Understanding the impact of slowing disease progression for individuals with biomarker-confirmed early symptomatic Alzheimer's disease.

Recent advances in development of amyloid-targeting therapies support the potential to slow the rate of progression of Alzheimer's disease. We conducted a narrative review of published evidence identified through a targeted search of the MEDLINE and EMBASE databases (2020-2023), recent presentations at disease-specific conferences, and data updates from cohort studies in Alzheimer's disease to describe the trajectory of the progression of Alzheimer's disease. Our findings enable the interpretation of clinical trial results and the value associated with slowing disease progression across outcomes of relevance to patients, care partners, clinicians, researchers and policymakers.

Migraine history and response to lasmiditan across racial and ethnic groups.

Objective: The robust enrollment in SPARTAN and SAMURAI provided the opportunity to present post-hoc descriptive details on migraine disease characteristics and treatment outcomes after treatment with lasmiditan, a selective serotonin (5-HT) receptor agonist, in racial and ethnic subgroups.

Methods: Descriptive data from racial (White [W]( = 3471) and Black or African American [AA]( = 792)) and ethnic (Hispanic or Latinx [HL]( = 775) and Non-Hispanic or Latinx [Non-HL]( = 3637)) populations are presented on pooled data from two double-blind, placebo-controlled, randomized Phase 3 studies (SAMURAI [NCT02439320] and SPARTAN [NCT2605174]). Patients were treated with lasmiditan (50 (SPARTAN only), 100, or 200 mg) or placebo for a single migraine attack of moderate-to-severe intensity.

Lasmiditan efficacy in migraine attacks with mild vs. moderate or severe pain.

Objective: To evaluate the efficacy of lasmiditan (LTN) in treating migraine attacks of mild vs. moderate or severe pain intensity.

Methods: 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.

Pharmacokinetics, Safety, and Tolerability of Lasmiditan in Pediatric Patients with Migraine.

Introduction: Lasmiditan is a selective serotonin (5-HT1F) receptor agonist approved in the US for the acute treatment ofmigraine in adults. This phase I, open-label, two-cohort study assessed the pharmacokinetics (PK), safety, and tolerability of lasmiditan in patients with migraine aged 6 to < 18 years.

Methods: Cohort 1 (15 to ≤ 40 kg) and Cohort 2 (> 40 to ≤ 55 kg) received single oral doses of lasmiditan (100 mg and 200 mg, respectively).

Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls.

Objective: To evaluate the impact of lasmiditan, an oral, centrally-penetrant, selective serotonin 1F (5-HT ) receptor agonist developed for the acute treatment of migraine, on simulated driving.

Methods: Healthy adult volunteers enrolled in two randomized, placebo and active comparator-controlled, crossover studies. Study 1 (N = 90) tested lasmiditan (50-, 100-, 200-mg), alprazolam (1-mg), and placebo at 1.

Acute Migraine Prescription Patterns Vary by Baseline Cardiovascular Risk and Clinical Characteristics: A Real-World Evidence Study.

Introduction: Migraine is a debilitating neurological disease and one of the most common disorders in the world. Although the triptans, potent 5-HT1B/1D receptor agonists, are an effective and widely used acute treatment of migraine, few studies have assessed how their cardiovascular risk warnings could impact prescription patterns. This study characterized cardiovascular risk factors and other aspects of people with migraine in real-world settings and confirmed patterns of acute migraine care.

The Influence of Migraine on Driving: Current Understanding, Future Directions, and Potential Implications of Findings.

Objective: To review the published findings relevant to migraine and driving performance, with an intent to encourage discussion on research which may broaden understanding in this area and help educate healthcare providers and their patients.

Background: Motor vehicle crashes result in more than 35,000 deaths and more than 2 million injuries annually in the United States. Migraine is one of the most prevalent diseases in the world, and many symptoms associated with migraine attacks have the potential to negatively influence driving ability.

Lasmiditan for acute treatment of migraine in patients with cardiovascular risk factors: post-hoc analysis of pooled results from 2 randomized, double-blind, placebo-controlled, phase 3 trials.

Background: 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.

Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine.

Lasmiditan, a serotonin 5-HT1F receptor agonist, was effective for acute treatment of patients with migraine in a phase 3 double-blind randomized controlled study. The current study was designed to replicate these findings in a generalizable population of patients with migraine, including those with a cardiovascular medical history. This prospective, double-blind, phase 3 multicentre study randomly assigned patients with migraine with and without aura (1:1:1:1 ratio) to oral lasmiditan 200 mg, 100 mg, 50 mg, or placebo.

Sustained response with ixekizumab treatment of moderate-to-severe psoriasis with scalp involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2, UNCOVER-3).

Background: Scalp is a frequently affected and difficult-to-treat area in psoriasis patients.

Objective: We assessed the efficacy of ixekizumab in the treatment of patients with scalp psoriasis over 60 weeks using the Psoriasis Scalp Severity Index (PSSI).

Methods: In three Phase 3, multicenter, double-blind, placebo-controlled trials, patients with moderate-to-severe psoriasis in UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224) and UNCOVER-3 (N = 1346) were randomized to subcutaneous 80 mg ixekizumab every two weeks (Q2W) or every four weeks (Q4W) after a 160 mg starting dose, or placebo through Week 12.

Ixekizumab Is Effective in Subjects With Moderate to Severe Plaque Psoriasis With Significant Nail Involvement: Results From UNCOVER 3.

Background: Ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, has been established as safe and effective in 3 Phase 3 trials for the treatment of moderate to severe plaque psoriasis. The lifetime incidence of psoriatic nail disease is 80%-90% of patients, and approximately 50% of patients with psoriasis have nail involvement.


Materials And Methods: The design of UNCOVER-3, a Phase 3, multicenter, double-blind, placebo- and active-controlled trial that evaluated the efficacy and safety of ixekizumab for moderate to severe psoriasis, has been published previously.

The Prevalence and Diagnostic Validity of Short-Duration Hypomanic Episodes and Major Depressive Episodes.

Current diagnostic criteria for a hypomanic episode, as outlined in both the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and DSM-5), require a minimum duration of four consecutive days of symptoms of mood elevation. The 4-day criterion for duration of hypomania has been challenged as arbitrary and lacking empirical support, with many arguing that shorter-duration hypomanic episodes are highly prevalent and that those experiencing these episodes are clinically more similar to patients with bipolar disorder than to those with unipolar major depressive disorder. We review the current evidence regarding the prevalence, diagnostic validity, and longitudinal illness correlates of shorter-duration hypomanic episodes and summarize the arguments for and against broadening the diagnostic criteria for hypomania to include shorter-duration variants.

Associations Between Glycemic Control, Depressed Mood, Clinical Depression, and Diabetes Distress Before and After Insulin Initiation: An Exploratory, Post Hoc Analysis.

Introduction: Although depression is often associated with poor glycemic control in patients with type 2 diabetes mellitus (T2DM), this observation has been inconsistent. This exploratory, post hoc analysis investigated associations between depression parameters and glycemic control using data from a 24-month, prospective, observational, non-interventional study evaluating glycemic response following insulin initiation for T2DM.

Methods: We analyzed data from a 24-month, prospective, observational study that evaluated glycemic response in patients with T2DM who initiated insulin therapy (N = 985) in 5 European countries.

Impact of non-remission of depression on costs and resource utilization: from the COmorbidities and symptoms of DEpression (CODE) study.

Objective: To determine the economic impact of sustained non-remission of depression on the total annual all-cause healthcare costs of patients with a history of depression.

Methods: Adults with ≥2 claims with depression diagnosis codes from the HealthCore Integrated Research Database were invited to participate in this retrospective/prospective fixed-cohort repeated-measures study. Patients with scores >5 at initial survey and 6 month assessment on the Quick Inventory of Depressive Symptomatology (QIDS-SR) were considered to be in 'sustained non-remission', while those with scores ≤5 at both assessments were considered to be in 'sustained remission'.

Qualitative Research on Fatigue Associated with Depression: Content Validity of the Fatigue Associated with Depression Questionnaire (FAsD-V2).

Background: Fatigue is one of the most common symptoms of major depressive disorder (MDD). The Fatigue Associated with Depression Questionnaire (FAsD) was developed to assess fatigue and its impact in patients with MDD. The current article presents the qualitative research conducted to develop and examine the content validity of the FAsD and FASD-Version 2 (FAsD-V2).

The importance of unresolved fatigue in depression: costs and comorbidities.

Objective: To assess the cost outcomes of patients with a history of depression and clinically significant fatigue.

Methods: Adults with ≥ 2 claims with depression diagnosis codes identified from the HealthCore Integrated Research Database were invited to participate in this study linking survey data with retrospective claims data (12-mo presurvey and postsurvey periods). Patient surveys included measures for depression (Quick Inventory of Depressive Symptomatology), fatigue (Fatigue Associated with Depression Questionnaire), anxiety (7-item Generalized Anxiety Disorder scale), sleep difficulty (Athens Insomnia Scale), and pain (Brief Pain Inventory).

Clinical and functional outcomes of patients who experience partial response to citalopram: secondary analysis of STAR*D.

Background: We analyzed the public STAR*D database to better characterize the baseline clinical characteristics and functional outcomes of patients with major depressive disorder (MDD) who experienced partial response in order to better understand the burden associated with this outcome.

Method: Patients (n=2,876) received treatment with citalopram. The last available Quick Inventory of Depressive Symptoms (QIDS-SR) from the 12-week treatment period was used to assign subjects to one of three groups: remitters QIDS-SR≤5; non-responders QIDS-SR >5 and <25% reduction from baseline; and partial responders QIDS-SR >5 and ≥25% reduction from baseline.

What happens next?: a claims database study of second-line pharmacotherapy in patients with major depressive disorder (MDD) who initiate selective serotonin reuptake inhibitor (SSRI) treatment.

Background: The objective of this research was to examine treatment patterns and health-care costs associated with second-step pharmacotherapy in patients with major depressive disorder (MDD) who initiated monotherapy with a selective serotonin reuptake inhibitor (SSRI) in 2010.

Methods: This claims database study analyzed patients diagnosed with MDD who were prescribed a monotherapy SSRI, with the first prescription identified as the index date. Patients were required to be ≥18 years old, to have continuous insurance coverage from 1 year prior (pre-index) through 1 year post (post-index) from the index date, and to have not received an antidepressant in the pre-index period.

Subscale validation of the neuropsychiatric inventory questionnaire: comparison of Alzheimer's disease neuroimaging initiative and national Alzheimer's coordinating center cohorts.

Objective: Neuropsychiatric symptoms are prevalent in mild cognitive impairment (MCI) and Alzheimer disease (AD) and commonly measured using the Neuropsychiatric Inventory (NPI). Based on existing exploratory literature, we report preliminary validation of three NPI Questionnaire (NPI-Q-10) subscales that measure clinically meaningful symptom clusters.

Methods: Cross-sectional results for three subscales (NPI-Q-4-Frontal, NPI-Q-4-Agitation/Aggression, NPI-Q-3-Mood) in amnestic MCI and AD dementia cases from the National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) databases were analyzed using confirmatory unrotated principal component analysis.

First controlled treatment trial of bipolar II hypomania with mixed symptoms: quetiapine versus placebo.

Objectives: To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation.

Methods: Participants included 55 adults (age 18-65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1-3 days apart).

Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease.

Background: Mibampator, an amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor potentiator, was evaluated for treatment of agitation and aggression (A/A) in Alzheimer's disease (AD).

Methods: Outpatients (n = 132) with probable AD and A/A randomized to 12 weeks of double-blind treatment with 3-mg po mibampator or placebo were assessed using the 4-domain A/A subscale of the Neuropsychiatric Inventory (NPI-4-A/A) derived from the Neuropsychiatric Inventory. Secondary measures included the Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia, Frontal Systems Behavior Inventory (FrSBe), and Alzheimer's Disease Assessment Scale-Cognitive.

Derivation of a brief measure of agitation and aggression in Alzheimer's disease.

Objective: Neuropsychiatric symptoms, including agitation and aggression (A/A), are highly prevalent in Alzheimer's disease (AD) and are associated with increased disability, functional impairment, caregiver distress, and institutionalization. Previous psychometric work suggests that individual items of agitation, irritability, disinhibition, and aberrant motor behavior from the Neuropsychiatric Inventory (NPI) may be a valid measure of A/A in AD. We provide additional confirmation of this subscale, as well as preliminary validation of it as a measure of A/A (the NPI-4-A/A).