Physical dependence potential of daily tramadol dosing in humans.
Level 2 - randomized trial
Individual randomized double-blind crossover human trial
PubMed 20589494 · doi:10.1007/s00213-010-1919-3
What was done
Nine residential opioid-dependent adults were maintained on daily oral tramadol at two doses (200 and 800 mg) for approximately 4-week intervals in a randomized, double-blind, crossover design. Acute challenges with intramuscular placebo, naloxone (0.25, 0.5, and 1.0 mg), and hydromorphone (1.5, 3.0, and 6.0 mg) were administered under double-blind, randomized conditions. Outcomes measured included observer- and subject-rated scales and physiologic indices.
What was found
Naloxone challenge doses produced significantly higher mean peak withdrawal scores compared to placebo, with withdrawal intensity generally greater during the 800 mg/day maintenance condition compared to 200 mg/day. Hydromorphone produced elevated mean peak ratings of agonist effects at higher doses, but these ratings did not differ significantly between tramadol maintenance doses. Physiologic measures responded to challenge conditions in a dose-dependent manner with few differences between tramadol dose conditions. Numerical values and exact statistics were not reported in the abstract.
Why it matters
These findings show that daily tramadol administration induces dose-related physical opioid dependence without establishing cross-tolerance or blockade against other mu-opioid agonists, indicating tramadol is unsuitable as an opioid maintenance therapy.
Limits
The sample size was very small (n = 9) and limited exclusively to residential opioid-dependent adults. Exact numerical data, standard deviations, and p-values were omitted from the abstract.
Cited by
- supports Tramadol is habit-forming and can lead to physical dependence or addiction with long-term use.