Headache due to Substance or its Withdrawal

• 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).

• Patients with medication overuse headache caused by simple analgesics or triptans should be advised to abruptly withdraw the overused medication. Patients should be warned that abrupt withdrawal initially results in worsening of the headaches.
• Medication overuse headache caused by opioids and opioid-containing analgesics should be managed by gradual withdrawal of the overused medication.
• Prophylactic agents may be effective if frequent headaches persist after the overused medication has been withdrawn.
• Prednisolone, naratriptan, amitriptyline and sodium valproate have been shown to be effective in patients abruptly withdrawing symptomatic medication in terms of fewer withdrawal symptoms, using fewer symptomatic medications and using symptomatic medication for a shorter period.
• Naproxen has been shown to reduce withdrawal symptoms in ergotamine-induced headache.