Drug-induced Headache Research Articles

The Need for Vigilance in Identifying Those at Risk from Drug-induced Headache

A case study is described to illustrate the need for vigilance in detecting drug-induced headache. A woman (“Jane”) volunteered for a headache research program, and assessment revealed a very high consumption of headache medication. Jane was taking an average of 21 tablets per day as well as receiving injections several times a week. The research staff directed her to record her medication, and to take these records to her doctor for review. Two general practitioners and a psychiatrist responded that there was no need for intervention, but the researchers were sufficiently concerned that they encouraged her to find another doctor. The fourth doctor admitted her to hospital immediately for detoxification with spectacularly beneficial results.

Treatment is available for drug-induced headaches

Treatment is available for drug-induced headaches

Easy therapeutical management of sumatriptan-induced daily headache

Drug-induced daily headache is a frequent problem in headache therapy. It can be caused by the daily intake of ergotamines and common analgesics. Drug-induced headache manifests itself as constant daily dull pressure with either frontal or occipital localization. Most patients wake up with headache in the morning. Skipping the usual daily dose of headache medication often causes an unbearable increase of headache severity. The therapy of druginduced headache is withdrawal of the responsible drugs. [1] There is little documentation of drug-induced headache caused by sumatriptan, [2,3] and we report our experience with five patients. Five women Table 1, Table 2 with migraine without aura were treated with daily sumatriptan before they attended our outpatient department. Four of five patients took sumatriptan …

Dexamethasone/amitriptyline treats drug-induced headache

Dexamethasone/amitriptyline treats drug-induced headache

Amitriptyline and dexamethasone combined treatment in drug-induced headache.

Frequent or regular intake of antimigraine drugs, including analgesics, constitutes a common cause of chronic daily headache. Discontinuation of symptomatic medication can produce an increase in head pain accompanied by withdrawal symptoms. We report the favourable outcome of treating a group of outpatients with the combination of amitriptyline, dexamethasone and sumatriptan. Dexamethasone (4 mg/day) was given intramuscularly for 2 weeks, amitriptyline orally at night (50 mg/day) for at least 6 months, and sumatriptan subcutaneously to treat acute headache attacks. Eighteen out of 20 patients abstained from drug abuse. Eleven of these 18 patients showed a marked reduction in headache frequency (at least 75% in relation to the basal value), and were considered "very good responders". The other seven patients experienced at least 50% reduction in headache frequency compared to baseline. This preliminary report suggests that drug-induced headache can be treated effectively in outpatients using dexamethasone, amitriptyline and sumatriptan in combination with significant benefit in everyday life conditions.

Felbamate-induced headache.

We prospectively investigated drug-induced headaches (HA) among 60 epileptic patients receiving felbamate (FBM). Twenty patients (33%) experienced HA. HA was pounding in 11 (55%), steady in 9 (45%), moderate or severe in 19 (95%), occurred at least once a week in all patients, and was relieved by nonnarcotic analgesics in 14 (70%). Mean duration on FBM before HA onset was 19 days. HA occurred with higher FBM doses and was relieved in 8 of 13 patients (62%) with FBM dose reduction. FBM was discontinued in most cases because of risks of anemia or hepatitis; not because of HA. Other side effects included insomnia (25%), gastrointestinal symptoms (27%), and agitation or restlessness (23%). HA is a common dose-related complication of FBM, occurs early after initiation of FBM treatment, and is relieved by dose reduction.

Reply from the Authors

Reply from the Authors: Evers et al described one patient with chronic and another with episodic cluster headache who developed ergotamine-induced headaches. This is an important observation. We have also observed patients who developed daily drug-induced headaches when ergotamine tartrate was taken on a daily …

Chronic use of symptomatic headache medications

Chronic use of symptomatic headache medication is believed to be a risk factor for drug-induced chronic headache. This study reports the frequency of chronic use of symptomatic headache medications implicated in drug-induced chronic headache among primary-care headache (PCH) patients and identifies predictors of chronic/frequent use. The design uses a 2-year cohort study of a sample of PCH patients in Group Health Cooperative of Puget Sound, a large health maintenance organization in Seattle, WA. Among 779 PCH patients (aged 18–74 years) interviewed at baseline, 662 (85%) completed both 1- and 2-year follow-up interviews. This study estimates the percent of PCH patients reporting: (1) frequent use of over-the-counter, non-steroidal anti-inflammatory, opioid, sedative-hypnotic, and ergot medications (defined as 14 or more days of use for each class in the prior month), (2) chronic/frequent use of these medications, defined as surpassing criteria for frequent use on at least 2 of the 3 study interviews, and (3) chronic/frequent polypharmacy, defined as chronic/frequent use of 2 or more classes of headache medication. Twenty-one percent of PCH patients were chronic/frequent users of symptomatic headache medications, while 2.6% met study criteria for chronic/frequent polypharmacy. Chronic/frequent use of over-the-counter medications (15.9%) was twice as common as chronic/frequent use of prescription medications (7.7%). Headache days at baseline was the strongest predictor of chronic/frequent medication use. After controlling for baseline persistence and severity, older patients were more likely to be chronic/frequent users of headache medications. The age effect was explained by chronic/frequent use of over-the-counter medications. Chronic/frequent use of symptomatic headache medications was common among PCH patients, especially among patients with persistent headache. Primary-care patients and physicians need to be informed of potential risks of drug-induced chronic headache resulting from chronic/frequent use of prescription and over-the-counter symptomatic headache medications.

The International Headache Society (IHS) Headache Classification as Applied to a Headache Clinic Population

Four hundred patients attending a headache clinic were classified using the IHS criteria. The majority required more than two, often three or four, diagnoses. Even though migraine was the most common diagnosis, only 1/4 of those with a migraine diagnosis had it as the only diagnosis. Seventy-five percent of migraine patients had coexistent chronic tension-type headache (CTTH), drug-induced headache or both. Ninety-six percent of patients diagnosed as having migraine with aura also suffered from migraine without aura. More than 1/3 of patients (37.7%) attending the clinic suffered from chronic daily headache (CDH) (chronic cluster headache excluded), which is not included as a separate entity in the IHS classification. Pure CTTH formed only a small minority of CDH, whereas 86.6% of CDH had migraine as one of the diagnoses. Drug-induced headache was a prominent second or third diagnosis. The advantages and disadvantages of multiple verses single diagnosis in CDH and the need to recognize the natural history of headache disorders in the classification are discussed.

Subcutaneous sumatriptan in a clinical setting: the first 100 consecutive patients with acute migraine in a tertiary care center.

The first 100 consecutive patients at our center receiving subcutaneous sumatriptan (6 mg) were evaluated over a total of 455 migraine attacks. Parameters included overall efficacy, average time to relief, recurrence rate, average time to recurrence, adverse events, comparison to previous abortive agents, and subjective global ratings. Overall efficacy (defined as headache severity reduction from severe or moderate to mild or none) was 84%. Average time to relief was 40 minutes. Nine percent failed to respond at all. Recurrence rate was 46.5% with 36% of patients having no recurrence. Fourteen percent of patients reported 100% recurrence (minimum 3 attacks; average 5.4 attacks). Time to recurrence varied widely, but averaged 9.1 hours. Eighty-one percent rated the drug better or much better than previous abortive medications in terms of sumatriptan's ability to abort the attack. Seventy-seven percent reported some adverse event (generally mild and transient) with 23% reporting no adverse events. Sixty-nine percent reported a global rating of Good to Excellent and 31% rated Poor or Fair. The rate of recurrence and average time to recurrence were the most significant factors affecting the global ratings. These parameters were further evaluated with respect to a variety of subgroups: 1) migraine alone 2) migraine with co-existent tension-type headache 3) drug-induced headache (analgesic rebound headache) 4) posttraumatic headache 5) preventive versus no preventive medication 6) presence or absence of adverse events 7) presence or absence of recurrence and 8) average duration of migraine with no medication.

A personal view of the classification and definition of drug dependence headache.

A review of the literature indicates that drug-induced headache exists. The criteria of the International Headache Society proposed for the diagnosis of "headache induced by chronic substance use or exposure", however, need to be modified in order to identify all patients with this headache form.

Drug-induced headache

Migraine or tension-type headache lasting for several years is frequently complicated by chronic daily headaches. Those patients recurrently take analgesics or ergotamines. Headache induced by chronic ergotamine use is well known. Recent studies, however, have shown that a similar form of headache is caused by analgesic abuse. Treatment of drug-induced headaches envisages withdrawal of the headache medication.

Ergotamine, flunarizine and sumatriptan do not change cerebral blood flow velocity in normal subjects and migraneurs.

Changes in the diameter of extracranial and intracranial arteries resulting in changes in cerebral blood flow have previously been assumed to be the most important pathophysiological factor in migraine. To test this hypothesis 20 normal subjects, and three groups of patients (n = 29) with migraine were investigated by means of transcranial Doppler sonography. Blood flow velocities in the middle cerebral (MCA) and in basilar (BA) arteries were measured. Data from patients were obtained in the interval between migraine attacks, during migraine attacks and following treatment with either ergotamine (0.5 mg i.m.; n = 10); flunarizine, a calcium overload blocker (20 mg i.v.; n = 13); or a 5-HT1-like agonist (sumatriptan, 4 mg s.c.; n = 6). Ergotamine and sumatriptan are constrictors of cerebral arteries in animal experiments. The arithmetic mean of flow velocity in the BA was reduced in normal subjects (45 cm/s) as compared with patients with migraine measured in between attacks (53 cm/s). Mean flow velocity in MCA was not different in normals (72.5 cm/s) as compared with migraineurs (75 cm/s). Neither ergotamine nor the 5-HT1 agonist and flunarizine resulted in a significant change in blood flow velocity in MCA and BA. This was true irrespective of whether the drugs were given in the headache-free period, during a migraine attack or during the withdrawal phase of drug-induced headache. Ergotamine was effective in improving headache during migraine attacks and sumatriptan attenuated headache during drug withdrawal from chronic analgesic intake. These results indicate that the action of ergotamine and the 5-HT1-receptor agonist is probably not mediated by their vasoconstrictor action on cerebral arteries.

Subcutaneous Sumatriptan in the Treatment of Headache During Withdrawal From Drug‐Induced Headache

In a pilot study (5 patients) we investigated the effects of subcutaneous sumatriptan, a 5-HT1-like receptor agonist, on headache experienced during the withdrawal period of drug-induced headache. The pilot study indicated that the substance was effective mostly in patients who originally suffered from migraine. In a patient with tension headache the substance was less effective. In a second double-blind study on six migraine patients with severe drug-induced headache, the drug was highly effective in ameliorating headache and autonomic disturbances. Blood flow velocities measured in extracranial parts of internal and external carotid arteries by duplex-sonography and in middle cerebral and basilar arteries by transcranial Doppler showed no changes after administration of sumatriptan or placebo. This result suggests sumatriptan does not act primarily via constriction of the large cerebral arteries.

Drug-Induced Headache

Headache induced by medications used for nonheadache conditions, and more importantly, headache perpetuated by symptomatic medications used for primary headache disorders are discussed in detail in this article. The clinical features and mechanisms of drug-induced headaches are reviewed. Ergotamine and analgesic rebound phenomena are described. Management strategies for drug-induced headaches are outlined.

Medikamentöse Migräneprophylaxe

If migraine attacks occur more frequently than 2 times a month, treatment of the acute attack with analgesics and ergotamine becomes problematic. An acute relief of migraine symptoms will be achieved only at the risk of developing a drug-induced chronic headache. Therefore, if migraine attacks occur frequently prophylactic treatment should be considered. A bewildering variety of drugs have been discussed for migraine prophylaxis in the past few decades. Only a few of them can be accepted to be effective on the basis of reliable clinical studies. Others have failed to show any superiority to placebo treatment when tested in controlled drug trials for a period long enough to rule out the placebo response, which may simulate effectiveness at the beginning of the trial. The efficacy of metoprolol and propranolol has been demonstrated beyond any doubt. It seems, however, that other beta-blocking drugs are less effective or even ineffective. In more than 20% of patients even prolonged treatment with metoprolol or propranolol does not provide sufficient relief. Flunarizine may be tried in these patients, as long as side effects do not occur or can be tolerated by the patient. Whether non-steroidal antirheumatics and dihydroergotamine can be considered as an effective and safe alternative in migraine prophylaxis is still not well established. There is, however, convincing evidence that neither clonidine, nor anti-histamines, nor barbiturates, nor antiepileptic drugs, nor anxiolytics are effective in the prophylactic treatment of migraine. Successful prophylactic treatment cannot be achieved by drug therapy alone. Any form of drug treatment should be complemented by providing the patient with detailed information about the nature of the disease and the properties of the prescribed drugs, as well as careful investigation of the patient's situation and habits and a careful search for precipitants, combined with an attempt to change the patient's habits and to avoid factors that trigger the attacks.

Longterm prognosis of analgesic withdrawal in patients with drug-induced headaches.

We studied long-term prognosis and prognostic variables for therapeutic outcome of analgesic withdrawal in 54 patients with drug-induced headaches. The duration of headache history was 21.9 +/- 12.8 years. Each patient took an average of 38.8 +/- 22.8 tablets or suppositories a week and an average of 2.5 distinct drugs. Most patients used drugs containing several components. Caffeine was contained in at least one drug in all cases, ergotamine in 80.0% and pyrazolone in 77.1%. All patients were admitted to the hospital for two weeks. The analgesics were discontinued abruptly and the withdrawal symptoms were alleviated by neuroleptics and neurotropics. During the second week of hospital stay we started a basic therapy with calcium antagonists or beta blockers in patients suffering from migraine initially and with tricyclic antidepressants, physical therapy or biofeedback in patients suffering from tension type headaches initially. At the end of the study (mean follow-up period = 16.8 +/- 13.6 months) 38 patients (70.1%) were evaluated. 76.3% of these patients had significantly reduced their analgesic intake, 60.5% had experienced a significant relief of headache both in intensity and frequency, and 23.7% were therapeutic failures. Analysis of the time course of relapse revealed the first six months after hospital discharge as the critical period determining long-term success. The variables tested for prognostic relevance (age, sex, duration of headache history, number of tablets or suppositories taken a week, organic mental syndrome, and type of initial headaches) were not statistically significant.

Drug-Induced Headache

Drug-Induced Headache

Analgesic-induced chronic headache: long-term results of withdrawal therapy.

Headache characteristics are described in 139 patients with chronic daily or almost daily headaches due to regular intake of analgesics and the short- and long-term results of drug withdrawal. Drug-induced headache was described as dull, diffuse, and band-like, and usually started in the early morning. The mean duration of the original headache (migraine or tension headache) was 25 years; regular intake of drugs and chronic daily headache had started 10 and 6 years prior to withdrawal therapy, respectively. Patients took an average of 34.6 tablets or analgesic suppositories or antimigraine drugs per week containing 5.8 different substances. The drugs most often used were caffeine (95%), ergotalkaloids (89%), barbiturates (64%), and spasmolytics, paracetamol, and pyrazolone derivates (45%-46%). A total of 103 patients (68 migraine, 35 tension or combination headache) were available for interviews at a mean time interval of 2.9 years after an inpatient drug withdrawal programme. Chronic headache had disappeared or was reduced by more than 50% in two-thirds of the patients. Positive predictors for successful treatment were migraine as primary headache, chronic headache lasting less than 10 years, and regular intake of ergotamine. Drug intake was significantly reduced and patients used single substances more often. Patients who originally suffered from migraine, superimposed on the daily headache, also experienced a significant improvement in the frequency of the migraines and their intensity. Migraine prophylaxis through beta-blocking agents and calcium channel antagonists was more efficient after drug-withdrawal therapy.

Drug Induced Headache - Diagnosing The Drug Induced Headache Based On The Course Of Pain, Drug-Taking-Habits, And Combined Drugs

Drug Induced Headache - Diagnosing The Drug Induced Headache Based On The Course Of Pain, Drug-Taking-Habits, And Combined Drugs