Headache as an Adverse Reaction to Medication

  • Anna Ferrari
  • Peer Carsten Tfelt-Hansen
Reference work entry


Headache is one of the most common adverse reactions induced by several drugs belonging to a wide variety of therapeutic classes, particularly cardiovascular drugs. It is probably more frequent than reported. In fact, identifying adverse reaction headache can be arduous, since headache is a non-pathognomonic symptom and a primary disorder widespread in the general population. Adverse reaction headache has no typical characteristics and can simulate a primary headache, be associated with symptoms of neurotoxicity, and be a sign of important conditions, such as pseudotumor cerebri or aseptic meningitis. Among subjects at risk are mainly the elderly. The International Classification of Headache Disorders (ICHD-II) (2004) includes headache – adverse drug reaction – in secondary forms, principally in Chap. 8, “Headaches attributed to drugs or their withdrawal,” codes 8.1, 8.3, and 8.4. Among these, the most known and easily recognized is certainly nitric oxide donor–induced headache, for example, induced by glyceryl trinitrate. Headache-provoking properties of nitric oxide donors have provided a human model of primary headache to study its pathophysiology and treatment.

The stronger evidence for the diagnosis of headache as adverse reaction, i.e., a negative event with a causal link with a drug, is disappearance with suspension, and the recurrence of headache with the resumption of the drug. Temporal association between exposure to a drug and headache may instead occur by pure coincidence. In most cases, adverse reaction headache does not endanger the patient’s life, it is of type A and dose-related, it occurs early in treatment (then tolerance develops), and its outcome is favorable. It can however also be very disturbing, and lead to discontinuation of the treatment. If not recognized, adverse reaction headache increases the suffering, worries the patient and the physician, and may lead to requests for investigations and the prescription of more drugs when the solution is the opposite (to reduce or stop drugs).


Adverse Reaction Adverse Drug Reaction Migraine Attack Intracranial Hypertension Migraine Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Lifting The Burden 2011

Authors and Affiliations

  1. 1.Headache and Drug Abuse Inter-Dep. Research Centre, Division of Toxicology and Clinical PharmacologyUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.Danish Headache Centre and Department of NeurologyGlostrup Hospital, University of CopenhagenGlostrupDenmark

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