Endpoint

Serious adverse event incidence

CAT:outcome/serious-adverse-event-incidencereported in event rate6 findings from 6 compounds

What moved it

6 findings · 6 compounds · 4 null · by evidence strength

Compound	Direction	Findings	Strongest evidence
cannabidiol	up	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
melatonin	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
quetiapine	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
tirzepatide	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
chondroitin sulfate	down	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.
methylphenidate	no effect	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.

Reported to move it

2 findings

cannabidiol — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Finding
“This analysis demonstrated an increased risk of serious AEs with the use of CBD when compared to placebo [RD=0.16 (95%CI 0.07–0.26; I2=72%)], NNT=6.”
Quoted verbatim from Use of cannabidiol in the treatment of epilepsy: Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex..
Study

meta-analysis
Dose

5 to 50 mg/kg/day in two divided doses
Population

Children and adults with Dravet syndrome, Lennox-Gastaut syndrome or tuberous sclerosis complex; CBD plus usual antiseizure therapy versus placebo plus usual therapy
Use of cannabidiol in the treatment of epilepsy: Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.2022PMID:36417631Permalink
chondroitin sulfate — decreases
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.Finding
“Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate).”
Quoted verbatim from Chondroitin for osteoarthritis..
Study

meta-analysis
Population

adults with osteoarthritis (knee, hip or hand); pooled across 6 trials
Effect 0.4 odds ratio, 95% CI 0.19 to 0.82
Chondroitin for osteoarthritis.2015PMID:25629804Permalink

Measured, no effect detected

4 findings

melatonin — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.FindingNull result
“In terms of safety, no serious adverse events were reported with either melatonin or placebo.”
Quoted verbatim from Effect of melatonin versus placebo for the prevention of delirium among medically hospitalised older patients: a double-blinded randomised controlled trial (project RESTORE)..
Study

RCT
Duration

5 days
Dose

5 mg or 8 mg oral melatonin nightly for up to 5 days (arms pooled)
Population

medically hospitalised patients aged 65 years and over; safety endpoint, ITT
Effect of melatonin versus placebo for the prevention of delirium among medically hospitalised older patients: a double-blinded randomised controlled trial (project RESTORE).2026PMID:41592826Permalink
quetiapine — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.FindingNull result
“Moreover, there was no significant difference between quetiapine and placebo in the likelihood of having at least one serious adverse event (RR 0.85, 95% CI 0.49 to 1.48).”
Quoted verbatim from Quetiapine for acute bipolar depression: a systematic review and meta-analysis..
Study

meta-analysis
Dose

150-600 mg/day
Population

Adults and children/adolescents with acute bipolar I or II depression; pooled RCTs of quetiapine versus placebo
Effect 0.85 risk ratio, 95% CI 0.49 to 1.48
Quetiapine for acute bipolar depression: a systematic review and meta-analysis.2014PMID:25028535Permalink
tirzepatide — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.FindingNull result
“Despite the side effects associated with tirzepatide, the RR for serious adverse events with once‐weekly tirzepatide compared with placebo was 0.93 (95% CI: 0.76–1.13, p = 0.45), which was not statistically significant.”
Quoted verbatim from Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials..
Study

meta-analysis
Dose

5, 10 or 15 mg or maximum tolerated dose, once weekly
Population

Adults with overweight or obesity without diabetes, six placebo-controlled randomised trials
Effect 0.93 risk ratio, 95% CI 0.76 to 1.13
Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.2025PMID:40510020Permalink
methylphenidate — no detected effect on
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.FindingNull result
“Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very low-certainty evidence).”
Quoted verbatim from Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)..
Study

meta-analysis
Participants

3,673
Population

children and adolescents with ADHD; primary outcome (serious adverse events)
Effect 0.8 risk ratio, 95% CI 0.39 to 1.67
Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).2025PMID:41342306Permalink

How it is measured

Proportion of participants experiencing at least one event meeting the trial protocol regulatory seriousness criteria (death, life-threatening event, inpatient hospitalisation or its prolongation, persistent or significant disability, congenital anomaly, or an event requiring intervention to prevent one of these).

Measured, not recorded

Subject: serious adverse event incidence
Measurements: 3 measurements
Recorded as a finding: No

Show what was measured

Serious adverse event incidence
no effect, no significant difference between arms
These serious adverse events (SAE) were deemed to be unrelated to the study by the DSMB and the IERB and no significant difference was observed between the placebo and l-Arg arms (P > 0.05).
PMID:36513483 · one of two readings recorded this
serious adverse event incidence
4/71 (4%) resveratrol vs 3/71 (3%) placebo, n = 142
Overall, 7 serious adverse events were reported in the 2 groups: 4 events for 3 participants (4%) in the resveratrol group and 3 events for 2 participants (3%) in the placebo group.
PMID:39137167 · one of two readings recorded this
serious adverse event incidence
RR 1.07 (95% CI 0.81-1.41), p = 0.64, n = 1493
Not recorded as a finding: direction stated but not statistically significant, and no sentence states the absence in words (direction_stated_but_not_significant)
The pooled analysis showed an RR of 1.07 (95% CI = 0.81–1.41; P =.64), suggesting a 7% increased risk of severe adverse events with semaglutide, although this was not statistically significant.
PMID:42499082 · one of two readings recorded this

Sources cited

6 papers

Subject: serious adverse event incidence
Findings: 6
Papers: 6

Compound

Direction

Findings

Strongest evidence

no effect

no effect

no effect

down

no effect

How it is measured

Measured, not recorded

Subject

serious adverse event incidence

Measurements

3 measurements

Recorded as a finding

Show what was measured

Serious adverse event incidence
no effect, no significant difference between arms
These serious adverse events (SAE) were deemed to be unrelated to the study by the DSMB and the IERB and no significant difference was observed between the placebo and l-Arg arms (P > 0.05).
PMID:36513483 · one of two readings recorded this
serious adverse event incidence
4/71 (4%) resveratrol vs 3/71 (3%) placebo, n = 142
Overall, 7 serious adverse events were reported in the 2 groups: 4 events for 3 participants (4%) in the resveratrol group and 3 events for 2 participants (3%) in the placebo group.
PMID:39137167 · one of two readings recorded this
serious adverse event incidence
RR 1.07 (95% CI 0.81-1.41), p = 0.64, n = 1493
Not recorded as a finding: direction stated but not statistically significant, and no sentence states the absence in words (direction_stated_but_not_significant)
The pooled analysis showed an RR of 1.07 (95% CI = 0.81–1.41; P =.64), suggesting a 7% increased risk of severe adverse events with semaglutide, although this was not statistically significant.
PMID:42499082 · one of two readings recorded this