Brief Report: A Double-Blind, Placebo-Controlled, Crossover, Proof-of-Concept Study of Minocycline in Autism Spectrum Disorder.

Neuroinflammatory mechanisms have been implicated in the pathophysiology of autism spectrum disorder (ASD). Minocycline is a matrix metalloproteinase inhibitor 9 (MMP9) inhibitor tetracycline antibiotic with known anti-inflammatory properties. In preclinical animal models of ASD, minocycline has demonstrated potential positive effects on phenotypes that may have relevance to ASD. We conducted the first placebo-controlled study of minocycline in ASD. This double-blind, placebo-controlled crossover trial employed four week treatment periods with a two week washout period. Twenty-four 12-22 year olds (mean age 17.4 years; range 12.9-22.5 years) with ASD were enrolled. Overall minocycline was well tolerated. No minocycline-associated clinical changes were noted with treatment on any performance or clinician or caregiver completed measures were noted. We hypothesize that either minocycline does not have potential therapeutic effects in ASD or our project was underpowered to define potential subject subgroups who may potentially respond positively to this drug.

Assessing characteristics of populations seen at Commission on Cancer facilities using Pennsylvania linked data.

Commission on Cancer (CoC) accreditation certifies facilities provide quality care. We assessed differences among patients who do and do not visit CoC facilities using Pennsylvania Cancer Registry data linked to facility records for patients diagnosed with cancer between 2018 and 2019 (n = 87 472). Predicted probabilities from multivariable logistic regression indicated patients in the most advantaged Area Deprivation Index quartiles were more likely to visit CoC facilities (78.0%, 95% confidence interval [CI] = 77.5% to 78.6%) compared with other quartiles. Urban patients (74.1%, 95% CI = 73.8% to 74.4%) were more likely than rural to be seen at a CoC facility (62.7%, 95% CI = 61.2% to 64.2%) as were Hispanic patients (88.0%, 95% CI = 86.7% to 89.3%) and non-Hispanic Black patients (79.1%, 95% CI = 78.1% to 80.0%) compared with White patients (72.0%, 95% CI = 71.7% to 72.4%). Differences in demographics suggest CoC data may underrepresent some groups, including low-income and rural patients.

Selective Serotonin Reuptake Inhibitor Monotherapy for Anxiety Disorders in Children and Adolescents with Autism Spectrum Disorder: A Chart Review.

Objective: Anxiety disorders are one of the most commonly co-occurring psychiatric diagnoses in youth with autism spectrum disorder (ASD), with a frequency ranging from 22% to 84%. Methods: We conducted a chart review of 29 children and adolescents with ASD who had been treated with selective serotonin reuptake inhibitor (SSRI) monotherapy for an anxiety disorder for at least 2 months. Subsequent chart reviews were conducted for the first follow-up visit within 2-6 months (M = 4.2 months) and the visit closest to 9 months posttreatment (ranging from 7 to 12 months; M = 10.5 months). The presence of adverse events (AEs) was examined, and a consensus Clinical Global Impressions Improvement (CGI-I) score was determined. Results: Fifty-five percent of patients were given a CGI-I of "improved" or "very much improved" at the 9-month follow-up. Four patients discontinued treatment owing to AEs. Other reported AEs not leading to discontinuation included vivid dreaming, increased emotional lability, and irritability. Responders included a number of patients who had failed previous SSRI trials. Conclusions: This study suggests that SSRI treatment should be considered for individuals with ASD and anxiety disorders, even if prior SSRI trials have been unsuccessful.

A 1.5-Year Follow-Up of Parent Training and Atomoxetine for Attention-Deficit/Hyperactivity Disorder Symptoms and Noncompliant/Disruptive Behavior in Autism.

OBJECTIVE: To examine status of children with autism spectrum disorder (ASD) 10 months after a 34-week clinical trial of atomoxetine (ATX) and parent training (PT). METHODS: In a 2 × 2 design, 128 children with ASD and attention-deficit/hyperactivity disorder (ADHD) were randomly assigned ATX, PT+placebo, PT+ATX, or placebo alone. PT was weekly for 10 weeks, and then monthly. ATX/placebo was titrated over 6 weeks [≤1.8 mg/kg/d], and then maintained until week 10. Responders continued to week 34 or nonresponse. Placebo nonresponders had a 10-week ATX open trial; ATX nonresponders were treated clinically. All continued to week 34. With no further treatment from the study, all were invited to follow-up (FU) at 1.5 years postbaseline; 94 (73%) participated. Changes from Week 34 to FU and from baseline to FU were tested by one-way analysis of variance or chi-squared test. PT versus no PT was tested by chi-squared test, Fisher's exact test, Welch's t-test, Student's t-test, and Mann-Whitney's U test. RESULTS: For the whole sample, the primary outcomes (parent-rated ADHD on the Swanson, Nolan, and Pelham [SNAP] scale and noncompliance on the Home Situations Questionnaire [HSQ]) deteriorated mildly from week 34 to FU, but were still substantially better than baseline (SNAP: t = 12.177, df = 93, p < 0.001; HSQ: t = 8.999, df = 93, p < 0.001). On the SNAP, 61% improved ≥30% from baseline (67% did at week 34); on noncompliance, 56% improved ≥30% from baseline (77% did at week 34). Outcomes with PT were not significantly better than without PT (SNAP p = 0.30; HSQ p = 0.27). Originally assigned treatment groups did not differ significantly. Only 34% still took ATX; 27% were taking stimulants; and 25% took no medication. CONCLUSIONS: The majority retained their 34-week end-of-study improvement 10 months later, even though most participants stopped ATX. For some children, ATX continuation may not be necessary for continued benefit or other drugs may be necessary. Cautious individual clinical experimentation may be justified. Twelve sessions of PT made little long-term difference. ClinicalTrials.gov Identifier: Atomoxetine, Placebo and Parent Management Training in Autism (Strattera) (NCT00844753).