Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

Background: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.

Methods: Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance.

Effect of a change in lasmiditan dose on efficacy and safety in patients with migraine.

: Lasmiditan is a selective serotonin (1F) receptor agonist approved for acute treatment of migraine with 3 doses: 50, 100, and 200 mg.: To help provide dosing insights, we assessed the efficacy and safety of lasmiditan in patients who treated two migraine attacks with the same or different lasmiditan doses.: Integrated analyses used data from the migraine attack treated in either of two controlled, Phase 3, single attack studies (SAMURAI/SPARTAN), and after the first attack treated in the open-label GLADIATOR extension study.

Lasmiditan in patients with common migraine comorbidities: a efficacy and safety analysis of two phase 3 randomized clinical trials.

Objective: Determine whether common migraine comorbidities affect the efficacy and safety of lasmiditan, a 5-HT receptor agonist approved in the United States for the acute treatment of migraine.

Methods: In SPARTAN and SAMURAI (double-blind Phase 3 clinical trials), patients with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100mg, 200 mg, or placebo. Lasmiditan increased the proportion of pain-free and most bothersome symptom (MBS)-free patients at 2 h after dose compared with placebo.

Lasmiditan mechanism of action - review of a selective 5-HT agonist.

Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to the discovery that calcitonin gene-related peptide (CGRP) is a key neuropeptide involved in pain signaling during a migraine attack. CGRP-mediated neuronal sensitization and glutamate-based second- and third-order neuronal signaling may be an important component involved in migraine pain.

Medical Writing Competency Model - Section 2: Knowledge, Skills, Abilities, and Behaviors.

This article provides Section 2 of the 2017 Edition 2 Medical Writing Competency Model that describes the knowledge, skills, abilities, and behaviors that professional medical writers need in order to perform effectively within the life sciences industry. What a medical writer should know, what they should be able to do, and how they should use this knowledge and these skills to facilitate their primary work function is a focus. Regulatory, publication, and other scientific writing as well as management of writing activities are covered.

Medical Writing Competency Model - Section 1: Functions, Tasks, and Activities.

This article provides Section 1 of the 2017 Edition 2 Medical Writing Competency Model that describes the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry. The functions in the Model are scientific communication strategy; document preparation, development, and finalization; document project management; document template, standard, format, and style development and maintenance; outsourcing, alliance partner, and client management; knowledge, skill, ability, and behavior development and sharing; and process improvement. The full Model also includes Section 2, which covers the knowledge, skills, abilities, and behaviors needed for medical writers to be effective in their roles; Section 2 is presented in a companion article.

A review of the efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in children and adult patients with common comorbidities.

Attention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that is often diagnosed during childhood, but has also increasingly been recognized to occur in adults. Importantly, up to 52% of children (including adolescents) and 87% of adults with ADHD also have a comorbid psychiatric disorder. The presence of a comorbid disorder has the potential to impact diagnosis and could affect treatment outcomes.

Clinical Impact of Not Achieving Recommended Dose on Duration of Atomoxetine Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

Aim: To compare atomoxetine (ATX) length of therapy (LoT) among adults with ADHD who reached the recommended dose of 80 mg/day (ATX ≥ 80) versus those who did not (ATX < 80) analyzed separately in patients prescribed ATX as monotherapy (mono) and in combination with other ADHD medications (combo).

Methods: This was a retrospective observational cohort study of the Truven Health Marketscan Commercial Claims Database from January 1, 2006-September 30, 2013, with a 6-month preindex period free of ATX (1st ATX claim as index event) and a 1-year follow-up. LoT during follow-up was calculated using prescription claim fill dates and included all days with medication on hand regardless of treatment gaps.

Atomoxetine Increased Effect over Time in Adults with Attention-Deficit/Hyperactivity Disorder Treated for up to 6 Months: Pooled Analysis of Two Double-Blind, Placebo-Controlled, Randomized Trials.

Introduction: Changes in the magnitude of efficacy throughout 26 weeks of atomoxetine treatment, along with impact of dosing, were evaluated in adults with ADHD from two randomized, double-blind, placebo-controlled studies.

Aims: Pooled placebo (n = 485) and atomoxetine (n = 518) patients, dosed 25, 40, 60, 80 (target dose), or 100 mg daily, were assessed. Change from baseline in Conners' Adult ADHD Rating Scale-Investigator Rated Scale: Screening Version (CAARS) total ADHD symptoms score and Adult ADHD Investigator Symptom Rating Scale (AISRS) total score were analyzed using mixed-model repeated measures, with least squares mean change, effect size, and response rate calculated at 1, 2, 4, 8, 12, 16, 22, and 26 weeks.

Misuse of Methylphenidate.

This chapter reviews methylphenidate misuse, abuse, dependence, diversion, and malingering associated with its use as a prescription medication for attention-deficit/hyperactivity disorder and the nonmedical use linked to its stimulant effects. Methylphenidate-induced regional elevations in brain dopamine appear to be integral to both efficacy in attention-deficit/hyperactivity disorder and potential for abuse, raising potential concerns for drug safety and prescription drug diversion costs associated with nonmedical use. Regardless, methylphenidate is an important treatment option, and detecting malingering for the purpose of illicit access to methylphenidate for subsequent misuse or diversion is a difficult challenge.

Atomoxetine monotherapy compared with combination therapy for the treatment of ADHD: a retrospective chart review study.

Objective: To analyze Clinical Global Impression-Severity (CGI-S) in ADHD patients treated with atomoxetine (ATX) monotherapy versus ATX combination therapy with another ADHD-indicated medication.

Methods: This was a 2-site retrospective observational chart review study of child and adult ADHD patients, not necessarily treatment naïve, but treated ≥50 days post baseline with an endpoint assessment. To adjust for measured confounders, monotherapy (n = 77) versus combination (n = 108) cohort comparisons were performed using propensity score stratification and adjusted ANCOVA.

Atomoxetine in patients with ADHD: A clinical and pharmacological review of the onset, trajectory, duration of response and implications for patients.

This article reviews data providing new insight into the trajectory of response and maintenance of response of atomoxetine in the treatment of child and adult attention-deficit hyperactivity disorder (ADHD). This nonsystematic review includes: onset of action and duration of effect, response rate, effect size, time to optimal response and norepinephrine transporter blockade biomarker data. Atomoxetine can have an onset of action within 1-2 weeks of starting treatment, but there is an incrementally increasing response for up to 24 weeks or longer.

Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a CNS disorder that has its onset in childhood, but often persists into adulthood. There is growing recognition that adult ADHD can result in multiple negative consequences for individuals. ADHD is also often associated with a number of comorbid psychiatric disorders.

Real-World Dosing Patterns of Atomoxetine in Adults with Attention-Deficit/Hyperactivity Disorder.

Aims: The aim was to investigate the dosing patterns of atomoxetine monotherapy in adult patients with attention-deficit/hyperactivity disorder (ADHD) in a retrospective analysis.

Methods: Adult (≥ 18 years) patients with ADHD newly initiated on atomoxetine with ≥ 1 outpatient pharmacy claim for atomoxetine between January 2006 and December 2011 were selected from the Truven Health MarketScan(®) Commercial database. After a 30-day titration period, dosing patterns of atomoxetine monotherapy were analyzed in the 12 months following initiation.

Medicines in Pregnancy Forum: Proceedings on Ethical and Legal Considerations.

To raise awareness and promote dialogue leading to action, this article provides proceedings on ethical and legal considerations associated with medicine use during pregnancy discussed during the 2014 DIA Medicines and Pregnancy Forum. A key focus of discussion at the forum was "When is it ethically appropriate to include or unethical not to include pregnant patients in clinical studies, and how can ethical barriers be addressed?" Also debated was the question "What are the most appropriate methods to collect and share data on medication use in pregnancy, and what is the best process for sharing such information?" Goals of the forum were to gain participant alignment on answers to these ethical questions, offer rationale for the answers, and provide insight into which stakeholders might be needed to facilitate discussion and action. Participants felt that under the right circumstances, drug research in pregnant women is justified and necessary.

Suboptimal dosing of Strattera (atomoxetine) for ADHD patients.

To raise awareness, this article provides a commentary on the frequent underdosing of atomoxetine for the treatment of adult attention-deficit/hyperactivity disorder (ADHD) that may be associated with poor patient outcomes. Data suggest an adequate atomoxetine dose for sufficient duration is important for ADHD symptom improvement. Despite the recommended 80 mg/day target dose, real-world data show that an approximately 60 mg/day average adult atomoxetine dose is utilized.

The potential for misuse and abuse of medications in ADHD: a review.

This article reviews the literature concerning attention-deficit/hyperactivity disorder (ADHD) medication misuse, abuse, dependence, diversion, and malingering. The review covers nonmedical use (NMU) of both stimulant (methylphenidate and amphetamine) and nonstimulant (α-adrenergic agonists and atomoxetine) prescription medications, and provides a discussion on the relevance for ADHD treatment today. The neural basis for ADHD medication mechanisms of action (increased norepinephrine and dopamine signaling) and their neurobiochemical relationship to the abuse potential is explored.

Atomoxetine effects on executive function as measured by the BRIEF--a in young adults with ADHD: a randomized, double-blind, placebo-controlled study.

Objective: To evaluate the effect of atomoxetine treatment on executive functions in young adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: In this Phase 4, multi-center, double-blind, placebo-controlled trial, young adults (18-30 years) with ADHD were randomized to receive atomoxetine (20-50 mg BID, N = 220) or placebo (N = 225) for 12 weeks. The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) consists of 75 self-report items within 9 nonoverlapping clinical scales measuring various aspects of executive functioning.

Clinical Data for Informed Medication Use in Pregnancy: Strengths, Limitations, Gaps, and a Need to Continue Moving Forward.

The objective of this paper is to explore the strengths, weaknesses, gaps, and needs in research on medication use in pregnancy, where opportunities have been bypassed to develop standards and collaborations for collecting data to better understand how medications can impact clinical outcomes in pregnant women and developing fetuses. The availability of existing data and the methods of its capture are reviewed, including registries, claims and health record databases, and meta-analyses. The paper focuses on why these efforts have not fundamentally provided benefit-risk information and clinical treatment algorithms for medication use in pregnant women.

A Proposed Framework to Address Needs of Clinical Data for Informed Medication Use in Pregnancy.

The objective of this paper is to communicate a proposed framework for addressing research limitations and communication barriers that contribute to a lack of data for making clinical treatment decisions about medication use in pregnancy. To address this global public health concern, a cross-stakeholder coalition composed of several workstreams is proposed. The intent is to foster collaborative discussion regarding potential solutions to address gaps in communication, engagement, and data generation and collection.

Duloxetine Compared with Pregabalin for Diabetic Peripheral Neuropathic Pain Management in Patients with Suboptimal Pain Response to Gabapentin and Treated with or without Antidepressants: A Post Hoc Analysis.

Objective: To examine the efficacy of duloxetine vs. pregabalin in the treatment for diabetic peripheral neuropathic pain (DPNP), comparing patient subgroups with and without concomitant antidepressant use.

Methods: This post hoc analysis assessed data from a randomized 12-week study that confirmed the noninferiority of duloxetine to pregabalin.

Long-term weight gain in patients treated with open-label olanzapine in combination with fluoxetine for major depressive disorder.

Objective: Patients with major depressive disorder (MDD) treated with olanzapine in combination with fluoxetine (OFC) demonstrate robust improvement in their depressive symptoms. Treatment with olanzapine may impact a patient's weight; thus, long-term weight gain and potential predictors (e.g.