Headache due to Substance or its Withdrawal

Headache due to a substance or its withdrawal may be divided into:

• A diagnosis of headache due to a substance usually becomes definite only when the headache resolves or greatly improves after withdrawing the substance.
• When exposure to a substance ceases but headache does not resolve or markedly improve after 3 months, a diagnosis of chronic post-substance exposure headache is considered.
• For medication-overuse headache, a period of 2 months after cessation of overuse is stipulated in which improvement must occur if the diagnosis is to be definite.

Migraine headaches may be provoked or activated in susceptible individuals by:

• Alcohol
• Food and food additives
• Chemical and drug ingestion and withdrawal

The association is often based on anecdotal data and reports of adverse drug reactions.

May be caused by an unwanted effect of a toxic substance, or by an unwanted effect of a substance in normal therapeutic use.

• Immediate nitric oxide donor-induced headache: all nitric oxide donors (e.g. amyl nitrate, erythrityl tetranitrate, glyceryl trinitrate (GTN), isosorbide mono- or dinitrate, sodium nitroprusside, mannitol hexanitrate, pentaerythrityl tetranitrate) can cause headache, especially in people with migraine.
• Carbon monoxide poisoning:
  • Typically mild headache without gastrointestinal or neurological symptoms with carboxyhaemoglobin levels in the range 10-20%.
  • Moderate pulsating headache and irritability with levels of 20-30%.
  • Severe headache with nausea, vomiting and blurred vision with levels of 30-40%.
  • With higher carboxyhaemoglobin levels (>40%) headache is not usually a complaint because of changes in consciousness.
• Immediate alcohol-induced headache.
• Headache induced by food components and additives: phenylethylamine, tyramine and aspartame have been incriminated; monosodium glutamate-induced headache.
• Cocaine, cannabis.
• Histamine.
• Calcitonin gene-related peptide (CGRP)-induced headache.
• Medications: headache has been reported after use of a number of drugs. The following are the most often incriminated: atropine, digitalis, disulfiram, hydralazine, imipramine, nicotine, nifedipine, nimodipine.
• Headache has been reported after exposure to a number of organic and inorganic substances. The
  following are the most commonly incriminated substances:
  • Inorganic compounds: arsenic, borate, bromate, chlorate, copper, iodine, lead, lithium, mercury,
    tolazoline hydrochloride.
  • Organic compounds: alcohols (long-chain), aniline, balsam, camphor, carbon disulfide, carbon tetrachloride, clordecone, EDTA, heptachlor, hydrogen sulfide, kerosene, methyl alcohol, methyl bromide, methyl chloride, methyl iodine, naphthalene, organophosphorous compounds (parathion, pyrethrum).

• Medication-overuse headache is an interaction between a therapeutic agent used excessively and a susceptible patient. The best example is overuse of symptomatic headache drugs causing headache in a headache-prone patient.
• By far the most common cause of migraine-like headaches occurring on 15 or more days per month and of a mixed picture of migraine-like and tension-type-like headaches on 15 or more days per month is overuse of symptomatic migraine drugs and/or analgesics.
• Use of the medication occurs both frequently and regularly, i.e. on at least several days each week.
• Bunching of treatment days with long periods without medication intake is much less likely to cause medication-overuse headache.
• Chronic tension-type headache is less often associated with medication overuse but episodic tension-type headache often becomes a chronic headache through overuse of analgesics.
• The headache associated with medication overuse often has a peculiar pattern shifting (even within the same day) from having migraine-like characteristics to having those of tension-type headache.
• The diagnosis of medication-overuse headache is very important because patients rarely respond to preventative medications while overusing acute medications.
• Common causes of medication overuse headache include:
  • Ergotamine.
  • Triptans.
  • Analgesics.
  • Opioids.
  • Combination medications: combination medications typically implicated are those containing simple analgesics combined with opioids or caffeine.
  • Exogenous hormones: regular use of exogenous hormones, typically for contraception or hormone replacement therapy, can be associated with increase in frequency or new
    development of headache or migraine.

• Usually follows daily intake of a substance for longer than 3 months, which is then interrupted.
• The headache develops in close temporal relation to withdrawal of the substance.
• The headache resolves within 3 months after withdrawal.
• Common examples of substances causing withdrawal headaches include:
  • Opioid-withdrawal headache.
  • Oestrogen-withdrawal headache.
  • Caffeine.
  • Headache attributed to withdrawal from chronic use of other substances; it has been suggested, but without sufficient evidence, that withdrawal of the following substances may cause headache: corticosteroids, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), non-steroidal anti-inflammatory drugs (NSAIDs).