Major
Quetiapine × Tramadol
Atypical antipsychotics×Other opioids
Mechanism
Additive CNS depression plus seizure threshold reduction (tramadol lowers it, quetiapine at high doses).
Symptoms
Deep sedation, drowsiness, ataxia. Seizures (especially with prior epilepsy) are possible. Older patients: fall risk.
Management
Avoid the combination with quetiapine above 300 mg. For analgesia on quetiapine, use paracetamol, an NSAID, or morphine/oxycodone (without serotonergic activity).