Medication Overuse Headache.

BACKGROUND: Medication overuse headache (MOH) is one of the highly disabling headache disorder and affects about 1% of the population of the world. It is associated with the development of headache for 15 days or more, with consumption of acute symptomatic medications for 10-15 days (depending on the class of drug, like, simple analgesics, triptans, and opioids) in a month, used for relief of headache for three or more months, in a known patient of primary headache disorder. OBJECTIVE: The aim of this study was to review the topic of MOH and present the details of this disorder with an emphasis on recent updates in the field of pathophysiology and treatment. MATERIAL AND METHODS: Literature search was performed in the PubMed/MEDLINE and Cochrane database with appropriate keywords and relevant full-text articles were reviewed for writing this article. RESULTS: Over the years, the concept of MOH has evolved, although the exact pathophysiology is still being explored. In a susceptible individual interplay of genetics, change in pain pathways, changes in areas of the brain associated with the perception of pain, and changes in the neurotransmitters have been implicated. It has to be differentiated from other secondary chronic daily headache disorders, by a careful history, targeted examination, details of intake of medications. Treatment predominantly involves patient education, removal of the offending agent, and initiation of prophylactic medications for primary headache disorder in the outpatient or inpatient services. CONCLUSIONS: MOH is a secondary headache disorder, which should be considered in any chronic headache patient. There are various pathophysiological mechanisms attributed to its development. Management includes educating the patients about the disorder, detoxification, and prophylactic therapy.

Clinical characterization of delayed alcohol-induced headache: A study of 1,108 participants.

OBJECTIVE: To evaluate the International Classification of Headache Disorders (ICHD) criteria and to characterize the clinical phenotype of delayed alcohol-induced headache (DAIH). METHODS: We conducted a cross-sectional study of university students who voluntarily consumed alcohol and experienced headache. Participants completed a survey that included demographic and clinical data. We analyzed the phenotype of the headache, validated ICHD phenotype criteria for DAIH, and analyzed whether participants fulfilled criteria for low-CSF-pressure headache or migraine. RESULTS: A total of 1,108 participants were included (58% female, mean age 23 years, 41% with headache history). Mean alcohol intake was 158 g; spirits were consumed by 60% of the participants; beer was consumed by 41%; and wine was consumed by 18%. The ICHD criteria for DAIH were met in 95% of the participants. Headache duration (mean, 6.7 hours) correlated with total grams of alcohol consumed (r = 0.62, p = 0.03). Pain was bilateral in 85% of patients with predominantly frontal topography (43%). Pain quality was mainly pressing (60%) or pulsatile (39%) and was aggravated by physical activity in 83% of participants. ICHD low-CSF pressure-headache criteria were fulfilled in 58% of patients, and migraine criteria were fulfilled by 36%. CONCLUSIONS: DAIH is a moderate-intensity headache, is typically bilateral, and presents with frontal predominance and a pressing quality. The phenotype of DAIH combines features of both migraine and low-CSF-pressure headaches.

Delta opioid receptor agonists are effective for multiple types of headache disorders.

Headaches are highly disabling and are among the most common neurological disorders worldwide. Despite the high prevalence of headache, therapeutic options are limited. We recently identified the delta opioid receptor (DOR) as an emerging therapeutic target for migraine. In this study, we examined the effectiveness of a hallmark DOR agonist, SNC80, in disease models reflecting diverse headache disorders including: chronic migraine, post-traumatic headache (PTH), medication overuse headache by triptans (MOH), and opioid-induced hyperalgesia (OIH). To model chronic migraine C57BL/6J mice received chronic intermittent treatment with the known human migraine trigger, nitroglycerin. PTH was modeled by combining the closed head weight drop model with the nitroglycerin model of chronic migraine. For MOH and OIH, mice were chronically treated with sumatriptan or morphine, respectively. The development of periorbital and peripheral allodynia was observed in all four models; and SNC80 significantly inhibited allodynia in all cases. In addition, we also determined if chronic daily treatment with SNC80 would induce MOH/OIH, and we observed limited hyperalgesia relative to sumatriptan or morphine. Together, our results indicate that DOR agonists could be effective in multiple headache disorders, despite their distinct etiology, thus presenting a novel therapeutic target for headache.

CO poisoning as an associated risk factor for CVT.

We report a 24year old female who presented with sudden and severe headaches after recent carbon monoxide poisoning. Imaging revealed an acute cerebral venous thrombosis. Prior studies have suggested that carbon monoxide is a risk factor for an acute hypercoagulable state (i.e. DVT). However, little data is available regarding the correlation between carbon monoxide poisoning and cerebral venous thrombosis. This case demonstrates that such a correlation should be considered in acute intracerebral thrombotic events.

Acute intractable headache and oculomotor nerve palsy associated with nicorandil: A case report.

Acute non-traumatic headaches with neurological deficits alarm emergency department (ED) physicians. Typically, a sudden headache with oculomotor nerve palsy involving a pupil indicates the possibility of a subarachnoid hemorrhage (SAH) due to an aneurysm originating from the posterior communicating artery. For the ED physician, thinking beyond the possibility of an SAH can be crucial. Here, we report on a 59-year-old woman who presented to the ED with an intractable headache and right ptosis. She had previously received nicorandil for paroxysmal atrial fibrillation in the cardiology clinic. Her vital signs were stable upon ED arrival. Neurological examination revealed a mild anisocoria with a sluggish response to light stimuli in the right eye. Adduction, supraduction, and infraduction were also limited in the right eye. Nuchal rigidity was not apparent. An urgent brain magnetic resonance image (MRI) with angiography was requested to assess for possible SAH, but revealed no aneurysm. Cerebrospinal fluid analysis was also unremarkable. The patient's headache and oculomotor nerve palsy improved completely after discontinuation of nicorandil for 3 days. To the best of our knowledge, this is the first case report on side effects of nicorandil presenting as a severe headache with reversible oculomotor nerve palsy involving a pupil, symptoms which mimicked a possible SAH due to aneurysm.

Caffeine and headache: specific remarks. / Cafeína y cefalea: consideraciones especiales.

Caffeine is the most widely used psychostimulant worldwide. Excessive caffeine consumption induces a series of both acute and chronic biological and physiological changes that may give rise to cognitive decline, depression, fatigue, insomnia, cardiovascular changes, and headache. Chronic consumption of caffeine promotes a pro-nociceptive state of cortical hyperexcitability that can intensify a primary headache or trigger a headache due to excessive analgesic use. This review offers an in-depth analysis of the physiological mechanisms of caffeine and its relationship with headache.

A Phase 3 Study to Evaluate the 1-Year Efficacy and Safety of Udenafil 75 mg Once Daily in Patients With Erectile Dysfunction.

INTRODUCTION: Once-daily administration of phosphodiesterase type 5 inhibitors has been shown to correct erectile dysfunction (ED). AIM: To evaluate the long-term efficacy and safety after once-daily oral administration of udenafil 75 mg in men with ED. METHODS: This clinical trial was an open-label, fixed-dose, 24-week extension study (DA8159_EDDL_III) of a 24-week double-blinded efficacy and safety study of once-daily udenafil (parent study: DA8159_EDD_III). Subjects received udenafil 75 mg once daily for 24 weeks during this extension study, and the follow-up visit occurred during the 4-week ED treatment-free period. MAIN OUTCOME MEASURES: Subjects were asked to complete the International Index of Erectile Function questionnaire and the Global Assessment Questionnaire at the 24-week extension and after the 4-week ED treatment-free period, and the development of adverse drug reactions was investigated. RESULTS: In total, 302 subjects were enrolled in this extension study. Improvement was shown with an increased erectile function (EF) domain score compared with baseline (14.60 ± 4.57) at extension week 48 (23.98 ± 5.44) and a slight increase in EF domain score compared with the last time point (week 24) of the parent study (P < .001). The Global Assessment Questionnaire showed a high improvement rate of 95.4% at the extension 48-week time point. For shift to normal, almost half the subjects (45.1%) recovered "normal" EF, and 14.2% of subjects reported normal erections after the 4-week ED treatment-free period. The occurrence rate of adverse drug reactions was 8%, which consisted mainly of flushing and headache. CONCLUSION: Once-daily dosing of udenafil 75 mg showed excellent efficacy and safety with long-term administration and allowed a more spontaneous sexual life.

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes.

OBJECTIVE: Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. METHODS: A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. RESULTS: In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. CONCLUSION: In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. TRIAL REGISTRATION: ClincialTrials.gov, clinicaltrials.gov, NCT00069329.

Adverse drug reactions of systemic antihistamines in children in the Netherlands.

BACKGROUND: Antihistamines are used for the treatment of allergic rhinitis, allergic conjunctivitis, chronic spontaneous urticaria and atopic eczema. OBJECTIVE: To study the reports of adverse drug reactions (ADRs) in children using antihistamines to provide prescribers with an overview of the possible toxicity. DESIGN: We studied ADRs in children reported to the Netherlands Pharmacovigilance Centre Lareb in the years 1991-2014, assessed the Naranjo score and, when possible, computed the reporting OR. RESULTS: Serious ADRs included one death (malignant neuroleptic syndrome), cardiac arrhythmia (one case) and convulsions (three cases). Skin eruptions, headache and somnolence were the most frequently reported ADRs. Aggression and agitation were also reported. CONCLUSIONS: Toxicity can occur with second-generation antihistamines. The main toxicity relates to skin eruptions and central nervous system problems.

Medication overuse headache in children and adolescents.

Medication overuse headache can be described as a chronic headache, presenting 15 or more days per month, in a patient who abuses symptomatic drugs. It has been called an unrecognized epidemic; this is in part true for adults, but is certainly so for children and adolescents. This paper reviews existing data concerning epidemiology, etiopathogenesis and treatment options, with a focus on pediatric age. This leads to evidence of a relevant number of still unanswered questions and some possible strategies to help children and adolescents with this disabling disorder.

Comparison of the efficacy of ondansetron and granisetron to prevent postoperative nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis.

BACKGROUND/AIMS: Our purpose was to assess the prophylactic antiemetic effects of ondansetron versus granisetron for laparoscopic cholecystectomy. METHODS: We searched Medline, Cochrane Central Register of Controlled Trials, PubMed, Embase, Science Citation Index Expanded, Foreign Medical Journal Full-Text Service, China National Knowledge Infrastructure Whole Article Database, Chinese Biomedical Database, and the Google Scholar. We calculated the risk ratio (RR) with 95% confidence interval (CI) for dichotomous data. The χ(2) test and I(2) value were used to assess heterogeneity. RESULTS: The merged early incidence of postoperative nausea and vomiting (PONV) in ondansetron group (42.9%) was higher than granisetron group (34.3%) (RR = 1.25, 95% CI, 0.82-1.92, P=0.31, I(2) = 48%). The merged total incidence of PONV in ondansetron group (38.7%) was higher than granisetron group (34.2%) (RR = 1.13, 95% CI, 0.82-1.56, P = 0.46, I(2) = 39%), although these differences were not statistically significant. CONCLUSIONS: Ondansetron is equivalent to granisetron for preventing early and total incidence of PONV after laparoscopic cholecystectomy.

Comentarios al artículo «Cefalea postpunción dural en obstetricia» / Comments on the article "Postdural puncture headache in obstetrics"

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Risk of development of medication overuse headache with nonsteroidal anti-inflammatory drug therapy for migraine: a critically appraised topic.

BACKGROUND: The development of medication overuse headache (MOH) is associated with frequent use of analgesics, especially opiates, for treatment of primary headache disorders, particularly migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat migraine. OBJECTIVE: To critically evaluate evidence estimating the risk of MOH associated with NSAID therapy in patients with migraine. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and headache neurology content experts. RESULTS: The 1-year incidence of MOH was 2.5%. In patients with low (0 to 4 d monthly) to moderate (5 to 9 d monthly) baseline headache frequency, NSAIDs were not associated with progression to MOH and may be protective (odds ratio=0.31; 95% confidence interval, 0.27-0.34). However, in patients with a high baseline headache frequency (10 to 14 d monthly), NSAIDs are associated with progression to MOH (odds ratio=1.93; 95% confidence interval, 1.82-2.06). CONCLUSIONS: Acute NSAID therapy is associated with progression to MOH in migraineurs with a high baseline migraine frequency but may be protective in patients with low baseline headache frequency. However, a causal role for NSAIDs in progression from episodic to chronic headache has not been established.

[Chronic migraine and headache by medication overuse. Evolution and revision of classification]. / Chronische Migräne und Kopfschmerz bei Medikamentenübergebrauch. Evolution und Revision der Klassifikation.

The first International classification of headache disorders (ICHD-I) described migraine as a recurring headache disorder manifesting in attacks lasting 4-72 h. The headache frequency was not considered in these first diagnostic criteria of migraine. Thus, a chronic migraine with at least 15 migraine days per month was only included in the ICHD-II in 2004. Meanwhile, the diagnosis of chronic daily headache and transformed migraine had been established in the USA. The term transformed migraine describes the transformation of an episodic migraine into a chronic one, whether medication overuse had been present or not. Up till now a widely accepted definition of chronic migraine and medication overuse headache has not been established due to different views. An overview of the evolution of the diagnostic criteria for both headache disorders in recent years is provided.

In-patient versus out-patient withdrawal programmes for medication overuse headache: a 2-year randomized trial.

BACKGROUND: Medication-overuse headache (MOH) management usually includes a medication withdrawal. The choice of withdrawal modalities remains a matter of debate. METHODS: We compared the efficacy of in-patient versus out-patient withdrawal programmes in 82 consecutive patients with MOH in an open-label prospective randomized trial. The main outcome measure was the reduction in number of headache days after 2 months and after 2 years. The responders were defined as patients who had reverted to episodic headaches and to an intake of acute treatments for headache less than 10 days per month. RESULTS: Seventy-one patients had a complete drug withdrawal (n = 36 in the out-patient group; n = 35 in the in-patient group). The reduction of headache frequency and subjective improvement did not differ between groups. The long-term responder rate was similar in the out- and in- patient groups (44% and 44%; p = 0.810). The only predictive factor of a bad outcome 2 years after withdrawal was an initial consumption of more than 150 units of acute treatments for headache per month (OR = 3.1; 95% confidence interval 1.1-9.3; p = 0.044). CONCLUSION: Given that we did not observe any difference in efficacy between the in- and out-patient withdrawals, we would recommend out-patient withdrawal in the first instance for patients with uncomplicated MOH.

Genomic expression patterns in medication overuse headaches.

BACKGROUND: Chronic daily headache (CDH) and chronic migraine (CM) are one of the most frequent problems encountered in neurology, are often difficult to treat, and frequently complicated by medication-overuse headache (MOH). Proper recognition of MOH may alter treatment outcome and prevent long term disability. OBJECTIVE: This study identifies the unique genomic expression pattern MOH that respond to cessation of the overused medication. METHODS: Baseline occurrence of MOH and typical pattern of response to medication cessation were measured from a large database. Whole blood samples from patients with CM with or without MOH were obtained and their genomic profile was assessed. Affymetrix human U133 plus2 arrays were used to examine the genomic expression patterns prior to treatment and 6-12 weeks later. Headache characterisation and response to treatment based on headache frequency and disability were compared. RESULTS: Of 1311 patients reporting daily or continuous headaches, 513 (39.1%) reported overusing analgesic medication. At follow-up, 44.5% had a 50% or greater reduction in headache frequency, while 41.6% had no change. Blood genomic expression patterns were obtained on 33 patients with 19 (57.6%) overusing analgesic medication with a unique genomic expression pattern in MOH that responded to cessation of analgesics. Gene ontology of these samples indicated a significant number were involved with brain and immunological tissues, including multiple signalling pathways and apoptosis. CONCLUSIONS: Blood genomic patterns can accurately identify MOH patients that respond to medication cessation. These results suggest that MOH involves a unique molecular biology pathway that can be identified with a specific biomarker.

Chronic daily headache in a patient with nasopharyngeal carcinoma.

Chronic daily headache (CDH) among nasopharyngeal carcinoma (NPC) patients is a multidisciplinary challenge. Although imaging studies are recommended to identify skull-base invasion, intracranial metastasis or skull-base osteoradionecrosis, a headache diary is also a practical approach. A 42-year-old woman had been bothered with CDH since she was diagnosed with T3N1M0 stage III NPC 2 years earlier. Although the imaging studies did not show any abnormality, the attending doctor informed her that there remained the possibility of an intracranial or skull-base lesion. She was regularly taking painkillers. Eventually, when her headache diary was examined, the diagnosis of chronic migraine superimposed on medication overuse headache was made according to the ICHD-IIR. The CDH abated after 1 week of outpatient detoxification. The following half year was uneventful. In reporting this case, we suggest that it would be of interest to a number of disciplines including otorhinolaryngologists, oncologists and radio-oncologists. By avoiding medication overuse in similar patients, we hope to improve the quality of life of these individuals.