The relation between the placebo response, observed treatment effect, and failure to meet primary endpoint: A systematic review of clinical trials of preventative pharmacological migraine treatments.

Objective: To evaluate the association between the degree of response to placebo in migraine studies and the observed difference between drug and placebo across studies of preventative treatments for migraine.

Methods: A systematic review was performed using MEDLINE and the Cochrane Central Register of Controlled Clinical Trials from January 1988 to June 2019. Randomized, double-blind, parallel-group, placebo-controlled trials on oral or injection preventative treatments for migraine were included.

Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine.

Objective To determine the efficacy, tolerability, and safety of ascending doses of Adhesive Dermally-Applied Microarray (ADAM) zolmitriptan versus placebo for acute migraine treatment. Background ADAM is a novel patient-administered system for intracutaneous drug administration. In a phase 1 pharmacokinetic study, zolmitriptan administered using ADAM had much faster absorption than oral administration with higher exposure in the first two hours.

Classification and Differential Diagnosis of Oral and Maxillofacial Pain.

Pain in the orofacial region is a common presenting symptom. The majority of symptoms are related to dental disease and the cause can readily be established, the problem dealt with, and the pain eliminated. However, pain may persist and defy attempts at treatment.

Lubiprostone for Opioid-Induced Constipation Does Not Interfere with Opioid Analgesia in Patients with Chronic Noncancer Pain.

Objective: To determine whether lubiprostone 24 μg twice daily (BID), administered to relieve opioid-induced constipation (OIC), affects opioid analgesia in patients with chronic noncancer pain.

Methods: Data were pooled from 3 randomized, double-blind, placebo-controlled trials of lubiprostone in adults with chronic noncancer pain receiving stable opioid analgesia and who had documented OIC. In each study, lubiprostone 24 μg BID or placebo was administered for 12 weeks for relief of OIC using a common protocol.

De Novo Headache During Pregnancy and Puerperium.

Background: A conservative estimate is that approximately 5% of pregnancies are affected by de novo headache, that is, new-onset or new-type headache.

Objectives: (1) Summarize the available literature, which is exclusively neurological, regarding de novo headache during the third trimester of pregnancy and puerperium; and (2) review the common pathologies of pregnancy and puerperium that may be relevant to de novo headache, with focus on the first and second trimester. We obtained the literature through a search of PubMed and references of the retrieved publications, without time limit.

Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study.

Background: Benefits of calcitonin-gene related peptide (CGRP) inhibition have not been established in chronic migraine. Here we assess the safety, tolerability, and efficacy of two doses of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of chronic migraine.

Methods: In this multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had chronic migraine.

Menstrual-Cycle and Menstruation Disorders in Episodic vs Chronic Migraine: An Exploratory Study.

Objective: Migraine is a chronic condition of recurring moderate-to-severe headaches that affects an estimated 6% of men and 18% of women. The highest prevalence is in those 18-49 years of age, generally when women menstruate. It is divided into episodic and chronic migraine depending on the total number of headache days per month being 14 or less or 15 or more, respectively.

Orofacial pain after invasive dental procedures: neuropathic pain in perspective.

Background: The neurologist is very familiar with the painful neuropathies of the trunk and extremities but, generally, to a lesser extent with those of the head and face. Of the latter, the neurologist is particularly familiar with ophthalmic zoster and trigeminal neuralgia.

Review Summary: This review deals with neuropathic orofacial pain: (1) to highlight its presentation; and (2) to contrast it with that of neuropathic pain elsewhere in the body, including the head, from which it seems to differ significantly.

A randomized, double-blind, placebo-controlled study of breath powered nasal delivery of sumatriptan powder (AVP-825) in the treatment of acute migraine (The TARGET Study).

Objective: To evaluate the efficacy and safety of AVP-825, a drug-device combination of low-dose sumatriptan powder (22 mg loaded dose) delivered intranasally through a targeted Breath Powered device vs an identical device containing lactose powder (placebo device) in the treatment of migraine headache.

Background: Early treatment of migraine headaches is associated with improved outcome, but medication absorption after oral delivery may be delayed in migraineurs because of reduced gastric motility. Sumatriptan powder administered with an innovative, closed-palate, Bi-Directional, Breath Powered intranasal delivery mechanism is efficiently absorbed across the nasal mucosa and produces fast absorption into the circulation.

Efficacy of treatment of insomnia in migraineurs with eszopiclone (Lunesta®) and its effect on total sleep time, headache frequency, and daytime functioning: A randomized, double-blind, placebo-controlled, parallel-group, pilot study.

Aims: A review on headache and insomnia revealed that insomnia is a risk factor for increased headache frequency and headache intensity in migraineurs. The authors designed a randomized, double blind, placebo-controlled, parallel-group, pilot study in which migraineurs who also had insomnia were enrolled, to test this observation.

Methodology: In the study, the authors treated 79 subjects with IHS-II migraine with and/or without aura and with DSM-IV primary insomnia for 6 weeks with 3 mg eszopiclone (Lunesta(®)) or placebo at bedtime.

Sufficiency and necessity in migraine: how do we figure out if triggers are absolute or partial and, if partial, additive or potentiating?

Migraine is, to a great extent, a genetically determined disorder and once it has manifested itself, it generally continues for years if not for decades. While the migraine is active, headaches can seemingly occur spontaneously but are often reportedly precipitated by events or factors, known as migraine triggers, the interplay of which is the topic of this paper. Among migraine triggers, the menstrual cycle is an important one that probably accounts for much of the excess of migraine in women compared with men.

Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study.

Background: Migraine remains poorly treated, with few effective preventive drugs available. We assessed the safety and efficacy of LY2951742, a fully humanised monoclonal antibody to calcitonin gene-related peptide, for migraine prevention.

Methods: We did a randomised, double-blind, placebo-controlled, phase 2 proof-of-concept study at 35 centres in the USA.

Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain.

Objective: To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs.

Methods: Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient's Global Assessment (PGA) of OA.

A randomized, rater-blinded, crossover study of the effects of oxymorphone extended release, fed versus fasting, on cognitive performance as tested with CANTAB in opioid-tolerant subjects.

Background: The maximum plasma concentration (Cmax ) of oxymorphone extended release (ER) 20 mg and 40 mg is approximately 50% higher in fed than in fasted subjects, with most of the difference in area-under-the-curve (AUC) occurring in the first 4 hours post-dose. Hence, the US FDA recommends in the approved labeling that oxymorphone ER is taken at least 1 hour before or 2 hours after eating.

Methods: In order to determine the potential impact on cognitive performance of the increased absorption of oxymorphone ER, fed versus fasting, we conducted a randomized, rater-blinded, crossover study in 30 opioid-tolerant subjects, using tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Headache and insomnia: their relation reviewed.

Objective: Headache and insomnia are both very common and burdensome complaints worldwide. Numerous articles have been written on the relation between them, but the number of scientific articles is limited. The purpose of this review is to summarize the current scientific literature and analyze it in light of the nature of the headache-insomnia relation.

Hemicrania continua should not be classified as a trigeminal autonomic cephalalgia.

Background: The pain of the so-called functional or primary headache disorders, such as tension headache, migraine, or cluster headache, can be associated with autonomic symptoms that are localized in nature. The localized autonomic symptoms probably involve higher centers of autonomic regulation, for example the hypothalamus, for which there is support from functional magnetic resonance imaging studies.

Method: Hemicrania continua, a continuous, unilateral, side-locked headache, absolutely responsive to preventive treatment with indomethacin, is contrasted with so-called medication-overuse headache, in which the paradoxical situation exists of tremendous suffering despite excessive use of abortive medications.

tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine.

Objective: We investigated in a sham-controlled trial the analgesic effects of a 4-week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high-resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation.

Methods: Thirteen patients with chronic migraine were randomized to receive 10 sessions of active or sham tDCS for 20 minutes with 2 mA over 4 weeks.

Orofacial pain following an invasive dental procedure.

Like headache, the etiology of orofacial pain is often an enigma. Orofacial pain resulting from invasive dental procedure may cause a patient to present to a neurologist for diagnosis and treatment. The cases presented here were personally seen by the first author, a consulting neurologist; they illustrate the diversity in clinical presentation and the differences between a musculoskeletal and neuropathic origin of pain.

OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program.

Objective: To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX(®) ) as headache prophylaxis in adults with chronic migraine.

Background: Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. OnabotulinumtoxinA is the only approved prophylactic therapy in this highly disabled patient population.

A randomized, placebo-controlled phase 3 trial (Study SB-767905/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.

Unlabelled: The balance between the pain relief provided by opioid analgesics and the side effects caused by such agents is of particular significance to patients who take opioids for the long-term relief of non-cancer pain. The spectrum of signs and symptoms affecting the gastrointestinal (GI) tract associated with opioid use is known as opioid-induced bowel dysfunction. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist, approved in the US for the management of postoperative ileus in patients undergoing bowel resection (short-term, in-hospital use only).