Caffeine in the management of patients with headache

Richard B Lipton, Hans-Christoph Diener, Matthew S Robbins, Sandy Yacoub Garas, Ketu Patel, Richard B Lipton, Hans-Christoph Diener, Matthew S Robbins, Sandy Yacoub Garas, Ketu Patel

Abstract

Caffeinated headache medications, either alone or in combination with other treatments, are widely used by patients with headache. Clinicians should be familiar with their use as well as the chemistry, pharmacology, dietary and medical sources, clinical benefits, and potential safety issues of caffeine. In this review, we consider the role of caffeine in the over-the-counter treatment of headache. The MEDLINE and Cochrane databases were searched by combining "caffeine" with the terms "headache," "migraine," and "tension-type." Studies that were not placebo-controlled or that involved medications available only with a prescription, as well as those not assessing patients with migraine and/or tension-type headache (TTH), were excluded. Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen, acetylsalicylic acid, and ibuprofen, showed significantly improved efficacy in the treatment of patients with TTH or migraine, with favorable tolerability in the vast majority of patients. The most common adverse events were nervousness (6.5%), nausea (4.3%), abdominal pain/discomfort (4.1%), and dizziness (3.2%). This review provides evidence for the role of caffeine as an analgesic adjuvant in the acute treatment of primary headache with over-the-counter drugs, caffeine doses of 130 mg enhance the efficacy of analgesics in TTH and doses of ≥100 mg enhance benefits in migraine. Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine.

Keywords: Acetaminophen; Acetylsalicylic acid; Caffeine; Ibuprofen; Migraine; Tension-type headache.

Conflict of interest statement

Competing interests

Richard B. Lipton has received personal fees from Alder, Allergan, Amgen, Electrocore, eNeura, Boston Scientific, Bristol Meyers Squibb, Dr. Reddys, Eli Lilly, Teva, Vedanta. He has also received grant funding from Alder, Electrocore, Novartis, the Migraine Research Fund, the National Headache Foundation, and the National Institute of Health. Dr. Lipton owns stock in eNeura and Biohaven.

Hans-Christoph Diener has received honoraria from Addex Pharma, Adler, Allergan, Almirall, Amgen, Autonomic Technologies, AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Chordate Medical, Coherex Medical, CoLucid Pharmaceuticals, Electrocore, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologicals, Eli Lilly, La Roche, 3 M Medica, Medtronic, Menarini, Minster Pharmaceuticals, MSD, NeuroScore, Novartis, Johnson & Johnson, Pierre Fabre, Schaper and Brummer, St. Jude Medical Foundation, Weber & Weber, and Pfizer. He has received research funding from Allergan, Almirall, AstraZeneca, Bayer, Electrocore, GlaskoSmithKline, Janssen-Cilag, MSD, Pfizer, the German Science Council, the German Secretary of Education, the European Union, and Teva.

Matthew S. Robbins has received honoraria for educational activities from the American Headache Society, American Academy of Neurology, Medlink, and Springer and has received book royalties from Wiley. He has participated as a site principal investigator for a clinical trial sponsored by eNeura, Inc. with funds sent directly to his institution.

Sandy Yacoub Garas is a salaried employee of GlaxoSmithKline Consumer Healthcare.

Ketu Patel is a salaried employee of GlaxoSmithKline Consumer Healthcare.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Molecular structure of caffeine [18]. The molecular structure of caffeine indicates that it is a part of a group of compounds called trimethyl xanthines, which also includes theobromine and theophylline

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