Panic Disorder

Introduction

 Background

Panic  disorder is characterized by the spontaneous and unexpected
occurrence  of panic attacks, the frequency of which can vary from
several  attacks per day to only a few attacks per year. Panic attacks
can occur  in other anxiety disorders but occur without discernible
predictable  precipitant in panic disorder.
To meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)¹ criteria
 for panic disorder, panic attacks must be associated with more than 1
month of subsequent persistent worry about (1) having another attack,  
(2) consequences of the attack, or (3) significant behavioral changes  
related to the attack.
Panic attacks are a period of intense fear  in which 4 of 13 defined
symptoms develop abruptly and peak rapidly less  than 10 minutes from
symptom onset. To make the diagnosis of panic  disorder, panic attacks
cannot directly or physiologically result from  substance use, medical
conditions, or another psychiatric disorder.
The DSM-IV-TR delineates the following potential symptom manifestations of a panic attack:

• Palpitations, pounding heart, or accelerated heart rate
  
• Sweating
  
• Trembling or shaking
  
• Sense of shortness of breath or smothering
  
• Feeling of choking
  
• Chest pain or discomfort
  
• Nausea or abdominal distress
  
• Feeling dizzy, unsteady, lightheaded, or faint
  
• Derealization or depersonalization (feeling detached from oneself)
  
• Fear of losing control or going crazy
  
• Fear of dying
  
• Numbness or tingling sensations
  
• Chills or hot flashes
  

Panic  disorder is usually qualified with the presence or absence
of  agoraphobia. Agoraphobia is defined as anxiety toward places or  
situations in which escape may be difficult or embarrassing. These  
anxiety-provoking situations are avoided or are endured with anxiety.  
(Note: Agoraphobia is not a stand-alone disorder; it is a descriptive  
term [eg, panic disorder with agoraphobia.])

Case study
A  22-year-old single female without past medical history or prior  
psychiatric care presents to the Emergency Department complaining of a 3
 year history of episodic anxiety, increasing over the last 6 months  
with an acute episode of anxiety this evening. She recollects anxiety  
attacks beginning around age 19, while working as a waitress after high
school. She describes the anxiety episodes as sudden episodes of
anxiety  with dizziness, abdominal distress, and fear of losing control,
which  would self resolve after 5-10 minutes in the break room or
walk-in  refrigerator. The anxiety attacks occurred infrequently (<1
per month  initially) and she did not seek any care because she had no
medical  insurance.

The woman cites the frequency and severity of these  unexpected attacks
increasing over the next 3 years. For the past 6  months, she reports
experiencing sudden episodes of anxiety 2-3 times  per week, which can
occur at work or at home, although they occur more  frequently at work
or when anticipating going to work or other social  functions in crowded
public places. She describes these episodes now as  acute attacks with a
sense of impending loss of control, palpitations,  shortness of breath,
chest tightness, dizziness, and hot flashes. She  affirms significant
worry about when the next attack will occur and  concedes missing work
when calling in sick and having her supervisor  send her home early due
to observed distress.

The woman denies  noting any specific triggers for her anxiety and
denies any recreational  drug use. She relates limited social alcohol
consumption (1-2 times per  week with 1-3 regular alcoholic drinks over
several hours), which she  notes seems to reduce her severity of anxiety
attacks. She denies any  escalation of alcohol use, tolerance,
withdrawal, excessive time spent  drinking or recovering, or social or
occupational consequences of  alcohol use. She denies excessive worry
about routine stressors and  denies any prior history of traumatic
events. She denies any sustained  depressed mood, manic symptoms,
psychotic symptoms, or  interpersonal/relational problems. She denies
any suicidal or homicidal  ideations, or history of self-injurious
behavior and reports future plan  to begin study at the local college
for business administration if she  can control her anxiety and avoid
losing her employment.    
Pathophysiology

Many  non–mutually exclusive theories and proposed  
abnormalities/inefficiencies in molecular signal processing in specific
neuronal regions or neurotransmitter pathways have recently been  
investigated to explain panic disorder (from a biologic perspective) in
response to the observed efficacy of certain pharmacologic agents for  
controlling the symptoms or from observations of investigational  
functional neuroimaging.

• The serotonergic  model suggests an exaggerated or inefficient
  postsynaptic receptor  response to synaptic serotonin, potentially in
  the signal transduction  cascade. Some studies report subsensitivity of
  5HT1A receptors. The 5HT  system or one of its subsystems may play a
  role in the pathophysiology  of panic disorder, the precise nature of
  which must be delineated by  further investigation.
  
• The catecholamine model postulates  increased sensitivity to or
  improper processing of adrenergic CNS  dischar
  

Related Subjects
Phobias (Diseases and Disorders)
USMLE Step 2 CK - Video Lectures From Doctors in Training - Psychiatry
Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (Synopsis of Psychiatry)
The Maudsley Prescribing Guidelines, Tenth Edition
Clinical Manual for the Psychiatric Interview of Children and Adolescents
CURRENT Diagnosis And Treatment Psychiatry, Second Edition (LANGE CURRENT Series)
New Oxford Textbook of Psychiatry (2 Volume Set)

Other Problems to Be Considered

Acute stress/posttraumatic stress disorder
Adrenal dysfunction
Alcohol/sedative-hypnotic withdrawal
Drug intoxication
Generalized anxiety disorder
Hyperthyroidism
Pulmonary disease
Temporal lobe seizure activity
Vestibular dysfunction
Workup

Laboratory Studies

No laboratory parameters are specific for panic disorder. Laboratory
evaluation is performed to exclude any of the aforementioned
differential diagnoses.
Imaging Studies

No imaging study findings are currently specific for panic disorder,
although they are performed to evaluate anatomic evidence of other
diagnostic possibilities. Studies may include an EEG to exclude partial
complex seizures. Investigational functional neuroimaging is not used
in routine clinical practice for diagnosis or for monitoring treatment
response.


Procedures

No invasive procedures are required to diagnose panic disorder,
although they may be useful in eliminating other differential
diagnoses. History, collateral information, and physical/Mental Status
Examinations remain the diagnostic cornerstones.

Treatment

Medical Care

Pharmacotherapy, cognitive and behavioral psychotherapy, and other
psychological treatment modalities are used to treat panic disorder.
Pharmacotherapy
Selective serotonin reuptake inhibitors (SSRIs) are generally used as
first-line agents, followed remotely by tricyclics. Benzodiazepines can
achieve long-term control but should be reserved for patients with
refractory panic disorder and should generate a psychiatric referral
for pharmacologic management review and potentially a psychotherapist
for any additional nonpharmacologic treatment options.
Fluoxetine (Prozac) can be used (especially if panic disorder occurs
with depression); however, patients may poorly tolerate it initially
because it 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.

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

Sedating antidepressants like Paxil, Remeron, and TCAs are usually
prescribed only at night before bed to help improve sleep but should
include a warning not to operate a motor vehicle or machinery if
feeling sedated or directly after the dose. Prozac alters metabolism of
cytochrome P-450 2D6–cleared agents; this fact should be considered.
Paxil (paroxetine) represents a partially sedating SSRI option that is
also available in a controlled release preparation (Paxil CR), which
may improve tolerability, but Paxil still inhibits P450 2D6.
Citalopram (Celexa) and escitalopram (Lexapro) are likely to cause
fewer hepatic enzyme interactions and may be appropriate initial
choices for patients with complicated medical regimens or those who are
concerned about drug interactions. Escitalopram also appears
particularly well tolerated in preliminary studies, although it may be
restricted from some formularies due to the large difference in cost
with Celexa without a commensurate improvement in efficacy or
tolerability for many patients. Sertraline (Zoloft) represents a
similar SSRI option with a slightly different pharmacodynamic profile,
including sigma receptor effects, although it has some P450 3A4
interactions.
Benzodiazepines act quickly but carry the liability of physiologic and
psychologic dependence. Benzodiazepines can be reasonably used as an
initial adjunct while SSRIs are titrated to an effective dose.
Benzodiazepines then can 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 not to
operate motor vehicles after taking benzodiazepines or if feeling
sedated.
Alprazolam (Xanax) has been widely used for panic disorder, but it is
currently discouraged because of its higher dependence potential;
alprazolam 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.
Cognitive and behavioral psychotherapy
Cognitive and behavioral psychotherapy can be used alone or in addition
to pharmacotherapy. The combination approach yields superior results
for most patients compared to either single modality.
Cognitive therapy helps patients understand how automatic thoughts and
false beliefs/distortions lead to exaggerated emotional responses, such
as anxiety, and can lead to secondary behavioral consequences.
Specific patterns of cognitive distortions (twisted thoughts) tend to
respond best to specific techniques described in cognitive behavior
therapy books (eg, The Feeling Good Handbook by David Burns,
MD). While intended for use in conjunction with therapy, patients can
purchase these books and complete the course themselves.

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 control
patients' levels of anxiety. Respiratory training can help control
hyperventilation during panic attacks and help patients control anxiety
with controlled breathing. Other forms of psychological treatment,
including psychodynamic psychotherapy for specific issues, are available
but exceed the scope of this article.
Prehospital care

• Reassure and calm the patient.
  
• Transport the patient to a medical treatment facility to exclude
  medical causes for the first attack or when suspected on subsequent
  attacks.
  

Emergency department care

• Acute panic disorder is best treated with benzodiazepines. The
  natural history of panic attacks is spontaneous remission of panic
  symptoms with anxiety about recurrence during the episode.
  
• Prompt use of benzodiazepines can ease the uncomfortable anxiety
  associated with the attack and can provide the patient with definitive
  confidence that treatment can control the symptoms. This is
  particularly helpful for preventing subsequent visits to emergency
  services while longer-term therapy is helping the patient gain control.
  
• Consultation with a psychiatrist is helpful to initiate longer-term
  therapy and to provide follow-up planning. Longer-term therapy
  currently consists of SSRIs, often with additional psychotherapeutic
  techniques.
  

Medication

Benzodiazepine therapy should be provided if acute symptoms are still
present at the time of the interview or if significant apprehension
about future attacks remains. If necessary, benzodiazepines are
continued for a brief period (<2 wk if prescribed on a scheduled
basis).
Clonazepam has become the benzodiazepine of choice for outpatient use.
Selecting patients for whom benzodiazepine therapy will be helpful
rests on the clinician's judgment of a patient's ability to control his
or her symptoms in their native environment, until the next
psychiatric appointment, or until an SSRI begins to control the
symptoms (about 2 wk, although sometimes much longer as the SSRI may
require dose escalation). Alprazolam (Xanax) has been reviewed in the
literature, although its use is currently discouraged because of its
higher potential to elicit dependency.
Some patients may benefit from a standing dose of a benzodiazepine,
whereas others do better with an as-needed (prn) dosing regimen.
Longer-term control should be attempted with SSRIs if appropriate
follow-up care (including the PCM) is available. SSRIs are usually well
tolerated, and appropriate follow-up care merely consists of meeting
with the patient in 2 weeks to assess treatment efficacy and to deal
with temporary symptom exacerbations right after beginning SSRIs and
ensuring the patient has no emergence of suicidal thoughts.
Serotonergic drugs may contain warnings about potential increases in
suicidal thoughts, particularly in those younger than age 25 years, but
this is generally NOT associated with an increase in completed
suicides compared with patients who receive no treatment. Potential
suicide risk should be assessed routinely for every patient, whether
they take SSRI treatment or not.
Other antidepressants that have an effect on the serotonergic system
have been used, especially when SSRIs have been ineffective or poorly
tolerated. Prior to SSRIs, the tricyclics and the monoamine oxidase
inhibitors (MAOIs) were used much more commonly. More recently,
venlafaxine (Effexor) and mirtazapine (Remeron) have been used, which
act on both serotonin and norepinephrine. Beta-blockers, clonidine,
calcium channel blockers, atypical antipsychotics (Abilify, Zyprexa,
Seroquel, Risperdal, Geodon), buspirone, and anticonvulsants such as
divalproex (Depakote) and gabapentin (Neurontin) have also been used as
adjunctive agents in patients with refractory panic disorder, although
these uses have not been approved by the US Food and Drug
Administration.
Intermediate-acting benzodiazepines

By binding to specific receptor-sites, these agents appear to
potentiate the effects of gamma-aminobutyrate (GABA) and facilitate
inhibitory GABA neurotransmission and other inhibitory transmitters.
These agents are effective on standing-dose and prn schedules.

Follow-up

Further Inpatient Care

Inpatient care is rarely considered for uncomplicated panic disorder.
Patients may get admitted if they display any evidence of dangerous
behavior, safety concerns, report suicidal or homicidal ideation as may
occur in context of acute anxiety, fear of anxiety or its
consequences. Patients may require hospitalization for intoxication or
withdrawal from sedative/hypnotics such as alcohol or Xanax, which
sometimes get ingested or abused in attempts to medicate or manage the
anxiety. Patients may also get hospitalized if they become so
incapacitated by their anxiety that they are unable to adhere to
outpatient care.
Further Outpatient Care

• Initial follow-up care should occur within 2 weeks because
  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.
  
• Providing a few doses of a benzodiazepine as needed (prn) can
  enhance patient confidence and compliance. Total tablet dispensing
  should remain limited to ensure patients understand they have a limited
  supply and that this medicine represents a temporary or emergency use
  option and reaffirm the importance of longer term management with SSRI
  medication and psychotherapeutic techniques (eg, cognitive behavior
  therapy). Avoid benzodiazepine prescriptions in patients with a known
  history of substance misuse or alcoholism.
  
• Assess potential suicide risk at all appointments.
  
• Ensure continuing treatment of any concurrent substance use disorders.
  

Prognosis

Prognosis is excellent with adherence to medical management.
Patient Education

• Educate patients on potential adverse effects of their treatment medications.
  
• Obtain informed consent for psychotropic medications.
  
• Document the discussion of the risks and benefits of treatment medications.
  
• Inform patients that causes are likely biological and psychosocial.
  
• Advise patients to avoid anxiogenic substances such as caffeine, energy drinks, other OTC stimulants or recreational drugs.
  
• Consider educating patients diagnosed with panic disorder on
  cognitive distortions that may help amplify anxiety. Also educate
  patients about recognizing trigger stimuli so they can contribute this
  to their psychological treatment approach.
  
• Discuss alcohol consumption and any recreational drug use because
  these psychoactive substances can impact the course of panic disorder.
  While some substances may seem to avert the anguish of an acute attack,
  they often compromise the long-term treatment plan.
  
• Educate the patient’s family, if available, on the important issues
  of minimizing any avoidance behaviors from the patient, ensuring
  adherence to therapy appointments and pharmacologic compliance, and
  understanding the nature of the anxiety symptoms with reasonable
  accommodation without enabling dysfunctional behaviors or
  alcohol/prescription drug use. Family members can be particularly
  helpful in helping the patient overcome unrealistic fears and ingrained
  avoidance behaviors, in context of ongoing cognitive behavior therapy
  where the patient has learned coping skills to manage the anxiety.
  
• National Institute of Mental Health, Panic Disorder
  
• MedlinePlus, Panic Disorder
  
• MayoClinic, Panic attacks and panic disorder
  
• For excellent patient education resources, visit eMedicine's Anxiety Center. Also, see eMedicine's patient education articles Anxiety, Panic Attacks, and Hyperventilation.