Focus on therapy of hypnic headache

Carlo Lisotto, Paolo Rossi, Cristina Tassorelli, Enrico Ferrante, Giuseppe Nappi

Research output: Contribution to journalArticlepeer-review


Hypnic headache (HH) is a primary headache disorder, which occurs exclusively during sleep and usually begins after 50 years of age. There are no controlled trials for the treatment of HH. We reviewed all the available papers, including 119 cases published in literature up to date, reporting the efficacy of the medications used to treat HH. Acute treatment is not recommended, since no drug proved to be clearly effective and also because the intensity and the duration of the attacks do not require the intake of a medication in most cases. As for prevention, a wide variety of medications were reported to be of benefit in HH. The drugs that were found to be effective in at least five cases are: lithium, indomethacin, caffeine and flunarizine. Lithium was the most extensively studied compound and demonstrated to be an efficacious treatment in 32 cases. Unfortunately, despite its efficacy, significant adverse effects and poor tolerability are not rare, mainly in elderly patients. Many patients reported a good response to indomethacin, but some could not tolerate it. Caffeine and melatonin treatments did not yield robust evidence to recommend their use as single preventive agents. Nevertheless, their association with lithium or indomethacin seems to produce an additional therapeutic efficacy. A course of lithium should be tried first, followed 3-4 months later by tapering. If headache recurs during tapering, a longer duration of therapy may be needed. If lithium treatment does not provide a significant response, indomethacin can be commenced as second-line approach. If these treatments prove to be ineffective or poorly tolerated, other agents, such as caffeine and melatonin, can be administered.

Original languageEnglish
Pages (from-to)349-354
Number of pages6
JournalJournal of Headache and Pain
Issue number4
Publication statusPublished - 2010


  • Caffeine
  • Hypnic headache
  • Indomethacin
  • Lithium
  • Melatonin
  • Therapy

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Clinical Neurology
  • Medicine(all)


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