Drug combinations in pain treatment: a review of the published evidence and a method for finding the optimal combination

What is synergy?

1989 • 1,315 citations

Sequential Application of Simplex Designs in Optimisation and Evolutionary Operation

1962 • 1,266 citations

Epidural Anesthesia and Analgesia

1995 • 1,142 citations

Side effects of intrathecal and epidural opioids

1995 • 579 citations

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review

2002 • 512 citations

A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia

1986 • 443 citations

Sequential Application of Simplex Designs in Optimisation and Evolutionary Operation

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Analgesic Effect of Intravenous Ketamine in Cancer Patients on Morphine Therapy

2000 • 251 citations

Morphine-sparing Effect of Acetaminophen in Pediatric Day-case Surgery

1999 • 232 citations

Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia

2002 • 229 citations

Oral Ketamine and Transdermal Nitroglycerin as Analgesic Adjuvants to Oral Morphine Therapy for Cancer Pain Management

1999 • 214 citations

Treatment of primary fibrositis/fibromyalgia syndrome with ibuprofen and alprazolam. A double‐blind, placebo‐controlled study

1991 • 209 citations

Comparison of morphine and morphine with ketamine for postoperative analgesia

1996 • 201 citations

Comparison of a bupivacaine-clonidine mixture with plain bupivacaine for caudal analgesia in children † †This paper was presented in part to the North East Thames Region Anaesthetists Society Meeting, April 24, 1993.

1994 • 176 citations

Intravenous Administration of Propacetamol Reduces Morphine Consumption After Spinal Fusion Surgery

2001 • 171 citations

Postoperative analgesia with i.v. patient-controlled morphine: effect of adding ketamine

1999 • 169 citations

Combination Analgesic Efficacy

2002 • 153 citations

Valdecoxib, a COX-2???Specific Inhibitor, Is an Efficacious, Opioid-Sparing Analgesic in Patients Undergoing Hip Arthroplasty

2002 • 143 citations

Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review

1996 • 140 citations

Analgesic efficacy of paracetamol and diclofenac in children receiving PCA morphine

1999 • 132 citations

Adrenaline markedly improves thoracic epidural analgesia produced by a low‐dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double‐blind, cross‐over study with and without adrenaline

1998 • 131 citations

EXTRADURAL CLONIDINE AND BUPIVACAINE FOR POSTOPERATIVE ANALGESIA

1992 • 126 citations

Acetaminophen as an Adjunct to Morphine by Patient-Controlled Analgesia in the Management of Acute Postoperative Pain

1998 • 124 citations

Amitriptyline and Fluphenazine in the Treatment of Postherpetic Neuralgia

2000 • 122 citations

Use of Ketorolac after Lower Abdominal Surgery Effect on Analgesic Requirement and Surgical Outcome

1994 • 120 citations

Adding Ketamine to Morphine for Patient-Controlled Analgesia After Major Abdominal Surgery: A Double-Blinded, Randomized Controlled Trial

2001 • 118 citations

Evaluation of Intravenous Ketorolac Administered by Bolus or Infusion for Treatment of Postoperative Pain A Double-blind, Placebo-controlled, Multicenter Study

1994 • 116 citations

Continuous Intravenous Administration of Ketorolac Reduces Pain and Morphine Consumption After Total Hip or Knee Arthroplasty

1995 • 116 citations

DOUBLE-BLIND CONTROLLED TRIAL OF INDOMETHACIN AS AN ADJUNCT TO NARCOTIC ANALGESIA AFTER MAJOR ABDOMINAL SURGERY

1982 • 109 citations

Dose-Response of Ketorolac as an Adjunct to Patient-Controlled Analgesia Morphine in Patients After Spinal Fusion Surgery

1998 • 106 citations

Epinephrine Markedly Improves Thoracic Epidural Analgesia Produced by a Small-Dose Infusion of Ropivacaine, Fentanyl, and Epinephrine After Major Thoracic or Abdominal Surgery: A Randomized, Double-Blinded Crossover Study With and Without Epinephrine

2002 • 104 citations

Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol

1997 • 100 citations

Combined infusions of morphine and ketamine for postoperative pain in elderly patients

1993 • 96 citations

Acetaminophen as an Adjunct to Morphine by Patient-Controlled Analgesia in the Management of Acute Postoperative Pain

1998 • 93 citations

Combination Therapy with Ibuprofen and Methadone for Chronic Cancer Pain

1984 • 93 citations

Dose-Response of Ketorolac as an Adjunct to Patient-Controlled Analgesia Morphine in Patients After Spinal Fusion Surgery

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Epidural Clonidine Enhances Postoperative Analgesia From a Combined Low-Dose Epidural Bupivacaine and Morphine Regimen

1992 • 86 citations

Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain-a meta-analysis

1996 • 84 citations

Combinations of Morphine with Ketamine for Patient-controlled Analgesia

2003 • 81 citations

Epinephrine Markedly Improves Thoracic Epidural Analgesia Produced by a Small-Dose Infusion of Ropivacaine, Fentanyl, and Epinephrine After Major Thoracic or Abdominal Surgery: A Randomized, Double-Blinded Crossover Study With and Without Epinephrine

2002 • 80 citations

A Direct Search Procedure to Optimize Combinations of Epidural Bupivacaine, Fentanyl, and Clonidine for Postoperative Analgesia

2000 • 73 citations

Comparison of tenoxicam and bromazepan in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial

1996 • 71 citations

Prolonged Epidural Infusions of Ropivacaine (2 mg/mL) After Colonic Surgery: The Impact of Adding Fentanyl

2001 • 61 citations

Epidural fentanyl markedly improves thoracic epidural analgesia in a low‐dose infusion of bupivacaine, adrenaline and fentanyl

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Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain

1998 • 54 citations

Morphine-sparing effect of diclofenac in cancer pain

1993 • 53 citations

Ibuprofen in the treatment of postoperative pain in small children. A randomized double–blindplacebo controlled parallel group study

1994 • 53 citations

Epidural Patient-Controlled Analgesia After Cesarean Section

1992 • 45 citations

Combined therapy with cyclobenzaprine and ibuprofen in primary fibromyalgia syndrome.

1992 • 45 citations

Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine in post-surgical pain: a meta-analysis

1998 • 44 citations

Patient-controlled extradural analgesia with bupivacaine, fentanyl, or a mixture of both, after Caesarean section

1996 • 43 citations

Comparison of extradural fentanyl, bupivacaine and two fentanyl-bupivacaine mixtures for pain relief after abdominal surgery

1995 • 42 citations

Bupivacaine 0.01% and/or Epinephrine 0.5 [micro sign]g/ml Improve Epidural Fentanyl Analgesia after Cesarean Section

1998 • 39 citations

A Double-Blind Comparison of Epidural Bupivacaine and Bupivacaine-Fentanyl for Caesarean Section

1990 • 37 citations

Continuous Intravenous Administration of Ketorolac Reduces Pain and Morphine Consumption After Total Hip or Knee Arthroplasty

1995 • 37 citations

The combination of ibuprofen and oxycodone/acetaminophen in the management of chronic cancer pain

1988 • 36 citations

Does Adrenaline Improve Epidural Bupivacaine and Fentanyl Analgesia after Abdominal Surgery?

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EFFECT OF THE ADDITION OF ADRENALINE TO EXTRADURAL DIAMORPHINE ANALGESIA AFTER CAESAREAN SECTION

1988 • 31 citations

A new method to evaluate central sensitization to pain following surgery. Effect of ketamine

1997 • 25 citations

Influence of epinephrine as an adjuvant to epidural morphine for postoperative analgesia.

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Epidural sufentanil for post-operative pain relief: effects of adrenaline.

1988 • 17 citations

Direct search methods in the optimisation of cancer chemotherapy regimens

1990 • 17 citations

The effect of the addition of adrenaline to pethidine for patient‐controlled epidural analgesia after Caesarean section

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Is Epinephrine Unfairly Neglected for Postoperative Epidural Mixtures?

2002 • 12 citations