Overuse of medications for headache pain

Ross Hauser, MD

If you are reading this article it is very likely that you have been on a long journey trying to find anything that will work for your headaches. If you are like the people that have come to our clinics, your journey has included:

  • frequent emergency room visits,
  • coping with sleep disorders or sleep apnea because the cluster headaches wake you up in the middle of the night,
  • a self-determined decision to stop taking medications that have not helped you,
  • a self-determined decision to stop seeing doctors because some of the ones you have seen have made your situation worse.
  • a consultation for nerve blocks, electrical nerve stimulation, and possible surgery.

Over the years we have seen many patients, who despite seeing many doctors, could not get help for their headaches. Why? Not all headache treatments work for all headaches. There are some patients that we have seen who had great success with a prescription for Verapamil. For these people, this success started to wane as they approached maximum dosage levels and a new prescription or treatment was necessary.

Cluster headache patients had MORE THAN 12 unique prescription drug claims. Medication overuse headaches.

In the medical journal Headache, (1) researchers looked at the medical history of 7589 patients suffering from cluster headaches. They found:

  • 25% of cluster headache patients had MORE THAN 12 unique prescription drug claims.

The most commonly prescribed drug classes for cluster headache patients included:

  • opiate agonists (41%), oxycodone, and hydrocodone as examples
  • corticosteroids (34%),
  • 5HT-1 agonists (32%), intranasal zolmitriptan as example
  • antidepressants (31%),
  • NSAIDs (29%),
  • anticonvulsants (28%),
  • calcium antagonists (27%),
  • and benzodiazepines (22%).

Only 30.4% of cluster headache patients received recognized cluster headache treatments without opioids during the 12-month post-index period. However, these patients were less likely to visit emergency departments or need hospitalizations (26.8%) as compared to cluster headache patients with no pharmacy claims for recognized cluster headache treatments or opioids (33.6%).

  • Note: Notice the difference – not even 7% between those who took medications and needed to visit an emergency room or hospital and those who did not.

Overuse of medications especially indomethacin, eletriptan, and tramadol

In August 2018, headache pain specialists in Italy published these findings in the journal Current Pain and Headache Reports (2):

Here are the points they learned from patients who had failed medication therapy:

  • Overuse of medications especially indomethacin, eletriptan, and tramadol
    • Patients who underwent medication withdrawal treatments were more likely to be overusers of multiple drug classes and overuse higher amounts of symptom relief medications, particularly, indomethacin, eletriptan, and tramadol.
      • Our comment: Notice in the above research that indomethacin often provides complete relief from symptoms. Not for these patients. These people took more than they should and were not benefitting.
  • Frequent relapses (people who were in medication withdrawal programs and relapsed) were more likely to be overusers of opioids or ergotamine and caffeine derivates or of multiple classes, particularly acetylsalicylic acid and ergotamine/caffeine derivatives.
  • The joint results of this review and clinical study do not seem to support the idea that Medication overuse headaches are drug-specific: rather, it points out that all drug classes may induce migraine chronification.

People who suffer most are the “worst patients” to get off of medications

  • Those drugs that are at higher risk of overuse are among those preferred by the “worst” patients, i.e. those who need one or more withdrawal treatments for Medication overuse headaches.
  • Our comment: The withdrawal treatment has now become one of the major treatments the patient needs. The medications have made the patient’s situation much worse.
  • These results reinforce the clinical impression that patients with chronic migraine and medication overuse headaches, particularly the most difficult to treat for their poor response to withdrawal treatments, are characterized by a particular drive towards the consumption of “whatever is likely to be perceived to provide some relief“, despite these drugs that are perceived as “more powerful”, are often indicated as second- or third-line medications.

This 2018 paper has been cited by other researchers in their works.

In October 2021, Italian researchers at the Neurological Institute C. Besta of Milano published their findings (3) on the management of chronic migraine with Medication Overuse Headache. As they note, “management consists of withdrawal therapy, education on medications’ use and prescription of prophylaxis.” While this is a successful program for weening many patients off medications, the researcher here says not enough attention is being paid to those patients where the treatment fails. In their study, 137 patients were managed for drug withdrawal, and 39 of the patients were not successful. Why?

The researchers say: the predictors included day-hospital-based withdrawal (outpatient-based programs), emergency room (ER) access before withdrawal, and baseline headache frequency of more than 69 days in three months. These patients were also suffering from anxiety and depression which did not improve during the study period.

Pain medications do help people. They do not help everyone. Some medications can make the situation worse.

In this section, we will briefly provide some research for you on the various medications you have been prescribed or are being recommended.

Valproic Acid (Valporate)

An October 2016 study in the Journal of Clinical Neurology (4) found that people with a history of hyperlipidemia [including hypertriglyceridemia, hypercholesterolemia, and abnormal levels of low-density lipoprotein (LDL) cholesterol] and hay fever and the complications of depression or other psychiatric disorder would not have a positive response to valproate and display a high risk of inconsistent responses to headache prevention treatment surrounded by Valproic Acid usage.

Flunarizine / Sibelium / Propanolol

A December 2018 study in the journal Pain (5) noted that flunarizine is considered a first-line preventative treatment for cluster migraines.

  • Pooled research comparing numerous studies found flunarizine reduces the headache frequency by 0.4 attacks per 4 weeks compared with placebo. (Statistically half an attack every 4 weeks).
  • The analysis also revealed that the effectiveness of flunarizine prophylaxis (as a prevention from future headaches) is comparable with that of propranolol.
  • The most frequent side effects were sedation and weight increase.

Patients with chronic migraine and medication overuse headache

An October 2021 study (6) from neurologists in Italy discussed the failure of medication withdrawal in patients with chronic migraine and medication overuse headaches. In fact, they describe this as a problem that “Little attention has been given to patients who fail in achieving a successful short-term outcome after withdrawal,” and that the researchers aimed to “describe predictors of failure.”

How the study was done: Methods: Patients with chronic migraine and medication overuse headaches were followed, who underwent withdrawal treatment. Withdrawal failure was defined as the situation in which patients either did not revert from chronic to episodic migraine, were still overusing acute medications, or both did not revert to episodic migraine and kept overusing acute medications.

  • In 39, out of 137 patients, withdrawal was unsuccessful:
    • the predictors included day-hospital (out-patient) based withdrawal, emergency room (ER) access before withdrawal, and baseline headache frequency of more than 69 days out of three months.
    • Patients who failed withdrawal did not improve on medication intake, use of prophylactic and non-pharmacological treatments, and symptoms of anxiety and depression.

Conclusions: “Patients who were treated in day-hospital (out-patient), those who recently attended ER for headache, and those with more than 69 headache/3 months, as well as those with relevant symptoms of anxiety and depression who did not improve, should be closely monitored to reduce the likelihood of non-improvement after structured withdrawal.”

A September 2023 update: Treatments are still unproven and problematic for many

A September 2023 paper in The Journal of Headache and Pain (7) found: “For acute treatment, the main problems are treatment response, availability, costs and, for triptans, contraindications and the maximum use allowed. Intermediate treatment with steroids and greater occipital nerve blocks is effective but cannot be used continuously. Preventive treatment is sparsely studied and overall limited by relatively low efficacy and side effects.”

Vitamins and Herbs? Do they help patients with chronic migraine? Is it a Lack of Sunshine?

We are big proponents for the use of nutrition in healing the body but we have to be realistic. Vitamins and diet can help, they may help a lot, but they may not help at all.

A July 2018 study in the International Journal of Clinical Practice (8) found that when compared with placebo, melatonin did not reduce the number of daily attacks. The good news was that when people took melatonin, it helped reduce daily painkiller analgesic consumption.

A January 2019 study in the journal Medicine, (9) was a little more optimistic if cautiously so. The researchers found that melatonin is very likely to benefit the prevention of migraines, BUT, it takes three months of consumption of melatonin to see benefits, and how much benefit is found is debatable.

A November 2022 study in the Journal of Oral & Facial Pain and Headache (10) suggested that “Melatonin showed a beneficial prophylactic role in migraine, with a better responder rate in comparison to placebo in reducing migraine severity, mean attack duration, mean attack frequency, and analgesic use . . . ”

Vitamin D

In The Journal of Headache and Pain, (11) researchers at Hallym University College of Medicine in Korea suggested that cluster headache attacks may be related to sunlight and vitamin D metabolism. They wrote: “Vitamin D deficiency is common in patients with cluster headache, but the role of vitamin D deficiency is uncertain, except for its seasonal influence (a lack of sunshine).”

A December 2023 study in the Journal of Clinical Pharmacology (12) suggested alpha-lipoic acid (ALA) may have potential benefits as a prophylactic agent for adolescent migraine, with fewer adverse events than existing medications.


1 Choong CK, Ford JH, Nyhuis AW, Joshi SG, Robinson RL, Aurora SK, Martinez JM. Clinical characteristics and treatment patterns among patients diagnosed with cluster headache in US healthcare claims data. Headache: The Journal of Head and Face Pain. 2017 Oct;57(9):1359-74. [Google Scholar]
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12 Puliappadamb HM, Satpathy AK, Mishra BR, Maiti R, Jena M. Evaluation of Safety and Efficacy of Add‐on Alpha‐Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial. The Journal of Clinical Pharmacology. 2023 Dec;63(12):1398-407. [Google Scholar]


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