment options. Benzodiazepines should not be used as monotherapy in panic disorder unless there is no co-occurring mood disorder.^[55]

Benzodiazepines act quickly but carry the liability of physiologic and psychological dependence. Benzodiazepines can be reasonably used as an initial adjunct while SSRIs are titrated to an effective dose; that is, these agents can then be tapered over 4-12 weeks while the SSRI is continued. This approach can improve short-term tolerability, although it may increase the risk of sedation and requires warnings for the patient to not operate motor vehicles after taking benzodiazepines or if they’re feeling sedated.

Alprazolam (Xanax) has been widely used for panic disorder, but its use is currently discouraged because of its higher abuse/dependence potential. This agent has a short half-life, which makes it particularly prone to rebound anxiety and psychological dependence. Clonazepam (Klonopin) has become a favored replacement, because it has a longer half-life and empirically elicits fewer withdrawal reactions upon discontinuation relative to alprazolam.

Complications of benzodiazepine use

Because panic disorder is usually a chronic disorder, sole reliance on habituating drugs is discouraged. Benzodiazepine dependence can occur in 30% of patients who are on therapy that lasts longer than 8 weeks.^[30]It is less likely to occur in patients without a history of chemical or emotional dependence. Benzodiazepine abuse is suggested by escalating dose consumption over time.

Note that benzodiazepine withdrawal can precipitate panic. The primary physician should gradually taper doses over several weeks or months.

Evaluating Treatment Efficacy and Changes in Treatment Strategy

Treatment is working if the patient’s key symptoms (e.g., frequency/intensity of panic attacks, level of anticipatory anxiety, degree of agoraphobic avoidance, severity of functional interference and distress related to the disorder) decrease.^[55]Be aware that changes may occur more quickly in some domains than others.

Regularly evaluate the severity of any co-occurring psychiatric conditions, such as major depression and other anxiety disorders. Useful adjunctive tools for evaluating treatment outcome include rating scales on an ongoing basis.^[55]

First-line treatments for panic disorder may result in a partial response or no response. In such cases, reevaluate the patient as early as possible for any untreated underlying medical conditions that could cause the patient’s symptoms, as well as the presence of any co-occurring general medical or psychiatric conditions (e.g., depression, substance abuse), treatment noncompliance, problems with the collaboration between therapist and patient, psychosocial stressors, motivational factors, and treatment intolerance.^{[55, 56]}Clinicians goals should be toward remission whenever feasible, rather than accepting partial improvements as satisfactory outcomes.

Consider a change in treatment strategy when the treatment outcome remains unsatisfactory despite an adequate trial, particularly when significant panic symptoms persist despite a long course of a specific treatment.^{[55, 56]}The types of changes must be personalized for each individual.

If, after any key clinical issues have been addressed, and a change in treatment is still desired: (1) The current treatment strategy can be augmented with either another medication or treatment modality, if some significant benefits were noted with the current treatment, or (2) the patient can switch to another treatment strategy with different drug or modality, if the initial therapy did not provide any significant relief of the patient’s symptoms.^[55]

The following are some recommendations from the American Psychiatric Association (APA)^[55]:

Add or switch to another first-line treatment, if one first-line treatment (e.g., cognitive behavioral therapy [CBT], a selective serotonin reuptake inhibitor [SSRI], a serotonin-norepinephrine reuptake inhibitor [SNRI]) was unsuccessful
Augment an antidepressant by adding a benzodiazepine to target residual symptoms
Consider alternatives with some empirical support (e.g., monoamine oxidase inhibitors [MAOIs], panic-focused psychodynamic psychotherapy [PFPP]) or less well-supported alternative therapies (monotherapy/augmentation with gabapentin or second-generation antipsychotic or with a psychotherapeutic modality other than CBT or PFPP) when standard treatment strategies have been ineffective or when first- and second-line treatment and augmentation strategies have failed
Consult with psychiatrists experienced in treating patients with refractory/resistant panic disorder

In general, pharmacologic management is continued for at least 1 year following an acute response to increase the potential for further reductions in the patient’s panic symptoms as well as to lower the risk for recurrence.^[55]Monthly “booster” sessions that target prevention of relapse may also be used.^[55]

The decision to taper or discontinue an effective pharmacotherapy must be tailored to the patient and discussed between the patient and clinician, based upon factors including the duration of the patient’s symptom stability, whether current/impeding psychosocial stressors are present, the extent of the patient’s motivation, as well as the potential outcomes following medication taper or discontinuation.^{[55, 56]}

Prevention Measures

Despite the effectiveness of standard management for panic disorder in a majority of affected patients, some individuals with good treatment responses may have persistent or recurrent symptoms following remission.^[55]Symptomatic fluctuations are not uncommon during treatment and symptoms may recur following remission. Provide patients with response plans in such situations.^[55]

Cognitive-behavioral therapy (CBT) with cognitive restructuring, relaxation techniques, breathing exercises, hypnotic suggestion, and interoceptive exposure may prevent recurrence. Pharmacotherapy and dietary modification (e.g., 5-hydroxytryptophan or inositol supplementation^[38]) may also prevent recurrence, as may exercise.^[39]

A study suggested that patients who give a high importance to religion and religious practices have improved panic symptoms and fewer recurrences.^[40]Internet-based CBT and virtual reality exposure therapy are promising possibilities for recurrence prevention.^[41]

Treatment Difficulties

Patients with panic disorder are reluctant to believe their symptoms are not life-threatening and have a high rate of emergency department use. Moreover, because of a reluctance to use medications (related to a fear of losing control), patients with panic disorder are frequently noncompliant. Psychiatrists need to not only assess and identify potential barriers to treatment compliance but also work with the patient to minimize or overcome these roadblocks.^[55]

Patients with panic disorder also have a 4-fold increase in the risk of adverse medication effects, which can result in noncompliance and temporarily increased anxiety. Psychiatrists should encourage patients to discuss such concerns as well as provide realistic expectations at various points in their treatment.^[55]

Consultations

Refer all patients with panic disorder for psychiatric or mental health follow-up care and to support groups. Consult a cardiologist for patients with abnormal electrocardiogram (ECG) findings, ventricular dysrhythmia, abnormal cardiac examination, or risk factors for ischemic heart disease,^[26]and consult an addiction treatment specialist in cases of significant intoxication or withdrawal.

Long-Term Monitoring

Initial follow-up care should occur within 2 weeks, because selective serotonin reuptake inhibitors (SSRIs) can cause an initial exacerbation of panic symptoms. For this reason, begin with the lowest dose—with the understanding that the dose must be increased at the initial follow-up visit.

Assess potential suicide risk at all appointments. Ensure continuing treatment of any concurrent substance use disorders. Follow-up care by a chemical dependence treatment specialist is recommended when indicated.

Patients with ventricular dysrhythmias, abnormal findings on electrocardiography (ECG), abnormal findings on cardiac examination, or significant risk factors for heart disease should be referred to a cardiologist.^[23]

Medication

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Author

Mohammed A Memon, MD Psychiatrist/Geriatric Psychiatrist, Carolina Center for Behavioral Health; Assistant Professor of Psychiatry, Virginia Commonwealth University School of Medicine

Mohammed A Memon, MD is a member of the following medical societies: American Association for Geriatric Psychiatry, American Medical Association, American Psychiatric Association

Disclosure: Nothing to disclose.

Chief Editor

Randon S Welton, MD Associate Professor of Psychiatry, Director of Residency Training, Department of Psychiatry, Wright State University, Boonshoft School of Medicine

Randon S Welton, MD is a member of the following medical societies: American Association of Directors of Psychiatric Residency Training, American Psychiatric Association, Dayton Psychiatric Association, Ohio Psychiatric Physicians Association

Disclosure: Nothing to disclose.

Acknowledgements

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine