Adverse event monitoring, assessment, and reporting in nutraceutical and phytoceutical trials for pediatric neuropsychiatric conditions: A systematic review.

This study looked at how researchers track side effects in 98 studies testing natural treatments for children with conditions like ADHD and autism. They found that while most studies tried to monitor side effects, the methods varied greatly. The most common side effects reported were stomach problems and headaches. The researchers concluded that there needs to be better, more consistent ways to track and report side effects in studies of natural treatments for children.

This systematic review examined adverse event monitoring practices in 98 trials testing natural treatments (nutraceuticals and phytoceuticals) for pediatric neuropsychiatric conditions. The review found significant variability in how adverse events were monitored, assessed, and reported across trials. While 76% of trials reported methods for adverse event monitoring, only 43% defined events to monitor a priori, 68% described collection methods, and fewer described severity assessment (49%) or attribution (26%). Over 100 different adverse events were reported, with gastrointestinal distress (65%) and headache (33%) being most common.

The most tested intervention was polyunsaturated fatty acids (36%), primarily for ADHD (59%) and autism spectrum disorder (21%).

Clinicians should be aware that gastrointestinal distress and headaches are common adverse events with natural treatments in children. The variability in adverse event monitoring suggests caution when comparing safety profiles across different natural treatments. Standardized monitoring protocols are needed to better evaluate the safety of these interventions in pediatric populations.

The review was limited to studies published from 2012-2024 and may not capture all relevant trials. The quality of adverse event reporting varied significantly across included studies, potentially affecting the comprehensiveness of identified adverse events. The review did not assess the severity or clinical significance of reported adverse events.

Natural treatments may be used as an alternative or adjunct treatment for childhood neuropsychiatric disorders. Knowledge of benefits and harms is needed to inform use guidelines. We aimed to systematically identify how and which adverse events are monitored, assessed, and reported in pediatric trials that tested nutraceutical and phytoceutical treatments. We searched MEDLINE, Embase, PsycINFO, ProQuest Dissertations and Theses Global, Cochrane Library, and Google Scholar from 2012 to 2024.

Eligible studies included nutraceutical and phytoceutical trials, experimental or quasi-experimental in design, involving children or adolescents (age 4-19 years) with neuropsychiatric conditions. Ninety-eight trials were included with 75 reported as completed (77%). The most common natural treatment tested was polyunsaturated fatty acids (36%, 35/98). Most trials focused on treating attention-deficit/hyperactivity disorder (59%, 58/98) or autism spectrum disorder (21%, 21/98).

Investigators from 74/98 trials (76%) reported methods that indicated adverse event monitoring. For these trials, events defined a priori for monitoring were identified in 43% (32/74), methods for collecting and recording events were described in 68% (50/74), and assessment of event severity and attribution was described in 49% (36/74) and 26% (19/74), respectively. Over 100 different adverse events were reported across completed trials. The most common events reported were gastrointestinal distress (65%, 49/75) and headache (33%, 25/75).

We found variability in monitoring, assessing, and reporting adverse events in pediatric trials of natural treatments. The adverse events identified in this review reinforces that specific events should be prospectively monitored in future trials.