Medication overuse headache (MOH) is a severe burden to sufferers and its treatment has few evidence-based indications. The aim of this study is to evaluate efficacy and safety of nabilone in reducing pain and frequency of headache, the number of analgesic intake and in increasing the quality of life on patients with long-standing intractable MOH. Thirty MOH patients were enrolled at the University of Modena’s Interdepartmental Centre for Research on Headache and Drug Abuse (Italy) in a randomized, double-blind, active-controlled, crossover study comparing nabilone 0.5 mg/day and ibuprofen 400 mg. The patients received each treatment orally for 8 weeks (before nabilone and then ibuprofen or vice versa), with 1 week wash-out between them. Randomization and allocation (ratio 1:1) were carried out by an independent pharmacy through a central computer system. Participants, care givers, and those assessing the outcomes were blinded to treatment sequence. Twenty-six subjects completed the study. Improvements from baseline were observed with both treatments. However, nabilone was more effective than ibuprofen in reducing pain intensity and daily analgesic intake (p < 0.05); moreover, nabilone was the only drug able to reduce the level of medication dependence (−41 %, p < 0.01) and to improve the quality of life (p < 0.05). Side effects were uncommon, mild and disappeared when nabilone was discontinued. This is the first randomized controlled trial demonstrating the benefits of nabilone on headache, analgesic consumption and the quality of life in patients with intractable MOH. This drug also appears to be safe and well-tolerated. Larger scale studies are needed to confirm these preliminary findings.

Drug interactions are one of the most common causes of side effects in polypharmacy. Alcoholics are a category of patients at high risk of pharmacological interactions, due to the presence of comorbidities, the concomitant intake of several medications and the pharmacokinetic and pharmacodynamic interferences of ethanol. However, the data available on this issue are limited. These reasons often frighten clinicians when prescribing appropriate pharmacological therapies for alcohol use disorder (AUD), where less than 15% of patients receive an appropriate treatment in the most severe forms. The data available in literature regarding the relevant drug-drug interactions of the medications currently approved in United States and in some European countries for the treatment of AUD (benzodiazepines, acamprosate, baclofen, disulfiram, nalmefene, naltrexone and sodium oxybate) are reviewed here. The class of benzodiazepines and disulfiram are involved in numerous pharmacological interactions, while they are not conspicuous for acamprosate. The other drugs are relatively safe for pharmacological interactions, excluding the opioid withdrawal syndrome caused by the combination of nalmefene or naltrexone with an opiate medication. The information obtained is designed to help clinicians in understanding and managing the pharmacological interactions in AUDs, especially in patients under multi-drug treatment, in order to reduce the risk of a negative interaction and to improve the treatment outcomes.

Migraine, a common neurovascular brain disorder, represents a severe and widespread health problem; along with medication‐induced (medication‐overuse) headache, it is the third‐leading cause of disability worldwide. Currently, its therapeutic management remains unsatisfactory for several reasons; up to 40% of migraineurs are eligible for prophylactic treatment, but there are issues of efficacy, safety, and adherence. In recent years the evidence on the role of calcitonin gene‐related peptide (CGRP) in migraine pathophysiology has been consolidated, so new and promising treatments for migraine pain and its possible prevention have been developed. The following review reports the results of the clinical trials conducted so far with each of the new monoclonal antibodies targeting CGRP or its receptor, with particular reference to safety, tolerance, and efficacy in migraine prevention. Moreover, the pharmacological characterization and further developments of each monoclonal antibody are reported, based on current knowledge.

Cluster Headache (CH) is a severe primary headache, with a poorly understood pathophysiology. Complex genetic factors are likely to play a role in CH etiology; however, no confirmed gene associations have been identified. The aim of this study is to identify genetic variants influencing risk to CH and to explore the potential pathogenic mechanisms. We have performed a genome-wide association study (GWAS) in a clinically well-defined cohort of 99 Italian patients with CH and in a control sample of 360 age-matched sigarette smoking healthy individuals, using the Infinium PsychArray (Illumina), which combines common highly-informative genome-wide tag SNPs and exonic SNPs. Genotype data were used to carry out a genome-wide single marker case-control association analysis using common SNPs, and a gene-based association analysis focussing on rare protein altering variants in 745 candidate genes with a putative role in CH. Although no single variant showed statistically significant association at the genome-wide threshold, we identified an interesting suggestive association (P = 9.1 × 10−6) with a common variant of the PACAP receptor gene (ADCYAP1R1). Furthermore, gene-based analysis provided significant evidence of association (P = 2.5 × 10−5) for a rare potentially damaging missense variant in the MME gene, encoding for the membrane metallo-endopeptidase neprilysin. Our study represents the first genome-wide association study of common SNPs and rare exonic variants influencing risk for CH. The most interesting results implicate ADCYAP1R1 and MME gene variants in CH susceptibility and point to a role for genes involved in pain processing. These findings provide new insights into the pathogenesis of CH that need further investigation and replication in larger CH samples.

Background: Chronic migraine (CM) affects about the 2% of the general population and it has been recognized as one of the most-disabling conditions worldwide by the World Health Organization. CM is often associated with the overuse of abortive medication, which determines the worsening of headache itself and the development of a secondary headache called medication overuse headache. The management of these associated conditions is difficult, but a growing amount of evidence is pointing out the effectiveness and the good safety profile of OnabotulinumtoxinA (OnabotA). Despite this, data on OnabotA effects and safety in long-term use lack. The purpose of the present article is to retrospectively assess the efficacy and safety of OnabotA in a cohort of chronic migraineurs with drug overuse from the 18th month of treatment until the third year. Materials and methods: 90 chronic migraineurs with medication overuse were enrolled between January 2013 and February 2017. All patients were treated with OnabotA according to PREEMPT dictates. Before every injection session the headache index, the analgesic consumption, the visual analog scale for pain score, the 36-items short form health survey questionnaire score, the 6-items headache impact test (HIT-6) score and the Zung self-rating anxiety and depression scale scores were collected. Adverse events were carefully registered. A simple linear regression was performed to explore the mean changes in the abovementioned parameters for a single injection session and mean comparison tests were performed using the one-way analysis of variance followed by Tukey–Kramer post-hoc test. Results: A significantly improvement for a single injection was registered for all the above-mentioned parameters. Headache index, analgesic consumption, visual analog pain scale, and 6-items HIT-6 scores were significantly lower than baseline from the 18th month of treatment onwards. The 36-items short form health survey questionnaire scores were significantly higher than baseline at every injections session from the 18th months onwards. Zung scales did not change. No serious adverse events were assessed and no adverse events-related drop-outs were seen. Conclusion: OnabotA effectiveness and safety last until 3 years of therapy, raising the possibility of the use of this therapy even for many years in CM prevention.