Introduction: Since the definition of chronic migraine as a new disease entity in 2004, numerous clinical trials have examined the efficacy of preventive treatments in chronic migraine. Our aim was to assess the adherence of these trials to the Guidelines of the International Headache Society published in 2008.

Methods: We searched PubMed for controlled clinical trials investigating preventive treatment for chronic migraine in adults designed after the release of the Guidelines and published until December 2017. Trial quality was evaluated with a 13-item scoring system enlisting essential recommendations adapted from the Guidelines.

Results: Out of 3352 retrieved records, we included 16 papers in the analysis dealing with pharmacological treatment of chronic migraine. The median score was 6.5 (range 2–13). All trials were randomized, the large majority (81.25%) were placebo-controlled and double-blinded (87.5%). Adherence was lowest on i) a priori definition of outcomes (31.25%), ii) primary endpoint definition (37.5%%) and iii) trial registration (37.5%).

Discussion: Most clinical trials adhered to the recommendations of the IHS, whereas adherence to migraine-specific recommendations was lower. Greater awareness and adherence to the guidelines are essential to improve the quality of clinical trials, validity of publications and the generalizability of the results.