Why do antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs), cause photosensitivity?

Mechanism of Antidepressant-Induced Photosensitivity

Antidepressants cause photosensitivity through their ability to absorb ultraviolet (UV) radiation and generate reactive compounds in the skin that trigger inflammatory responses when exposed to sunlight. 1

Mechanisms of Photosensitivity

Antidepressant-induced photosensitivity occurs through two main mechanisms:

1. Phototoxic reactions (more common):

   • Direct cellular damage occurs when the drug absorbs UV radiation and becomes activated
   • The activated drug molecules generate reactive oxygen species that damage cell membranes and DNA
   • Results in an exaggerated sunburn-like reaction limited to sun-exposed areas
   • Occurs without prior sensitization and can affect anyone taking sufficient doses

2. Photoallergic reactions (less common):

   • Involves the immune system
   • UV radiation transforms the drug into a hapten that binds to proteins in the skin
   • This drug-protein complex is recognized as foreign by the immune system
   • Presents as eczematous, lichenoid, or urticarial eruptions
   • Requires prior sensitization and can occur with lower drug concentrations

Specific Antidepressant Classes and Photosensitivity

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Several cases of photosensitivity have been reported with fluvoxamine, paroxetine, and fluoxetine 2, 3
• Cross-reactivity between different SSRI molecules has been observed 2
• Methylation metabolism may explain the common photosensitization mechanism 2

TCAs (Tricyclic Antidepressants)

• Particularly photosensitizing due to their tricyclic structure
• Can cause both phototoxic and photoallergic reactions
• May induce pseudoporphyria in some cases

Clinical Presentation

Photosensitivity reactions typically present as:

• Burning and tingling sensation in sun-exposed skin
• Erythema (redness) disproportionate to sun exposure
• Distribution limited to or predominating in sun-exposed areas (face, neck, hands, forearms)
• Morphological spectrum ranging from sunburn-like responses to eczematous, lichenoid, or bullous lesions 1
• In severe cases, can resemble porphyria cutanea tarda 1

Risk Factors

Factors that increase the risk of antidepressant-induced photosensitivity:

• Higher drug dosages
• Fair skin (Fitzpatrick skin types I-II)
• Time of day (midday exposure carries higher risk)
• Season (summer months)
• Geographical location (higher altitude, proximity to equator)
• Weather conditions (clear skies)
• Reflection from water, sand, or snow 4

Management and Prevention

For patients taking potentially photosensitizing antidepressants:

Prevention:

• Advise patients to seek shade when outside, particularly around midday
• Recommend protective clothing covering as much of the body as possible
• Suggest wearing broad-brimmed hats and sunglasses
• Recommend broad-spectrum sunscreens with SPF 30 or higher 4
• Consider switching to less photosensitizing alternatives if prolonged sun exposure is anticipated

Management of reactions:

• Discontinue the offending medication if possible
• Topical corticosteroids for inflammatory reactions
• Oral antihistamines for symptomatic relief
• In severe cases, systemic corticosteroids may be necessary

Important Considerations

• When a patient presents with skin lesions typical of photosensitivity, always consider medication as a potential cause 5
• Photosensitivity reactions can be misdiagnosed as sunburn, eczema, or other dermatological conditions
• Although widely prescribed, photosensitivity reactions to antidepressants are relatively rare 2
• Patients should be warned about this potential side effect before starting treatment, especially if they will have significant sun exposure

Diagnostic Approach

When suspecting antidepressant-induced photosensitivity:

• Obtain detailed medication history
• Note temporal relationship between drug initiation and symptom onset
• Observe distribution pattern (limited to sun-exposed areas)
• Consider phototesting to confirm photosensitivity
• Rule out other causes of systemic photosensitivity (lupus erythematosus, porphyria) 1

Remember that antidepressant-induced photosensitivity is a diagnosis of exclusion, and proper identification requires careful clinical evaluation and sometimes specialized testing.