Day # 70: Panic Disorder

Today we will discuss panic disorder. We will cover the clinical features, epidemiology, clinical pearls, and treatment options for panic disorder.

Today's Content Level: Beginner, Intermediate

CLINICAL FEATURES

•Panic attacks are an abrupt surge of intense anxiety/discomfort. This surge of fear is accompanied with multiple physical and cognitive symptoms.

•Panic attacks typically reach a peak within minutes (typically lasting 5-10 minutes). They may continue to feel anxious for hours afterwards and confuse this for a prolonged panic attack.

•Panic attacks are classically associated with panic disorder (which we will discuss today), however panic attacks alone are not diagnostic of panic disorder. They can also be experienced with many other medical and psychiatric conditions. A panic attack “specifier” can be added to a diagnosis to indicate the presence of these attacks (ex: social anxiety disorder with panic attacks).

The diagnostic criteria for a panic attack are as follows 1:

• Abrupt surge of intense anxiety/discomfort that peaks within minutes.

• Presence of at least four of the following symptoms:

  • Physical -> palpitations/tachycardia, sweating, trembling, shortness of breath, choking sensation, chest pain/discomfort, GI upset, pre-syncope, diaphoresis, and extremity tingling.

  • Cognitive -> fear of losing control, fear of death, derealization (people/surroundings seem unreal), or depersonalization (sense of detachment from your body/identity).

The diagnostic criteria for panic disorder are as follows 2:

• Recurrent and unexpected panic attacks with no known trigger.

• At least one of the attacks are followed by ≥1 month of one or both of the following:

  • Persistent concern about additional attacks or their consequences.

  • A significant maladaptive change in behavior related to the attacks (especially avoidance behaviors).

•The frequency of these attacks varies widely between and within individuals. Attacks may occur daily or weekly and may even be separated by months without attacks.

•Patients will often flee the situation and may present to the emergency department due to fear of complications. There is also a significant component of anticipatory anxiety that leads to avoidance of situations that might cause panic.

EPIDEMIOLOGY AND PATHOGENESIS

Epidemiology 3, 4

• 12-month prevalence ~ 3%

• Lifetime prevalence ~ 5%

• Can present at any age, but median age of onset is 24 years old. 95% onset by age 56.

• More common in woman with a ratio of 2:1.

• Some estimate that in the primary care setting, incidence might be as high as 7%.

• Contrast these numbers with the lifetime prevalence of a panic attacks themselves, occurring in up to one third of individuals at some point in their lives.

Risk Factors 5

• Childhood adversity including trauma or abuse.

• Major stressor in the past 12 mo, especially loss, threat, or medical illness.

• Anxious temperament during childhood as measured by neuroticism and anxiety sensitivity.

• Some data demonstrating that asthma in childhood may increase risk.

Pathogenesis 6

• Genetic: First-degree relatives of individuals with panic disorder having significantly higher rates themselves. Twin studies estimate a heritability of 40%.

• Neurobiology: May be related to hyper-excitable circuits between the amygdala and hypothalamus. The attacks are proposed to be dysfunctional/excessive discharge of norepinephrine from the locus ceruleus which causes the autonomic symptoms of panic attacks. Also, patients with panic disorder have been found to have decreased volume of the amygdala.

• The combination of these underlying predispositions and life stressors leads to unexpected feelings of intense anxiety in combination with autonomic symptoms (palpitations, shortness of breath, etc...). This initiates a feedback loop of anxiety and subsequent autonomic response.

CLINICAL PEARLS

Evaluation

• Examples of screening questions include -> Have you ever experienced an abrupt surge of intense fear? Ever felt severe anxiety with racing heart, sweating, difficulty breathing, dizziness, or other physical symptoms?

• Even more so than for other psychiatric conditions, it is very important in panic disorder to rule out underlying medical causes, particularly life threatening conditions (heart attack, pulmonary embolism, thyrotoxicosis, etc...). After the patient is stabilized, the first step may be to order routine labs. Consider thyroid function tests, complete blood count (CBC), chemistry panel (BMP or CMP), urine drug screen (UDS), ± ECG. For a full discussion on this topic please see our post titled "Medical Workup for Anxiety".

• Review all medications as some may be implicated (stimulants, corticosteroids, albuterol, levothyroxine, or decongestants).

• Optional questionnaire: Panic Disorder Severity Scale (PDSS).

• Screen for other psychiatric disorders. Panic may be due to another mental disorder (ex: PTSD flashbacks, paranoia in psychosis, social anxiety, etc...).

• Other important features of the clinical interview include:

  • Screen for stressful events or trauma within the past 12 months.

  • Substance history (including nicotine, caffeine, stimulants, PCP, hallucinogens, opioid or alcohol withdrawal).

  • Family history of anxiety, panic, or depressive disorders.

Comorbid Conditions

• Panic disorder is strongly comorbid with other anxiety disorders (particularly GAD and SAD), mood disorders (especially depression), impulse-control disorders, PTSD, and substance abuse.

• Agoraphobia is also common in patients with panic disorder. Agoraphobia can be described as the fear of being in situations where escape might be difficult or that help wouldn't be available if things go wrong. It can be diagnosed alone or concurrently with panic disorder. Agoraphobia will be addressed in our next post.

Medical/Substance Differential Diagnosis

• This was discussed in detail in this post (Medical Workup for Anxiety), but will provide a reference list here. Many medical conditions and substance can cause a surge of anxiety.

• Endocrine/Autoimmune-> Hypercortisolism, hyperthyroidism, pheochromocytoma, hyperparathyroidism, hypoglycemia, systemic lupus erythematosus (SLE), carcinoid syndrome.

• Neurologic-> Temporal lobe epilepsy, stroke or transient ischemic attacks (TIA), multiple sclerosis, traumatic brain injury (TBI), migraine headaches, brain tumors, Huntington disease, porphyria, PANDAS.

• Cardiac-> Angina or infarct, arrhythmia, congestive heart failure (CHF), mitral valve prolapse, hypertensive emergency.

• Pulmonary-> Asthma, pulmonary embolism, chronic obstructive pulmonary disease (COPD), pneumonia, pneumothorax.

• Substances -> Caffeine, stimulants (amphetamines or cocaine), phencyclidine (PCP), hallucinogens, alcohol (intoxication or withdrawal), tobacco (intoxication or withdrawal), anabolic steroids, opioid withdrawal, and also marijuana (paradoxically).

• Medications -> Stimulants, corticosteroids, albuterol, theophylline, levothyroxine, anticholinergics, or decongestants.

TREATMENT

•Treatment for all anxiety disorders are similar, so we have written a detailed post titled "Treatment of Anxiety Disorders" where we discuss treatment options in detail. Please refer to that post for a more thorough discussion.

•Treatment options for panic disorder include psychotherapy, pharmacotherapy, and other alternative treatments. Therapy and medications are both effective separately and together and the most effective treatment is probably a combination of these approaches. Discuss patient’s preference for psychotherapy and/or pharmacotherapy

Psychotherapy

• Cognitive Behavioral Therapy (CBT): Considered first-line with strong evidence for effectiveness. May have more lasting benefit than pharmacotherapy. If poor response after a course of CBT then recommend pharmacotherapy.

• Psychodynamic Psychotherapy (PDP): Mixed results with less overall support compared to CBT.

• Acceptance-Based Approaches: Challenges avoidance of experiences and encourages awareness and acceptance. Evidence is limited but promising.

• See this post for more details on each of these forms of therapy.

Pharmacotherapy

• SSRIs and SNRIs: Considered first-line treatment of panic disorder. No specific drug has been shown to have significantly higher efficacy than any other, however FDA approval for sertraline, fluoxetine, paroxetine, and venlafaxine. Consider avoiding those that are particularly activating (ex: fluoxetine). Effective but takes weeks to see treatment effect. Start at half the normal starting dose and titrate up slowly. Often requires a higher dose than treating depression. If good response, continue at least 8-12 months before discontinuing. If poor response after 6 weeks at therapeutic dose, switch to different SSRI. If partial response consider augmentation with low-dose benzodiazepine.

• Benzodiazepines: Highly effective and has rapid treatment effect. Risk of tolerance/dependence/addiction and rebound anxiety. Ideally for short-term use only (3-4 weeks) while initiating SSRI/SNRI, but may be considered as augmentation in severe panic disorder. Favor longer half lives (such as clonazepam) unless slow metabolizers (increased age or liver disease). Used as PRN backup (such as lorazepam) to abort panic, however this engenders dependency on the medication as a safety cue and interferes with exposure to and mastery of avoided situations.

• Buspirone: Partial agonist of serotonin receptors. Sometimes effective. Used to augment SSRI/SNRI, but takes weeks for full effectiveness.

• Pregabalin/Gabapentin: Often used off-label for treatment or augmentation of anxiety disorders. Studies demonstrate mixed results. Relatively quick onset of action and response may be seen in the first week of treatment.

• Treatment-Refractory cases: In these cases other medications can be tried, but are not first line due to adverse effects and no evidence of greater efficacy. Examples include: TCAs (clomipramine in particular), MAOIs, mirtazapine, antipsychotics, antiepileptics, hydroxyzine, and beta-blockers.

CONCLUSION

Thanks for reading. I hope you found it helpful. I believe that a daily dose of learning goes a long way! Next up will be a discussion about agoraphobia.

Resources for today's post include: Kaplan and Sadock's Synopsis of Psychiatry, The Maudsley Prescriber's Guide, DSMV, Pocket Psychiatry, and First Aid for the Psychiatry Clerkship. If you want more learning resources then check out our recommended resources page.

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