Codeine is so grossly inferior and yet addictive, I can't even see why it is allowed to be manufactured and sold.  It should banned.  At most, it should have a very minimal role in the field of medicine and be regulated much more tightly than at present.  It has been found inferior to other pain relievers in every study to date and adds very little, if anything, to the pain relief of non-narcotic pain relievers.  Despite overwhelming evidence of no benefit, yet significant evidence of harm, physicians continue to prescribed codeine millions of times each year.  Even for cough suppression, other alternatives appear more sensible.  Many codeine addicts graduate to more powerful drugs.

In 16 studies, codeine or codeine plus acetaminophen was inferior a non-narcotic pain relievers (ketorolac(3), Vioxx(2), naproxen, etorbicoxib, flurbiprofen (Ansaid)(3), meclofenac, ibuprofen(2), aspirin, diclofenac(2), acetaminophen, and ketoprofen).  In one study, codeine plus acetaminophen did as well as ibuprofen, but caused more side-effects.  In just one study, codeine plus acetaminophen did as well a lysine clonixinate and that may have been due to the acetaminophen alone.  In no study did codeine or acetaminophen plus codeine do better than anything.  

Thus, codeine's record is 0 wins, 1 tie, and 17 losses.  Codeine is a miserable loser.  In nine more studies, adding codeine to acetaminophen or ibuprofen or another pain reliever had no beneficial effect.  In one study for cough, the non-narcotic levodropripizine did just as well with fewer side-effects.

Codeine causes many people to become addicted to codeine and many graduate to still more addictive narcotics.  Codeine should be banned.  It serves no useful function whatsoever.  If it were banned, the world would be a better off.

If a doctor wants to give you codeine, print out this webpage and give it to him.  If he still insists on giving you a narcotic, get another doctor.  If a doctor gave you codeine and you became addicted and suffered some unfortunate consequence, the doctor and the narcotic manufacturer could be liable for malpractice.  Also, consider whether you should report the doctor to the state licensing board.  In view of the research, prescribing codeine is or at least should be ruled malpractice.

Cancer: Diclofenac Alone as Good as With Codeine or With Imipramine: In a 4-day DB random assignment study of 184 cancer patients with moderate to severe chronic pain, diclofenac alone (50 mg q.i.d.) did as well as for pain relief as the combination of diclofenac and codeine 40 mg q.i.d., or the combination of diclofenac and imipramine, 10 or 25 mg t.i.d.. Withdrawal rates were similar in all groups. Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain. Minotti V, et al. Divisione Oncologia Medica, Policlinico Monteluce, Perugia, Italy. Pain. 1998 Feb;74(2-3):133-7.

Children: Myringotomy and Tube Placement: Ketorolac Better Pain Relief than Butorphanol or Acetaminophen with Codiene: In a DB study of 120 children undergoing bilateral myringotomy and tube placement, IM ketorolac 1 mg/kg had the longest time to first rescue analgesic, and there was no associated postoperative vomiting or nausea. It was followed in effectiveness by transnasal butorphanol 25 mcg.  Both were superior to plain acetaminophen 10 mg/kg orally, and to acetaminophen 10 mg/kg with 1 mg/kg of codeine orally. All children received oral midazolam (0.6 mg/kg) before surgery. Children who received ketorolac versus butorphanol had less vomiting in the 24 h after surgery. Postoperative analgesia in children undergoing myringotomy and placement equalization tubes in ambulatory surgery. Pappas AL, et al. Loyola University Medical Center, Illinois. . Anesth Analg. 2003 Jun;96(6):1621-4

Children: Tonsillectomy: Acetaminophen as Good as Acetaminophen with Codeine; Fewer Side-effects: In a DB study of 51 children ages 3 to 12 with outpatient tonsillectomy, there was no difference in the level of postoperative pain reported by the parents and children between plain acetaminophen and acetaminophen with codeine. The acetaminophen with codeine group tended to have increased problems with nausea, emesis, and constipation. Children in the acetaminophen group consumed a significantly higher percentage of a normal diet on the first 6 postoperative days (P < .05, all time points). Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Moir MS, et al. Stanford University. Laryngoscope. 2000 Nov;110(11):1824-7.

Children: Myringotomy and Tube Placement: Added Codeine No Value to Acetaminophen: In a DB study of 95 children ages 1-12 undergoing myringotomy and tube placement, a compound preparation Painstop (Paedpharm Pty Ltd) containing paracetamol 12 mg, codeine 0.5 mg and promethazine 0.65 mg per 1.0 ml, dosage 1.0 ml/kg, did no better for pain relief than paracetamol 20 mg/kg alone. Times to eye opening (P = 0.05) and first oral intake (P = 0.006) were significantly longer in the Painstop group. Late sedation was more common in the Painstop group (P = 0.03). Comparison of the efficacy of paracetamol versus paracetamol, codeine and promethazine (Painstop) for premedication and analgesia for myringotomy in children. Ragg P, et al. Royal Children's Hospital, Melbourne, Victoria. Anaesth Intensive Care. 1997 Feb;25(1):29-32.

Cough: Levodropropizine as Effective as Narcotic Dihydrocodiene with Less Drowsiness: In a 7-day DB study of 140 adults with primary or metastatic lung cancer and a nonproductive cough, levodropropizine drops (75 mg t.i.d.) was just as effective in reducing subjective cough and cough severity as well as the number of night awakenings as dihydrocodeine drops (10 mg t.i.d.; 7 days). Side-effects were similar and mild except for significantly more somnolence with dihydrocodeine (22% vs. 8%). Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer. Luporini G, et al. Ospedale San Carlo Borromeo, Milan, Italy. Eur Respir J. 1998 Jul;12(1):97-101.

Dental Extraction: Codeine No Added Benefit to Diclofenac (Voltaren) Plus Acetaminophen: In an 8-hour DB PC study of 120 adults with moderate to strong pain after surgical removal of wisdom teeth, single oral doses of: 100-mg enteric-coated diclofenac tablets; 1 g acetaminophen; 1 g acetaminophen plus 60 mg codeine; 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen; or 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine were compared. While acetaminophen plus codeine was a little better than acetaminophen, diclofenac plus acetaminophen with and without codeine had superior analgesic effect compared with diclofenac, acetaminophen, or acetaminophen plus codeine. Addition of 60 mg codeine increased the degree of side effects. Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study. Breivik EK, et al. University of Oslo, Norway. Clin Pharmacol Ther. 1999 Dec;66(6):625-35.

Dental Extraction: Codeine with Tylenol Inferior to Vioxx for Dental Pain: Rofecoxib (VIOXX(R)) is a selective inhibitor of cyclo-oxygenase-2 and is indicated for the treatment of acute pain. In a DB PC study of 393 patients with moderate to severe pain after extraction of at least two 3rd molars, a single dose of rofecoxib 50 mg (n = 182), codeine 60 mg with acetaminophen 600 mg (n = 180), or placebo (n = 31) found total pain relief much better with rofecoxib than with codeine/acetaminophen. Proportion of patients who rated the study medication as good, very good, or excellent at 6 hours was 64.6% on rofecoxib, 36.4% on codeine/acetaminophen, and 10.3% on placebo (rofecoxib> codeine/acetaminophen; p < 0.001). Patients receiving codeine/acetaminophen versus rofecoxib had higher incidences of nausea (25.0% vs. 6.0%; p < 0.001) and vomiting (18.3% vs. 3.8%; p < 0.001). Rofecoxib was more effective than codeine with acetaminophen in the treatment of acute pain. Chang DJ, Fricke JR Jr, Bohidar NR, Bird SR, Dobbins TW, Wyatt-Knowles ES, Jennifer EL, Geba GP. Merck & Co., Inc. Pain Med. 2001 Sep;2(3):239-40. Codeine with acetaminophen was slightly better than acetaminophen alone in a 204 patient DB PC study, but details are sketchy. Dtsch Zahnarztl Z. 1990 Jan;45(1):36-8.

Dental Extraction: Codeine with Tylenol Much Inferior to Naproxen (Naprosyn) or Etorecoxib: In a 201 patient DB PC study of moderate to severe dental pain from surgical extractions using doses of placebo (n = 50), etoricoxib 120 mg (n = 50)(a new COX-2 inhibitor), naproxen sodium 550 mg (n = 51), or acetaminophen/codeine 600/60 mg (n = 50), patient evaluation of pain relief over eight hours was naproxen 21.3, etoricoxib 20.9, acetaminophen/codeine 11.5 and placebo 5.4. The duration of analgesic effect, defined as median time to rescue medication use, was >24 hours for etoricoxib, 20.8 hours for naproxen sodium, 3.6 hours for acetaminophen/codeine, and 1.6 hours for placebo. A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model. Malmstrom K, Kotey P, Coughlin H, Desjardins PJ. Merck Research Laboratories. Clin J Pain. 2004 May-Jun;20(3):147-55

Dental Extraction: Codeine with Tylenol Inferior to Non-Narcotic Flurbiprofen; Codeine Had Most Side-Effects: In a DB PC study of adults having extractions of 3rd molars, 50 and 100 mg flurbiprofen were compared with acetaminophen 650 mg, acetaminophen 650 mg plus codeine 60 mg, and placebo. Flurbiprofen resulted in the least pain, while acetaminophen with codeine had the most side-effects. Analgesic efficacy of flurbiprofen in comparison with acetaminophen, acetaminophen plus codeine, and placebo after impacted third molar removal. Dionne RA, et al. National Institute of Dental Research, Bethesda, MD. J Oral Maxillofac Surg. 1994 Sep;52(9):919-24

Dental Extraction: Cocaine No Add-On Benefit to Acetaminophen: In a DB study of surgery with general anesthesia for impacted 3rd molars, there was no difference in pain relief between a paracetamol/codeine combination and paracetamol alone A double-blind placebo-controlled study to assess the efficacy of a compound analgesic to prevent postoperative pain following oral surgery. Sandhu S, et al. Turner Dental School, Manchester. Br Dent J. 1996 May 11;180(9):335-8.

Dental Extractions: Codeine Added Nothing to Ibuprofen Except Many More Side-Effects: In a 3-day DB PC study of 100 adults having extractions of 3rd molars, the combination product had no advantages but showed definite disadvantages when compared to an effective non-steroidal anti-inflammatory product. A comparison of ibuprofen and ibuprofen-codeine combination in the relief of post-operative oral surgery pain. Walton GM, et al. Turner Dental School, Manchester. Br Dent J. 1990 Oct 20;169(8):245-7. Ed: Four other studies, none recent, did find minor added pain relief, but also higher side-effects. Details were unavailable as to the amount of added relief.

Dental Extractions: Codeine No Added Benefit to Meclofenac and Inferior by Itself with More Side-Effects:  In a DB PC study of 200 adults with extractions of impacted 3rd molars, meclofenamate 100 mg plus codeine 60 mg, meclofenamate 50 mg plus codeine 30 mg, meclofenamate 100 mg, codeine 60 mg, and placebo treatment groups were compared. Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective (P less than .005) than placebo for all variables and for codeine for all but one variable. Double-blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars. Giglio JA, et al. Medical College of Virginia. J Oral Maxillofac Surg. 1990 Aug;48(8):785-90.

Dental Extractions: Codeine 15 mg No Benefit For Pain; Ibuprofen or Aspirin Help: In a DB PC study of 202 adults ungoing extraction of 3rd molars, aspirin, placebo, ibuprofen, codeine, or an ibuprofen/codeine combination were compared. Ibuprofen 200 mg (with or without codeine phosphate 15 mg) and aspirin 600 mg were significantly superior to either placebo or codeine phosphate 15 mg alone. Codeine phosphate at a dose of 15 mg was ineffective as an analgesic either alone or in combination. A single dose assessment of an ibuprofen/codeine combination in postoperative dental pain. Giles AD, et al. Int J Oral Maxillofac Surg. 1986 Dec;15(6):727-32.

Dental Extractions: Codeine Added Nothing to Acetaminophen and Flurbiprofen (Ansaid) Was Superior: In a DB PC study of 182 adults having 3rd molar extractions, single oral doses of 50 and 100 mg of flurbiprofen were compared with 100 mg of zomepirac sodium, 650 mg of acetaminophen plus 60 mg of codeine, 650 mg of acetaminophen alone, and placebo. The mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours. The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine. Side-effects were more with codeine. Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain. Sunshine A, et al. Am J Med. 1986 Mar 24;80(3A):50-4.

Dental Extractions: Codeine-Barbital Combination Inferior to Diclofenac (Voltaren): In a 5-day DB PC study of 190 adults having extraction of 3rd molars, 100 mg Voltaren (diclofenac-sodium) just before surgery and then 50 mg 3 times a day for 5 days; the other group received  widely used fixed combination tablets (acetylsalicylic acid 500 mg, caffeine 50 mg, aprobarbital 20 mg, codeine phosphate 10 mg) in the highest recommended dose, 2 tablets when needed at most 3 times a day. Patients treated with Voltaren had significantly less pain and swelling (p less than 0.001), and fewer days away from work (p less than 0.01). Voltaren as an analgesic after surgical removal of a lower wisdom tooth. Henrikson PA, et al. Int J Oral Surg. 1985 Aug;14(4):333-8.

Dental Extractions: Codeine Inferior to Ketoprofen: Ketoprofen, 25, 50, and 100 mg, was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth as a single oral dose in a DB PC study of 129 patient. Ketoprofen had a more rapid onset and longer duration of action than codeine, as well as superior pain relief. Double-blind parallel comparison of single oral doses of ketoprofen, codeine, and placebo in patients with moderate to severe dental pain. Mehlisch D, et al. J Clin Pharmacol. 1984 Nov-Dec;24(11-12):486-92.

Dental Extractions: Codeine Inferior to Acetaminophen:  In a 10-hour 2-dose DB PC study of 108 adults having extraction of 3rd molars, 60 mg codeine gave less pain relief than 500 mg acetaminophen, or 1000 mg acetaminophen. Codeine patients increased their reports of pain relief from 20 to 60 per cent after the second dose. Clinical comparisons including codeine may therefore be better carried out in a repeated-dose regimen. Analgesic efficacy after single and repeated doses of codeine and acetaminophen. Quiding H, et al. J Clin Pharmacol. 1984 Jan;24(1):27-34.

Dental Extractions: Rofecoxib (Vioox) Much Better Than Codeine/Acetaminophen: In a DB PC study of 393 patients experiencing moderate or severe pain after extraction of 3rd molars, rofecoxib 50 mg did much better at pain relief than codeine 60 mg/acetaminophen 600 mg over the first 6 hours (12.4 vs 7.0; P < 0.001). Significantly more patients on codeine/acetaminophen had side-effects (P < 0.050) and nausea in particular (P < 0.001). Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial. Chang DJ, et al. Merck Pharmaceuticals, West Point, Pennsylvania. . Clin Ther. 2001 Sep;23(9):1446-55.

Dental: Endodontic Pain Much Less with Ketorolac than Acetaminophen/Codeine: In a DB study of 66 patients with severe endodontic pain (root canals) ( 7 cm on 10 cm scale), ketorolac (Toradol, 10 mg p.o.) was considerably better at relieving pain than acetaminophen with codeine (325 mg/15 mg p.o.)(p = 0.005). A comparison of ketorolac tromethamine and acetaminophen codeine in the management of acute apical periodontitis. Sadeghein A, et al. Tehran University of Medical Science, Iran. J Endod. 1999 Apr;25(4):257-9.

Dihydrocodeine Inferior to Ibuprofen:  Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. In an extensive review of the literature, authors could find only one study of 120 patients comparing dihydrocodeine (30 mg or 60 mg) to ibuprofen 400 mg. When compared to ibuprofen 400 mg both dihydrocodeine 30 mg and 60 mg were significantly inferior for pain relief. Single dose dihydrocodeine for acute postoperative pain. Edwards, et al. Churchill Hospital, Oxford, UK. . Cochrane Database Syst Rev. 2000;(4):CD002760.

Episiotomy Pain: Ibuprofen as Good as Acetaminophen with Codeine with Fewer Side-Effects and Lower Cost: In a DB study of 237 women who gave birth vaginally with episiotomy or a third- or fourth-degree tear, ibuprofen (400 mg) did as well at pain relief during the first 24 hours as acetaminophen (600 mg) with codeine (60 mg) and caffeine (15 mg) (Tylenol No. 3)(3.4 and 3.3 cm on a 10 cm VAS, mean number of doses in 24 hours 3.4 and 3.3, and proportion of treatment failures 14% and 16% respectively). Significantly fewer subjects in the ibuprofen group than in the acetaminophen with codeine group experienced side effects (52% v. 72%) (p = 0.006). Overall, 78% of the treatment failures were in women with forceps-assisted deliveries. Ibuprofen is the preferred choice because it is less expensive and requires less nursing time to dispense. Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial. Peter EA, et al. University of British Columbia, Vancouver. CMAJ. 2001 Oct 30;165(9):1203-9.

Episiotomy Pain: NSAID Lysine Clonixinate Just as Good as Acetaminophen/Codeine: In a DB study of 131 primiparous women in delivery with moderate to severe postepisiotomy pain, Lysine Clonixinate (an NSAID) 125 mg did as well at reducing pain as Paracetamol/Codeine 500 mg/30 mg 6 qh during 24 hours. Onset of benefit was just as fast with both treatments. Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain. De los Santos AR, et al. Universidad de Buenos Aires, Argentina. Acta Physiol Pharmacol Ther Latinoam. 1998;48(1):52-8.

Foot Surgery: Flurbiprofen (Ansaid) Superior to Acetaminophen/Codeine: In a DB study of 83 patients undergoing foot surgery, flurbiprofen 50 mg. provided greater pain relief than acetaminophen 300 mg. plus codeine 30 mg. both initially and for the first 24 hours and both in regards to relief of pain and pain intensity. The efficacy of ANSAID (flurbiprofen) as an analgesic in foot surgery. Soulier SM, et al. Upjohn Company: Kalamazoo, MI. J Foot Ankle Surg. 1997 Nov-Dec;36(6):414-7

Hip Arthroplasty: Ibuprofen as Good as Ibuprofen plus Codeine: In a DB PC study of 123 hip arthroplasty operations, all received oral diazepam as premedication and spinal anaesthesia with bupivacaine 5 mg/ml 3-4 ml. Postoperatively, when the spinal anaesthesia started to wear off, ibuprofen 800 mg. did as well as ibuprofin with codeine 60 mg and better than placebo (P < 0.05) after 2 and 4 hours, but not after 1, 3 and 5 hours. The P group also received 45% more opioids (P < 0.001) compared with the two other groups during the same period. No significant differences in bleeding or side-effects were observed. Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty. Dahl V, et al. Martina Hansens Hospital, Sandvika, Norway. Acta Anaesthesiol Scand. 1995 Apr;39(3):323-6.

Low Back Pain: Ketorolac as Good as Acetaminophen-Codeine with Fewer Side-Effects: In a DB study of 123 patients with  acute low back pain, ketorolac 10 mg every 4-6 hours as needed did as well as acetaminophen-codeine for analgesic efficacy, functional capacity, or overall pain relief. Those on acetaminophen-codeine had significantly more side-effects and serious side-effect. Seven patients--all in the ACOD group--withdrew from the study because of adverse drug events. The authors conclude that ketorolac is preferable to acetaminophen with codeine for the treatment of acute low back pain in the ED. Ketorolac versus acetaminophen-codeine in the emergency department treatment of acute low back pain. Innes GD, et al. Royal Columbian Hospital, New Westminster, BC, Canada. J Emerg Med. 1998 Jul-Aug;16(4):549-56.

Post-Op Pain: Codeine-Acetaminophen No Better than Ibuprofen; Non-Addictive Diclofenac Better: In a DB PC study of preoperative ibuprofen 600 mg, diclofenac 100 mg, paracetamol (acetaminophen) 1g with codeine 60 mg or placebo for relief of postoperative pain in 119 patients who had operations under general anesthesia, there was no significant difference in the extent of postoperative pain among the four groups, but the placebo group had significantly shorter times before their first request for postoperative analgesics (median 17 minutes) than the diclofenac group (median 32 minutes). A double-blind randomised controlled clinical trial of the effect of preoperative ibuprofen, diclofenac, paracetamol with codeine and placebo tablets for relief of postoperative pain after removal of impacted third molars. Joshi A, Parara E, Macfarlane TV. University Dental Hospital of Manchester, UK. Br J Oral Maxillofac Surg. 2004 Aug;42(4):299-306.

Thomas E. Radecki, M.D., J.D.

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