Compare and contrast Serotonin Syndrome with Neuroleptic Malignant Syndrome
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Serotonin syndrome (SS) |
Neuroleptic malignant syndrome (NMS) |
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Precipitants & Risk factors |
Serotonergic Agents such as TCAs, SSRIs, SNRIs, MAOIs, triptans, nefazodone, buspirone, mirtazapine, carbamazepine, tramadol, linezolid, MDMA (ecstasy), dextromethorphan, St. John's wort, lithium, methadone, cocaine, levodopa, reserpine, and amphetamines. *naming a few drugs/classes adequate Usually concurrent use of multiple agents |
Dopamine Antagonists such as antipsychotics and antiemetics. Also, abrupt withdrawal of dopamine agonists, for instance, those used in the management of Parkinson's disease, may produce signs and symptoms correlating with NMS. NMS does not necessarily correspond with high doses of antipsychotics, as it can occur with lower doses |
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Concurrent use of serotonergic agents Use of illicit drugs, especially when used in patients concurrently taking a serotonin enhancing drug. |
Use of first- &/or second-generation antipsychotics. Use of higher doses of first- &/or second-generation antipsychotics Rapid escalation of dosing, switching among agents, higher potency agents, and long-acting depot formulations |
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Incidence |
Rare |
0.02–2.4% in patients being treated with neuroleptics |
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Time of onset following inciting agent |
Usually < 24 hours of initiation or change in a medication |
Usually 1-3 days (can be later) of exposure to a dopamine antagonist or withdrawal of a dopamine agonist |
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Autonomic features |
Tachypnoea Hyperthermia (> 40°C) Tachycardia Hypertension Diaphoresis Hypersalivation |
Tachypnoea Hyperthermia (> 40°C) Tachycardia Hypertension Diaphoresis Hypersalivation |
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Neuromuscular |
Increased tone, worse in the lower extremities than upper extremities Hyperreflexia Clonus (unless masked by increased muscle tone) Dilated pupils Classically agitation then coma |
'Lead-pipe' rigidity globally Rapid, increasing signs of extrapyramidal symptoms Hyporeflexia Normal pupils Classically alert then coma |
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Treatment |
Discontinue serotonergic agents Benzodiazepines Cyproheptadine Supportive management |
Discontinue dopaminergic agents Cooling Fluids Benzodiazipines Dopamine agonists e.g. Bromocriptine or amantidine Dantrolene Supportive management |
Examiners Comments:
Marks were allocated to descriptions of Precipitants and Risk factors, Clinical Features/Diagnosis and Management – the specific headings in the Table were not required.
Many candidates lacked the basic knowledge to pass the question, and many did not complete it. Many confused Neuroleptic Malignant Syndrome with Malignant Hyperthermia.
As a "compare and contrast" question, this one would benefit from a tabulated answer. The college table is of a sufficiently high quality that any attempt to "improve" on it would only lead to a messier more confusing answer model. As such, it would be completely consistent with the spirit of this revision resource.
| SS | NMS | |
| Causative agents | Serotonin agonists or antagonists | Dopamine antagonists or withdrawal of dopamine agonists |
| Onset | Rapid (hours) | Gradual (days) |
| Relationship to drug dose | Usually overdose or the effect of using a combination of several agents | Can occur with normal dosing, even after years of treatment with the same agent |
| Level of consciousness | Agitation, hypervigilance, delirium | Encephalopathy, stupour, coma, mutism |
| Pupils | Dilated | Normal |
| Other cranial nerves | Usually unaffected | Dysphagia, aspiration |
| Tone | Increased | Increased ("lead pipe") |
| Reflexes | Increased | Decreased |
| Clonus | Present (a diagnostic discriminator) | Absent |
| Temperature | Raised | Raised |
| Mucosa | Siallorhoea | Siallorhoea |
| Cardiovascular findings | Tachycardia and hypertension | Haemodynamically unstable, may be either high or low |
| Biochemistry | Rhabdomyolysis; CK rise | Rhabdomyolysis, CK rise Low serum iron |
| Acid-base | Normal | Acidosis |
| Haematology | May be normal | Raised white cell count |
| Bowel sounds | Vigorously hyperactive | Reduced, sluggish |
| Management | Cyproheptadine, olanzapine, chlorpromazine | Amantadine, bromocryptine, dantrolene |
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