📋 Panic Attack - Clinical Note

1. DEFINITION

2. DSM-5 DIAGNOSTIC CRITERIA (Panic Attack)

• Persistent concern about future attacks, OR
• Significant maladaptive behavioral change (e.g., avoidance of exercise, unfamiliar situations)

3. CLINICAL FEATURES

• Onset typically in 20s; later onset (>40 years) usually signals underlying depression
• Attacks often occur during relative calm, not necessarily in threatening circumstances
• Symptoms escalate over minutes to an hour, then abate over 20-30 minutes leaving fatigue and perplexity
• Pathophysiology: excessive sympathoadrenal hyperactivity ("fight-or-flight" reaction)
• Consciousness is practically never lost during a panic attack - this is a key distinguishing feature
• Familial pattern: ~1/5 of first-degree relatives affected; high monozygotic twin concordance (Adams and Victor's Principles of Neurology, 12th Edition)

4. DIFFERENTIAL DIAGNOSIS

A. Temporal Lobe (Focal) Epilepsy - THE KEY DIFFERENTIAL FROM THE QUIZ

Key point from quiz: The absence of "classic" TLE teaching features (déjà vu, automatisms, olfactory aura) is precisely why TLE gets misdiagnosed as panic. The pure fear presentation without these hallmarks is the diagnostic trap.

• EEG - sleep-deprived first; if normal, proceed to prolonged or video-EEG (interictal EEG is often normal in TLE)
• MRI brain - to look for mesial temporal sclerosis
• These are the priority investigations when TLE is suspected

B. Pheochromocytoma

• Recurrent short-lived surges of fear with autonomic features (hypertension, sweating, palpitations) are the hallmark
• Must be excluded before accepting a psychiatric diagnosis
• Investigation: 24-hour urine catecholamines (metanephrines/VMA); plasma metanephrines
• The autonomic symptoms in pheochromocytoma directly duplicate those of panic because both involve excessive sympathoadrenal discharge

C. Cardiac Causes

• Chest discomfort and respiratory distress during acute panic may be mistaken for myocardial ischemia
• Patients are often subjected to multiple cardiac studies
• Cardiac arrhythmias can also present with palpitations, near-syncope, and fear
• Investigations: ECG, Holter monitor, chest X-ray
• A cardiac consultation is often needed to reassure patients and alleviate fear of heart disease

D. Other Medical Differentials

E. Psychiatric Differentials

5. MANAGEMENT

A. Non-Pharmacological (First-line alongside medications)

1. Cognitive-Behavioral Therapy (CBT)
   • Most evidence-based psychological intervention
   • Includes cognitive restructuring + behavioral experiments + in vivo exposure
   • Particularly effective when agoraphobia is a major symptom
2. Progressive exposure therapy
   • Graduated exposure to panic-provoking situations
3. Relaxation techniques
   • Biofeedback, meditation, diaphragmatic breathing
   • Must be practiced daily; less effective once an attack has begun
4. Psychoeducation
   • Explaining benign nature of symptoms reduces "fear of fear" cycle
   • Cardiac/respiratory reassurance often needed

B. Pharmacological

First-line: SSRIs (Selective Serotonin Reuptake Inhibitors)

• Effective for prevention of panic attacks and agoraphobia
• Onset delayed by weeks - not useful for acute attacks
• Doses similar to those used for depression
• Note: Anxiety symptoms may worsen in the initial weeks of SSRI treatment - cover with anxiolytic until antidepressant effect establishes
• Standard treatment duration: 6-12 months minimum (attacks recur on discontinuation)
• SNRIs (e.g., venlafaxine) are an equivalent alternative

Second-line: Benzodiazepines

• Alprazolam, lorazepam, clonazepam (preferred over alprazolam - less dependence risk)
• Effective for acute attacks and initial stabilization
• In mild cases: use intermittently rather than around the clock
• Less useful once an attack has become established
• Risk: dependence and withdrawal symptoms that simulate panic/anxiety
• Discontinuation must be gradual
• Role: bridge to SSRI efficacy, or acute rescue

Tricyclic Antidepressants (TCAs)

• Imipramine is the classic choice
• Effective but less preferred due to side effects and overdose risk
• Use when SSRIs are not tolerated

Beta-blockers (Propranolol 10-20 mg TID or long-acting)

• Reduce autonomic accompaniments of anxiety (palpitations, tremor, sweating)
• Useful adjunct for somatic symptoms
• Not sufficient as monotherapy for panic disorder

Buspirone

• 5-HT1A partial agonist; promoted as GABA-free anxiolytic
• Modest benefit at best for panic; more useful in GAD

Anticonvulsants (Valproic acid)

• Consider in panic disorder refractory to conventional anxiolytic treatment, given the neurophysiologic overlap with temporal lobe epilepsy (Kaplan & Sadock's Comprehensive Textbook of Psychiatry)

6. QUIZ SUMMARY - KEY TEACHING POINTS

• Option B (24-hr urine catecholamines for phaeochromocytoma) - While phaeochromocytoma is an important differential and must always be excluded in recurrent fear + autonomic surges, the specific features here (impaired awareness, stereotypy, SSRI non-response, brief duration peaking in seconds) point definitively toward TLE, not phaeochromocytoma
• Option D (Structured interview for dissociative disorders) - Derealization alone does not explain impaired awareness noticed by others, absence of situational trigger, and SSRI non-response

TLE presenting as pure ictal fear, without classic aura features (déjà vu, olfactory hallucination, automatisms), is the most common psychiatric mimic of panic disorder. The amygdala origin of the fear makes it phenomenologically indistinguishable from panic - until you notice the seconds-to-peak onset, rigid stereotypy, impaired awareness, and SSRI failure.

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry - Definition, DSM-5 criteria, EEG overlap with TLE, management
• Adams and Victor's Principles of Neurology, 12th Edition - Clinical features, differential diagnosis, pharmacological treatment
• Quiz explanation from ipsquiz.com - Temporal lobe epilepsy vs panic disorder distinguishing features

📘 Recent Clinical Guidelines: Panic Disorder Treatment & SSRI Recommendations

🏛️ PRIMARY GUIDELINE: NICE CG113

1. STEPPED CARE MODEL (NICE CG113)

2. PSYCHOLOGICAL TREATMENT (Step 3)

Delivery specifications:

• Optimal duration: 7-14 hours total (1.3.15)
• Format: Weekly sessions of 1-2 hours, completed within maximum 4 months (1.3.16)
• Brief CBT (~7 hours) is acceptable but must be supplemented with structured self-help materials (1.3.17-18)
• Intensive short-course CBT may suit a small number of patients (1.3.19)

Evidence from network meta-analysis:

3. PHARMACOLOGICAL TREATMENT (Step 3)

Key NICE rule (1.3.20 - 1.3.21):

⚠️ Benzodiazepines are associated with a less good long-term outcome and should NOT be prescribed for panic disorder treatment (NICE 1.3.20) Sedating antihistamines and antipsychotics should also not be prescribed (NICE 1.3.21)

SSRI / SNRI Recommendations

Licensed agents for panic disorder (NICE CG113, as of June 2020 update):

Choice of agent:

• Start with an SSRI as first-line pharmacotherapy
• If SSRI fails: switch to an alternative SSRI, or to venlafaxine (SNRI), considering:
  • Tendency to produce withdrawal syndrome (especially venlafaxine, paroxetine)
  • Side-effect profile and tolerability
  • Interactions with other medications
  • Cost and patient preference
  • Suicide/self-harm risk - especially in patients under 30: see within 1 week of prescribing; monitor weekly for the first month
• TCAs (e.g., clomipramine, imipramine) remain an option supported by evidence but are used less due to side-effect burden and overdose risk

Dosing principles:

• Start at a low dose and titrate slowly to minimise initial anxiety exacerbation
• Antidepressants may worsen anxiety in initial weeks - cover with short-term anxiolytic if needed
• Full therapeutic effect takes several weeks

Duration:

• If effective: continue for at least 1 year - likelihood of relapse is high (NICE 1.3.33)
• Review every 2-4 weeks in first 3 months, then every 3 months
• Discontinuation must be gradual to avoid withdrawal symptoms

Monitoring (NICE 1.2.32):

Review effectiveness AND side effects every 2-4 weeks in the first 3 months, then every 3 months thereafter.

4. TREATMENT-RESISTANT PANIC DISORDER

• SSRIs or clomipramine remain effective in treatment-resistant panic disorder (TR-PD) after CBT failure (based on RCT evidence) [PMID: 40946318]
• Pindolol augmentation of SSRI has RCT support in TR-PD
• Augmentation options (open-label evidence): buspirone, divalproex sodium (valproate), levetiracetam, cannabidiol
• Ketamine - preliminary evidence in treatment-resistant anxiety disorders
• After pharmacotherapy failure: CBT remains effective and should be offered
• After CBT failure: Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Cognitive Therapy (MBCT) show emerging evidence

"If 2 interventions (any combination of psychological intervention, medication, or bibliotherapy) have been provided and significant symptoms remain, referral to specialist mental health services should be offered."

5. SUMMARY COMPARISON TABLE

6. NIMH (2025 Update) - Key Points

• CBT is the "gold standard" psychotherapy
• Interoceptive exposure (exposure to bodily sensations mimicking panic) is highlighted as a specific CBT technique
• Telehealth delivery of CBT is recognized as equally effective
• SSRIs/SNRIs are the preferred medications; "may take several weeks to start working"
• Starting at a low dose with slow titration minimizes side effects

📑 Key References