The preventive effect of the combination of atorvastatin and nortriptyline in migraine-type headache: a randomized, triple-blind, placebo-controlled trial

ABSTRACT

Background and purpose

Migraine ranked as the eighth cause of disability worldwide. Statins with anti-inflammatory and vasodilatory endothelial effects have been introduced as an option for the prevention of migraine-type headaches. The current study aimed to assess the efficacy and tolerability of atorvastatin for the prevention of migraine in adults.

Method

This prospective, triple-blind, randomized controlled clinical trial was performed in adult migraineurs from mid-July 2019 to late-April 2020. Patients were randomly assigned to receive atorvastatin or placebo in combination with nortriptyline for 24-weeks. The frequency of headache was the primary outcome, and intensity of the headache and quality of life (QOL) were the secondary outcomes for this study.

Results

With 34 patients in each arm, 68 patients with migraines based on the International Headache Society (IHS) criteria were enrolled in the study. At week 24, patients in the atorvastatin group experienced significantly fewer migraine attacks than the placebo group (P-value = 0.004). Moreover, there were significant differences between the two groups in QOL at follow-up intervals of 14 (P-value = 0.001) and 24 (P-value < 0.001) weeks. However, no significant difference was observed in the intensity of headache was observed in both groups (P-value > 0.05). The most common adverse effects in intervention and control groups were constipation and insomnia, respectively.

Conclusion

In patients with migraine, prophylaxis with atorvastatin significantly improved the frequency of headache and QOL over 24 weeks compared with placebo with no effect on the intensity of headache. Statins seem to be a potential promising drug for prophylaxis of migraine headaches.

KEYWORDS:

• Migraine disorders
• headache
• atorvastatin
• clinical status

Acknowledgments

This article is derived from the thesis “Evaluation of the effectiveness of Atorvastatin and Nortriptyline in the prophylaxis of migraine attacks in patients whit migraine compared to standard treatment Nortriptyline: a randomized triple-blind controlled clinical trial” supervised by Assistant Professor Dr. Fatemeh Saghafi and submitted by Dr. Fatemeh Saghafi to the Faculty of Pharmacy of Shahid Sadoughi University of Medical Sciences, Yazd, Iran, in partial fulfillment of the requirements for Doctor of Pharmacy (Pharm.D.) degree.

Authors’ contributions

F.S. and A.S. were involved in the conception and design of the study. R.R. and A.S. collected the data. F.M. and R.R. prepared the placebo tablets. F.S., A.R., and R.R. analyzed the data and drafted the first manuscript. All authors read and approved the final manuscript.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Consent for publication

Consent for publication was agreed upon in the written consent forms signed by the patients.

Competing interests

The authors declare that they have no competing interests regarding the publication of this paper.

Ethics approval and consent to participate

All patients signed an informed consent form prior to participation in the study. All methods were carried out following relevant guidelines and regulations. This study was approved by the Ethics Committee of Yazd University of Medical Sciences (Ethics ID:IR.SSU.MEDICINE.REC.1398.197). This study was also approved in the Iranian Registry of Clinical Trials (IRCT20190620043953N2) on the date of 02/04/2020.

Additional information

Funding

The manuscript was financially supported by a grant from the Research and Technology Department of Shahid Sadoughi University of Medical Sciences (grant no. 6669), Yazd, Iran. The role of the funding was in study design, data collection, and analysis.