Can Zoloft (sertraline) cause interstitial lung disease?

Can Zoloft Cause Interstitial Lung Disease?

Yes, sertraline (Zoloft) can cause interstitial lung disease, though this is a rare but potentially life-threatening adverse effect that requires immediate recognition and discontinuation of the medication. 1

Evidence for Sertraline-Induced ILD

The association between sertraline and ILD is documented in case reports and pharmacovigilance databases, though it remains uncommon. A 36-year-old male developed dry cough, pleuritic chest pain, hypoxia, and diffuse ground-glass attenuation with mediastinal lymphadenopathy after 7 weeks of sertraline therapy, with rapid improvement following drug discontinuation and corticosteroid treatment. 1

The broader class of selective serotonin reuptake inhibitors (SSRIs) has been implicated in drug-induced ILD. Fluoxetine, another SSRI, has documented cases in pharmacovigilance databases (36 cases in VigiAccess, 36 in EudraVigilance), suggesting this may be a class effect rather than drug-specific. 2 Given the structural and pharmacologic similarities within the SSRI class, sertraline should be considered capable of causing similar pulmonary toxicity.

Clinical Presentation

Patients typically present with dyspnea, dry cough, and pleuritic chest pain, often developing weeks to months after drug initiation. 1 The presentation is nonspecific and can mimic infectious or other inflammatory lung processes. 3

Key clinical features include:

• Respiratory symptoms: Dry cough and progressive dyspnea are the most common presenting complaints 1
• Imaging findings: Ground-glass opacities, diffuse infiltrates, and mediastinal lymphadenopathy on CT imaging 1
• Hypoxia: Oxygen desaturation may be present and can be severe 1
• Temporal relationship: Symptoms typically develop within weeks to months of drug exposure 2, 1

Diagnostic Approach

The diagnosis of sertraline-induced ILD is primarily one of exclusion, requiring systematic elimination of other causes. 3

Critical diagnostic steps include:

• Detailed medication history: Document timing of sertraline initiation relative to symptom onset, with particular attention to patients on long-term therapy 2
• Infectious workup: Rule out bacterial, viral, fungal, and opportunistic infections through appropriate cultures and serologies 1
• Imaging: High-resolution CT chest is essential, showing patterns that may include ground-glass opacities, organizing pneumonia, or nonspecific interstitial pneumonia patterns 1, 3
• Exclusion of other causes: Rule out connective tissue disease, hypersensitivity pneumonitis, and other drug exposures 3

Lung biopsy is rarely necessary but may show histologic patterns mimicking idiopathic interstitial pneumonias, including nonspecific interstitial pneumonia, organizing pneumonia, or diffuse alveolar damage. 3

Management

Immediate discontinuation of sertraline is the cornerstone of treatment, with corticosteroids providing additional benefit in most cases. 1

Treatment algorithm:

1. Stop sertraline immediately upon suspicion of drug-induced ILD 1
2. Initiate corticosteroids: A weaning course of oral dexamethasone or prednisone typically leads to rapid clinical improvement 1
3. Provide supportive care: Supplemental oxygen for hypoxia and monitoring for respiratory decompensation 1
4. Monitor response: Clinical improvement should occur within days to weeks of drug discontinuation 1

Early withdrawal of sertraline is critical for complete remission of this adverse reaction. 2 The prognosis is generally favorable with prompt recognition and appropriate management, though delayed diagnosis can result in life-threatening respiratory failure. 1

High-Risk Populations

Special attention should be given to female and elderly patients, who may be at increased risk for SSRI-induced ILD. 2 Patients on long-term sertraline therapy warrant heightened vigilance for respiratory symptoms. 2

Clinical Pitfalls

A common pitfall is attributing respiratory symptoms to anxiety or panic disorder in patients taking antidepressants, potentially delaying diagnosis. 1 Any patient on sertraline who develops dyspnea with or without dry cough should undergo chest imaging and oxygen saturation assessment to exclude drug-induced ILD. 2, 1

The lack of dose-response relationship and unpredictable timing of onset make prevention challenging, emphasizing the importance of maintaining clinical suspicion throughout the duration of therapy. 3