Long term tramadol

The short version: tramadol carries a real seizure risk even at therapeutic doses, and the long-term safety data is thin and industry-funded.

The best evidence on tramadol’s most serious risk comes from a 2019 systematic review and meta-analysis of 51 studies covering about 102,000 people [11]. It found that about 3 in 100 people taking tramadol therapeutically had a seizure. In overdose, that jumped to about 38 in 100. The risk was dose-dependent and about twice as high in men as in women. Seizures typically happened within hours to a day of taking the drug. Naloxone, the opioid antidote, did not clearly reduce seizure risk. This is a real, dose-linked neurological hazard that many prescribers do not mention.

The long-term tolerability data comes mostly from a single open-label phase III trial funded by the manufacturer, published in 2005 [3]. It followed 202 patients for up to 6 months. Nearly half had an adverse event. About 15 in 100 stopped the drug because of side effects. The most common problems were constipation (14 in 100), nausea (13 in 100), dizziness (10 in 100), and vomiting (8 in 100). Two patients died, though only one death was considered possibly related to the drug. The trial had no placebo group, so these numbers cannot be compared to background rates. It was also open-label, meaning both patients and doctors knew who was getting the drug, which inflates the reported side effect rate.

Animal data from 2005 suggests tramadol may raise liver enzymes. In rats, tramadol increased ALT and AST compared to controls, though less than morphine did [6]. Human long-term liver and kidney safety has not been studied in a controlled trial. A 2023 genetic study found that certain gene variants (OPRM1, MIR23B, MIR107) predict who gets constipation, nausea, and chronic pain after tramadol, but this is early work, not a safety trial [5].

A 2008 case report documented a newborn with severe withdrawal after the mother took tramadol through pregnancy, with cord blood levels of 630 ng/ml [1]. This is a known risk of any opioid in pregnancy, but it is rarely discussed with patients.

My call: tramadol is not a harmless painkiller. The seizure risk at therapeutic doses is real and dose-dependent. The long-term safety evidence is weak, industry-funded, and lacks a placebo comparison. For chronic use, the burden of proof has not been met. Confidence: moderate.