Efficacy and tolerability of combined dipyrone, isometheptene and caffeine in the treatment of mild-to-moderate primary headache episodes

Abstract

The efficacy and tolerability of a combination of dipyrone 600 mg, isometheptene 60 mg and caffeine 60 mg for the acute treatment of mild-to-moderate episodic primary headaches were evaluated against paracetamol 1000 mg and placebo. A total of 84 adult patients with two to six primary headache episodes (mild or moderate severity) per month were enrolled in this prospective, multicenter, randomized, two-period crossover study. Patients had a mean of 4.4 headache episodes/month (mean duration: 13 h; mean severity: 50.5 mm; assessed by visual analog scale (VAS). In patients with no improvement, rescue medications were allowed after 2 h. The primary outcome parameter was sustained pain-free rate. Secondary outcomes were evolution of pain severity (at 30, 60, 90, 120 and 240 min after treatment), presence of associated symptoms, and recurrence of episodes. Analyses included 243 headache episodes (81 patients). Sustained pain-free rates were 57.1% for combination therapy, 46.8% for paracetamol and 46.8% for placebo (not statistically significant). Pain improvement (assessed by VAS) occurred in 72.5, 54.5 and 49.2% of patients, respectively, after 120 min. The mean reduction in pain severity (assessed by VAS) was significantly lower in those receiving placebo and paracetamol compared with combination therapy (p < 0.001 at 90 and 120 min). Fewer patients required rescue medication after receiving combination therapy (18.4%), compared with paracetamol (37.7%; p = 0.008) or placebo (43.8%; p = 0.0007). Adverse events were infrequent and mild. We conclude that, despite failing to meet the primary outcome, the combination of dipyrone, isometheptene and caffeine is effective for the acute treatment of mild-to-moderate primary headache episodes, with excellent tolerability.

Keywords::

• attack treatment
• headache
• migraine
• mild-to-moderate headache
• primary headache
• tension-type headache

Acknowledgements

The authors thank Francisco Engelken for his assistance with the development of the study protocol and for providing support in writing the manuscript; Gabriela Stangenhaus (Statistika Consultoria) for the statistical analysis; Janaina M Bigal (Publish Your Paper) for the careful revision and suggestions to the manuscript, and editorial assistance.

The authors acknowledge the coinvestigators who participated in this study across Brazil: Thais Rodrigues Villa and Mariana Machado Pereira Pinto from Division of Investigation and Treatment of Headaches of Hospital São Paulo, Escola Paulista de Medicina (EPM) at the Federal University of São Paulo (UNIFESP); José Otávio Dorsewski Soares and Marlise de Castro Ribeiro, Professor of Clinical Neurology from Department of Neurology, Federal University of Health Sciences of Porto Alegre (UFCSPA – RS); Ricardo Krause Martinez de Souza from Division of Headaches, Federal University of Parana; Sector of Neurology, Neurology Institute, Curitiba, Paraná.

Financial & competing interests disclosure

The study was sponsored by Nycomed Pharma (manufacturer of the combination of dipyrone, isometheptene and caffeine) through an unrestricted grant (medical grant). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial assistance was provided by David P Figgitt PhD, Content Ed Net; funding for this assistance was provided by Nycomed Pharma, Brazil.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.