Tramadol vs Other Analgesics

Based on "Basic and Clinical Pharmacology"
written by Bertram G. Katzung, MD, PhD

Tramadol hydrochloride

Tramadol hydrochloride is an orally active, centrally acting analgesic with a dual mechanism of action. It has been used in post-surgical pain, obstetric pain, and chronic pain of mechanical and neurogenic origin.

Unlike other opioids, tramadol has no clinically relevant effects on respiratory or cardiovascular parameters. Tramadol may prove particularly useful in patients with poor cardiopulmonary function, including the elderly, the obese and smokers, in patients with impaired hepatic or renal function, and in patients in whom nonsteroidal anti-inflammatory drugs are not recommended or need to be used with caution.

Tramadol has a dose-dependent analgesic efficacy that lies between that of codeine and morphine, with a parenteral potency comparable to that of pethidine, i.e. about 10-20% of the gold standard morphine. Oral bioavailability is high (85-100%) and permits easy conversion from the oral to the parenteral route and visa versa.

Mechanism of action

Structurally tramadol is not an opiate, but it exhibits some opioid properties.

Tramadol shows a selective interaction with mu receptors, which are responsible for nociception, and has weak pharmacodynamic activity on other opioid receptors. At the same time, it acts synergistically on neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine) reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT) release.

Side effects

Respiratory depression with tramadol is less pronounced, and occurs less often, in comparison to equianalgesic doses of morphine. In large clinical and post-marketing studies including over 21,000 patients, no clinically relevant respiratory depression was reported. However, respiratory depression can occur, in particular with overdose or with impaired renal function.

Another opioid side effect, which is reduced with tramadol use, is constipation. Clinically this has proven to be a significant advantage with long-term therapy, but could also be beneficial in the prevention of ileus postoperatively.

Sweating is a side effect specific to tramadol, due to its monoaminergic effects.

Tramadol appears to carry the same risk of urinary disorders (difficulty in micturition, urinary retention) as other opiates.


Tramadol vs. Codeine

Tramadol is more potent than codeine 21. It has fewer constipating, euphoric, and respiratory depressant effects.

Chronic back pain

Codeine/paracetamol combination provides more effective pain improvement in moderate-to-severe low back pain and has better tolerability compared to tramadol/paracetamol 22.

Pain in dentistry

Tramadol maximum analgesic efficacy for relieving acute pain after oral surgery appears to be similar to that of 60 mg of codeine alone but less than that of a full therapeutic dose of codeine combination, such as aspirin/codeine or acetaminophen/codeine 20.

Tramadol has limited indication for management of acute pain in dentistry, possibly as an alternative analgesic when gastrointestinal side effects contraindicate the use of nonsteroidal anti-inflammatory drugs and when codeine/acetaminophen combination analgesics are not well-tolerated or are contraindicated.

Tramadol vs. Meperidine (Pethidine)

Meperidine is a synthetic opioid agonist at mu and kappa opioid receptors. Structurally, meperidine is similar to atropine, and exhibits a mild atropine-like antispasmodic effect. Meperidine has poor oral bioavailability and a variable absorption after intramuscular injection.

Meperidine has rapid onset and relatively short duration of analgesia (about 2-3 hours).

Labour pain

Pethidine produces better analgesic efficacy than tramadol, especially in the second stage of labour. However, tramadol provides a shorter duration of labour and is better tolerated 6.

Results of randomised clinical comparison of tramadol and pethidine analgesia on the duration of labour6
Regimen 100 mg intramuscularly 50 mg intramuscularly
Duration of labour for first stage
140 min
190 min
Duration of labour for second stage
25 min
33 min
Median visual analog scores (VAS) for pain at 10 min and one hour after drug administration
Maximum VAS for pain at 10 min and one hour after drug administration
VAS pain scores in the second stage of labour
Nausea and vomiting
Conclusion: Both tramadol and pethidine provide moderate analgesia in first stage of labour. Tramadol provides a shorter duration of labour and lower rate of side-effects. However, its analgesic efficacy was not found to be as effective as pethidine, especially in the second stage of labour.

Analgesia for adenotonsillectomy

The results of comparative study suggest that pethidine given with induction of anaesthesia provides better analgesia during and after tonsillo-adenoidectomy than does tramadol. The delay to recovery of spontaneous respiration with pethidine suggests a greater safety profile of tramadol 2.

Another study has shown that meperidine appears to be more effective for pain relief and provides better emergence characteristics than tramadol after tonsillectomy in children 5.

Postoperative pain

In clinical trial meperidine and tramadol produced comparable analgesia in patients after orthopedic surgery4. Onset of analgesia for meperidine was 10 min and for tramadol more than 30 min.

Side effects and tolerability

Tramadol has superior safety profile. Pethidine is associated with a significantly higher frequency of adverse events and a significantly lower respiratory rate in the neonates 6.
In comparative study tramadol was shown not to be associated with respiratory depression, unlike equipotent dose of pethidine 3.

Tramadol vs. Morphine

Morphine is the prototype pure mu-receptor agonist opioid, against to which all other opioid analgesics are compared.

Tramadol may produce a set of symptoms similar to opioids, including dizziness, somnolence, nausea, constipation, sweating and pruritus. However, tramadol causes significantly less respiratory depression than morphine. In contrast to morphine, tramadol has not been shown to induce histamine release. At therapeutic doses, tramadol has no effect on heart rate, left-ventricular function or cardiac index.

Different studies have shown:

  • Tramadol may represent a superior choice over morphine for children undergoing adenotonsillectomy, because of its potential to cause less postoperative sedation and respiratory depression 9.
  • Tramadol is as effective as morphine for moderate postoperative pain but it is less effective for severe acute pain 10.
  • Tramadol has been compared with morphine in patients with post-traumatic musculoskeletal pain in the pre-hospital setting. Intravenous tramadol 100 mg was equivalent to morphine 5-10 mg, with similar incidence of side effects and similar degree of patient satisfaction 11.
  • Tramadol has the least osteoporotic effect as compared to morphine 18.
  • Tramadol has smaller inhibitory effect on gastric emptying compared with morphine 19.

Radicular pain

Morphine provides greater (albeit not statistically significant) relief of radicular pain than tramadol 13.

Postoperative analgesia after tonsillectomy

Both analgesics are effective for postoperative pain relief in children after tonsillectomy. However, morphine may give better postoperative pain relief 15. Tramadol is better tolerated.

Postoperative analgesia after urological surgery

In the postoperative period, pain scores and the average time for analgesic requirement are similar for both. However, the incidences of allergic rash, itching, respiratory depression and sedation score are greater with the morphine 8.

Posttraumatic pain

Analgesia is similar with both tramadol and morphine for the management of pain in trauma 14.

Pain after abdominal surgery

Tramadol intramuscularly has postoperative analgesic activity similar to that of morphine. In multicenter trial comparing tramadol and morphine for pain after abdominal surgery after the first dose, pain intensity was reduced 36.2% with tramadol, and 51% with morphine 16.

Chronic pancreatitis

Tramadol and morphine are potent analgesics in severe chronic pancreatitis pain when individually titrated. However, in clinical study tramadol interfered significantly less with gastrointestinal function and was more often rated as an excellent analgesic than morphine 12.

Intraoperative analgesia

In clinical study there was no difference between the use of tramadol and morphine to treat pain after laparoscopic cholecystectomy from 90 min after the end of surgery. Morphine was more effective than tramadol as an intraoperative analgesic 17.

Tramadol vs. Acetaminophen/propoxyphene (Darvocet)

Tramadol has been demonstrated to provide superior analgesia to combined acetaminophen-propoxyphene in patients experiencing severe postoperative pain 7.

Drug abuse and dependence

Unlike other opioids, tramadol is not usually associated with the development of tolerance, physical dependence or psychological addiction.

Although tramadol can produce drug dependence of the mu-opioid type (like codeine or dextropropoxyphene) and potentially may be abused, there has been little evidence of abuse in foreign clinical experience. In clinical trials, tramadol produced effects similar to an opioid, and at supratherapeutic doses was recognized as an opioid in subjective/behavioral studies. Tolerance development has been reported to be relatively mild and withdrawal when present, is not considered to be as severe as that produced by other opioids. Part of tramadol's activity and some extension of the duration of mu-opioid activity. Delayed mu-opioid activity is believed to reduce a drug's abuse liability.

References & Resources

  • 1. The Merck Manual of Medical Information. Mark H. Beers et al., eds. 2nd Home Edition. Whitehouse Station, NJ: Merck; 2003.
  • 2. van den Berg AA, Montoya-Pelaez LF, Halliday EM, Hassan I, Baloch MS. Analgesia for adenotonsillectomy in children and young adults: a comparison of tramadol, pethidine and nalbuphine. Eur J Anaesthesiol. 1999 Mar;16(3):186-94. PubMed
  • 3. Tarkkila P, Tuominen M, Lindgren L. Comparison of respiratory effects of tramadol and pethidine. Eur J Anaesthesiol. 1998 Jan;15(1):64-8. PubMed
  • 4. Tarradell R, Pol O, Farre' M, Barrera E, Puig MM. Respiratory and analgesic effects of meperidine and tramadol in patients undergoing orthopedic surgery. Methods Find Exp Clin Pharmacol. 1996 Apr;18(3):211-8. PubMed
  • 5. Ozer Z, Gorur K, Altunkan AA, Bilgin E, Camdeviren H, Oral U. Efficacy of tramadol versus meperidine for pain relief and safe recovery after adenotonsillectomy. Eur J Anaesthesiol. 2003 Nov;20(11):920-4. PubMed
  • 6. Khooshideh M, Shahriari A. A comparison of tramadol and pethidine analgesia on the duration of labour: a randomised clinical trial. Aust N Z J Obstet Gynaecol. 2009 Feb;49(1):59-63. PubMed
  • 7. Sunshine A, Olson NZ, Zighelboim I, DeCastro A, Minn FL. Analgesic oral efficacy of tramadol hydrochloride in postoperative pain. Clin Pharmacol Ther. 1992 Jun;51(6):740-6. Related Articles, Links PubMed
  • 8. Demiraran Y, Kocaman B, Akman RY. A comparison of the postoperative analgesic efficacy of single-dose epidural tramadol versus morphine in children. Br J Anaesth. 2005 Oct;95(4):510-3. PubMed
  • 9. Hullett BJ, Chambers NA, Pascoe EM, Johnson C. Tramadol vs morphine during adenotonsillectomy for obstructive sleep apnea in children. Paediatr Anaesth. 2006 Jun;16(6):648-53. PubMed
  • 10. Lewis KS, Han NH. Tramadol: a new centrally acting analgesic. Am J Health Syst Pharm. 1997 Mar 15;54(6):643-52. PubMed
  • 11. Vergnion M, Degesves S, Garcet L, Magotteaux V. Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation. Anesth Analg. 2001 Jun;92(6):1543-6. PubMed
  • 12. Wilder-Smith CH, Hill L, Osler W, O'Keefe S. Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis. Dig Dis Sci. 1999;44:1107-1116. PubMed
  • 13. Park CH. Comparison of morphine and tramadol in transforaminal epidural injections for lumbar radicular pain. Korean J Pain. 2013 Jul;26(3):265-9. PubMed
  • 14. Vergnion M, Degesves S, Garcet L, Magotteaux V. Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation. Anesth Analg. 2001 Jun;92(6):1543-6. PubMed
  • 15. Ozalevli M, Unlügenç H, Tuncer U, Güneş Y, Ozcengiz D. Comparison of morphine and tramadol by patient-controlled analgesia for postoperative analgesia after tonsillectomy in children. Paediatr Anaesth. 2005 Nov;15(11):979-84. PubMed
  • 16. Gritti G, Verri M, Launo C, Palermo S, Novelli GP, Casali R, Paoletti F, Boanelli A, Tufano R, Leone D. Multicenter trial comparing tramadol and morphine for pain after abdominal surgery. Drugs Exp Clin Res. 1998;24(1):9-16. PubMed
  • 17. Naguib M, Seraj M, Attia M, Samarkandi AH, Seet M, Jaroudi R. Perioperative antinociceptive effects of tramadol. A prospective, randomized, double-blind comparison with morphine. Can J Anaesth. 1998 Dec;45(12):1168-75. PubMed
  • 18. Boshra V. Evaluation of osteoporosis risk associated with chronic use of morphine, fentanyl and tramadol in adult female rats. Curr Drug Saf. 2011 Jul;6(3):159-63. PubMed
  • 19. Crighton IM, Martin PH, Hobbs GJ, Cobby TF, Fletcher AJ, Stewart PD. A comparison of the effects of intravenous tramadol, codeine, and morphine on gastric emptying in human volunteers. Anesth Analg. 1998 Aug;87(2):445-9. PubMed
  • 20. Moore PA. Pain management in dental practice: tramadol vs. codeine combinations. J Am Dent Assoc. 1999 Jul;130(7):1075-9. PubMed
  • 21. Moore PA, Crout RJ, Jackson DL, Schneider LG, Graves RW, Bakos L. Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction. J Clin Pharmacol. 1998 Jun;38(6):554-60.
  • 22. Colini Baldeschi G, Cobianchi MR. Study of codeine-paracetamol combination treatment compared with tramadol-paracetamol in the control of moderate-to-severe low back pain. Minerva Med. 2012 Jun;103(3):177-82. PubMed

Published: May 05, 2007
Last updated: August 07, 2014


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