piperidines and Headache-Disorders

Headache disorders are common worldwide and often disabling. Until recently, treatments were borrowed from other branches of neurology and medicine. Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) ligand and receptor, small molecule CGRP receptor antagonist gepants, serotonin

Topics: Antibodies, Monoclonal; Calcitonin Gene-Related Peptide; Headache Disorders; Humans; Neurotransmitter Agents; Piperidines; Pyridines; Serotonin Receptor Agonists; Treatment Outcome

Chronic migraine (CM) patients frequently overuse symptomatic medications (SM). These medications may create a cycle of rebound, worsening of headache and withdrawal symptoms that perpetuate the headache itself. In addition, the overuse of such substances is believed to counteract the efficacy of preventive treatments. We conducted a prospective randomized open-label trial comparing approaches to out-patient management in 150 CM patients (125 women, 25 men; ages 18-80 years, mean 40.3 +/- 13.8) with overuse of SM. In each group, 50 patients received education and orientation and were then abruptly withdrawn from all SM. Immediately following withdrawal, the first group took prednisone (60 mg/ day 2 days, 40 mg/day 2 days and 20 mg/day 2 days) for 6 days, the second group did not have any regular medications to take and the third group took naratriptan (2.5 mg twice a day) during this initial period. All patients had similar profiles of headache characteristics and consumption (quality and quantity) of SM before initiation of the treatment, but most were not severe headache sufferers, heavy SM overusers or were overusing opioids. After 5 weeks the headache frequency and intensity, the prevalence and frequency of withdrawal symptoms and consumption of rescue medications during the first 6 days were compared between groups. In addition, adherence to treatment (who returned or not and for which reasons, between groups) and headache frequency, week by week, among the groups of patients were also compared. Forty-four (88%) patients from the prednisone group, 41 (82%) from the 'nothing' group and 35 (70%) from the naratriptan group adhered to the treatment and returned. The were no differences between groups with regard to treatment adherence (P = 0.072), headache frequency as well as intensity (P = 0.311) and decreasing of days with headache after 5 weeks and weekly (P = 0.275). However, the incidence of withdrawal symptoms and consumption of rescue drugs was higher among the patients who did not take regular medications during the first 6 days (P = 0.0001 and P = 0.006). We concluded that CM patients with moderate overuse of SM other than opioids may be detoxified on an out-patient basis regardless of the strategy adopted with regard to the use of regular drugs during the initial days of withdrawal, but prednisone and naratriptan may be useful for reducing withdrawal symptoms and rescue medication consumption. Further controlled studies are necessary to confir

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care; Chi-Square Distribution; Female; Headache Disorders; Humans; Indoles; Male; Middle Aged; Migraine Disorders; Piperidines; Prednisone; Prospective Studies; Statistics, Nonparametric; Substance Withdrawal Syndrome; Tryptamines

Chronic migraine (CM) is a common disorder, affecting 2% to 3% of the general population. Glutamate is implicated in cortical spreading depression, trigeminovascular activation, central sensitization, and may be linked to migraine chronification. Triptans brought a novel option for the acute migraine treatment. As the development of central sensitization impacts upon the effectiveness of triptan therapy, we hypothesized that glutamate might be related to triptan response mechanisms.. We studied 19 patients diagnosed with CM according to the International Headache Society (2004) criteria. Patients were divided in those overusing analgesics (NSAIDs); those without overuse, and those overusing triptans.. Cerebrospinal fluid (CSF) glutamate levels were similar in patients overusing acute medications (0.335 +/- 0.225 micromol) compared to those without overuse (0.354 +/- 0.141 micromol), P= NS). In contrast, patients overusing triptans had CSF glutamate levels significantly lower than that observed in nonoverusers (0.175 +/- 0.057 vs 0.354 +/- 0.141 micromol, P= 0.015), and significantly higher than controls (0.175 +/- 0.057 vs 0.109 +/- 0.066 micromol, P= 0.039). In triptan overusers, CSF glutamate levels, although lower, were not significantly different from patients overusing other types of analgesics.. Our study showed lower glutamate levels in CSF of CM patients overusing triptans. Glutamate may be implicated in triptan response mechanisms, triptans may work in part by reducing extracellular glutamate levels in the brain.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Glutamic Acid; Headache Disorders; Headache Disorders, Secondary; Humans; Male; Middle Aged; Migraine Disorders; Piperidines; Serotonin Receptor Agonists; Triazoles; Tryptamines

Topics: Headache Disorders; Humans; Indoles; Migraine Disorders; Piperidines; Primary Health Care; Serotonin Receptor Agonists; Sumatriptan; Treatment Outcome; Tryptamines; Vasoconstrictor Agents

(1) Like other analgesics and antimigraine drugs, the 5HT1 receptor agonists, or triptans, can cause a self-sustaining headache syndrome. (2) Headache due to 5HT1 receptor agonists should be suspected when a patient presents with an increased frequency of migraine or non migraine headache associated with daily intake of such drugs. Withdrawal usually leads to the disappearance of those headaches that are due to the drug, or at least a reduction in their frequency.

Topics: Analgesics; Headache; Headache Disorders; Humans; Indoles; Oxazolidinones; Piperidines; Prospective Studies; Serotonin Receptor Agonists; Sumatriptan