Safety and Risk of Medication Overuse Headache in Lasmiditan and Second-Generation Gepants: A Rapid Review.
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ABSTRACT:
SUBMITTER: Lo Castro F
PROVIDER: S-EPMC8627250 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Safety and Risk of Medication Overuse Headache in Lasmiditan and Second-Generation Gepants: A Rapid Review.
Lo Castro Flavia F Guerzoni Simona S Pellesi Lanfranco L
Drug, healthcare and patient safety 20211123
The treatment of migraine is often complicated by insufficient headache relief, a miscellany of side effects and the risk of developing Medication Overuse Headache (MOH). Novel acute therapies have been recently developed and are now in the early post-marketing phase. Lasmiditan is a highly selective serotonin receptor agonist that binds to the 5-HT<sub>1F</sub> receptor, while ubrogepant and rimegepant antagonize the calcitonin gene-related peptide receptor. All three medications are now prescr ...[more]
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Project description: Not available
| S-EPMC4759138 | biostudies-literature
Project description:Medication-overuse headache (MOH) is a secondary form of headache related to the overuse of triptans, analgesics and other acute headache medications. It is believed that MOH and substance addiction share some similar pathophysiological mechanisms. In this study we examined the whole brain resting state functional connectivity of the dorsal and ventral striatum in 30 patients (15 MOH and 15 non-MOH patients) to investigate if classification algorithms can successfully discriminate between MOH and non-MOH patients on the basis of the spatial pattern of resting state functional connectivity of the dorsal and ventral striatal region of interest. Our results indicated that both nucleus accumbens and dorsal rostral putamen functional connectivity could discriminate between MOH and non-MOH patients, thereby providing possible support to two interpretations. First, that MOH patients show altered reward functionality in line with drug abusers (alterations in functional connectivity of the nucleus accumbens). Second, that MOH patients show inability to break habitual behavior (alterations in functional connectivity of the dorsal striatum). In conclusion, our data showed that MOH patients were characterized by an altered functional connectivity of motivational circuits at rest. These differences could permit the blind discrimination between the two conditions using classification algorithms. Considered overall, our findings might contribute to the development of novel diagnostic measures.
| S-EPMC4900511 | biostudies-literature
Project description:Medication-overuse headache is an increasing problem in headache clinics and therapy includes drug withdrawal. Although it has been shown that the orbitofrontal cortex is hypo-metabolic and exhibits less gray matter in these patients the functional role of this finding is still unclear as virtually no functional imaging studies exploring withdrawal of medication have been published. We compared structural and functional magnetic resonance images of 18 patients before and after drug withdrawal with age and gender matched controls using a well-established trigeminal, nociceptive fMRI paradigm. We reproduced structural changes in the orbitofrontal cortex of the patients which highly correlated with the clinical outcome of medication withdrawal. The neuronal activity before drug withdrawal in pain related regions (operculum, insula, spinal trigeminal nucleus) was reduced compared to after drug withdrawal and the orbitofrontal cortex showed a reduced functional connectivity to the nociceptive input region (spinal trigeminal nucleus) and the cerebellum which regained after withdrawal. These data suggest the seminal role of the orbitofrontal cortex as a mediator between bottom-up and top-down stream in headache processing.
| S-EPMC6026656 | biostudies-literature
Project description:BACKGROUND AND AIMS:Medication-overuse headache (MOH) is a common chronic headache caused by overuse of headache analgesics. It has similarities with substance dependence disorders. The treatment of choice for MOH is withdrawal of the offending analgesics. Behavioral brief intervention treatment using methods adapted from substance misuse settings is effective. Here we investigate the severity of analgesics dependence in MOH using the Severity of Dependence Scale (SDS), validate the SDS score against formal substance dependence diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and examine whether the SDS predicts successful withdrawal. METHODS:Representative recruitment from the general population; 60 MOH patients, 15 chronic headache patients without medication overuse and 25 population controls. Headaches were diagnosed using the International Classification of Headache Disorders, medication use was assessed and substance dependence classified according to the DSM-IV. The SDS was scored by interviewers blinded to patient group. Descriptive statistics were used and validity of the SDS score assessed against a substance dependence diagnosis using ROC analysis. RESULTS:Sixty-two percent of MOH patients overused simple analgesics, 38% centrally acting analgesics (codeine, opiates, triptans). Fifty percent of MOH patients were classified as DSM-IV substance dependent. Centrally active medication and high SDS scores were associated with higher proportions of dependence. ROC analysis showed SDS scores accurately identified dependence (area under curve 88%). Lower SDS scores were associated with successful withdrawal (P = 0.004). CONCLUSIONS:MOH has characteristics of substance dependence which should be taken into account when choosing treatment strategy. TRIAL REGISTRATION:Based on data collected in previously reported randomized BIMOH trial (; in the present manuscript, Clinical trials registration number: NCT01314768). The present part, however, represents observational data and is not a treatment trial.
| S-EPMC6791494 | biostudies-literature
Project description:BackgroundMigraine is a debilitating neurological disorder that presents significant management challenges, resulting in underdiagnosis and inappropriate treatments, leaving patients at risk of medication overuse (MO). MO contributes to disease progression and the development of medication overuse headache (MOH). Predicting which migraine patients are at risk of MO/MOH is crucial for effective management. Thus, this systematic review aims to review and critique available prediction models for MO/MOH in migraine patients.MethodsA systematic search was conducted using Embase, Scopus, Medline/PubMed, ACM Digital Library, and IEEE databases from inception to April 22, 2024. The risk of bias was assessed using the prediction model risk of bias assessment tool.ResultsOut of 1,579 articles, six studies with nine models met the inclusion criteria. Three studies developed new prediction models, while the remaining validated existing scores. Most studies utilized cross-sectional and prospective data collection in specific headache settings and migraine types. The models included up to 53 predictors, with sample sizes from 17 to 1,419 participants. Traditional statistical models (logistic regression and least absolute shrinkage and selection operator regression) were used in two studies, while one utilized a machine learning (ML) technique (support vector machines). Receiver operating characteristic analysis was employed to validate existing scores. The area under the receiver operating characteristic (AUROC) for the ML model (0.83) outperformed the traditional statistical model (0.62) in internal validation. The AUROCs ranged from 0.84 to 0.85 for the validation of existing scores. Common predictors included age and gender; genetic data and questionnaire evaluations were also included. All studies demonstrated a high risk of bias in model construction and high concerns regarding applicability to participants.ConclusionThis review identified promising results for MO/MOH prediction models in migraine patients, although the field remains limited. Future research should incorporate important risk factors, assess discrimination and calibration, and perform external validation. Further studies with robust designs, appropriate settings, high-quality and quantity data, and rigorous methodologies are necessary to advance this field.
| S-EPMC11450990 | biostudies-literature
Project description:BackgroundControversy exists whether prophylactic drugs are necessary in the treatment of medication overuse headache (MOH).ObjectivesTo determine comparative benefits and safety of available drugs for the treatment of MOH including elimination of medication overuse (MO).MethodsWe systematically reviewed randomized controlled trials though an extensive literature search comparing different drug effects on MOH. A random-effect network meta-analysis was conducted to rank comparative effects of interventions. Outcome improvements from baseline include responder rate defined as ≥ 50% reduction of headache frequency, proportion of patients who revert to no acute medication overuse (nMO), and reduction in monthly headache and acute medication intake frequency. Certainty of evidence was classified using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE).ResultsOf 8,248 screened publications, 28 were eligible for analysis. Topiramate was found to be beneficial based on its responder rate (odds ratios [OR] 4.93), headache frequency (weighted mean difference [WMD] -5.53) and acute medication intake frequency (WMD - 6.95), with fewer safety issues (i.e., tolerability, or more adverse events) than placebo (OR 0.20). Fremanezumab, galcanezumab and botulinum toxin type A (BTA) were beneficial for increased responder rates (OR 3.46 to 3.07, 2.95, and 2.57, respectively). For reversion to nMO, eptinezumab, fremanezumab and BTA were superior to placebo (OR 2.75 to 2.64, 1.87 to1.57, and 1.55, respectively). Eptinezumab, fremanezumab, erenumab 140 mg, and BTA were more efficacious than erenumab 70 mg (OR 3.84 to 3.70, 2.60 to 2.49, 2.44 and 2.16, respectively) without differences in safety and tolerability.ConclusionDespite lower safety and greater intolerability issues, topiramate has large beneficial effects probably on increasing responder rates, reducing headache frequency, and might reduce monthly medication intake frequency. Fremanezumab, galcanezumab, and eptinezumab are promising for increasing responder rates. For reversion to nMO, eptinezumab has large beneficial effects, fremanezumab has a smaller effect. BTA might have a moderate effect on responder rates and probably has a small effect on reversion to nMO.Trial registrationPROSPERO, CRD42021193370.
| S-EPMC11457448 | biostudies-literature
Project description:BackgroundMedication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or other acute headache compounds. It has been suggested that MOH could share some pathogenetic mechanisms with other kinds of drug addiction. In this regard, histone deacetylases 3 (HDAC3) seems to have a role in the memory processes involved in extinction of drug-seeking behavior in animal models. HDAC3 is inhibited by sodium valproate, a drug with proven efficacy in MOH. Recent evidence suggests an involvement of genetic factors in predisposition to medication overuse.ResultsIn this association study, we sequenced all exons, intron/exon junctions, and 3'-5'UTR regions of HDAC3 in 23 MOH patients to investigate its role in medication overuse. Associations between genotypes with continuous and dichotomous clinical characteristics were tested by multivariate analysis and Fisher's exact test, respectively. Sequencing of HDAC3 revealed six single-nucleotide polymorphisms. The G allele of rs2530223 was significantly associated with the number of acute medications/month used and with the number of days/month in which medications were used (p = 0.006 and p = 0.007, respectively), but neither with headache frequency or intensity. None of the single-nucleotide polymorphisms (SNPs) was associated with clinical characteristics or response to sodium valproate.ConclusionsHDAC3 could be implicated in excessive medication consumption in MOH patients. Our preliminary findings provide support for the need of further investigation on larger independent samples to confirm and extend the role of HDAC3 in medication overuse headache.
| S-EPMC4635554 | biostudies-literature
Project description:ObjectiveTo estimate the relative frequency of acute medication overuse (AMO) among people with episodic migraine and chronic migraine, to characterize the types of acute medications overused for migraine, and to identify factors associated with AMO.MethodsWe analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study (ClinicalTrials.gov, NCT01648530), a cross-sectional and longitudinal internet study that included a systematic sampling of the US population. From September 2012 to November 2013, the CaMEO Study respondents participated in different modules to collect data on the clinical course of migraine, family burden, barriers to care, endophenotypes, and comorbidities. Among people who met the criteria for migraine consistent with the International Classification of Headache Disorders, third edition (ICHD-3), we evaluated types and frequency of medications used for headache/migraine, selected comorbidities, and emergency department (ED) and urgent care (UC) use. AMO was defined by days per month of medication use as specified by ICHD-3 criteria for medication overuse headache (MOH) without the requirement for ≥15 monthly headache days (MHDs). Nested, multivariable binary logistic regression modeling was used to identify factors associated with an increased risk of AMO.ResultsOf 16,789 CaMEO respondents with migraine, 2,975 (17.7%) met the AMO criteria. Approximately 67.9% (2,021/2,975) of AMO respondents reported <15 MHDs. Simple analgesics, combination analgesics, and opioids were the medication classes most commonly overused. Factors associated with AMO in the final multivariable logistic regression model included ≥15 MHDs, moderate to severe disability, severe migraine interictal burden, use of preventive medication, and an ED/UC visit for headache within 6 months.ConclusionsApproximately two-thirds of respondents with AMO reported <15 MHDs and therefore did not meet the criteria for MOH. Those with AMO had greater disease burden and increased ED/UC utilization relative to people with migraine but not AMO.
| S-EPMC8382341 | biostudies-literature
Project description:BackgroundMedication-overuse headache (MOH) is caused by the regular use of medications to treat headache. There has been a lack of research into awareness of MOH. We distributed an electronic survey to undergraduate students and their contacts via social networking sites. Analgesic use, awareness of MOH, perceived change in behaviour following educational intervention about the risks of MOH and preferred terminology for MOH was evaluated.Findings485 respondents completed the questionnaire (41% having received healthcare training). 77% were unaware of the possibility of MOH resulting from regular analgesic use for headache. Following education about MOH, 80% stated they would reduce analgesic consumption or seek medical advice. 83% indicated that over the counter analgesia should carry a warning of MOH. The preferred terminology for MOH was painkiller-induced headache.ConclusionsThis study highlights the lack of awareness of MOH. Improved education about MOH and informative packaging of analgesics, highlighting the risks in preferred lay terminology (i.e., painkiller-induced headache), may reduce this iatrogenic morbidity and warrants further evaluation.
| S-EPMC3942071 | biostudies-literature
Project description:ObjectivesThe management of chronic migraine (CM) with Medication Overuse Headache (MOH) consists of withdrawal therapy, education on medications' use and prescription of prophylaxis. Little attention has been given to patients who fail in achieving a successful short-term outcome after withdrawal: we aim to describe predictors of failure.MethodsPatients with CM and MOH were enrolled at the Neurological Institute C. Besta of Milano, and included if they completed the three months follow-up. Withdrawal failure was defined as the situation in which patients either did not revert from chronic to episodic migraine (EM), were still overusing acute medications, or both did not revert to EM and kept overusing acute medications. Predictors of failure were addressed with a logistic regression, and for all variables, the longitudinal course in the two groups was described.ResultsIn 39, out of 137 patients, withdrawal was unsuccessful: the predictors included day-hospital-based withdrawal (OR: 2.37; 95% CI: 1.06-5.29), emergency room (ER) access before withdrawal (OR: 2.81; 95% CI: 1.13-6.94) and baseline headache frequency >69 days/three months (OR: 2.97; 95% CI: 1.32-6.65). Patients who failed withdrawal did not improve on medications intake, use of prophylactic and non-pharmacological treatments, symptoms of anxiety and depression.ConclusionsPatients who were treated in day-hospital, those who recently attended ER for headache, and those with more than 69 headache/3 months, as well as to those with relevant symptoms of anxiety and depression who did not improve should be closely monitored to reduce likelihood of non-improvement after structured withdrawal.
| S-EPMC8453823 | biostudies-literature