Neurological

Wide range of drug interactions in the prevention and treatment of migraines

A narrative review emphasized that drug interactions (DDIs) should be considered when formulating a treatment plan for migraineurs, according to results published in Headache.

The beta blockers propranolol and timolol have been approved by the Food and Drug Administration (FDA) for migraine prevention. Propranolol and timolol are metabolized by the liver and are likely to interact with other drugs such as antidiabetic drugs, antiarrhythmics, neuroleptics, anti-ulcer drugs, lipid-lowering drugs, calcium channel blockers, nonsteroidal anti-inflammatory drugs (NSAIDs), ergot alkaloids, and rizatriptan, among others.

Clinicians should be aware of the wide range of DDIs that are possible for patients taking beta blockers, especially those with comorbid conditions. In addition, beta-blockers have been associated with an increased risk of cardiovascular events, severe hypoglycaemia in patients with diabetes, and depression in the elderly.

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Two classes of antidepressants are approved for migraine prevention, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors. Like beta blockers, these drugs are subject to hepatic metabolism and can interact with antiarrhythmics, antiulcer drugs, antihypertensive drugs, thyroid drugs, anticoagulants, antifungals, antipsychotics, and other antidepressants, among others.

Doctors should be careful with comorbid bipolar disorder or unipolar depression and avoid prescribing antidepressants as they are associated with an increased risk of mania, hypomanic states, and psychotic symptoms.

The anti-epileptic divalproex sodium is approved for migraine prevention. It has been found to interact with antibiotics, enzyme-inducing drugs, and other anti-epileptic drugs. These drugs should not be used if the patient is considering pregnancy.

Recent studies of monoclonal antibodies have shown that these drugs can be effective in preventing migraines. In 2018, fremanezumab and galcanezumab were approved by the FDA and in 2020 eptinezumab. These drugs are metabolized by the cytochrome P450 pathway and are likely to only interact with drugs that affect the same metabolic pathway. No DDIs have been set up at this point.

The Gepants, Rimegepant and Ubrogepant, have been approved by the FDA for the treatment of acute migraines. These drugs are also metabolized by the cytochrome P450 pathway and interact with antibiotics, antifungals, calcium channel blockers, antidepressants, antiarrhythmics, anti-epileptics, and beta-blockers.

Although there are a wide range of prevention options available for migraineurs, it remains a challenge for clinicians in general to successfully manage migraine symptoms, particularly in those with comorbidities. Even in patients with no comorbidities, some preventive therapies interact with the pain relieving medications that patients often take to manage their migraine symptoms.

The review authors concluded that clinicians should understand the metabolic mechanisms of prescribed drugs in order to optimize patient care and avoid potentially harmful DDIs.

Disclosure: Several authors stated links to the pharmaceutical industry. For a full list of the details, see the original article.

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Joshi S, Tepper SJ, Lucas S, Rasmussen S, Nelson R. A narrative overview of the importance of pharmacokinetics and drug interactions of preventive therapies in migraine management. Headache. 2021; 61 (6): 838-853. doi: 10.1111 / head.14135

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