piperidines and Headache

Atogepant is the latest calcitonin gene-related peptide (CGRP) antagonist approved exclusively for prophylaxis of episodic migraine and is administered orally in doses of 10-60 mg/day. This article aims to provide a systematic review of the efficacy and safety of atogepant in migraine prevention.. The literature was searched in different databases, i.e., the National Institute of Health clinical trials registry, PubMed, and the Cochrane library between 2018 to October 2021 using the keywords atogepant, MK-8031, and migraine. Conference abstracts listed in the Cochrane database (includes Embase) and drug information provided by the US Food and Drug Administration (FDA) label were also reviewed. Only English-language clinical trials were included. The authors retrieved 58 articles. Eventually, two randomized, double-blind, multicenter clinical trials involving 1,727 participants and one open-label trial were analyzed.. The FDA approved atogepant for migraine prevention in September 2021 based on two randomized, double-blind, placebo-controlled trials. Atogepant approved for migraine prevention acts as a CGRP receptor antagonist and is administered orally. Based on the 12-week clinical trials, atogepant was efficacious in prevention of migraine and it was well tolerated. The most common treatment-emergent adverse events were nausea, constipation, and upper respiratory infection.. Atogepant had a statistically significant change from baseline in monthly migraine days, monthly headache days, and acute medication use days.. Atogepant seems to be beneficial for migraine prevention, and it may be of more benefit in individuals who do not wish to take the drug as an injection or do not require a prolonged duration of drug effect. However, head-to-head trials with other CGRP antagonists are required to ascertain its place in migraine prevention.

Topics: Analgesics; Calcitonin Gene-Related Peptide; Double-Blind Method; Headache; Humans; Migraine Disorders; Multicenter Studies as Topic; Piperidines; Pyridines; Pyrroles; Randomized Controlled Trials as Topic; Spiro Compounds; Treatment Outcome

Aspiration is a significant cause of anesthetic morbidity, occurring most commonly during the induction of anesthesia. For patients with a high likelihood of aspiration, rapid sequence intubation (RSI) techniques may minimize this risk by reducing the time between the loss of protective airway reflexes and the placement of a cuffed endotracheal tube. Although RSI frequently involves the administration of a neuromuscular-blocking agent (NMBA) such as succinylcholine or rocuronium, there are times when the administration of an NMBA is contraindicated or undesirable. We present an 11-year-old boy who presented with vomiting, papilledema, and a history concerning for an undiagnosed neuromuscular disorder. Deep sedation or anesthesia was required during an emergent lumbar puncture to evaluate his symptoms. Rapid sequence intubation was successfully performed with propofol and remifentanil without the use of an NMBA. We highlight the anesthetic considerations in such a clinical scenario and review the literature regarding the combination of remifentanil and propofol for RSI.

Topics: Anesthesia, Inhalation; Child; Contraindications; Deep Sedation; Emergencies; Headache; Humans; Hypnotics and Sedatives; Intracranial Hypertension; Intubation, Intratracheal; Laryngoscopy; Male; Methyl Ethers; Muscle Weakness; Neuromuscular Depolarizing Agents; Neuromuscular Diseases; Piperidines; Propofol; Remifentanil; Respiratory Aspiration of Gastric Contents; Risk; Sevoflurane; Spinal Puncture; Succinylcholine; Vision Disorders; Vomiting

Topics: Animals; Blood Pressure; Clinical Trials as Topic; Cycloheptanes; Cyproheptadine; Dogs; Ergolines; Guinea Pigs; Haplorhini; Headache; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Lethal Dose 50; Methysergide; Mice; Migraine Disorders; Phenothiazines; Piperidines; Rabbits; Rats; Serotonin Antagonists; Thiophenes; Vascular Headaches

This MONONOFU trial subgroup analysis evaluates the efficacy of lasmiditan across patient and migraine characteristics in Japanese patients with migraine.. MONONOFU trial was a multicenter, randomized, double-blind, placebo-controlled study. The patients were randomly assigned in a 3:7:6:7 ratio to receive lasmiditan 50 mg, 100 mg, 200 mg, or placebo for a single migraine attack within 4 h of pain onset. Efficacy of lasmiditan vs placebo was evaluated at 2 h post dose for proportion of patients with headache pain freedom. Efficacy was assessed across patient characteristics (age, sex, body weight, cardiovascular risk factors (CVRF), and comorbidity of tension-type headache), migraine disease characteristics (history of migraine with aura, migraine prevention therapy, triptan response, and triptan use or nonuse), and migraine attack characteristics (headache severity, aggressive headache, attack during perimenstrual period, time to dosing, time of dosing, experienced treatment-emergent adverse event (TEAE) of dizziness, and experienced TEAE of somnolence). Logistic regression was used; all subgroup analyses were not analyzed with multiplicity-adjusted statistical tests.. Treatment-by-subgroup interactions (by each arm) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups and lasmiditan doses, except for CVRF (100 mg and 200 mg), migraine with aura (50 mg), triptan response (50 mg), and time to dosing (200 mg). Treatment-by-subgroup interactions (by overall) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups, except for CVRFs. Higher proportions of patients were pain free at 2 h post dose when treated with lasmiditan (50 mg, 100 mg, and 200 mg) versus placebo, irrespective of most patient characteristics, migraine disease characteristics, and migraine attack characteristics.. Although few interactions were observed, lasmiditan could be a promising acute treatment option in a wide range of Japanese patients with migraine, as efficacy is not generally influenced by patient and migraine characteristics.

Topics: Benzamides; Double-Blind Method; Headache; Humans; Japan; Migraine Disorders; Migraine with Aura; Piperidines; Pyridines; Serotonin Receptor Agonists; Treatment Outcome; Tryptamines

To evaluate the efficacy of lasmiditan (LTN) in treating migraine attacks of mild vs. moderate or severe pain intensity.. Pooled data from two single-attack, placebo-controlled studies (SAMURAI [NCT02439320] and SPARTAN [NCT02605174]), and a prospective, randomized, open-label study (GLADIATOR [NCT02565186]) were assessed. Efficacy measures included the proportion of attacks with 2-h pain freedom (PF), 2-h most bothersome symptom (MBS) freedom, and 24-h sustained pain freedom (SPF). Fisher's exact test was used to compare the proportion of PF, SPF, or MBS freedom outcomes among attacks treated at mild, moderate, or severe pain.. In SAMURAI and SPARTAN, most treated attacks were of moderate (. Data from two placebo-controlled, single-attack trials, and an open-label study including treatment of multiple attacks, suggested a tendency to relatively better efficacy outcomes when LTN treatment was initiated at mild vs. moderate to severe pain. Further research is needed to better understand the relationship of lasmiditan outcomes to the time of administration in the course of a migraine attack.

Topics: Benzamides; Double-Blind Method; Headache; Humans; Migraine Disorders; Piperidines; Prospective Studies; Pyridines; Serotonin Receptor Agonists; Treatment Outcome

In addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events. This analysis was designed to evaluate the safety and efficacy of oral lasmiditan, a selective serotonin 5-hydroxytryptamine 1F receptor agonist, in acute treatment of migraine attacks in patients with CVRFs.. SAMURAI and SPARTAN were similarly designed, Phase 3, randomized, double-blind, placebo-controlled trials in adults treating a single migraine attack with lasmiditan 50, 100, or 200 mg. Both studies included patients with CVRFs, and SPARTAN allowed patients with coronary artery disease, clinically significant arrhythmia, or uncontrolled hypertension. Efficacy and safety of lasmiditan in subgroups of patients with differing levels of CVRFs are reported. For efficacy analyses, logistic regression was used to assess treatment-by-subgroup interactions. For safety analyses, Cochran-Mantel-Haenszel test of general association evaluated treatment comparisons; Mantel-Haenszel odds ratio assessed significant treatment effects.. In this pooled analysis, a total of 4439 patients received ≥1 dose of study drug. A total of 3500 patients (78.8%) had ≥1 CVRF, and 1833 patients (41.3%) had ≥2 CVRFs at baseline. Both trials met the primary endpoints of headache pain freedom and most bothersome symptom freedom at 2 h. The presence of CVRFs did not affect efficacy results. There was a low frequency of likely CV treatment-emergent adverse events (TEAEs) overall (lasmiditan, 30 [0.9%]; placebo, 5 [0.4%]). There was no statistical difference in the frequency of likely CV TEAEs in either the absence or presence of any CVRFs. The only likely CV TEAE seen across patients with ≥1, ≥ 2, ≥ 3, or ≥ 4 CVRFs was palpitations.. When analyzed by the presence of CVRFs, there was no statistical difference in lasmiditan efficacy or the frequency of likely CV TEAEs. Despite the analysis being limited by a single-migraine-attack design, the lack of differences in efficacy and safety with increasing numbers of CVRFs indicates that lasmiditan might be considered in the treatment algorithm for patients with CVRFs. Future studies are needed to assess long-term efficacy and safety.. ClinicalTrials.gov NCT02439320 (SAMURAI), registered 18 March 2015 and ClinicalTrials.gov NCT02605174 (SPARTAN), registered 11 November 2015.

Topics: Adult; Benzamides; Cardiovascular Diseases; Double-Blind Method; Female; Headache; Humans; Male; Middle Aged; Migraine Disorders; Piperidines; Pyridines; Receptor, Serotonin, 5-HT1F; Receptors, Serotonin; Serotonin Receptor Agonists; Treatment Outcome

While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013.. The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events.. Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use.. Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.

Topics: Cambodia; Dizziness; Headache; Humans; Insect Repellents; Mosquito Control; Piperidines; Rural Population; Treatment Outcome

To prospectively evaluate the efficacy and safety of alogliptin versus glipizide in elderly patients with type 2 diabetes mellitus (T2DM) over 1 year of treatment.. This was a randomized, double-blind, active-controlled study of elderly T2DM patients (aged 65-90 years) with mild hyperglycaemia on diet/exercise therapy alone [glycosylated haemoglobin (HbA1c) 6.5-9.0%] or plus oral antidiabetic monotherapy (HbA1c 6.5-8.0%). Patients were randomized to once-daily alogliptin 25 mg or glipizide 5 mg titrated to 10 mg, if needed. Hypoglycaemic episodes were systematically captured under predefined criteria.. In the primary analysis, HbA1c mean changes from a baseline of 7.5% were -0.14% with alogliptin (n = 222) and -0.09% with glipizide (n = 219) at the end of the study, demonstrating non-inferiority of alogliptin to glipizide [least squares (LS) mean difference = -0.05%; one-sided 97.5% confidence interval (CI): -∞, 0.13%]. More clinically relevant HbA1c reductions occurred among patients who completed the study: -0.42 and -0.33% with alogliptin and glipizide, with non-inferiority again confirmed (LS mean difference = -0.09%; one-sided 97.5% CI: -∞, 0.07%). Overall, alogliptin was safe and well tolerated, with notably fewer hypoglycaemic episodes than glipizide [5.4% (31 episodes) vs. 26.0% (232 episodes), respectively]; three patients experienced severe hypoglycaemia, all with glipizide. Alogliptin also resulted in favourable weight changes versus glipizide (-0.62 vs. 0.60 kg at week 52; p < 0.001).. Alogliptin monotherapy maintained glycaemic control comparable to that of glipizide in elderly patients with T2DM over 1 year of treatment, with substantially lower risk of hypoglycaemia and without weight gain.

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dizziness; Double-Blind Method; Female; Glipizide; Glycated Hemoglobin; Headache; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Piperidines; Prospective Studies; Treatment Outcome; Triglycerides; Uracil; Weight Gain

In recent years, there has been an increased interest in using a multimodal approach with combined agents to treat postoperative nausea and vomiting. This study evaluated whether the addition of an oral dose of the neurokinin-1 receptor antagonist casopitant improved the antiemetic efficacy of an intravenous dose of ondansetron hydrochloride.. The authors enrolled 702 premenopausal or perimenopausal, nonsmoking, female patients aged 18-55 yr with a history of postoperative nausea and vomiting and/or motion sickness undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia. Subjects were randomized to one of five treatment arms: standard ondansetron 4 mg with casopitant at 0, 50, 100, or 150 mg, or 0 mg ondansetron with casopitant at 150 mg (the latter arm was considered an exploratory study group and was included in the safety analysis but not in the efficacy analysis).. A significantly greater proportion of patients in all of the active casopitant plus ondansetron groups achieved a complete response (i.e., no vomiting, retching, rescue medication, or premature withdrawal) during the first 24 h postoperatively versus those in the ondansetron-alone group (59-62% vs. 40%, respectively; P = 0.0006). All active doses seemed to be well tolerated; headache, dizziness, and constipation were the most frequently reported adverse events.. Compared with ondansetron alone, the casopitant and ondansetron combination results in superior emesis prevention during the first 24 h postoperatively in female patients with known risk factors for postoperative nausea and vomiting.

Topics: Administration, Oral; Adolescent; Adult; Anesthesia, General; Antiemetics; Cholecystectomy, Laparoscopic; Constipation; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Gynecologic Surgical Procedures; Headache; Humans; Middle Aged; Neurokinin-1 Receptor Antagonists; Ondansetron; Piperazines; Piperidines; Postoperative Nausea and Vomiting; Risk Factors; Treatment Outcome; Young Adult

To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response.. Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks.. By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all CP-690,550 treatment arms.. Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.

Topics: Arthritis, Rheumatoid; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Headache; Humans; International Cooperation; Janus Kinases; Male; Middle Aged; Nausea; Piperidines; Pyrimidines; Pyrroles; Treatment Outcome

The purpose of this phase III trial was to evaluate the efficacy and safety of regimens containing casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting during the first cycle in patients receiving moderately emetogenic chemotherapy (MEC).. Predominantly female patients (98%) diagnosed with breast cancer (96%) who were chemotherapy-naïve and scheduled to receive an anthracycline and cyclophosphamide (AC) -based regimen were enrolled onto this multinational, randomized, double-blind, parallel-group, placebo-controlled clinical trial. All patients received dexamethasone 8 mg intravenously (IV) on day 1 and oral ondansetron 8 mg twice daily on days 1 to 3. Patients were randomly assigned to a control arm (placebo), a single oral dose casopitant arm (150 mg orally [PO] on day 1), a 3-day oral casopitant arm (150 mg PO on day 1 plus 50 mg PO on days 2 to 3), or a 3-day IV/oral casopitant arm (90 mg IV on day 1 plus 50 mg PO on days 2 to 3). The primary end point was the proportion of patients achieving complete response (no vomiting/retching or rescue medications) in the first 120 hours after the initiation of MEC.. A significantly greater proportion of patients in the single-dose oral casopitant arm, 3-day oral casopitant arm, and 3-day IV/oral casopitant arm achieved complete response (73%, 73%, and 74%, respectively) versus control (59%; P < .0001). The study did not demonstrate a reduced proportion of patients with nausea or significant nausea in those receiving casopitant. Adverse events were balanced among study arms.. All casopitant regimens studied were more effective than the control regimen. Casopitant was generally well tolerated.

Topics: Administration, Oral; Alopecia; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Constipation; Cyclophosphamide; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Headache; Humans; Injections, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Neutropenia; Ondansetron; Piperazines; Piperidines; Treatment Outcome; Vomiting

Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD.. Patients (n=603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d (n=198), donepezil 10 mg/d (5 mg/d for first 28 days; n=206), or placebo (n=199). Analyses were based on the intent-to-treat population.. At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale-cognitive subscale (mean change from baseline score effect size: donepezil 5 mg/d, -1.90; P=0.001; donepezil 10 mg/d, -2.33; P<0.001). Significant improvements in patients' global function were seen versus placebo at week 24 (observed cases), on the Clinician's Interview-Based Impression of Change-Plus version only for patients on donepezil 5 mg/d (P=0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d (P=0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale (mean change from baseline score effect size at week 24: donepezil 5 mg/d, -1.31, P=0.02; donepezil 10 mg/d, -1.31, P=0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low (placebo, 11.1%; donepezil 5 mg/d, 11.1%; donepezil 10 mg/d, 21.8%; P=0.005 versus placebo).. These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Cardiovascular System; Cholinesterase Inhibitors; Cognition; Dementia, Vascular; Diarrhea; Donepezil; Double-Blind Method; Female; Headache; Humans; Indans; Internationality; Male; Middle Aged; Nausea; Neuropsychological Tests; Nootropic Agents; Piperidines; Severity of Illness Index; Treatment Outcome

Complete withdrawal from headache medication is the treatment of choice for medication-overuse headache. Discontinuation of the overused headache medication, however, results in the development of withdrawal headache, often associated with nausea, vomiting, and sleep disturbances.. In a prospective study of 95 patients, the authors investigated the duration and severity of withdrawal headache after overuse of various headache drugs, including single and combination analgesics, ergots, and triptans. All patients underwent standard inpatient withdrawal therapy for 14 days.. The duration of withdrawal headache was shorter in patients overusing triptans (4.1 days) than in patients overusing ergots (6.7 days) or analgesics (9.5 days; p < 0.002). The mean headache intensity on the first day of withdrawal did not differ between the groups (p = 0.821). By day 14, however, it was lower in patients overusing triptans (0.08) than in patients overusing ergots (0.4) or analgesics (0.9; p < 0.005). Rescue medication was requested less by patients undergoing triptan withdrawal (0.25 requests) than by patients undergoing ergot withdrawal (1.25) or analgesic withdrawal (1.85; p < 0.05). Similar to findings in the entire patient population, withdrawal headache was shorter and less severe in migraineurs overusing triptans than in those overusing ergots or analgesics. Because only patients with migraine, but no patient with tension-type headache, overused triptans, withdrawal headache was shorter in the group of patients with migraine alone (6.7 days versus 9.6 days for patients with tension-type headache and 8.5 days for patients with combination headache, p < 0.02).. The duration and severity of withdrawal clearly depend on the type of overused headache drug only.

Topics: Adult; Analgesics; Drug Therapy, Combination; Ergotamine; Female; Headache; Humans; Indoles; Male; Middle Aged; Oxazolidinones; Piperidines; Prospective Studies; Substance Withdrawal Syndrome; Sumatriptan; Triazoles; Tryptamines; Vasoconstrictor Agents

The single-dose effects of the cytochrome P-450 inhibitors erythromycin and ketoconazole on the steady-state pharmacokinetics and electrocardiographic repolarization pharmacodynamics of intranasal levocabastine, a potent and selective H1-receptor antagonist, were evaluated in healthy young male subjects. Two randomized, open-label, placebo-controlled, two-way crossover studies were performed. Levocabastine nasal spray was administered as two sprays per nostril (0.05 mg/spray) twice daily (for a total daily dose of 0.4 mg) for 6 days. On Day 7, a single dose of 0.2 mg was administered followed immediately by a single dose of either oral placebo, erythromycin 333 mg, or ketoconazole 200 mg. In all treatment groups, levocabastine was rapidly absorbed, with peak plasma concentrations reached at approximately 3 hours in the erythromycin study and 2.8 hours in the ketoconazole study. The mean terminal half-life was approximately 45 and 44 hours, respectively. In both studies, mean steady-state plasma concentrations and pharmacokinetics of levocabastine following the single doses of erythromycin or ketoconazole were not significantly different from corresponding values seen with the concomitant administration of the placebo. No clinically significant mean changes from baseline in QT or QTc (QT corrected for heart rate) intervals occurred in any of the treatment groups, and none of the subjects in either study experienced abnormally prolonged QTc intervals. Intranasal levocabastine was well tolerated, with no difference in the incidence of adverse events between treatment groups in either study; adverse events were generally mild in severity. Since levocabastine undergoes only minimal hepatic metabolism and is not a substrate for or an inhibitor of cytochrome P-450, the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 system is minimal.

Topics: Administration, Intranasal; Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Area Under Curve; Biological Availability; Bradycardia; Cross-Over Studies; Drug Interactions; Electrocardiography; Erythromycin; Headache; Heart Block; Histamine H1 Antagonists; Humans; Ketoconazole; Male; Middle Aged; Piperidines; Rhinitis; Time Factors; Virus Diseases

Previous studies have shown that both selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) are effective in the treatment of panic disorders (PD). In this study, the SSRI fluvoxamine (Fluv) was compared with the MAO-A-I brofaromine (Brof). Thirty patients with the diagnosis of PD with or without agoraphobia were treated with either Fluv or Brof (150 mg daily) in a double-blind design. After 12 weeks of treatment, 93% of the Brof group and 87% of the Fluv group considered themselves much or very much improved. Taking a reduction in the Hamilton Rating Scale for Anxiety score of 50% or more, 33% of the Fluv patients and 47% of the Brof patients were responders to treatment. After an increase in anxiety in the 1st week, which was more severe in Fluv-treated patients than for Brof, a clinically relevant decrease in anxiety symptoms and reduction in panic attacks and avoidance behavior was observed. There was no significant difference between the treatment groups. The most prominent side effects were middle-sleep disturbance (Brof), tiredness (Fluv), and nausea after taking the medication (Brof and Fluv). During a double-blind follow-up period of another 12 weeks, a further improvement was found in both treatment groups without significant differences between the two groups. The selective and reversible MAO-A-I brofaromine and the SSRI fluvoxamine are equally effective in the treatment of PD. Both compounds lead to a reduction in the number of panic attacks and a subsequent reduction in agoraphobic avoidance.

Topics: Adult; Anti-Anxiety Agents; Double-Blind Method; Female; Fluvoxamine; Headache; Humans; Male; Middle Aged; Monoamine Oxidase Inhibitors; Nausea; Panic Disorder; Piperidines; Selective Serotonin Reuptake Inhibitors

The exact relationship between depression and chronic headache remains unclear. Considerable clinical and pharmacological evidence suggests the existence of a common biological terrain. Many antidepressant drugs are effective in the treatment of migraine and chronic headache disorders. Ritanserin, a new very selective serotonin-2 (5-HT2) antagonist, has recently shown both analgesic and antidepressant properties. The present study compares in a double-blind design, the effectiveness of ritanserin and amitriptyline, a well-known antidepressant extensively used in migraine prophylaxis. Thirty-eight patients (30 females and 8 males ranging in age from 20 to 50 yrs) were classified according to the International Headache Society criteria as: patients with chronic tension-type headache (CTH) (11 cases) and patients with coexisting migraine and CTH (MCTH) (27 cases). Only patients with a score equal to or higher than 18 on the Hamilton Rating Scale for Depression (HRSD) were included. Ritanserin was highly effective in reducing Pain Total Index and analgesic consumption in chronic headache, and its activity was similar to that observed during amitriptyline treatment. A significant improvement of HRSD and HRSA (Hamilton Rating Scale for Anxiety) scores was observed during both treatments. The main results of our study concern the demonstration of antiheadache and antidepressive properties of ritanserin. To better define the profile of the patients and their clinical responsiveness to the treatment, dexamethasone suppression test, clonidine test and nociceptive flexion reflex were investigated in our patients. Our data confirm the usefulness of these methods as markers of chronic headache with depression.

Topics: Adult; Amitriptyline; Chronic Disease; Depression; Double-Blind Method; Female; Headache; Humans; Male; Piperidines; Ritanserin

A controlled double blind clinical trial has been conducted in 16 patients with "angina pectoris" in order to investigate the effect of Perexiline maleate as compared with prenilamine. Perexiline at the dose of 400 mg/die and prenilamine at the dose of 120 mg/die have been administered over a period of 4 weeks each. Between these periods placebo has been administered for two weeks. The number of attacks of angina and the number of tablets of nitroglycerine used per week by the patient during each period has been used for the evaluation. Furthermore ECG at rest and after exercise has been performed every two weeks. Our results statistically evaluated show a definite antianginal effect of Perexiline. According to our experience Perexiline should be considered the drug of choise in the treatment of angina complicated by bradicardia, left ventricular failure, bronchospasm, and in angina unresponsive to other drugs.

Topics: Angina Pectoris; Blood Pressure; Body Weight; Drug Evaluation; Electrocardiography; Headache; Humans; Perhexiline; Piperidines; Prenylamine; Pulse; Sleep Wake Disorders

Topics: Animals; Blood Pressure; Clinical Trials as Topic; Cycloheptanes; Cyproheptadine; Dogs; Ergolines; Guinea Pigs; Haplorhini; Headache; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Lethal Dose 50; Methysergide; Mice; Migraine Disorders; Phenothiazines; Piperidines; Rabbits; Rats; Serotonin Antagonists; Thiophenes; Vascular Headaches

Topics: Adolescent; Adult; Body Weight; Clinical Trials as Topic; Cycloheptanes; Feeding and Eating Disorders; Female; Headache; Humans; Male; Methysergide; Middle Aged; Migraine Disorders; Piperidines; Thiophenes; Time Factors

Topics: Benzocycloheptenes; Diagnosis, Differential; Headache; Humans; Migraine Disorders; Piperidines; Placebos; Thiophenes; Time Factors

The second-generation antihistamines at licensed doses are first-line treatment in urticaria and up-dosing is recommended as second-line treatment. To assess the efficacy and safety of escalated doses of ebastine in patients with chronic urticaria (CU), we designed this study. Recruited patients with CU were treated with increasing doses of ebstine. Treatment started at the daily dose of 10 mg. The symptom is assessed weekly, and if there is no significant improvement, the dose is increased from 10 mg to 20 mg, and if still no significant improvement, up to 40 mg. Pruritus, number, diameter, duration and frequency of wheals, and adverse reactions were assessed. One hundred and forty (76.50%) patients achieved marked effect with ebastine 10 mg/day, 27 (14.75%) patients with ebastine 20 mg/day and 13 (7.10%) patients with ebastine 40 mg/day, while 3(1.64%) patients did not get marked effect. There was no significant difference of effect between factitious urticaria, CSU, cholinergic urticaria and CSU with factitious urticaria in different dose (all p > 0.05). Common adverse reactions of ebstine treatment, included dry mouth, somnolence, tiredness and headache, were mild or moderate. There was no significant difference between the degree score of dry mouth with different doses of ebastine, and the same to somnolence, tiredness and headache (all p > 0.05). Doses escalation of ebastine should be effective in treatment of factitious urticaria, CSU and cholinergic urticaria with poorly treated by standard of double doses. Increasing ebastine dose did not increase the incidence of adverse reactions.

Topics: Butyrophenones; Cholinergic Agents; Chronic Disease; Chronic Urticaria; Headache; Histamine H1 Antagonists; Humans; Piperidines; Prospective Studies; Sleepiness; Urticaria; Xerostomia

While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing.. Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.. Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.. This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint.. SAMURAI ( NCT02439320 ); SPARTAN ( NCT02605174 ).

Topics: Benzamides; Double-Blind Method; Freedom; Headache; Humans; Migraine Disorders; Piperidines; Pyridines; Treatment Outcome

To asses the long-term safety and efficacy of pitolisant, an histamine H3-receptor antagonist, on narcolepsy.. This open-label, single-arm, pragmatic study, recruited adult patients with narcolepsy and Epworth Sleepiness Scale (ESS) score ≥12. After a titration period, patients were treated for up to 1 year with oral pitolisant once-a-day at up to 40 mg. Concomitant stimulants and anti-cataplectic agents were allowed. The primary endpoint was safety; secondary endpoints included ESS, cataplexy, and other diary parameters.. Patients (n = 102, 75 with cataplexy) received pitolisant, for the first time in 73 of them. Sixty-eight patients (51 with cataplexy) completed the 12-month treatment. Common treatment-emergent adverse events were headache (11.8% of patients), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depressive symptoms (4.9%), and nausea (4.9%). Seven patients had a serious adverse effect, unrelated to pitolisant except for a possibly related miscarriage. One-third of patients stopped pitolisant, mostly (19.6%) for insufficient benefit. ESS score decreased by 4.6 ± 0.6. Two-thirds of patients completing the treatment were responders (ESS ≤ 10 or ESS decrease ≥ 3), and one third had normalized ESS (≤10). Complete and partial cataplexy, hallucinations, sleep paralysis, and sleep attacks were reduced by 76%, 65%, 54%, 63%, and 27%, respectively. Pitolisant as monotherapy (43% of patients) was better tolerated and more efficacious on ESS than on add-on, but efficacy was maintained in this last case.. Long-term safety and efficacy of pitolisant on daytime sleepiness, cataplexy, hallucinations, and sleep paralysis is confirmed.

Topics: Adult; Anxiety; Central Nervous System Stimulants; Depression; Female; Headache; Histamine H3 Antagonists; Humans; Male; Narcolepsy; Piperidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Topics: Adult; Headache; Humans; Lymphocytic Choriomeningitis; Male; Piperidines; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Tryptamines

A 54-year-old woman with acute onset of hematochezia and lower abdominal pain proved to have ischemic colitis associated with the use of naratriptan. The diagnosis was established by colonoscopy with biopsy. There were no other obvious risk factors for intestinal ischemia. The condition resolved within 4 days. Because the use of triptans for the treatment of migraine is increasing, health care providers should be aware of their potential for inducing ischemic colitis.

Topics: Abdominal Pain; Colon; Colonic Diseases; Female; Headache; Humans; Indoles; Ischemia; Middle Aged; Piperidines; Serotonin Receptor Agonists; Tryptamines

Topics: Administration, Oral; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Female; Headache; Humans; Indoles; Male; Migraine Disorders; Oxazolidinones; Piperidines; Placebos; Pyrrolidines; Serotonin Receptor Agonists; Sumatriptan; Time Factors; Tryptamines

Topics: Analgesics; Headache; Humans; Indoles; Oxazolidinones; Piperidines; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Sumatriptan; Time Factors; Triazoles; Tryptamines

Topics: Adult; Female; Headache; Humans; Indoles; Middle Aged; Migraine Disorders; Oxazoles; Oxazolidinones; Piperidines; Serotonin Receptor Agonists; Tryptamines

Topics: Analgesics, Non-Narcotic; Ergotamine; Headache; Humans; Indoles; Oxazoles; Oxazolidinones; Piperidines; Serotonin Receptor Agonists; Sumatriptan; Tryptamines

(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

A 36-year-old woman with positional headache was found to have primary low cerebrospinal fluid (CSF) pressure syndrome and galactorrhea. The CSF pressure at lumbar puncture was not measurable. Magnetic resonance imaging demonstrated that the ventricle and cerebral sulcus were narrowed and the pituitary stalk was oppressed by the brain. Hyperresponsiveness of prolactin was noted after stimulation with thyrotropin-releasing hormone. These abnormalities disappeared with normalization of CSF pressure with the treatment. Galactorrhea was apparently due to oppression of the pituitary stalk by downward movement of the brain.

Topics: Adult; Cerebrospinal Fluid Pressure; Female; Galactorrhea; Headache; Humans; Hypothalamo-Hypophyseal System; Infusions, Intravenous; Magnetic Resonance Imaging; Piperidines; Posture; Syndrome

The results of a well-controlled multicenter shortterm safety and efficacy study, supported by results from several long-term studies, indicate that therapeutic doses of flecainide are well tolerated by most patients. The most frequently reported extracardiac adverse experiences were dizziness (30%) and visual disturbances (28%), often occurring in tandem. Headache, nausea, dyspnea and chest pain occurred at incidences of 6 to 9%; other adverse experiences occurred at incidences of greater than or equal to 5%. Because of study design, it is likely that these figures are overestimates; they include all reports, whether or not they were caused by flecainide. Extracardiac adverse experiences were given as reasons contributing to discontinuation of therapy in 10% of patients in the short-term and 6% of patients in the long-term studies. In most cases the inability to tolerate flecainide became evident early in therapy. No new adverse experiences indicative of any chronic toxic effect of flecainide were reported during the long-term studies. Side effects tended to be intermittent and to decrease over time.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dizziness; Dyspnea; Flecainide; Headache; Humans; Nausea; Piperidines; Vision Disorders

Sixteen patients with a headache resembling the so-called "tension headache" and a clear response to doxepin (demonstrated in a previous work) were given femoxetine, 400 mg p.d., and placebo in a cross-over, double-blind fashion. Only single blindness was kept in the last third of the study. Placebo and femoxetine tablets were each given for four weeks. Whereas there was a daily or practically daily occurring headache untreated, placebo was associated with a headache frequency of 92%. The corresponding figures for doxepin and femoxetine were 27% and 41%, respectively. Femoxetine led to transitory nausea and gastrointestinal discomfort, but in contrast to doxepin, no weight gain and only slight, if any, sedation. Most patients preferred femoxetine to doxepin. Femoxetine, an antidepressant phenylpiperidine derivative with predominant serotonin re-uptake inhibition (little effect on noradrenaline), thus seems to counteract so-called "tension headache".

Topics: Adolescent; Adult; Double-Blind Method; Doxepin; Female; Headache; Humans; Male; Middle Aged; Piperidines; Serotonin; Serotonin Antagonists; Stress, Psychological

Topics: Amides; Analgesics; Colic; Drug Evaluation; Female; Fumarates; Headache; Humans; Male; Neuralgia; Pain; Pain, Postoperative; Piperidines; Propionates; Pyridines; Sampling Studies; Suppositories

Topics: Benzocycloheptenes; Diagnosis, Differential; Ergotamine; Headache; Humans; Methysergide; Migraine Disorders; Pain; Piperidines; Thiophenes

Topics: Aggression; Criminal Psychology; Feeding and Eating Disorders; Headache; Humans; Nitriles; Phenothiazines; Piperidines; Sleep Wake Disorders; Tranquilizing Agents

Topics: Aged; Albuminuria; Amides; Brain; Clopamide; Diuresis; Diuretics; Ergoloid Mesylates; Fundus Oculi; Headache; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Obesity; Piperidines; Sodium; Vertigo