Influence of metabolic state and body composition on the action of pharmacological treatment of migraine

Abstract

Migraine is a disabling neurovascular disorder among people of all ages, with the highest prevalence in the fertile years, and in women. Migraine impacts the quality of life of affected individuals tremendously and, in addition, it is associated with highly prevalent metabolic diseases, such as obesity, diabetes mellitus and thyroid dysfunction. Also, the clinical response to drugs might be affected in patients with metabolic disease due to body composition and metabolic change. Therefore, the efficacy of antimigraine drugs could be altered in patients with both migraine and metabolic disease. However, knowledge of the pharmacology and the related clinical effects of antimigraine drugs in patients with metabolic disease are limited. Therefore, and given the clinical relevance, this article provides a comprehensive overview of the current research and hypotheses related to the influence of metabolic state and body composition on the action of antimigraine drugs. In addition, the influence of antimigraine drugs on metabolic functioning and, vice versa, the influence of metabolic diseases and its hormonal modulating medication on migraine activity is outlined. Future exploration on personalizing migraine treatment to individual characteristics is necessary to enhance therapeutic strategies, especially given its increasing significance in recent decades.

Keywords: CGRP; Diabetes mellitus; Lifestyle; Metabolic disorders; Migraine; Obesity.

Fig. 1

Overview of the influence of obesity on the efficacy of antimigraine drugs. Absorption: Gut permeability is increased and gastric emptying is accelerated in obesity, however more evidence regarding the effect of this on bioavailability is warranted. Distribution: Highly lipophilic drugs could be largely distributed in adipose tissue in obesity; Obesity may impair cardiac function, reducing tissue perfusion. Metabolism: CYP3A4 and CYP2C19 both show reduced activity in obesity. MAO activity might be increased, however more scientific research is needed to confirm this in humans; Obesity can alter liver blood flow. Elimination: Obesity is associated with an initial increase in renal excretion, followed by decreased renal excretion due to chronic kidney disease at later stages; Phase II conjugation can increase in obese morbid obesity

Fig. 2

Overview of the influence of diabetes mellitus on the efficacy of antimigraine drugs. Absorption: Delayed gastric emptying in DM and changes in subcutaneous blood flow might cause decreased absorption. Distribution: Presence of comorbid obesity can increase the distribution of lipophilic drugs; Elevated free fatty acids in DM increases unbound fraction of propranolol. Metabolism: DM might downregulate CYP3A4 and CYP2C19, decreasing metabolism of some drugs; Concerning gepants and CGRP mAbs, contradictory evidence exists on the role of CGRP in glucose metabolism. Elimination: Renal hyperfiltration in diabetes mellitus can cause an increased elimination of renally eliminated drugs

Fig. 3

Overview of the influence of thyroid dysfunction on the efficacy of antimigraine drugs. Absorption: Increased gut motility in hyperthyroidism might cause decreased absorption. Distribution: Possible comorbid obesity in hypothyroidism may increase distribution of lipophilic drugs. Metabolism: Thyroid hormone reduces CYP3A4 and MAO, decreasing metabolism of some drugs; In hyperthyroidism propranolol is a preferred β-blocker, due to blockage of peripheral conversion of fT4 to fT3. Elimination: Renal clearance can be influenced by thyroid state via either an increased or decreased cardiac output in hyper- and hypothyroidism, respectively