Can antihistamines (anti-allergic medications) be used to treat headaches?

Antihistamines for Headaches

Antihistamines are generally not recommended as primary therapy for headaches, as there is insufficient evidence supporting their efficacy for this indication. 1

Types of Headaches and First-Line Treatments

Migraine Headaches

For migraine headaches, the evidence-based treatment algorithm is:

• Mild to moderate migraines: First-line treatments are acetaminophen and NSAIDs 1

  • Examples: Aspirin (650-1000mg), ibuprofen (400-800mg), naproxen sodium (275-550mg)

• Moderate to severe migraines: First-line treatments are triptans 1

  • Examples: Sumatriptan, rizatriptan, naratriptan, zolmitriptan

• Second-line options: Dihydroergotamine (DHE), combination analgesics with caffeine 1

• For accompanying nausea/vomiting: Antiemetics like metoclopramide or prochlorperazine 1

Allergic Rhinitis-Related Headaches

If headaches are secondary to allergic rhinitis:

• First-line: Intranasal corticosteroids 1
• Second-line: Second-generation (non-sedating) antihistamines 1
  • Examples: Fexofenadine, loratadine, desloratadine

Role of Antihistamines in Headache Management

Limited Evidence for Primary Headache Treatment

• Antihistamines have not shown proven efficacy for treating primary headaches 2
• A 2016 randomized clinical trial showed that diphenhydramine as adjuvant therapy with metoclopramide did not improve migraine outcomes compared to metoclopramide alone 3

Histamine and Migraine Connection

• While histamine can trigger migraine-like headaches, most antihistamines have been ineffective as acute migraine treatments 4, 5
• Only two centrally-acting H1 antagonists (cinnarizine and cyproheptadine) have shown some efficacy in migraine prevention, but evidence is limited 4

Sedating vs. Non-Sedating Antihistamines

• First-generation (sedating) antihistamines have significant drawbacks:

  • Cause drowsiness, performance impairment, and anticholinergic effects 1
  • Impairment can persist into the next day even when taken at bedtime 1
  • Particularly problematic in older adults who are more sensitive to these effects 1

• Second-generation (non-sedating) antihistamines are preferred when treating allergic rhinitis that may be contributing to headaches 1

  • Fexofenadine, loratadine, and desloratadine do not cause sedation at recommended doses 1
  • Cetirizine and intranasal azelastine may cause mild sedation 1

Special Considerations

When Antihistamines Might Be Considered

• In erythromelalgia (a rare condition with burning pain), antihistamines have shown limited value, but cyproheptadine (which has both antihistamine and serotonin antagonist properties) has helped some patients 1

Cautions and Contraindications

• First-generation antihistamines should be avoided or used with extreme caution in:
  • Older adults (increased risk of falls, fractures, cognitive impairment) 1
  • Patients who need to drive or operate machinery 1
  • Patients with narrow-angle glaucoma, benign prostatic hypertrophy 1
  • Those taking other CNS depressants 1

Bottom Line

For patients seeking headache relief, clinicians should focus on evidence-based treatments specific to the headache type rather than antihistamines. If allergic rhinitis is contributing to headache symptoms, treating the underlying allergy with second-generation antihistamines may indirectly help relieve headache symptoms, but antihistamines themselves are not recommended as direct headache treatments.