Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder.

BACKGROUND: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses. METHODS: We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4-15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions-Improvement (CGI-I) was a secondary endpoint. RESULTS: Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (- 12.5 ± 3.18 [mean ± SE]) vs. placebo (- 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65). CONCLUSION: Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27-0419-6116. CLINICALTRIALS: Gov registration ID is NCT06058962, last update posted 2023-09-28.

Comorbidities in adult attention-deficit/hyperactivity disorder: a practical guide to diagnosis in primary care.

Diagnosis and management of attention-deficit/hyperactivity disorder (ADHD) in adults is complex and challenging because of the frequent comorbidity of other psychiatric disorders that have symptoms overlapping with those of ADHD. The presence of comorbidities can create challenges to making an accurate diagnosis and also impact treatment options and outcomes. This review discusses disorders that may be comorbid with ADHD in adults, including anxiety, mood, substance use disorder, antisocial personality disorder, and borderline personality disorder. Suggestions for recognizing these comorbidities and distinguishing them from ADHD and perspectives on their possible impact on ADHD treatment are included. Adjunctive nonpharmacologic modalities may be especially helpful in the case of comorbid mood, anxiety, substance abuse, or personality disorders.

A physician's guide to helping patients with ADHD find success in the workplace.

The impact of untreated adult attention-deficit/hyperactivity disorder (ADHD) in the workplace can be substantial, and employees with ADHD often confront frustration, employer disappointment, and low performance ratings. As a result, adults with ADHD may seek treatment from primary care providers to improve occupational performance. Previously considered a behavior disorder primarily affecting children and adolescents, ADHD in adulthood presents primarily as a cognitive disorder. Self-management deficits play a greater role in adult ADHD, particularly with respect to occupational and interpersonal functioning. Although specialized resources are available to assist adults with ADHD, many afflicted individuals may be unaware or unable to access them. Primary care providers who may be treating adults with ADHD are in a unique position to help them obtain the care and support needed to build appropriate skills and manage occupational issues. In this review, a literature search of the past 10 years was conducted to identify articles concerning ADHD and its impact on individuals in the workplace. The influence of ADHD on occupational functioning is discussed in the context of self-management impairments, diagnosis and assessment, and management strategies. With early and successful intervention, adults with ADHD may be able to become more aware of the impact of ADHD on work performance and achieve successful occupational experiences.

ADHD in adults: current treatment trends with consideration of abuse potential of medications.

OBJECTIVE: To review the literature describing impairments in educational, occupational, and social functioning in adults with attention-deficit/hyperactivity disorder (ADHD), current treatment trends, and factors that may influence the abuse potential of long-acting medications used to treat ADHD in adults. METHODS: A MEDLINE search was conducted to identify articles relating to functional impairments and treatment options for adults with ADHD, as well as the abuse potential of ADHD medications. RESULTS: ADHD is one of the most common psychiatric behavioral disorders in children, and its symptoms have been shown to persist into adulthood. Symptoms of ADHD may occur at home, school, work, or in social situations, and symptom occurrence in these different settings can have a profound negative impact for adults with ADHD. Impairments in educational, occupational, and social functioning in adults with ADHD have been described and are summarized in this review article. Although long-acting medications are more frequently prescribed for children with ADHD than short-acting medications, adults with ADHD are equally likely to be treated with short- and long-acting medications. While all medications used to treat ADHD in adults have potential for abuse, there are a number of factors that may contribute to a lower potential for abuse for long-acting agents compared with immediate-release medications. CONCLUSION: Impairments from ADHD can be chronic and persistent and they can affect daily educational, occupational, and personal functioning. Adults, in particular, have responsibilities that can extend into the late evening hours so that clinicians need to consider medication duration of action when selecting a pharmacotherapy intervention for adults with ADHD.

Improving Communication in ADHD Care: Results from In-office Linguistic Research.

UNLABELLED: IntroductionAn in-office linguistic study was conducted to help improve understanding of how to better evaluate and treat attention-deficit/hyperactivity disorder (ADHD). METHODS: Naturally occurring interactions were recorded among 7 psychiatrists and 23 patients and 8 pediatricians along with 22 patients and their parents. Participants were interviewed separately post-visit. Transcripts of interactions and interviews were analyzed using sociolinguistic techniques. RESULTS: Visits were variable in length and lacked concrete treatment plans. In the pediatric setting, children were typically excluded from dialogues, accounting for only 8% of words spoken. School was the primary metric used to evaluate symptoms. Pediatricians allayed parents' concerns about stimulant therapy by promising to prescribe the lowest possible dose, rather than discussing titrating to an optimal dose. Adults were evaluated idiosyncratically without the use of scales or tools. Stimulants were positioned as short-term "trials" without strong physician recommendations.DiscussionConversations about stimulant therapy lacked goal- and expectation-setting. Also missing from conversations was a definitive treatment plan based on the core symptoms of ADHD. Incorporating open-ended questions and tools or rating scales may result in a more effective and efficient in-office dialogue. CONCLUSION: Further research is warranted to assess the efficacy of communication strategies to enhance in-office discussions of ADHD and stimulant therapy.

Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) adversely impacts the educational achievement, mood and emotion processing, and interpersonal relationships of children and adolescents. Effective treatments include a number extended-release (ER) methylphenidate-(MPH) and amphetamine-based drugs. Some formulations release a comparatively larger bolus after dosing and can result in different onset and duration of efficacy. OBJECTIVE: Provide an evidence-based description of the time course of efficacy of psychostimulant medications used in ADHD treatment of children and adolescents. DATA SOURCES: A literature search from 1998 to 2008 was conducted using a MEDLINE database and the keywords "attention-deficit/hyperactivity disorder," "extended-release," "sustained-release," "methylphenidate," "amphetamine," "randomized," "controlled," "placebo," "efficacy," "time course," and "classroom study." DATA EXTRACTION: Selection criteria included randomized, blinded, placebo- or active comparator-controlled clinical studies that evaluated an ER formulation of a psychostimulant treatment for ADHD in at least 30 children and adolescents aged 6 to 17 years. STUDY SELECTION: Eighteen clinical trials met the chosen criteria and evaluated: d, l-MPH, long-acting (d, l-MPH-LA); d, l-MPH-OR; d, l-MPH-CD (MCD); d-MPH-ER; MPH transdermal system (MTS); mixed amphetamine salts, ER (MAS-XR); and lisdexamfetamine dimesylate (LDX). DATA SYNTHESIS: Onset of efficacy was earliest for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5 hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and LDX at approximately 2 hours. Duration of efficacy for each treatment was: MCD 7.5 hours; d, l-MPH-LA 8 to 12 hours; and 12 hours for MTS, d-MPH-ER, d, l-MPH-OR, MAS-XR, and LDX. However, data should be interpreted with caution given the different trial designs and assessment time points. CONCLUSIONS: d-MPH-ER has the earliest onset of efficacy at 0.5 hours postdose, and MTS, d-MPH-ER, d, l-MPH-OR, MAS-XR, and LDX have a long duration of action at 12 hours postdose. Clinicians should consider differences in the onset of efficacy of each drug in the context of individual patient needs.

Dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study compared once-daily dexmethylphenidate extended release (D-MPH-ER) 20 mg/day and placebo over 12 hours in children ages 6 to 12 with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. METHOD: All of the children were stabilized for > or =2 weeks on a total dose (nearest equivalent) MPH 40 mg/day or immediate-release D-MPH 20 mg/day before screening. After a practice day, they received 6 days of D-MPH-ER 20 mg/day or placebo at home, returning on day 7 for one dose. Subjects were evaluated at predose and postdose hours 0.5, 1, 3, 4, 5, 7, 9, 10, 11, and 12 and then crossed over to the other treatment arm using the identical protocol. The primary efficacy variable was the change from predose in Swanson, Kotkin, Agler, M-Flynn, and Pelham rating scale (SKAMP) combined score from 1 to 12 hours. Secondary efficacy variables included SKAMP combined score at 0.5 hours, SKAMP subscale scores, and math test results over 12 hours. RESULTS: Sixty-eight children were randomized, with 67 completing the study. Onset of action was indicated by a significant difference between D-MPH-ER and placebo at 0.5 hour on the SKAMP combined score (p = .001). For efficacy measures, differences from placebo were significant at all points between 0.5 and 12 hours (p < .001 top = .013). CONCLUSIONS: D-MPH-ER provided sustained improvement in attention, deportment, and academic productivity throughout the 12-hour laboratory day.