What are the most appropriate first‑line antidepressants for a patient with globus sensation caused by anxiety or depression?

Treatment of Globus Sensation with Antidepressants

For globus sensation caused by anxiety or depression, selective serotonin reuptake inhibitors (SSRIs)—specifically sertraline, escitalopram, or fluoxetine—are the recommended first-line antidepressants, with sertraline preferred due to its optimal balance of efficacy, safety, and tolerability. 1

Evidence Base and Rationale

The use of antidepressants for globus sensation is based on evidence from overlapping functional disorders causing esophageal and pharyngeal discomfort, though no randomized controlled trials specifically target functional dysphagia or globus pharyngeus. 2 Globus sensation shows strong links to psychological stress, with many patients reporting symptom exacerbation during periods of high emotional intensity, and studies demonstrate that patients with globus score significantly higher on neuroticism, anxiety, depression, and somatic concern compared to controls. 2, 3, 4

First-Line SSRI Selection

Sertraline (Preferred)

• Start at 50 mg daily (or 25 mg daily for the first week if the patient appears highly anxious or agitated, then increase to 50 mg). 1
• Titrate in 50 mg increments at 1–2 week intervals if response is inadequate, up to a maximum of 200 mg daily. 1
• Sertraline has the lowest risk of drug interactions among SSRIs, minimal CYP450 inhibition, and lower risk of QTc prolongation compared to citalopram or escitalopram. 1
• Lower risk of discontinuation syndrome compared to paroxetine. 1

Alternative First-Line Options

• Escitalopram or fluoxetine are acceptable alternatives, with escitalopram having the least effect on CYP450 enzymes and lowest propensity for drug interactions. 1
• Paroxetine is FDA-approved for the widest range of anxiety disorders but carries higher risk of severe discontinuation syndrome and should be reserved for cases requiring broader anxiety coverage. 1

Treatment Timeline and Monitoring

• Allow 6–8 weeks for adequate trial, including at least 2 weeks at maximum tolerated dose, before concluding treatment failure. 1
• Approximately 38% of patients do not achieve treatment response during the initial 6–12 weeks, and 54% do not achieve remission. 1
• Monitor at 4 weeks and 8 weeks to assess symptom relief, treatment-emergent suicidality (especially in patients under age 24), side effects, medication adherence, and patient satisfaction. 1
• Close monitoring for suicidality is essential during the first 1–2 weeks after initiation or dose changes, as all SSRIs carry FDA black box warnings for treatment-emergent suicidal thinking. 1

Treatment Duration

• Continue SSRI treatment for a minimum of 4–9 months after satisfactory response for first-episode anxiety or depression. 1
• Consider longer duration (≥1 year) for patients with recurrent episodes or chronic symptoms, as globus sensation has a strong tendency to recur. 1, 5

Augmentation Strategy

• Combining cognitive-behavioral therapy (CBT) with SSRI treatment yields superior outcomes compared to either modality alone for anxiety disorders. 1
• Proper investigation to rule out underlying serious pathology may lead to improvement of globus sensation through reduction of anxiety, particularly in patients without comorbid esophagitis. 6

Critical Considerations

• Rule out organic causes first: Globus must be distinguished from true dysphagia, gastroesophageal reflux disease (GORD), and histopathology-based esophageal motility disorders through endoscopic investigation. 2, 6
• Approximately 20% of patients with functional dysphagia experience globus sensation with swallowing, and comorbid esophagitis may require specific treatment in addition to antidepressants. 2, 6
• Anxiety may be an outcome rather than a predisposing factor in globus sensation, though it commonly complicates the somatic distress experienced by these patients. 2, 3

Common Pitfalls to Avoid

• Do not discontinue prematurely—full response may take 6–8 weeks; partial response at 4 weeks warrants continued treatment, not switching. 1
• Do not abruptly discontinue SSRIs—taper gradually when stopping to minimize discontinuation symptoms, particularly with paroxetine. 1
• Never combine SSRIs with MAOIs due to serotonin syndrome risk; allow at least 2 weeks washout when switching. 1

When to Switch Medications

• If inadequate response after 6–8 weeks at therapeutic doses, switch to another first-line SSRI (escitalopram, fluoxetine) or consider an SNRI (venlafaxine), which may have statistically better response rates for depression with prominent anxiety symptoms. 1
• One in four patients becomes symptom-free after switching medications. 1