Tremor, clonus and a new tramadol script

Serotonin toxicity (serotonin syndrome).

She meets the Hunter criteria: a serotonergic agent plus inducible clonus with agitation or diaphoresis (she has all three), and tremor with hyperreflexia.

Supporting features

• Onset within days of adding a new serotonergic drug.
• Neuromuscular excitation: inducible clonus, hyperreflexia (more marked in the lower limbs), tremor.
• Autonomic overactivity: diaphoresis, tachycardia, temperature 38.4 C.
• Mental state change: agitation.

Discriminating from other toxidromes

• Neuroleptic malignant syndrome: needs dopamine antagonist exposure, develops over days, and shows lead-pipe rigidity, bradyreflexia, reduced bowel sounds, marked CK rise and leucocytosis. Clonus and hyperreflexia are not typical.
• Anticholinergic toxicity: dry skin and mucosa, mydriasis, urinary retention, reduced bowel sounds, flushed and dry. The patient is 'hot, dry and mad'. Clonus and hyperreflexia are absent, and she is sweating.
• Sympathomimetic toxicity: hypertension, tachycardia, dilated pupils, but clonus is not a feature and there is usually no hyperreflexia.

Severity - her temperature is under 38.5 C with no rigidity, so this looks moderate rather than severe, but it needs same-day medical assessment because deterioration to hyperthermia with rigidity and rhabdomyolysis can be rapid.

Contributors

• Sertraline 100 mg: a selective serotonin reuptake inhibitor - the baseline serotonergic load.
• Tramadol: the classic precipitant. It inhibits serotonin reuptake as well as being an opioid agonist and a noradrenaline reuptake inhibitor. Adding it to an SSRI is one of the most common causes of serotonin toxicity, and it also lowers the seizure threshold.
• St John's wort: serotonergic in its own right (reuptake inhibition with MAOI-like activity) and also an enzyme inducer, so its net effect on sertraline concentrations is unpredictable. A classic hidden contributor that patients do not report as a medicine.
• Sumatriptan: a 5-HT1B/1D agonist. The theoretical interaction with SSRIs is widely flagged but the clinically important risk is low; it is a contributing possibility, not the main driver.
• Ask specifically about other hidden serotonergic agents: dextromethorphan in cough products, tryptophan, linezolid, methylene blue, ondansetron.

Immediate management

1. Stop sertraline, tramadol and St John's wort now.
2. Arrange urgent same-day medical assessment or emergency department referral. She should not drive herself.
3. Supportive care is the mainstay: intravenous fluids, benzodiazepines for agitation and clonus, active cooling if the temperature rises above 38.5 C, and monitoring for rhabdomyolysis (CK), hyperthermia, rigidity and arrhythmia.
4. Antipyretics do not work for hyperthermia caused by muscle activity; if temperature exceeds 38.5 C with rigidity, that is severe toxicity requiring intensive care, paralysis and intubation.
5. Serotonin antagonists such as cyproheptadine are used by some toxicologists but are not the definitive treatment - cessation and supportive care are.
6. Do not restart any serotonergic agent until she has been reviewed and a plan documented.

At the point of dispensing

• Ask about all medicines, including anything from a health food shop or supermarket. St John's wort was invisible to the prescriber and to anyone who only reads the dispensing history.
• Recognise tramadol plus an SSRI (plus St John's wort) as a high-risk combination and contact the prescriber before supplying rather than after. A short conversation at that point prevents this presentation.
• Warn the patient specifically: what serotonin toxicity looks like (agitation, tremor, sweating, muscle twitching, fever), and to stop the tramadol and seek urgent care if it occurs.

Alternatives for acute low back pain

• Paracetamol at appropriate dose, plus staying active, heat and physiotherapy; most acute back pain settles within weeks.
• Topical NSAID gel is a reasonable option for localised pain.
• An oral NSAID would be more effective than paracetamol for some patients, but note the SSRI interaction: SSRIs impair platelet serotonin uptake and NSAIDs inhibit platelet thromboxane, so combined use roughly triples the risk of upper gastrointestinal bleeding. If used, use the lowest dose for the shortest time and add a proton pump inhibitor.
• Codeine has poor evidence and predictable harms; a short, reviewed course of low-dose oxycodone would be safer than tramadol in this patient, but non-opioid measures should come first.

Also flag: SSRIs plus opioids and NSAIDs increase the risk of hyponatraemia; check her sodium if she becomes confused or unwell, and document the interaction alert so it surfaces at every future dispensing.