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:

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:

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

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%).

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:

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

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.

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.

References

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]
2 Grazzi L, Grignani E, D’Amico D, Sansone E, Raggi A. Is Medication Overuse Drug Specific or Not? Data from a Review of Published Literature and from an Original Study on Italian MOH Patients. Current pain and headache reports. 2018 Nov 1;22(11):71. [Google Scholar]
3 D’Amico D, Grazzi L, Guastafierro E, Sansone E, Leonardi M, Raggi A. Withdrawal failure in patients with chronic migraine and medication overuse headache. Acta Neurologica Scandinavica. 2021 Oct;144(4):408-17. [Google Scholar]
4 Ichikawa M, Katoh H, Kurihara T, Ishii M. Clinical response to valproate in patients with migraine. Journal of Clinical Neurology. 2016 Oct 1;12(4):468-75. [Google Scholar]
5 Stubberud A, Flaaen NM, McCrory DC, Pedersen SA, Linde M. Flunarizine as prophylaxis for episodic migraine: a systematic review with meta-analysis. Pain. 2018 Dec. [Google Scholar]
6 D’Amico D, Grazzi L, Guastafierro E, Sansone E, Leonardi M, Raggi A. Withdrawal failure in patients with chronic migraine and medication overuse headache. Acta Neurologica Scandinavica. 2021 May 25. [Google Scholar]
7 Lund NL, Petersen AS, Fronczek R, Tfelt-Hansen J, Belin AC, Meisingset T, Tronvik E, Steinberg A, Gaul C, Jensen RH. Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments—a consensus article. The Journal of Headache and Pain. 2023 Sep 4;24(1):121. [Google Scholar]
8 Leite PR, de Oliveira CL, Adriano LF, Luiza CM, Vianna PD, Riera R. Melatonin for preventing primary headache: A systematic review. International journal of clinical practice. 2018 May 24:e13203. [Google Scholar]
9 Long R, Zhu Y, Zhou S. Therapeutic role of melatonin in migraine prophylaxis: A systematic review. Medicine. 2019 Jan 1;98(3):e14099. [Google Scholar]
10 Sohn JH, Chu MK, Park KY, Ahn HY, Cho SJ. Vitamin D deficiency in patients with cluster headache: a preliminary study. The journal of headache and pain. 2018 Dec;19(1):54. [Google Scholar]
11 Puliappadamb HM, Maiti R, Mishra A, Jena M, Mishra BR. Efficacy and Safety of Melatonin as Prophylaxis for Migraine in Adults: A Meta-analysis. Journal of Oral & Facial Pain and Headache. 2022;36(3-4). [Google Scholar]
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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