Serotonin toxicity

Agitation, tremor, hyperreflexia, clonus, diaphoresis after serotonergic exposure

EmergentReview due

At a glance

High risk: Yes
Onset: Hours
Course: Rapid
Treatable: Yes

Safety snapshot

Watch forHyperthermiasevere autonomic instabilityseizures

Presentation hinge

Characteristic motor syndrome rather than simple low mood, psychosis, or "behavioural refusal". Mood disorders are a very common substrate.

Separates the Catatonia / Psychomotor Shutdown / Malignant Syndromes group. It is not specific to Serotonin toxicity.

Do now

1Cease all serotonergic agents immediately (including tramadol, fentanyl, linezolid, triptans, and St John's wort); strictly avoid electroconvulsive therapy (ECT under anaesthesia with succinylcholine is potentially lethal)
2Assess Hunter Criteria: spontaneous clonus, inducible clonus with agitation or diaphoresis, ocular clonus with agitation or diaphoresis, tremor plus hyperreflexia, or hypertonia with marked pyrexia and ocular or inducible clonus
3Provide aggressive supportive care: IV fluids, active external cooling, and IV diazepam for neuromuscular agitation and rigidity
4Administer cyproheptadine as specific serotonin antagonist antidote under clinical toxicology guidance
5Escalate to intensive care immediately for hyperthermia or severe autonomic instability; intubation requires non-depolarizing neuromuscular blockade (strictly avoid succinylcholine and suxamethonium due to lethal hyperkalemic cardiac arrest risk)

Locally authored, reviewed by PsychSift on 6 October 2026

Clinical review

Rows marked “Whole group”: Applies to the Catatonia / Psychomotor Shutdown / Malignant Syndromes group — not specific to Serotonin toxicity

Why it fits

Agitation, tremor, hyperreflexia, clonus, diaphoresis after serotonergic exposure

Key features

Must-not-miss

Hyperthermia, severe autonomic instability, seizures.

High-risk causes3 causes

Hyperthermia
severe autonomic instability
seizures

Bedside question

Applies to the Catatonia / Psychomotor Shutdown / Malignant Syndromes group.

Characteristic motor syndrome rather than simple low mood, psychosis, or "behavioural refusal". Mood disorders are a very common substrate.

Helpful clues

Immediate action

Applies to the Catatonia / Psychomotor Shutdown / Malignant Syndromes group.

Use structured screen (Bush-Francis), examine motor signs, check vitals/hydration/CK, think benzodiazepine challenge early Catatonia is more often mood-linked than many clinicians expect Treat the catatonia specifically Benzodiazepines and/or ECT are first-line Run a full delirium workup Hypoactive delirium is a major mimic

Priority steps6 steps

1Use structured screen (Bush-Francis), examine motor signs, check vitals/hydration/CK, think benzodiazepine challenge early
2Catatonia is more often mood-linked than many clinicians expect
3Treat the catatonia specifically
4Benzodiazepines and/or ECT are first-line
5Run a full delirium workup
6Hypoactive delirium is a major mimic

Investigations

Applies to the Catatonia / Psychomotor Shutdown / Malignant Syndromes group.

Vitals, oxygen saturation, Creatine kinase, Neuroimaging (CT/MRI), EEG, Lumbar puncture / CSF studies

Core tests5

Vitals, oxygen saturation
Creatine kinase
Neuroimaging (CT/MRI)
EEG
Lumbar puncture / CSF studies

Mimics / overlap

Applies to the Catatonia / Psychomotor Shutdown / Malignant Syndromes group.

None listed

Consider

Do now

1Cease all serotonergic agents immediately (including tramadol, fentanyl, linezolid, triptans, and St John's wort); strictly avoid electroconvulsive therapy (ECT under anaesthesia with succinylcholine is potentially lethal)
2Assess Hunter Criteria: spontaneous clonus, inducible clonus with agitation or diaphoresis, ocular clonus with agitation or diaphoresis, tremor plus hyperreflexia, or hypertonia with marked pyrexia and ocular or inducible clonus
3Provide aggressive supportive care: IV fluids, active external cooling, and IV diazepam for neuromuscular agitation and rigidity
4Administer cyproheptadine as specific serotonin antagonist antidote under clinical toxicology guidance
5Escalate to intensive care immediately for hyperthermia or severe autonomic instability; intubation requires non-depolarizing neuromuscular blockade (strictly avoid succinylcholine and suxamethonium due to lethal hyperkalemic cardiac arrest risk)

Locally authored, reviewed by PsychSift on 6 October 2026

First-line tests

Applies to the Catatonia / Psychomotor Shutdown / Malignant Syndromes group — not specific to Serotonin toxicity

Vitals, oxygen saturation
Creatine kinase
Neuroimaging (CT/MRI)
EEG
Lumbar puncture / CSF studies

Watch for

Hyperthermia
severe autonomic instability
seizures

Also consider

Source and review

Review due· Unverified

v10 · exported 2026-07-11

Clinical reference — not validated decision support. Review before use.