1.
A randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of extended-release metadoxine in adults with attention-deficit/hyperactivity disorder.
Manor, I, Ben-Hayun, R, Aharon-Peretz, J, Salomy, D, Weizman, A, Daniely, Y, Megiddo, D, Newcorn, JH, Biederman, J, Adler, LA
The Journal of clinical psychiatry. 2012;(12):1517-23
Abstract
OBJECTIVE To evaluate the efficacy, safety, and tolerability of an oral extended-release (ER) formulation of the nonstimulant metadoxine in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). METHOD This was a 1:1 randomized, double-blind, placebo-controlled, parallel-design, phase 2 study of metadoxine ER 1,400 mg/d treatment for 6 weeks, following a 2-week baseline/screening period, involving 120 adults with DSM-IV-defined ADHD. A follow-up assessment occurred 2 weeks after the trial was completed. Efficacy measures included changes in Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS-INV) total ADHD symptoms score with adult ADHD prompts (primary measure), response rates (≥ 25% or 40% improvement in CAARS-INV total ADHD symptom score), Test of Variables of Attention (TOVA) performance, and Adult ADHD Quality of Life (AAQoL) total score. The study was conducted from March 15, 2011, to August 21, 2011. RESULTS Intent-to-treat analysis revealed that subjects receiving metadoxine ER showed statistically significant improvement in CAARS-INV total ADHD symptoms score (P = .02), higher rate of response (≥ 25% [P = .03] or ≥ 40% [P = .04] improvement) on the CAARS-INV total ADHD symptoms score, and improvement in TOVA score (P = .02) and AAQoL score (P = .01) compared with the placebo group. Improvements in ADHD symptoms (scored by CAARS-INV) were significantly different in subjects treated with metadoxine ER versus placebo as early as 2 weeks following treatment initiation. Metadoxine ER was generally well tolerated, with nausea (17% [10/58] vs 0% [0/59]), fatigue (31% [18/58] vs 27% [16/59]), and headaches (29% [17/58] vs 39% [23/59]) being the most frequently reported adverse effects for the metadoxine ER and placebo groups, respectively. CONCLUSIONS Findings suggest that metadoxine ER is a well-tolerated and effective treatment for adults with ADHD. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01243242.
2.
Androgen replacement therapy in Turner syndrome: a pilot study.
Zuckerman-Levin, N, Frolova-Bishara, T, Militianu, D, Levin, M, Aharon-Peretz, J, Hochberg, Z
The Journal of clinical endocrinology and metabolism. 2009;(12):4820-7
Abstract
CONTEXT Women with Turner syndrome (TS) have reduced levels of androgens due to ovarian failure. HYPOTHESES Morbidity associated with TS, such as bone fragility, metabolic changes, obesity, neurocognitive profile, and sexual problems may partly relate to androgen insufficiency and improve on androgen replacement therapy (ART). OBJECTIVES The objective of the study was to determine the effect of androgens on morbidity in TS. DESIGN Fourteen TS women (aged 17-27 yr) participated in a randomized, double-blind, placebo-controlled crossover pilot. The study was conducted in a hospital outpatient clinic between December 2001 and July 2004. INTERVENTION TS patients were on estrogen/progestin replacement therapy. Subjects received oral 1.5 mg methyl testosterone (ART) or placebo for 1 yr and the alternative for another year. MAIN OUTCOME MEASURES The study compared body composition as a primary outcome, and physiology, biochemistry, visceral fat, cognition, and quality of life (QOL) as secondary outcomes. RESULTS ART as compared with placebo reduced total cholesterol, triglycerides, and high-density lipoprotein cholesterol. It improved bone mineral density, increased lean body mass, and decreased fat mass. ART improved attention, reaction time, and verbal memory and had no effect on executive functions and spatial cognition. Patients reported improved QOL, including general health, coping with stress, and sexual desire. CONCLUSIONS Androgen insufficiency plays a role in TS-impaired body composition, neurocognition, and QOL, and these aspects improve with ART, which was safe and effective when given for 1 yr.