Bell, R., Eccleston, C., & Kalso, E. (2003). Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD003351. DOI: 10.1002/14651858.CD003351.

The object of the systemic review was to assess the effectiveness of ketamine as an adjuvant therapy in treating cancer pain.

Medline (1996-2002); EMBASE (1980-2002); CancerLit (1966-2002); Cochrane Controlled Trials Registar and Database of Systematic Reviews (Cochrane Library, Issue 1, 2002); Specialized Registar of the Cochrane Pain, Palliative and Supportive Care Group (2001), PARDLARS (inhouse datadase of Pfizer UK, February 2002), hand searching reference lists

Two RCT met inclusion criteria. Two other RCT appeared to meet the criteria but were considered methodologically flawed. There were 32 case reports or open-label uncontrolled trials that could not be included.

Thirty patients, 17 men and 13 women, ages 21-69. Cancers included stomach, cervix, liver, lung, colon, pancreas, bladder, rectum, histiocytoma, and uterus. Study 1 with 20 had patients whose pain had been treated successfully with opioids. Study 2 had 10 whose pain had been unrelieved by their dose of morphine. Study 2 defined the pain as “neuropathic,” and the patients had a Karnofsky of 50 or more.

There was a reduction in pain scores for those receiving the ketamine. Four patients experienced hallucinations (most common adverse effect associated with ketamine). Two of these four patients also experienced a sensation of insobriety. All of these effects were relieved by diazepam.

Treatments evaluated:

• Ketamine 0.25 mg/kg adjuvant to morphine given IV
• Ketamine 0.5 mg/kg adjuvant to morphine given  IV
• Ketamine 1 mg/kg co-administered intrathecally with   morphine (reducing the morphine dose)

Outcomes Measured:

The primary outcome measure was patient-reported pain intensity and pain relief, using validated measures on movement and at rest ( e.g., visual analog scale and verbal rating scale).

Secondary outcomes included: total opioid consumption, rescue medication, adverse events, study withdrawals, and dropouts.

Because of the small number of RCTs , the small sample sizes, and the lack of other acceptable research, there is insufficient evidence for the use of ketamine as an adjuvant to opioids to make a recommendation for practice.

Suggested for research are crossover designs, larger patient groups, comparisons with other opioids, comparisons of routes of administration, and clearly defined outcomes. Research into ketamine’s role as an NMDA antagonist also would be welcomed.