vortioxetine and Attention-Deficit-Disorder-with-Hyperactivity

Stimulants remain the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) but are often associated with insufficient response or poor tolerability, leading to many patients not wishing to be treated with controlled substances.. This randomized, placebo-controlled, proof-of-concept study (NCT02327013) evaluated the efficacy of a multimodal antidepressant, vortioxetine, in the treatment of ADHD, using a two-stage sequential parallel comparison design.. Patients aged 18-55 years with a diagnosis of ADHD (DSM-5) and a total score ⩾24 on the Adult ADHD Investigator Symptom Rating Scale (AISRS) were randomized in study stage I with a 1:1:3 ratio to six weeks of treatment with vortioxetine 10 or 20 mg/day, or placebo ( n = 227). In study stage II, placebo non-responders (AISRS total score reduction <30% from stage I baseline) were re-randomized with a 1:1:1 ratio to six weeks of vortioxetine 10 or 20 mg/day, or placebo ( n = 59).. Across the two study stages combined, ADHD symptoms improved by approximately eight AISRS points in all treatment groups, showing no difference from placebo for either dose of vortioxetine, the study thus failing to meet its primary endpoint. However, both doses of vortioxetine separated from placebo in improving overall patient functioning, as measured by the Sheehan Disability Scale.. Studies are warranted to further investigate this suggested benefit of a multimodal antidepressant for patient functioning in ADHD while addressing issues of non-adherence and placebo response. The study confirmed vortioxetine 10 mg and 20 mg as generally well-tolerated.

Topics: Adolescent; Adult; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Double-Blind Method; Female; Humans; Male; Middle Aged; Treatment Outcome; Vortioxetine; Young Adult

The primary objectives of this study were to evaluate the pharmacokinetics (PK) and tolerability of single and multiple doses of vortioxetine in children and adolescents with a depressive or anxiety disorder and to provide supportive information for appropriate dosing regimens for pediatric clinical trials.. This prospective, open-label, multinational, multisite, multiple-dose trial enrolled 48 patients (children and adolescents; 1:1 ratio) divided into 8 cohorts (4 adolescent and 4 child), with each cohort including 6 patients. The cohorts in each age group were assigned to receive one of four dosing regimens: vortioxetine 5, 10, 15, or 20 mg q.d. for 14 days. The total treatment period lasted 14-20 days with patients in the higher dose cohorts uptitrated over 2-6 days. Plasma samples for PK analysis were obtained on the first and last days of dosing.. Among children and adolescents, respectively, 62% and 92% had depression and 58% and 33% had anxiety disorder. Comorbid attention-deficit/hyperactivity disorder (ADHD) was present in 50% of children and 38% of adolescents. After 14 days q.d. at the target dose, the PK of vortioxetine concentrations was generally proportional to the dose in both age groups. Exposure, as assessed by maximum plasma concentrations and area under the plasma concentration-time curve from time 0 to 24 hours, was 30%-40% lower in adolescents than in children. There was no significant relationship between sex, height, or ADHD diagnosis and PK parameters. Most adverse events were mild in severity and consistent with those seen in adults.. The results suggest that the dosages of vortioxetine evaluated (5-20 mg q.d.; approved for treatment in adults) and the uptitration schedule used are appropriate for pediatric efficacy and safety trials.

Topics: Adolescent; Anti-Anxiety Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Child; Comorbidity; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Male; Piperazines; Sulfides; Vortioxetine

Topics: Animals; Antidepressive Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Benzodiazepines; Cognitive Aging; Cognitive Behavioral Therapy; Cognitive Dysfunction; Cognitive Remediation; Dementia; Drosophila melanogaster; Female; Humans; Hypnotics and Sedatives; Intellectual Disability; Neural Pathways; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sleep; Vortioxetine

Topics: Adolescent; Anti-Anxiety Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Drug Therapy, Combination; Female; Humans; Methylphenidate; Vortioxetine