Opioids · Pain & inflammation
Tramadol
Ultram® · Tridural®(brand names vary by market)
Part opioid, part antidepressant, and it lowers the seizure threshold.
Also: modified release, capsule
Mechanism
A weak mu agonist whose active metabolite does most of the opioid work, combined with serotonin and noradrenaline reuptake inhibition. The dual mechanism is why it interacts like an antidepressant as well as an opioid.
Indications
- Moderate pain
- Neuropathic pain, second-line
Formulations
Dosing concepts
Ceiling
It has a maximum daily dose set by seizure risk rather than by analgesic plateau.
CYP2D6
Like codeine, conversion to the active metabolite depends on CYP2D6, so analgesia is unpredictable while the serotonergic effects are not.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~70%
- Half-life
- 5 to 7 h
- Elimination
- hepatic: CYP2D6 to the active O-desmethyl metabolite; CYP3A4 to inactive ones
- Protein binding
- ~20%
Adverse effects
- Nausea and dizzinesscommonMore than most opioids at equivalent analgesia.
- SeizureseriousDose-related, and increased by SSRIs, SNRIs, bupropion and tricyclics.
- Serotonin syndromeseriousEspecially with SSRIs, SNRIs, MAO inhibitors or triptans.
- Hyponatremiaserious
- Constipation and sedationcommon
- Dependenceserious
Contraindications & precautions
Contraindications
- Concurrent or recent MAO inhibitor
- Uncontrolled epilepsy
- Children under 12
- Severe respiratory depression
Precautions
- Concurrent serotonergic drugs
- Seizure risk factors
- Renal or hepatic impairment
- Older adults
Interactions
Monitoring
The rest of the medication list for serotonergic drugs
This is the interaction that catches people, and it is checkable in seconds
Seizure history and threshold-lowering co-medications
The dose ceiling exists for this
Sodium in older adults
Hyponatremia is described and easy to miss
Counselling points
- Tell us about every other medicine, especially antidepressants and migraine treatments.
- Do not exceed the stated maximum daily dose.
- Report agitation, sweating, tremor, or a racing heart.
- Do not stop it abruptly after prolonged use.
Clinical pearls
- Tramadol plus an SSRI is one of the most common serotonin-syndrome-precipitating combinations in general practice, and both drugs are often prescribed by different people for different problems.
- It is frequently regarded as a mild, safe analgesic. Its seizure, serotonergic, hyponatremic and dependence profiles make that reputation undeserved.
References & review
- Tramadol product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.