A case of serotonin syndrome following the reintroduction of aripiprazole after dextromethorphan overdose
Naoko Saito, Nobuhiko Noguchi, Maki Toida, Masatoshi Miyauchi, Takeshi Asami
Psychiatry and Clinical Neurosciences July 15, 2025 DOI: 10.1002/pcn5.70162 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study Case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | An 18-year-old female with ADHD and comorbid depressive symptoms |
| Interventions | Dextromethorphan Aripiprazole |
| Dose | 600 mg |
| Measures | Hunter Serotonin Toxicity Criteria |
| Topics | Serotonin |
| Key findings | The authors report that an 18-year-old woman developed serotonin syndrome, meeting Hunter Serotonin Toxicity Criteria (hyperreflexia, hypertonia, fever), after aripiprazole was restarted following an estimated 600 mg DXM overdose. They argue that serotonergic or dopaminergic medications should be reintroduced cautiously after DXM overdose, with adequate washout periods, especially in individuals with reduced CYP2D6 activity. |
Abstract
Abstract Background 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. Case Presentation 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. Conclusion 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.
Comparable studies
Other case reports and case series on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Lasting Neuropsychiatric Sequelae of (??)Methylenedioxymethamphetamine (???Ecstasy???) in Recreational Users Persons who ingested large doses of MDMA | 1991 | Case study | n = 2 |
| Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user Chronic MDMA user | 2000 | Case study | n = 1 |
| Death following ingestion of MDMA (ecstasy) and moclobemide People who died after ingesting moclobemide and MDMA | 2003 | Case series | n = 4 |
| Ecstasy Intoxication: An Overlap Between Serotonin Syndrome and Neuroleptic Malignant Syndrome A 19-year-old woman and 15 other cases reported in the literature | 1996 | Case report and literature review | n = 16 |
| Recurrent seizures and serotonin syndrome following "2C-I" ingestion. 19-year-old male who insufflated 2C-I | 2013 | Case report | n = 1 |