While morphine is claimed to be a powerful pain reliever, numerous research studies show that it and other opiates are actually inferior pain relievers which may actually increase pain over time.  Numerous studies find non-narcotic pain relievers superior to narcotics with some studies finding narcotics, including morphine, little better than placebo.  Actually, opiates do usually help relieve pain somewhat, but any benefit is far outweighed with disadvantages, both to the patient and to society.

Several companies attempt to cash in on the morphine market.  Purdue, maker of OxyContin, sells sustained-release MS Contin, and MSIR capsules, solution, and tablets.  Faulding Labs sells sustained-release Kadian.  Ligand Pharmaceuticals sells extended release Avinza.  Still more brand names are sold and carefully designed to be slightly different so as to make generic substitution by pharmacists difficult, thus guaranteeing profits to the brandname manufacturer.  Generic tablets, liquid, and sustained release are also available.

In studies comparing morphine to non-narcotic pain relievers, the non-narcotics did better 13 times (Ketorolac 8 times, parecoxib 4 times, clonidine twice, ketamine, lidocaine, naproxen, carbamazepine), four times morphine did as well but caused more side-effect (dipyrone, lornoxicam, propacetamol, ketorolac), seven times morphine did as well (dexamethasone, bupivacaine, ketamine, ibuprofen, neostigmine, clonidine), and only three times did morphine do better.  Of those three, only against the weak pain reliever gabapentin was it much better. Against nortriptyline, an anti-depressant with some pain relieving properties, and against IV acetaminophen (injectible Tylenol), morphine's advantage was very slight.  In another study of neonates, morphine did better than tetracaine, but caused considerably more respiratory depression for 24 hours (tie). Thus, morphine's score is 17 losses, 9 ties, and 3 wins with the wins against the weakest pain relievers tested. Morphine is a loser.  

Morphine also was of no value in 8 studies as an add-on medication or when it was injected intra-articularly into the knee.  I am sure that I did not find all of the studies, but these were all of the easiest to find ones in recent years.  So far as I can tell, it is unclear if morphine or other opiates ever need to be used for any treatment in the field of medicine.  I have been unable to find any even barely adequate scientific evidence that it does despite over 100 hours of diligent effort.  

Purdue Pharmaceuticals has made huge profits pushing MS-Contin, a long-acting form of morphine, while another company has come out with a similar long-acting morphine Avinza.  Avinza is being promoted as an essentially life-long treatment for osteoarthritis on the basis of flimsy research.  The manufacturers of both have been highly unethical in avoiding any direct comparaisons of their highly addictive narcotics with non-narcotic pain relief treatments. 

Morphine and other opiates are being poured into human beings by physicians in every way imaginable: orally, oral-transmucosally, intra-muscularly, intra-venously, by inhalation, by nasal sprays, intrathecally, intravesicularly (into the bladder), epidurally, rectally, intra-articularly (in a joint space), injection into wounds, intraperitoneally (into the abdominal cavity), and transcutaneously.  Yet many studies have intentionally bogus designs, comparing opiates only to other opiates.  The cancer pain common is particularly prone to dope up patients on morphine and other opiates and is strongly hostile to the idea of even scientifically studying whether non-narcotic pain relievers may do as well or better.  They even make the bizarre claim that it would be unethical not to give cancer patients powerfully addictive narcotics, even for those with only moderate pain and those not in advanced stages of disease.

Many research studies show clear biases in favor of the opiates.  For instance, they often say that the patients "required" so many milligrams of opiates, where they should say that patients "used" so many milligrams, since there is no evidence that opiates are required at all for pain relief with many more powerful non-narcotic treatments available.  

Virtually none of the double-blind opiate studies ask patients to guess whether or not they were in the opiate group, and yet at least one author found that it was virtually impossible to keep such studies blinded.  This means that patients may have the same biases as many physicians and be glad that they received the "more powerful" opiate pain reliever.  Research shows that normal, healthy adults develop a liking for opiates after just two doses.  Thus, a few patients may even think that if they don't respond favorably about how good the pain relief is, that they may be cut off from the opiate medication.  

In patients previously on opiates, even according to one study those receiving opiates during their birthing process via their mothers or as infants, may be primed to a more powerful liking.  In modern America, opiates are given out so freely that many patients have experienced them earlier in life.  Some particularly corrupt studies even include patients withdrawn from opiates as recently as two weeks before the new study and claim that this fits the definition of an "opiate-naive" patient.

Huge numbers of studies show that the use of non-narcotics before or after surgery reduce the use of opiate use after surgery, but not a single study looks at whether the narcotics are needed at all and whether a second non-narcotic pain medication would work as well or better at giving additional pain relief although many non-surgical pain studies do find an added benefit by combining two or more non-narcotic pain strategies.  I personally do not think that there is any scientific proof that any opiate is needed in any phase of medical treatment under any condition.  The small added benefits of narcotics can definitely be achieved in many and perhaps all situations with other strategies.

There is absolutely no scientific research showing that opiates are required in the management of cancer pain.  The cancer pain treatment community is extremely hostile to even researching the idea.  In fact, many cancer patients are deprived of more effective non-narcotic pain relievers because their physicians have the mistaken notion that opiates are such powerful pain relievers than non-narcotic pain relievers would not be of added benefit.

In numerous studies comparing opioids to each other or comparing opioids to placebos, no non-narcotic pain reliever is given to any patients.  This suggests that large numbers and possibly of majority of pain patients are being deprived of powerful non-narcotic pain interventions and are simply given highly addictive opiates as routine treatment rather than at very least reserving it as an add-on should more effective non-narcotic interventions all fail to bring pain down below moderate pain levels.  It also suggests that there is no informed consent by patients that they will be given highly addictive pain treatments and that no non-addictive alternatives are offered as an alternative.  Indeed, this was my own personal experience twice after out-patient surgeries.  In fact, I never got the prescriptions filled and the pain was never that bad (arthroscopic knee surgery and lazer dermatologic surgery).

If a doctor wants to give you morphine, 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 morphine 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, until morphine is proven to serve some function which cannot be served by non-narcotics, prescribing morphine is not evidence-based medicine and is wrong.  It's bad medicine.  Narcotics have been compared to non-narcotics for most types of surgery and chronic pain.  So far as I have been able to find, there is no indication for which narcotics have ever been shown necessary or superior.  

Doctors are responsible for knowing whether or not narcotics are necessary.  This research is readily available to anyone with a computer and an internet connection.  Just go to Pubmed, and enter "morphine and double-blind."  

Morphine and Other Opiates Cause Pain: Hyperalgesia has been demonstrated to be a cardinal sign of physical withdrawal from opioids in preclinical models for more than 30 years. In a study using an acute opioid physical dependence (APD) model to test for the presence of hyperalgesia to experimental cold-pressor pain in 4 healthy non-opioid-dependent men through 3 different pretreatment opioid administration protocols (morphine 18 mg/70 kg intramuscular, morphine 10 mg/70 kg intravenous, hydromorphone 2 mg/70 kg intravenous), repeated on 2 separate occasions, and placebo. Cold-pressor pain threshold and tolerance were examined before opioid administration and 5 and 15 minutes after precipitated withdrawal with naloxone 10 mg/70 kg intravenous. Paired t tests comparing change scores between the opioid pretreatments and placebo showed that pain threshold and tolerance to the cold-pressor uniformly decreased across all APD induction methods, and the effect size was large (approximately 70% of baseline) and reproducible. These findings support the existence of opioid-induced hyperalgesia, which has been conceptualized as a coexisting opponent process to opioid-induced analgesia and proposed to be an alternative explanation for the development of analgesic tolerance to opioids. Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study. Compton P, et al. University of California at Los Angeles. . J Pain. 2003 Nov;4(9):511-9.

Morphine Damages Bone and Increases Cancer Pain: Sustained morphine exposure enhances both bone cancer-induced pain and bone loss. Anna Vardanyan. American Pain Society Annual Meeting, San Antonio, May 3, 2006.

Studies Comparing Morphine to Non-Narcotics for Pain

Abdominal Surgery: Ketorolac Markedly Decreased Morphine Usage by 82%: In a DB study of 191 patients with at least moderate pain after major abdominal surgery, comparing ketorolac by patient-controlled analgesia (PCA) bolus alone (Ket B), ketorolac by bolus plus infusion (Ket I), and morphine by PCA bolus (morphine), with injectable morphine available for supplementation found ketorolac patients used more supplemental morphine (p < or = 0.001)(6.0 mg Ket I, 6.2 mg Ket B, 4.0 mg morphine). However, there was a huge morphine-sparing effect in both ketorolac groups (total morphine 6.0 mg Ket I, 6.2 mg Ket B, vs. 33.3 mg for morphine group). Overall pain relief scores were similar for morphine and Ket I groups, and were lower for Ket B than for morphine (p = 0.002). Evaluation of the safety and efficacy of ketorolac versus morphine by patient-controlled analgesia for postoperative pain. O'Hara DA, Fanciullo G, Hubbard L, Maneatis T, Seuffert P, Bynum L, Shefrin A. Robert Wood Johnson Medical School, New Brunswick, New Jersey. Pharmacotherapy. 1997 Sep-Oct;17(5):891-9. Ed: Ketorolac dramatically decreased morphine usage by 82%. The total amount of extra morphine supplemental usage by the ketorolac patients was a miniscule 2.1 mg. It could well be that the extra morphine wasn't helpful at all for pain, but served merely as a marker for pain or that morphine patients were too sedated to complain about pain, or that some morphine patients had too much nausea to want another dose of the pain medicine that was giving them the nausea. Also, the use on supplemental non-narcotic pain relief may have done as well or better than supplemental morphine. In any case, the maximum benefits of morphine were slight and not enough to justify priming people for opiate addiction. Also, any physician using morphine instead of ketorolac for the PCA pump is being irresponsible according to this study.  No human should ever be needlessly exposed to opiates. (This study not counted since not a comparaison)

Arthritis: Intra-Articular Morphine No Better Than Dexamethasone: In a DB PC study of 44 patients with chronic arthritis, intraarticular morphine (3 mg) did no better at pain relief during the first 6 hours or first 5 days than dexamethasone (4 mg)  although both did better than placebo. and saline (3 ml) in 44 patients with chronic inflammatory arthritis or osteoarthritis of the knee. Intraarticular morphine versus dexamethasone in chronic arthritis. Stein A, et al. Universitat Munchen, Klinische Immunologie, Germany. Pain. 1999 Dec;83(3):525-32. (tie)

Arthroscopic Meniscectomy: Bupivacaine as Good as Morphine for Intra-Articular Injection: In a DB study of 103 patients ages 16-80 having arthroscopic meniscectomy, 0.25% bupivacaine (50 mg) intra-articular, was just as good at pain relief as 1 mg of 0.1% morphine, or both combines and better than normal saline. Ketorolac [ 30 mg IM] was used as rescue medication. Intra-articular analgesia after arthroscopic knee surgery: comparison of three different regimens. De Andres J, et al. Valencia General University Hospital, Spain. Eur J Anaesthesiol. 1998 Jan;15(1):10-5. (tie)

Cancer Pain: Dipyrone NSAID as Good as Morphine with fewer Side-Effects: In a 7-day DB PC study of 121 cancer pain patients without gastric involvement,  dipyrone 2 g every 8 h did as well as 10 mg of oral morphine given every 4 h for the relief of chronic cancer pain. Both did better than dipyrone 1 g. Dipyrone tended to be better tolerated than morphine. Efficacy and tolerance of oral dipyrone versus oral morphine for cancer pain. Rodriguez M, et al. Malaga , Spain . Eur J Cancer 1994;30A(5):584-7. (Favors Non-Narcotic)

Cancer: Naproxen Better Than Morphine SR for Malignant Nerve Pain: In a DB 1-week/phase crossover study of 20 patients with malignant nerve pain, naproxen 1500 mg provided better pain relief than slow-release morphine 60 mg/day. At day 7, significant pain relief of 32% (P < 0.05) was observed in the naproxen group, but not in the morphine group (21%, P = 0.14). Patients using morphine needed approximately twice as much paracetamol rescue than patients using naproxen. Medical therapy of malignant nerve pain. A randomised double-blind explanatory trial with naproxen versus slow-release morphine. Dellemijn PL, et al. University Hospital Rotterdam, The Netherlands. Eur J Cancer 1994;30A(9):1244-50.

Cancer: Indoprofen IV as Effective as Morphine IM for Severe Cancer Pain: PRL response to thyrotropin-releasing hormone nor serum GH levels. Indoprofen may be a safer alternative to opiates for relief of moderate to severe pain in women with breast tumors suspected of being prolactin-dependent. Effect of i.v. indoprofen on cancer pain and serum prolactin and growth hormone levels--a controlled pharmacologic study vs i. m. morphine and placebo. Pellegrini A, et al. Int J Clin Pharmacol Ther Toxicol 1983 Sep;21(9):483-6

Children: Newborns on Ventilation: Huge Study Finds Morphine No Benefit: The Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) study of 898 preterm babies on ventilation received either placebo or morphine for up to 14 days. Additional open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Both groups had similar outcomes with no impact on neonatal death (11% placebo vs. 13% morphine),  severe intraventricular hemorrhage (11% vs. 13%), or periventricular leucomalacia (9% vs. 7%). Those given extra open-label morphine did much worse, but this may not have been related to the extra morphine. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Anand KJ et al. University of Arkansas. . Lancet. 2004 May 22;363(9422):1673-82.

Children: Tonsillectomy: Ketamine Does Just About as Well as Morphine: Ketamine is an NMDA agonist. In a DB study of 80 children ages 6-15 undergoing tonsillectomy, IM morphine 0.1-0.15 mg/kg after induction did slightly better after 30 minutes of extubation than ketamine 0.5-0.6 mg/kg (7 vs. 6 on 10-point CHEOPS scale), but pain relief was similar thereafter. There were no differences in supplemental analgesia requirements (8 vs. 7 patients), or bad dreams (1 vs. 2). Ketamine can be used with NSAIDs, but additive side-effects may occur if combined with morphine. Authors conclude that ketamine is an alternative analgesic for children undergoing tonsillectomy. Comparison of ketamine and morphine for analgesia after tonsillectomy in children. Marcus RJ, et al. Leicester Royal Infirmary, UK. Br J Anaesth. 2000 Jun;84(6):739-42. (tie)

Children: Tonsillectomy: Ketorolac Caused Much Less Vomiting but Slightly More Bleeding than Morphine: In a DB study of 96 children after tonsillectomy, received morphine 0.1 mg/kg or ketorolac 1 mg/kg IV, those given ketorolac had many fewer episodes of vomiting than morphine subjects (median 1 vs 3; P = 0.006). While ketorolac patients had a a little more bleeding requiring intervention; 5/49 vs 0/47, P = 0.03) in the first 24 h after surgery, there was no greater overall highly incidence of bleeding than the morphine subjects. Recovery and complications after tonsillectomy in children: a comparison of ketorolac and morphine. Gunter JB, Varughese AM, Harrington JF, Wittkugel EP, Patandar SS, Matar MM, Lowe EE, Myer CM 3rd, Willging JP.  University of Cincinnati. Anesth Analg. 1995 Dec;81(6):1136-41. Ed: This study is strange in that it didn't study pain, which is the primary reason these medicines were given. If Ketorolac was better for pain (very likely), that would be an important benefit to consider, in addition to its lack of priming for future addiction, in making a decision on which to use. According to the above, for every extra bleeding requiring intervention caused by ketorolac, morphine causes 20 episodes of vomiting.  If I had my choice, I would gladly choose to avoid the narcotic and its 20 extra episodes of vomiting by accepting the extra unit of packed cells.  If a doctor asked me if I would rather accept a unit of packed cells or have 20 episodes of vomiting, there is no doubt in my mind which I would choose! (loss for morphine on side-effects)

Children: Post-Op Pain Relief was Somewhat Better with Ketorolac than with Morphine: In a DB study of 102 children receiving post-op care, a single dose of did better at pain relief than a single dose of morphine with fewer needing additional although the differences did not reach statistical significance. There was no abnormal postop bleeding or altered renal function from the ketorolac. A randomized comparison of ketorolac tromethamine and morphine for postoperative analgesia in critically ill children. Lieh-Lai MW, et al. Children's Hospital of Michigan, Detroit. Crit Care Med. 1999 Dec;27(12):2786-91. (loss for morphine)

Children: Neonate IV Placement: Morphine Superior to Tetracaine But Causes Respiratory Depression: In a DB PC study of 132 ventilated neonates (mean gestational age, 30.6 weeks), prior to central line insertion, neonates were randomly assigned to receive tetracaine (n = 42), morphine (n = 38), or both (n = 31); a separate nonrandomized group of 21 neonates receiving neither tetracaine nor morphine was used as a control group. Compared with no treatment, pain scores were lower in the morphine and tetracaine-morphine groups during skin preparation (mean difference, -0.22; P = .02 and -0.29; P = .01), and needle puncture (mean difference, -0.35; P = .003 and -0.47; P<.001, respectively), but pain scores did not differ statistically for tetracaine alone vs no treatment. Morphine-treated neonates required larger increases in ventilation rate in the first 12 hours (mean difference, 3.9/min; P = .003). Local skin reactions occurred in 30% of neonates given tetracaine vs 0% for morphine (risk difference, 0.30; P<.001). Morphine caused respiratory depression and tetracaine caused erythema. Intravenous morphine and topical tetracaine for treatment of pain in preterm neonates undergoing central line placement. Taddio A, et al. University of Toronto, Ontario. . JAMA 2006 Feb 15;295(7):793-800. Ed: It is extremely unlikely that the brief pain experienced by the neonates is going to be remembered by their brains. The respiratory depression would appear at least as big a concern. One study found neonate exposure to opiates during delivery was more common in opiate addicts. I wonder about other interventions, such as freezing the skin. (tie for morphine)

Dental Surgery: Acetaminophen IV as Good as Morphine IM with Fewer Side-Effects: In a DB study of injectable acetaminophen, administered as IV propacetamol 2 g, an injectable prodrug formulation, compared to IM morphine 10 mg or placebo for patients with moderate to severe pain from removal of bone-impacted third-molars under general anesthesia, propacetamol and morphine were significantly more effective than placebo. After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. Side effects were significantly less frequent with propacetamol than morphine (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability. Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery. Van Aken H, Ehys L, Veekman L, Buerkle H. University of Munster, Germany. . Anesth Analg. 2004 Jan;98(1):159-65.  (loss for morphine on side-effects)

Dental Surgery: Lornoxicam NSAID as Powerful as Morphine and with Fewer Side-Effects: Lornoxicam is NSAID not available in the U.S. In a DB PC study of intramuscular (IM) injections of lornoxicam (4, 8, 16 and 20 mg) vs. morphine (10 and 20 mg) and placebo in 252 patients with moderate to severe pain following surgical removal of an impacted mandibular third molar, patients treated with lornoxicam or morphine had significantly greater cumulative pain relief over the 4-h post-injection period than placebo recipients. Patients in the lornoxicam 4 mg or morphine 10 mg groups had significantly less pain relief than patients in the higher dosage groups of these drugs. There was no significant difference between the morphine 20 mg group and the lornoxicam 8, 16 and 20 mg groups. Lornoxicam was well tolerated at all doses and had significantly lower incidence of adverse events than morphine 10 or 20 mg. Thus, lornoxicam 8 mg is at least as effective as IM morphine 20 mg.  Pain control after dental surgery: a double-blind, randomised trial of lornoxicam versus morphine. Norholt SE, Sindet-Pedersen S, Larsen U, Bang U, Ingerslev J, Nielsen O, Hansen HJ, Ersboll AK. Aarhus University, Denmark. Pain. 1996 Oct;67(2-3):335-43.  (loss for morphine on side-effects)

Fibromyalgia Pain: Morphine Inferior to Ketamine: In a DB PC study of 31 patients with fibromyalgia, morphine did not show any significant changes. Lidocaine showed a pain decrease during and after the infusion. Ketamine showed a significant reduction in pain intensity during and after the test period. Tenderness at tender points decreased and endurance increased significantly, while muscle strength remained unchanged. The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia. These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Sorensen J, et al. University Hospital, Linkoping, Sweden. Scand J Rheumatol. 1995;24(6):360-5.  (loss for morphine)

Hysterectomy Surgery: Parecoxib and Ketorolac Better than Morphine 4 mg.: In a randomized DB study of 208 women after surgical hysterectomy comparing single-dose intravenous placebo, parecoxib sodium 20 mg or 40 mg, ketorolac 30 mg, or morphine 4 mg followed by multiple-dose parecoxib sodium or ketorolac as needed, single-dose parecoxib sodium 40 mg provided significantly better pain responses to placebo or morphine 4 mg and was comparable to ketorolac 30 mg. Multiple-dose parecoxib sodium 20 mg, 4 times daily, or 40 mg, twice daily, was comparable to ketorolac 30 mg, 4 times daily. A clinical trial demonstrates the analgesic activity of intravenous parecoxib sodium compared with ketorolac or morphine after gynecologic surgery with laparotomy. Bikhazi GB, Snabes MC, Bajwa ZH, Davis DJ, LeComte D, Traylor L, Hubbard RC. University of Miami. Am J Obstet Gynecol. 2004 Oct;191(4):1183-91.  (loss for morphine)

Hysterectomy: Epidural Block in Radical Hystectomy: Morphine Not of Value as Addition to Bupivacaine: In a DB study of 40 patients having radical hysterectomy and pelvic lymphadenectomy with post-op epidural blocks, the addition of morphine to postoperative epidural bupivacaine had only limited effect on pain relief and increases time to normalization of gastrointestinal function. Effect of epidural bupivacaine vs combined epidural bupivacaine and morphine on gastrointestinal function and pain after major gynaecological surgery. Jorgensen H, et al. Herlev University Hospital, Copenhagen County, Denmark. Br J Anaesth. 2001 Nov;87(5):727-32.

Injection Pain of Propofol: Lidocaine Better than Fentanyl or Morphine and as Good as Meperidine with Fewer Side-Effects: In a DB PC study comparing I.V. pretreatment with fentanyl 150 microg, morphine 4 mg, meperidine 40 mg, 2% lidocaine 3 mL or placebo in reducing propofol injection pain in 175 patients, lidocaine and meperidine significantly reduced propofol injection pain more than placebo (P < 0.05), but there were more side effects in the meperidine group. Fentanyl and morphine reduced the intensity of propofol injection pain (P < 0.05) and had some effect in reducing the incidence of propofol injection pain, but the difference did not reach statistical significance. The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study. Pang WW, et al. Show-Chwan Memorial Hospital, Changhua, Taiwan. Anesth Analg 1998 Feb;86(2):382-6.  (loss for morphine)

Knee Arthroscopy: Morphine No Value: In a DB study of 50 patients undergoing knee arthroscopy under general anesthesia, morphine, bupivacaine, and epinephrine did no better than bupivacaine and epinephrine. Bupivacaine and epinephrine yielded lower pain scores and rescue medication consumption than patients receiving epinephrine alone, which was statistically significant irrespective of the timing of injection (P < .0001). Patients receiving the study medication preoperatively had significantly lower pain scores at the first measurement (t = 0) than those receiving the study medication postoperatively (P = .0343). Short-term analgesic effects of intra-articular injections after knee arthroscopy. Goodwin RC, et al. The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. Arthroscop 2005 Mar;21(3):307-12.

Knee Arthroscopy: Intra-Articular Ketorolac 60 mg Reduced Pain Better than Morphine and Add-On Morphine No Significant Increased Benefit: In a DB study of 100 patients ages 15-60 undergoing knee arthroscopy, intra-articular ketorolac 60 mg did better than placebo and better than morphine 3 mg.  Morphine 3 mg combined to ketorolac did not add a significant advantage compared to ketorolac alone for pain relief over the first 48 hours. Postoperative pain following knee arthroscopy: the effects of intra-articular ketorolac and/or morphine. Gupta A, et al. Orebro Hospital Medical Center, Sweden. Reg Anesth Pain Med. 1999 May-Jun;24(3):225-30.  (loss for morphine)

Knee Arthroscopic Surgery: Intra-Articular Morphine of No Value: In a DB study of 320 patients undergoing arthroscopic knee surgery, 15 ml of bupivacaine 0.5%, 5 mg of morphine in 15 ml of isotonic saline solution, 15 ml of bupivacaine 0.5% with epinephrine 0.0005%, or 15 ml of isotonic saline solution were compared. In terms of reducing postoperative pain and decreasing the consumption of analgesics after arthroscopic knee surgery, bupivacaine 0.5% with epinephrine 0.0005% was found to be the most effective. Postoperative analgesic value of the intra-articular instillation of bupivacaine and morphine after arthroscopic knee surgery. Follak N, et al. Ernst Moritz Arndt University, Greifswald, Germany. Arch Orthop Trauma Surg. 2001 May;121(5):278-81.

Knee Arthroscopic Surgery: Anterior Cruciate: Intraarticular Morphine No Value: In a DB study of 62 patients undergoing anterior cruciate reconstruction, postoperative femoral nerve block was effective, and intraarticular morphine provided no additional benefit. Does intraarticular morphine improve pain control with femoral nerve block after anterior cruciate ligament reconstruction? McCarty EC, et al. Vanderbilt Sports Medicine Center, Nashville. Am J Sports Med. 2001 May-Jun;29(3):327-32.

Knee Replacement: Clonidine Much Better than Morphine at Prolonging Surgical Analgesia: In a DB study of 36 elderly patients undergoing knee replacement, 0.15 mg clonidine but not 0.15 mg morphine prolonged surgical analgesia when added to 10 mg plain bupivacaine. 1/9 in the clonidine group, 8/10 in placebo and 8/11 in morphine (P < 0.05) received reinjection of bupivacaine for surgical pain. These injections were given about 2 1/2 hr after the initial intrathecal injection, the duration of anaesthesia being about four hours. Comparison of clonidine, morphine or placebo mixed with bupivacaine during continuous spinal anaesthesia. Brunschwiler M, et al. University Hospital of Geneva, Switzerland. Can J Anaesth. 1998 Aug;45(8):735-40.  (loss for morphine)

Knee Replacement: Morphine Inferior to Both IV Parecoxib and Ketorolac: In a DB study of 208 adults after unilateral total knee replacement of IV parecoxib sodium 20 and 40 mg, morphine 4 mg, and ketorolac 30 mg or placebo within 6 hours of discontinuation of patient-controlled analgesia on postoperative day 1. Onset of analgesia was similarly rapid with IV parecoxib sodium 40 mg, morphine, and ketorolac. Level and duration of analgesia were significantly superior for both ketorolac and parecoxib compared to morphine. Intravenous parecoxib sodium foracute pain after orthopedic knee surgery. Rasmussen GL, et al. Orthopedic Specialty Hospital, Murray, Utah. Am J Orthop. 2002 Jun;31(6):336-43.  (loss for morphine)

Knee Replacement: Intrathecal Neostigmine Preferred to Morphine: In a DB PC study of 60 patients undergoing Knee joint replacement, intrathecal (IT) 0.5% hyperbaric bupivacaine 15 mg with either normal saline 0.5 mL, neostigmine 50 µg, or morphine 300 µg were compared. There was no significant difference in maximal level of sensory block among the three. The morphine had a later onset of postsurgical pain and longer time to first rescue analgesics than neostigmine (P <0.05). Overall 24-hr VAS pain scores were higher with saline vs morphine and neostigmine (P <0.05). Motor block lasted longer with neostigmine than with morphine and saline (P <0.05). Side-effects were similar with neostigmine and morphine except pruritus (70%) occurred much more frequently with morphine (0%; P <0.05). Overall satisfaction was better with neostigmine than morphine or saline (P <0.05). Intrathecal bupivacaine with morphine or neostigmine for postoperative analgesia after total knee replacement surgery. Tan PH, et al. Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China. . Can J Anaesth. 2001 Jun;48(6):551-6.  (loss for morphine)

Knee Surgery Arthroscopic: Clonidine Gave Longer Pain Relief than Morphine: In a DB study of 30 patients having arthroscopic knee surgery under epidural anesthesia, 150 mcg of clonidine gave longer lasting pain relief post-operatively for 12 hours than did morphine 5 mg, although both did better than placebo. Intra-articular clonidine vs. morphine for post-operative analgesia following arthroscopic knee surgery (a comparative evaluation). Iqbal J, et al. Chandigarh, India. Knee. 2000 Apr 1;7(2):109-113.  (loss for morphine)

Knee Arthroplasty: Intra-Articular Morphine No Better than Bupivacaine and Neither Much Good: In a DB PC study of 105 patients undergoing total knee arthroplasty, intra-articular injections of morphine or bupivacaine were only of minor benefit over placebo with no significant difference between the two. The authors state that the results put into question the benefit of postoperative intra-articular administration of morphine or bupivacaine in patients undergoing TKA. Intra-articular morphine and/or bupivacaine in the management of pain after total knee arthroplasty. Mauerhan DR, et al. Miller Orthopaedic Clinic, Charlotte, NC. J Arthroplasty. 1997 Aug;12(5):546-52.

Knee Surgery: Intra-Articular Morphine No Better than Clonidine and Also of no Add-On Benefit: In a DB study of 90 patients undergoing arthroscopy of the knee under general anaesthesia, intra-articular morphine was no better than clonidine and adding the morphine to the clonidine did not increase the benefit.  Intra-articular morphine and clonidine produce comparable analgesia but the combination is not more effective. Gentili M, et al. Rennes, France. Br J Anaesth. 1997 Nov;79(5):660-1.  (tie)

Knee Arthroscopic Surgery: No Benefit IA Morphine, Even in Those with Moderate-Severe Pain: 30-40% of all knee arthroscopic patients have mild or no pain after surgery. Yet, many surgeons inject all patients with intra-articular morphine for pain relief, even those patients with no need for any treatment.  In a DB study of only the 40 out of 57 patients who developed moderate-to-severe pain within 1 h after an arthroscopic procedure under general anesthesia, researchers found no difference in pain relief between an IA injection of saline 10 ml and saline 10 ml with morphine 2 mg. Effective pain relief from intra-articular saline with or without morphine 2 mg in patients with moderate-to-severe pain after knee arthroscopy: a randomized, double-blind controlled clinical study. Rosseland A, et al. Rikshospitalet University Hospital, Oslo, Norway. . Acta Anaesthesiol Scand. 2003 Jul;47(6):732-8.  

Laparotomy GYN Surgery: Parecoxib Better than Morphine 6 mg, and Equal to 12 mg (High Dose):  Parecoxib sodium, the injectable prodrug of valdecoxib, is a cyclooxygenase-2-specific inhibitor that is effective for postoperative pain. In a DB PC study, a single dose of parecoxib sodium 40 mg IM was more effective than a single dose of morphine 6 and similar to morphine 12 mg IM in treating postoperative pain after gynecologic surgery requiring a laparotomy incision. By nearly all efficacy measures (including total pain relief and patient's global evaluation of study medication), parecoxib sodium 40 mg IM demonstrated pain relief and a decrease in pain intensity that was statistically similar to that with morphine 12 mg IM and superior to that with morphine 6 mg IM. Parecoxib also had a longer time to use of rescue medication than patients treated with both morphine doses, and this dose provided sustained pain relief over the 12-h study period. The cyclooxygenase-2-specific inhibitor parecoxib sodium is as effective as 12 mg of morphine administered intramuscularly for treating pain after gynecologic laparotomy surgery. Malan TP Jr, Gordon S, Hubbard R, Snabes M. University of Arizona, Tucson, AZ. . Anesth Analg. 2005 Feb;100(2):454-60. Ed: The FDA has been blocking approval, although it is widely sold in Europe and recent studies show no increase in cardiovascular risk when use of post-surgery pain.  (tie)

Laparotomy Hysterectomy: Morphine Inferior to Both IM Parecoxib and to IM Ketorolac: In a DB PC study of 202 women experiencing moderate-to-severe pain on the first day after laparotomy abdominal hysterectomy or myomectomy, IM parecoxib 20-40 mg, a COX-2-specific inhibitor, and IM ketorolac 30 mg. both did much better than IV morphine 4 mg or placebo for most measures of analgesic efficacy at most time points, including a 2-3 fold longer time to rescue analgesia (P </= 0.05). All treatments were well tolerated. Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery. Barton SF, et al. Columbia St. Mark's Hospital, Salt Lake City. Anesthesiology. 2002 Aug;97(2):306-14.  (loss for morphine)

Limb Injury: Ketorolac Better Pain Relief than Morphine at Lower Cost, Faster and Fewer Side-Effects: In a study of 148 adults with painful isolated limb injuries, no difference was found in the median time taken to achieve pain relief at rest between the group receiving IV ketorolac and the group receiving IV morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour compared with 0.87 in the morphine group (P=0.003). The odds of experiencing adverse events was 144 times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $44 in the ketorolac group vs. $229 in the morphine group (P<0.0001). The median score for patients' satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial. Rainer TH, et al. Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. BMJ. 2000 Nov 18;321(7271):1247-51.  (loss for morphine)

Neuropathy: Gabapentin and Morphine Studied in Mild-Moderate Neuropathy Pain: In a poorly designed and small 5-week each DB crossover study of 57 patients with either painful diabetic neuropathy or postherpetic neuralgia, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine. Only 41 completed the trial. Mean daily pain at a maximal tolerated doses was as follows: 5.72 at baseline, 4.49 with lorazepam, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Morphine, gabapentin, or their combination for neuropathic pain. Gilron I, et al. Queen's University, Kingston, Ont, Canada. . N Engl J Med. 2005 Mar 31;352(13):1324-34. Ed: These patients had mostly mild pain, i.e. 14 points of pain on a 45 point scale. Mixing two totally different causes of pain is poor research practice.  Why anyone would want to use a highly addictive narcotic for chronic mild to moderate pain in conditions that are likely to last for many years, like diabetic neuropathy, or for short-term conditions like PHN, I simply can't understand.  There are so many better non-narcotic treatments for diabetic neuropathy than expensive gabapentin or highly addictive morphine. Thiamine, carnitines, nortriptyline, SSRIs like citalopram (Celexa), and lipoic acid would be better initial choices for diabetic neuropathy before gabapentin. (win for morphine)

Neuropathic Peripheral Pain Helped by Carbamazepine But Not by Morphine: In a DB PC study of 43 patients with peripheral neuropathic pain, exclusively pain reduced by spinal cord stimulation (SCS), were switched into a painful state after SCS inactivation. This mode was used to assess the pain-relieving effect of carbamazepine (600 mg/d) or placebo during an SCS-free period of 8 days. In Phase 2, 38 patients received either sustained-release morphine (90 mg/d) or placebo for 8 days. In cases of intolerable pain, the patients were authorized to reactivate their SCS. A delay in pain increase was observed in the CMZ group as compared with placebo (P = 0.038), however, the benefit of morphine was insignificant (P = 0.41). The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Harke H, et al. Klinikum Krefeld, Germany. Anesth Analg. 2001 Feb;92(2):488-95.  (loss for morphine)

Orthopedic Surgery: IM Morphine No Better than Oral Ibuprofen 400 mg.: In a 6-hour DB study of 120 patients after orthopedic surgery for moderate to severe pain, the visual analogue scales decreased by 35 mm at 1 hour for morphine 5 mg IM, 24 mm for morphine 10 mg IM and 21 mm for ibuprofen 400 mg orally. Verbal rating scores showed a similar pattern. Comparing the groups over the whole study, the sum of pain intensity differences showed no significant differences in pain experience between the groups. Assessment of total pain relief also showed no significant differences. A comparison of ibuprofen arginine with morphine sulphate for pain relief after orthopaedic surgery. Mansfield M, Firth F, Glynn C, Kinsella J. Glasgow Royal Infirmary, UK. Eur J Anaesthesiol. 1996 Sep;13(5):492-7.  (tie)

Pain Relief: Marijuana No Value: Morphine Very Little Added Benefit: From folk medicine and anecdotal reports, it is claimed that Cannabis reduces pain. In a DB PC crossover study of 12 healthy volunteers given single doses of THC (20 mg), morphine (30 mg), THC-morphine (20 mg THC+30 mg morphine), or placebo in pain tests with heat, cold, pressure, single and repeated transcutaneous electrical stimulation, THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine. A slight additive analgesic effect could be observed for THC-morphine in the electrical stimulation test. No analgesic effect resulted in the pressure and heat test, neither with THC nor THC-morphine. Psychotropic and somatic side-effects (sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc.) were common, but usually mild. The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions. Naef M, et al. University of Bern, Switzerland. Pain. 2003 Sep;105(1-2):79-88. (This study not counted since not patients).

Postherpetic Neuralgia: Nortriptyline Almost as Good as Morphine In a DB PC crossover study of 76 patients with postherpetic neuralgia, morphine 91 mg or methadone 15 mg did not better than nortriptyline 89 mg or desipramine 63 mg. Opioids and tricyclics (TCA) reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001). The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). The opiates were non-significantly better than the anti-depressants at pain relief (p=0.06). Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Raja SN, et al. Johns Hopkins. . Neurology. 2002 Oct 8;59(7):1015-21. Ed: Nortriptyline is much preferred over desipramine both because nortriptyline is much better researched for pain relief and has a much higher safety index in overdose. Nortriptyline plus a non-narcotic pain relievers would undoubtedly have been far superior to a narcotic by itself and very likely just as good as the narcotic with a non-narcotic pain reliever.  It borders on medical malpractice to give opiates for PHN, since PHN is a temporary condition, the narcotics are obviously unnecessary, and the narcotics too often lead to serious addiction problems.  (slight win for morphine against weak opponent)

Post-Op Pain: Morphine Only Modestly Better than Propacetamol (IV Acetaminophen): In a DB study of 80 patients after elective surgery with expected mild to moderate post-op pain, propacetamol 30 mg/kg as a 15 min IV infusion had only a modest disadvantage in pain relief scores with 7 vs. 2 patients needing supplement pain medication (p=0.05). Nausea occurred in 4 vs. 3 but pruritis occurred in 2 vs. 7 cases. The respiratory rate was slightly slower with morphine (p=.02). No significant differences were observed in blood oxygen saturation, blood pressure, heart rate, body temperature and vigilance. Comparison of propacetamol and morphine in postoperative analgesia. Vuilleumier PA, et al. Hopital Daler, Fribourg. Schweiz Med Wochenschr. 1998 Feb 14;128(7):259-63.  (slight win for morphine against weak opponent)

Prescription of Heroin to Treatment Resistant Heroin Addicts: Double Blinding is not Possible. DeHue T. BMJ. 2004 Jan 24;328(7433):228. Ed: This study strongly suggests that double-blinding is also not possible with opiate medication studies, at least in patients with previous experience.

Surgery: Poor Quality 30 Minutes Study Proclaims Morphine Better than Ketorolac: In a difficult to understand report of a DB study of 1,003 adult surgical patients initially receiving 30 mg ketorolac or 0.1 mg/kg morphine intravenously, at 30 minutes 50% of morphine vs. 31% of ketorolac patients had pain less the 4 out of 10. Then, patients with inadequate relief received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10. The ketorolac-morphine group required significantly less morphine (6.5 mg less) and had a lower incidence of side effects (11% less) than the morphine group. Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial. Cepeda MS, et al. Javeriana University, Bogota, Colombia. . Anesthesiol 2005 Dec;103(6):1225-32. Ed: This does not appear to be a good study, since the morphine-free phase lasted only 30 minutes.  Other studies have found opiates better at 30 minutes, but inferior thereafter.  I am not counting this study in my collection.

Vaginoplasty: Intrathecal Neostigmine as Good as Morphine: In a DB study of 48 women undergoing anterior and posterior vaginoplasty, intrathecal neostigmine did as well as morphine for pain relief. Combining both at lower doses also did as well. Increasing doses of intrathecal morphine (50 micrograms, 100 micrograms, and 200 micrograms) and intrathecal neostigmine (50 micrograms, 100 micrograms, and 200 micrograms) showed a dose-dependent pattern of analgesia (P < 0.001). The M50 + N50 combination resulted in a better analgesic effect with fewer side effects than M50, N50, and control groups. Dose-response study of intrathecal morphine versus intrathecal neostigmine, their combination, or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty. Lauretti GR, Reis MP, Prado WA, Klamt JG. Faculdade de Medicina de Ribeirao Preto-USP, Sao Paulo, Brazil. Anesth Analg. 1996 Jun;82(6):1182-7.  (tie)

Babies: Morphine Bad for Premees, But Use Goes On: In a DB PC study of 898 premees (gestational age 23-32 weeks) given morphine or placebo until they were weaned from the ventilator or for 14 days, whichever occurred earlier, morphine results in significantly longer ventilator therapy : 7 days vs 6 days). Some of the sicker Infants in both groups received open-label intermittent morphine doses. After adjustment for birth weight, Clinical Risk Index for Babies scores, maternal chorioamnionitis, RDS requiring surfactant, and patent ductus arteriosus in a logistic regression model, the use of additional analgesia with morphine was associated independently with increased air leaks and longer durations of high-frequency ventilation, nasal continuous positive airway pressure, and oxygen therapy. Morphine did not improve short-term pulmonary outcomes among ventilated preterm neonates. Additional morphine was associated with worsening respiratory outcomes among preterm neonates with RDS. Morphine administration and short-term pulmonary outcomes among ventilated preterm infants. Bhandari V, et al. NEOPAIN Trial. Albert Einstein, Philadelphia. . Pediatrics 2005 Aug;116(2):352-9. 

Examples of the Numerous Poor Quality Studies

Canada: Doping Up Children with Appendicitis with Morphine: In a DB PC study of 108 children in the emergency room with acute abdominal pain thought to possibly require emergency surgery (appendectomy), children given IV morphine had somewhat less pain than those given an IV with no pain reliever whatsoever. The reduction in the mean pain score was significantly greater in the morphine group (2.2 vs 1.2 cm). Early analgesia for children with acute abdominal pain. Green R, et al. Dalhousie University, Halifax, Canada. Pediatrics. 2005 Oct;116(4):978-83. Ed: At very least, these doctors should have used a non-narcotic pain reliever as a control.  Non-narcotics have been found as good or better than opiates for surgical pain in many studies. An IV form of acetaminophen would not have interfered with future surgery.  NSAIDs have been used before and after many surgical studies with only minor increases in bleeding.

Osteoarthritis: Irresponsible Study Comparing to Brandname Morphines to Placebo: In a 4-week DB study of 295 patients with moderate to severe osteoarthritis pain who had supposedly failed on NSAIDs and acetaminophen, extended-release morphine 30 mg (Avinza), MS Contin 15 mg twice daily, or placebo twice daily were compared. Avinza and MS Contin equally reduced pain and improved several sleep measures versus placebo. The most common side-effects were constipation and nausea. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. Caldwell JR, Rapoport RJ, Davis JC, Offenberg HL, Marker HW, Roth SH, Yuan W, Eliot L, Bablul N, Lynch PM. Radiant Research, Daytona Beach, FL 32114, USA. J Pain Symptom Manage. 2002 Apr;23(4):278-91. Ed: This is a typical, irresponsible study done for a narcotic manufacturer.  The physicians were careful not to include any non-narcotic pain reliever.  None of the osteoarthritis patients are reported to have been on glucosamine and chondroitin, a treatment far superior to NSAIDs.

Stanford Pushes Morphine for Obsessive-Compulsive Disorder in Flimsy Study with Minimal Possible Benefit: In a small and supposedly double-blind crossover study of 23 OCD patients, the authors claim that once-weekly oral morphine was effective in for some SRI-resistant OCD patients. Patients were randomly assigned to random-order, 2-week blocks of once-weekly morphine, lorazepam, and placebo. However, as best I can tell, the authors didn't check to see whether patients could accurately guess whether they had been given the morphine or not. The OCD (Y-BOCS) score after the highest dose of morphine decreased by an average of only 13% vs. 6% with lorazepam and 7% with placebo, hardly a significant difference. Double-blind treatment with oral morphine in treatment-resistant obsessive-compulsive disorder. Koran LM, et al. Stanford University. . J Clin Psychiatry. 2005 Mar;66(3):353-9. Ed: This is an incredibly irresponsible article. To promote the equivalent of heroin for a possible 6% improvement in OCD scores is unethical. In addition to this, it is extremely likely that patients could tell which drug they had been given, yet researchers never asked the patients.  If the patients figured out more often than not which drug they received, that knowledge may have influenced their answers in a way favorable to morphine. When someone feels like that have taken a real medicine, they may be more likely to report that they feel better than if they are pretty sure that they just took a placebo sugar pill.  Wouldn't you be a little disappointed if you realized that your doctor had given you sugar pills for two weeks?  Do you think that you could tell the difference between a highly addictive narcotic and a sugar pill?  Also, being blissed out on narcotics might have had a little non-specific impact on the ratings.  Of course, once patients have developed tolerance, had their doses increased, and become addicted, any blissful benefit might have turned into a huge liability.  Very few narcotic addicts whom I have met are happy campers.

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

 modern-psychiatry.com