We aimed to investigate the frequency of serotonin toxicity following overdose of antidepressants that inhibit serotonin reuptake and the factors that influence the probability of serotonin toxicity occurring.
This was a retrospective cohort study of overdoses that included selective serotonin reuptake inhibitors (SSRIs) (70%) and serotonin norepinephrine reuptake inhibitors (SNRIs) (30%) admitted to a tertiary toxicology unit over 23 years. A multivariate mixed effects logistic regression model using NONMEM (7.2.0) was used to determine factors that influenced the probability of serotonin toxicity occurring.
There were 1978 overdoses in 1520 patients; median age 33 y (range: 13-86 years) and 64% female. Median defined daily dose equivalent (DDD) was 15 (1-420). Co-ingestants were taken in 1678/1978 (85%) overdoses: 11 co-ingested the monoamine oxidase-A inhibitor (MAOI) moclobemide, 99 (5%) co-ingested olanzapine, 58 (3%) co-ingested risperidone and 417 co-ingested a benzodiazepine (21%). Serotonin toxicity occurred in 269 overdoses (13.6%). The probability of serotonin toxicity increased slightly per 10 DDD units dose [OR, 1.01; 95% confidence intervals (CIs): 0.93-1.10], increased for an SNRI vs. an SSRI [OR, 1.07; 95% CI: 0.99-1.15], and markedly increased with co-ingestion of moclobemide [OR, 33.12; 95% CI: 7.5-147]. The probability decreased per 10 y age [OR, 0.84; 95% CI: 0.74-0.95], and with co-ingestion of the serotonin 2 A receptor (5-HT2A) antagonists olanzapine [OR, 0.40; 95% CI: 0.17-0.94] or risperidone [OR, 0.13; 95% CI: 0.02-0.99]. The probability of serotonin toxicity was 12.5% at 1 DDD (therapeutic), 12.7% at 15 DDDs and 19% at 420 DDDs. In overdoses of the median dose of 15 DDDs, co-ingestion of moclobemide increased the probability to 83%, and co-ingestion of olanzapine or risperidone decreased it to 5.5% and 1.8%, respectively.
Serotonin toxicity is common following SSRI/SNRI overdose. Although dose increases probability, this was only a small effect. Co-ingestion with olanzapine or risperidone reduced the risk 2-6-fold, and moclobemide increased the risk 5-fold.
Pharmacology, Toxicology and Pharmaceutical Science
1
5%
Other
1
5%
Unknown
9
45%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 April 2023.
All research outputs
#12,440,495
of 34,560,275 outputs
Outputs from Clinical Toxicology (15563650)
#1,450
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Outputs of similar age
#186,248
of 542,972 outputs
Outputs of similar age from Clinical Toxicology (15563650)
#13
of 31 outputs
Altmetric has tracked 34,560,275 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,698 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.0. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
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We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.
