Tramadol for Cancer Pain Management

Tramadol has limited efficacy for cancer pain and should not be considered a first-line treatment for moderate to severe cancer pain. 1

Efficacy and Position in Cancer Pain Management

Tramadol is classified as a "weak" opioid (WHO level 2) indicated for moderate to moderately severe pain, making it appropriate only for mild to moderate cancer pain 1, 2
There is widespread use of tramadol in palliative care, despite limited data on its efficacy and potentially severe adverse effects 1
A 2017 Cochrane review concluded that there is very low quality evidence supporting tramadol's use for cancer pain, and its role as step 2 of the WHO analgesic ladder remains unclear 3
Tramadol is considered approximately one-tenth as potent as morphine, limiting its utility in more severe cancer pain 2

Tramadol has a dual mechanism of action as a weak mu-opioid receptor agonist with norepinephrine and serotonin reuptake inhibition 1
Its analgesic effect is highly dependent on metabolism via CYP2D6 enzyme, with poor metabolizers experiencing reduced pain relief 1, 4
The maximum recommended daily dose is 400 mg for immediate-release formulations or 300 mg for extended-release formulations 1

Tramadol can cause significant side effects including dizziness, nausea, vomiting, and constipation 1
It affects serotonin metabolism, potentially leading to serotonin toxicity, particularly in elderly patients 1, 4
Tramadol can lower seizure thresholds and should be used with caution in patients with epilepsy risk 1, 4
It should not be combined with monoamine oxidase inhibitors (MAOIs) and requires caution when used with other serotonergic medications like SSRIs 1
Lower doses are recommended for older adults (≥75 years) and those with hepatic or renal dysfunction 1, 4
Tramadol is associated with cognitive impairment including memory problems, which may be particularly problematic in elderly cancer patients 4

High-dose tramadol (≥300 mg/day) has shown comparable analgesic efficacy to low-dose morphine (≤60 mg/day) in one non-randomized observational study, but with lower rates of constipation, neuropsychological symptoms, and pruritus 5
However, a more recent Cochrane review found very low quality evidence that tramadol is not as effective as morphine for cancer pain 3
When compared to other opioids in clinical trials, tramadol produced more adverse effects including vomiting, dizziness, and weakness than hydrocodone and codeine 1

For moderate to severe cancer pain, strong opioids like morphine are preferred over tramadol 1, 6
If tramadol is used for mild to moderate cancer pain, monitor closely for adverse effects, particularly in elderly patients or those with renal/hepatic impairment 1
When tramadol fails to provide adequate pain relief, rapid escalation to strong opioids is appropriate rather than increasing tramadol beyond recommended doses 6
Consider tramadol's potential for drug interactions, particularly with serotonergic medications, when selecting pain management options 1
For patients requiring opioid analgesia who are at risk for cognitive impairment, consider alternatives to tramadol 4

Tramadol may be appropriate as part of step 2 of the WHO analgesic ladder, particularly if other step 2 drugs are not tolerated 1
The effectiveness of step 2 medications including tramadol has a time limit of 30-40 days for most cancer patients, after which strong opioids may become necessary 6
Consider multimodal analgesia approaches including non-opioid analgesics to enhance pain control and potentially reduce tramadol requirements 6