Endpoint

Withdrawal due to adverse events

CAT:outcome/withdrawal-due-to-adverse-eventsreported in event rate10 findings from 9 compounds

What moved it

10 findings · 9 compounds · 4 null · by evidence strength

Compound	Direction	Findings	Strongest evidence
quetiapine	up	2	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
cannabidiol	up	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
curcumin	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
fluconazole	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
nicotinamide	up	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
paroxetine	up	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
propranolol	up	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
coenzyme Q10	no effect	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.
magnesium(2+)	no effect	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.

Reported to move it

6 findings

quetiapine — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Findingreplicated ×1
“The rates of pooled overall discontinuation and discontinuation due to adverse events of quetiapine-XR were greater than placebo.”
Quoted verbatim from Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials..
Study

meta-analysis
Population

Adults with generalized anxiety disorder, pooled from three randomized controlled trials of quetiapine-XR
Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials.2016PMID:26834458Permalink
nicotinamide — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Finding
“The percentage of patients who permanently discontinued the intake of study medication due to AEs was significantly higher in the NAMR group compared with the placebo group [NAMR: 21.5% (n = 116) versus placebo: 11.5% (n = 21), P =.003].”
Quoted verbatim from Modified-release nicotinamide for the treatment of hyperphosphataemia in haemodialysis patients: 52-week efficacy and safety results of the phase 3 randomized controlled NOPHOS trial..
Study

RCT
Duration

12 months
Dose

modified-release nicotinamide 250-1500 mg/day (one to six 250 mg capsules once daily before bed)
Population

Safety population of adults on maintenance haemodialysis with hyperphosphataemia, modified-release nicotinamide versus placebo, both arms on their individual phosphate binders
Modified-release nicotinamide for the treatment of hyperphosphataemia in haemodialysis patients: 52-week efficacy and safety results of the phase 3 randomized controlled NOPHOS trial.2023PMID:35751625Industry fundedPermalink
propranolol — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Finding
“We found high certainty evidence that propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo with a risk difference of 0.02 (95% CI 0.00 to 0.03); absolute risk difference: 20 more per 1,000 (95% CI 0 to 30).”
Quoted verbatim from European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol..
Study

meta-analysis
Participants

1,291
Population

Adults with migraine; meta-analysis of 20 randomized trials of oral propranolol versus placebo for migraine prophylaxis
European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol.2024PMID:39044170Permalink
paroxetine — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Finding
“Discontinuation rate due to AEs was higher in paroxetine group than placebo group (OR = 3.41, 95%CI 2.45–4.72, P <.00001) whereas the rate due to lack of efficacy was higher in placebo group as compared with paroxetine group (OR = 0.14, 95%CI 0.09–0.22, P <.00001).”
Quoted verbatim from Efficacy and tolerability of paroxetine in adults with social anxiety disorder: A meta-analysis of randomized controlled trials..
Study

meta-analysis
Dose

fixed 20, 40 or 60 mg/day, or flexible 12.5 to 60 mg/day
Population

Adults with social anxiety disorder in placebo-controlled randomised trials of paroxetine (13 RCTs, 2593 patients)
Effect 3.41 odds ratio, 95% CI 2.45 to 4.72
Efficacy and tolerability of paroxetine in adults with social anxiety disorder: A meta-analysis of randomized controlled trials.2020PMID:32243377Permalink
quetiapine — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Findingreplicated ×1
“While dropouts due to inefficacy were significantly lower in the quetiapine group (RR 0.31, 95% CI 0.19 to 0.53), dropouts due to adverse events were significantly higher in the quetiapine group (RR 1.88, 95% CI 1.20 to 2.96).”
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 11 short-term RCTs of quetiapine versus placebo
Effect 1.88 risk ratio, 95% CI 1.2 to 2.96
Quetiapine for acute bipolar depression: a systematic review and meta-analysis.2014PMID:25028535Permalink
cannabidiol — increases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Finding
“Withdrawal due to adverse events was also higher in CBD groups compared with placebo (OR 2.65, 95% CI: 1.04–6.80), although there was no significant correlation with CBD dose in the meta-regression (β = 0.0014; p = 0.274).”
Quoted verbatim from Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials..
Study

meta-analysis
Dose

20 mg to 3000 mg per day, mostly oral; one trial sublingual 20 mg
Population

Participants in 12 double-blind placebo-controlled trials of CBD lasting 7 days or more, across indications (childhood epilepsy, schizophrenia, Huntington's disease, type 2 diabetes, fatty liver disease, Crohn's disease, cannabis use disorder, healthy adults); all doses pooled
Effect 2.65 odds ratio, 95% CI 1.04 to 6.8
Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials.2020PMID:32268347Permalink

Measured, no effect detected

4 findings

curcumin — 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
“There was no difference between patients receiving curcuminoids and those receiving placebo with regard to incidence of treatment withdrawal due to adverse events (RR: 0.90 [95% CI: 0.21, 3.79]).”
Quoted verbatim from Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis..
Study

meta-analysis
Population

adults with knee osteoarthritis; curcuminoid vs placebo; safety endpoint
Effect 0.9 risk ratio, 95% CI 0.21 to 3.79
Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis.2018PMID:29622343Permalink
fluconazole — 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
“The proportion of patients colonised with or infected with fluconazole-resistant fungi (RR = 0.66, 95% CI = 0.22–1.96, P = 0.46; I2 = 0%) and the proportion of patients with adverse events leading to cessation of the study drug (RR = 0.75, 95% CI = 0.22–2.58, P = 0.65; I2 = 0%) were not different between the fluconazole group and the placebo group.”
Quoted verbatim from The use of prophylactic fluconazole in immunocompetent high-risk surgical patients: a meta-analysis..
Study

meta-analysis
Dose

100 to 800 mg/day
Population

Immunocompetent high-risk surgical adult patients in randomised trials of prophylactic fluconazole versus placebo; pooled routes (five intravenous, one enteral, one either)
Effect 0.75 risk ratio, 95% CI 0.22 to 2.58
The use of prophylactic fluconazole in immunocompetent high-risk surgical patients: a meta-analysis.2005PMID:16280069Industry fundedPermalink
magnesium(2+) — no detected effect on
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.FindingNull result
“Major adverse events (occurring in 2 out of 72 magnesium recipients and 3 out of 68 placebo recipients), and withdrawals due to adverse events, were not significantly different from placebo.”
Quoted verbatim from Magnesium for skeletal muscle cramps..
Study

meta-analysis
Population

people with skeletal muscle cramps, all cramp settings pooled
Magnesium for skeletal muscle cramps.2020PMID:32956536Permalink
Source retracted Do not rely on it.
coenzyme Q10 — no detected effect on
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.FindingNull result
“In safety outcomes, only the risk ratios (RR) of pharyngitis (RR 1.04, 95% CI 0.18 to 5.89) and diarrhea (RR 1.39, 95% CI 0.62 to 3.16) are mild elevated between coenzyme Q10 therapy and placebo and there were no differences in the number of withdrawals due to adverse effects (RR 0.61, 95% CI 0.23 to 1.62).”
Quoted verbatim from Coenzyme Q10 for Parkinson's disease..
Study

meta-analysis
Dose

1200 mg/d for 16 months
Population

patients with early and midstage Parkinson's disease; Cochrane meta-analysis of 4 RCTs, 452 patients, coenzyme Q10 versus placebo
Effect 0.61 risk ratio, 95% CI 0.23 to 1.62
Coenzyme Q10 for Parkinson's disease.2011PMID:22161420Permalink

How it is measured

Proportion of randomised participants who permanently discontinued study treatment with an adverse event recorded as the reason for discontinuation, taken from the trial disposition table or CONSORT flow diagram.

Measured, not recorded

Subject: withdrawal due to adverse events
Measurements: 2 measurements
Recorded as a finding: No

Show what was measured

withdrawal due to adverse events
no effect
Withdrawals due to adverse events were not significantly different than placebo.
PMID:22972143 · one of two readings recorded this
Withdrawal due to adverse events
increases
Withdrawal due to adverse events was also higher in CBD groups compared with placebo (OR 2.65, 95% CI: 1.04–6.80)
PMID:32268347 · one of two readings recorded this

Sources cited

10 papers

Subject: withdrawal due to adverse events
Findings: 10
Papers: 10

Compound

Direction

Findings

Strongest evidence

no effect

no effect

no effect

no effect

Measured, not recorded

Subject

withdrawal due to adverse events

Measurements

2 measurements

Recorded as a finding

Show what was measured

withdrawal due to adverse events
no effect
Withdrawals due to adverse events were not significantly different than placebo.
PMID:22972143 · one of two readings recorded this
Withdrawal due to adverse events
increases
Withdrawal due to adverse events was also higher in CBD groups compared with placebo (OR 2.65, 95% CI: 1.04–6.80)
PMID:32268347 · one of two readings recorded this