Rizatriptan in Acute Treatment of Migraine in Patients With Unilateral Trigeminal-autonomic Symptoms.
Condition: Migraine
MeSH terms: Migraine Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      Triptans are first choice drugs in the acute treatment of migraine and cluster headache.
      However, while in cluster headache the response rate to subcutaneous sumatriptan is 96%,
      around 30% of patients fail to respond to a particular triptan. Nonresponse is likely to be
      due to a variety of factors, including low and inconsistent absorption, inadequate dosing,
      and variability in individual response5. Timing of administration is also a crucial issue. In
      fact, an early treatment of the attack, when the pain is still mild, may increase the
      responders rate by circumventing the development of cutaneous allodynia (expression of
      central sensitization of pain pathway) during the course of the attack.

      Several studies have been performed in an attempt to genetically, psychologically and
      clinically characterize the triptan responders but failed to provide conclusive results.

      Nevertheless, we suggested that the presence of UAs during the migraine attack might predict
      a good response to triptans. UAs are common in migraine patients. They have been reported in
      almost one out of two migraineurs (45.8%) attending a tertiary headache centre and in more
      than one out of four (26.9%) in a population-based study. In an open study with sumatriptan
      50 mg performed on 72 migraine patients with UAs, we described pain relief in 65.3% of the
      patients at 1 h and in 81.9% at 2 h, while pain-free in 30.6% at 1 h and in 61.1% at 2 h. We
      hypothesized a large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors
      consequent to the activation of the trigeminal-autonomic reflex in such patients. Our
      hypothesis has received further confirmation by the demonstration of higher levels of
      calcitonin gene-related peptide, neurokinin A and vasoactive intestinal peptide (the hallmark
      of the activation of the trigeminal autonomic reflex) in external jugular blood in
      rizatriptan responders than in non-responders.

      The investigators therefore postulate that migraineurs with UAs may respond better to
      rizatriptan than "general" migraine population.

      The aim of the study is to evaluate the efficacy of rizatriptan 10 mg lyophilized wafer (MLT)
      compared to placebo in the treatment of acute migraine in patients with unilateral autonomic
      symptoms (UAs: unilateral lacrimation, eye redness, eyelid oedema, nasal congestion or
      rhinorrhoea, miosis or ptosis, forehead or facial sweating) during the migraine attack.
    

Detailed description: 
      We tested the hypothesis that the presence of unilateral cranial autonomic symptoms in
      migraine predicts a good response to triptans. In this randomized, double-blind,
      placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were
      assigned to rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate
      or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine
      freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and
      sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h
      after taking rizatriptan than after placebo (54% vs 8%; p<0.001). Similarly, significantly
      more patients reported total migraine freedom at 2 h after rizatriptan than after placebo
      (51% vs 8%; p<0.001). Rizatriptan was also more effective than placebo on most secondary
      endpoints. Migraineurs with unilateral cranial autonomic symptoms respond better than the
      general migraine population to rizatriptan, probably owing to intense trigeminal peripheral
      afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors.
      Acute and preventive pharmacological trials in migraine should focus also on this subset of
      migraine patients.
    

Intervention name(s): rizatriptan or placebo
Intervention type(s): Drug
Intervention description(s): Patient took 1 rizatriptan 10 mg wafer or placebo as soon as their migraine headache became of moderate or severe intensity.
Intervention MeSH terms: Rizatriptan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: migraine; rizatriptan; unilateral trigeminal autonomic symptoms; Migraine with or without aura