# A case of serotonin syndrome following the reintroduction of aripiprazole after dextromethorphan overdose

**Authors:** Naoko Saito, Nobuhiko Noguchi, Maki Toida, Masatoshi Miyauchi, Takeshi Asami

PMC · DOI: 10.1002/pcn5.70162 · PCN Reports: Psychiatry and Clinical Neurosciences · 2025-07-15

## TL;DR

A young woman developed serotonin syndrome after restarting aripiprazole following a dextromethorphan overdose, highlighting the risks of combining serotonergic drugs.

## Contribution

This case emphasizes the need for caution when reintroducing psychotropic medications after dextromethorphan overdose.

## Key findings

- The patient developed serotonin syndrome after aripiprazole was reintroduced following a dextromethorphan overdose.
- Symptoms included hyperreflexia, hypertonia, and fever, meeting the Hunter Serotonin Toxicity Criteria.
- The case suggests the importance of allowing washout periods before restarting serotonergic medications.

## Abstract

Serotonin syndrome is a potentially life‐threatening condition that arises from excessive serotonergic activity. Dextromethorphan (DXM), commonly used as a non‐prescription antitussive, can induce serotonin syndrome when taken in high doses or in combination with other serotonergic agents. At supratherapeutic levels, DXM acts as a serotonin reuptake inhibitor and N‐methyl‐D‐aspartate (NMDA) receptor antagonist, thereby significantly increasing the risk of serotonin toxicity.

We present the case of an 18‐year‐old female diagnosed with attention‐deficit/hyperactivity disorder (ADHD) and comorbid depressive symptoms who developed serotonin syndrome after the reinitiation of aripiprazole in the context of recent DXM overdose. Following ingestion of an estimated 600 mg of DXM, the patient exhibited signs of toxicity. The subsequent administration of aripiprazole was temporally associated with the emergence of serotonin syndrome, evidenced by hyperreflexia, hypertonia, and fever, in accordance with the Hunter Serotonin Toxicity Criteria.

This case illustrates the necessity of cautious reintroduction of serotonergic or dopaminergic medications following DXM overdose. Given the potential for prolonged metabolism and interaction—especially in individuals with reduced CYP2D6 activity—clinicians should allow for adequate washout periods before restarting psychotropic agents, such as aripiprazole.

## Linked entities

- **Chemicals:** dextromethorphan (PubChem CID 5360696), aripiprazole (PubChem CID 60795), serotonin (PubChem CID 5202)
- **Diseases:** serotonin syndrome (MONDO:0018546), attention-deficit/hyperactivity disorder (MONDO:0007743)

## Full-text entities

- **Genes:** CYP2D6 (cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene)) [NCBI Gene 1565] {aka CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2}
- **Diseases:** overdose (MESH:D062787), hypertonia (MESH:D009122), fever (MESH:D005334), Serotonin Toxicity (MESH:D020230), toxicity (MESH:D064420), depressive symptoms (MESH:D003866), hyperreflexia (MESH:D012021), ADHD (MESH:D001289)
- **Chemicals:** DXM (MESH:D003915), dopaminergic medications (-), aripiprazole (MESH:D000068180)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

10 references — full list in the complete paper: https://tomesphere.com/paper/PMC12264311/full.md

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Source: https://tomesphere.com/paper/PMC12264311