A 14 WEEK, RANDOMIZED, PLACEBO-CONTROLLED CROSS-OVER STUDY OF MULTILAYER RELEASE METHYLPHENIDATE CAPSULES (PRC-063) IN ADULT ADHD WITH AND WITHOUT ANXIETY DISORDER COMORBIDITY
Bibliographic record
Abstract
Abstract Background Psychiatric comorbidity is the rule rather than the exception in adult Attention-deficit Hyperactivity Disorder (ADHD) subjects, with the commonest being anxiety disorders [1]. Anxiety comorbidity has been shown to be associated with greater symptom severity, treatment resistance, and greater functional impairment in ADHD [2]. Stimulant medications have been proven to be effective in improving symptoms of ADHD, however, the data comes from subjects without comorbidity. This trial evaluated the benefit of stimulant medication in ADHD subjects with and without anxiety comorbidity. Aims & Objectives To evaluate the efficacy and tolerability of multilayer (sustained) release methylphenidate capsules (PRC-063) in adult patients with DSM-5 ADHD with and without anxiety disorder comorbidity. Methods This was a 14-week, double-blind, placebo-controlled, flexible dose (25-100mg/day), crossover study conducted at 2 sites. Adult ADHD subjects fulfilling DSM5 criteria (N=61) with or without an anxiety disorder comorbidity of panic disorder, agoraphobia, generalized anxiety or social anxiety disorder were included. After 1 week placebo run in, participants were randomized to PRC-063 or placebo; the initial dose was 25mg/day and the dose was titrated up based on efficacy and tolerability to a maximum of 100mg/day over 4 weeks and the maximum dose was maintained for 2 more weeks (Phase 1). At week 7, all subjects were switched to placebo for 1 week before crossing over to the other condition (Phase 2). The ADHD Rating Scale (ADHD-RS-5) total score was the primary efficacy variable and response was defined as >or equal to 30% drop in ADHD-RS-5 plus a Clinical Global Impression- Improvement (CGI-I) score of Results Comorbid anxiety disorder occurred in 49.2%. At Phase I baseline, there were no significant differences in ADHD-RS-5 or CGI-S between groups, but mean HAM-A score was significantly higher in those with comorbid anxiety (p=.01). The analyses showed that PRC-063 groups had significant improvement in both phases on the ADHD-RS-5 compared to placebo (p<.01). The mean change in ADHD- RS-5 for those who started with PRC-063 in phase 1 was 6.03 ± 2.38 (standard deviation=SD) (D=0.46) and 6.42 ± 2.14 SD (D=0.59) for those who received PRC-063 in phase 2. Also, the proportion of responders in the PRC-063 group was significantly greater than those in the placebo group in both Phase 1 (24.2% vs. 0%; χ2=7.8, df=1 p=.005) and Phase 2 (38.5% vs.3.3%, χ2=10.9, df=1 p<.001). No significant differences were found between those with and without comorbidity on change scores from Phase 1 baseline to end of Phase 1 or between Phase 2 baseline to the end of Phase 2, on either primary or secondary outcomes. Adverse events associated with PRC-063 were decreased appetite, insomnia, nasal congestion, headache, and dry mouth. Discussion & Conclusion The rates of response to PRC-063 did not differ between ADHD subjects with and without anxiety comorbidity. It is suggested that this agent would be equally effective in the treatment of ADHD with and without anxiety comorbidity. Contrary to common misconception, PRC-063 was not observed to worsen anxiety symptoms. References [1]Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. American Journal of Psychiatry. 2016;163(4):716-723. [2]Sobanski E, Brü ggemann D, Alm B, et al. Psychiatric comorbidity and functional impairment in a clinically referred sample of adults with attention-deficit/hyperactivity disorder (ADHD). European Archives of Psychiatry and Clinical Neuroscience. 2017;257(7):371-377.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".