What are the key differences between triptans (serotonin 5-HT1B/1D receptor agonists)?

Key Differences Between Triptans for Migraine Treatment

While all triptans are effective for acute migraine treatment, they differ significantly in onset of action, half-life, route of administration, and side effect profiles, which should guide selection based on the specific characteristics of a patient's migraine attacks.

Pharmacokinetic Differences

• Onset of action:

  • Subcutaneous sumatriptan has the fastest onset (approximately 15 minutes) and highest efficacy (70-82% effectiveness) 1
  • Oral rizatriptan reaches peak concentration in 60-90 minutes, faster than most other oral triptans which take 2-3 hours 1

• Half-life:

  • Naratriptan has the longest half-life among commonly used triptans, potentially reducing headache recurrence 1
  • Frovatriptan has an extended half-life of 26-30 hours compared to sumatriptan's 2 hours 2

• Bioavailability:

  • Sumatriptan has low oral bioavailability (14%)
  • Newer triptans have improved oral bioavailability 2

Administration Routes

• Multiple formulation options:

  • Sumatriptan: available as oral tablets, subcutaneous injection, and nasal spray
  • Rizatriptan: available as standard tablets and orally disintegrating wafers (Maxalt MLT)
  • Zolmitriptan: available as standard tablets and orally disintegrating formulations 1

• Benefits for patients with nausea/vomiting:

  • Non-oral routes (subcutaneous, intranasal) or orally disintegrating formulations are preferable when significant nausea/vomiting accompanies migraine 1

Efficacy Differences

• Therapeutic gain (percentage response for active minus percentage for placebo):
  • Subcutaneous sumatriptan 6mg: 51%
  • Oral rizatriptan 10mg: 37%
  • Oral eletriptan 40mg: 37%
  • Oral sumatriptan 100mg: 32%
  • Oral zolmitriptan 2.5mg: 32%
  • Oral naratriptan 2.5mg: 22%
  • Oral frovatriptan 2.5mg: 16% 2

Side Effect Profiles

• CNS side effects:

  • Lowest incidence: almotriptan 12.5mg, naratriptan 2.5mg, sumatriptan 50mg
  • Highest incidence: eletriptan 40-80mg, rizatriptan 10mg, zolmitriptan 2.5-5mg 3

• Factors affecting CNS side effects:

  • Presence of active metabolites: eletriptan, rizatriptan, and zolmitriptan have active metabolites
  • Lipophilicity: lowest for almotriptan and sumatriptan, affecting blood-brain barrier penetration 3

Clinical Application

• For rapid relief:

  • Subcutaneous sumatriptan or intranasal formulations
  • Among oral options, rizatriptan has quickest onset 4

• For prolonged attacks or prevention of recurrence:

  • Naratriptan or frovatriptan with their longer half-lives 4

• For patients concerned about side effects:

  • Almotriptan, naratriptan, or lower-dose sumatriptan 3, 5

Important Considerations

• Contraindications (common to all triptans):

  • History of coronary artery disease or vasospasm
  • Wolff-Parkinson-White syndrome
  • History of stroke, TIA, or hemiplegic/basilar migraine
  • Peripheral vascular disease
  • Uncontrolled hypertension
  • Use within 24 hours of another triptan or ergotamine-containing medication 6, 7

• Drug interactions:

  • All triptans: avoid concurrent use with MAO-A inhibitors
  • All triptans: risk of serotonin syndrome with SSRIs/SNRIs
  • Zolmitriptan: dose adjustment needed with cimetidine 7

• Practical approach:

  • If one triptan is ineffective, try another before abandoning this class of medication 1
  • Triptans are most effective when taken early in an attack while pain is still mild 1
  • Avoid use during the aura phase of migraine 1

Pitfalls to Avoid

• Medication overuse headache: Repeating triptan doses increases risk of medication overuse headache 1
• Oral administration during severe nausea: Gastric motility is inhibited during migraine attacks, making oral absorption erratic; consider non-oral routes 8
• Assuming all triptans will fail: If one triptan is ineffective, others may still provide relief 1
• Delayed administration: Triptans are most effective when taken early in an attack 1