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.

DATABASES USED: MEDLINE (1996–2002); EMBASE (1980–2002); CANCERLIT (1966–2002); Cochrane Controlled Trials Register and Database of Systematic Reviews (Cochrane Library, Issue 1, 2002); Specialized Register of the Cochrane Pain, Palliative and Supportive Care Group (2001); PARDLARS (in-house database of Pfizer UK, February 2002); hand-searching reference lists

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two RCTs met inclusion criteria. Two other RCTs appeared to meet the criteria but were considered methodologically flawed. Thirty-two case reports or open-label uncontrolled trials could not be included.

FINAL NUMBER STUDIES INCLUDED = 2

TOTAL PATIENTS INCLUDED IN REVIEW: 30

KEY SAMPLE CHARACTERISTICS: Seventeen men and 13 women aged 21–69 years. Cancers included stomach, cervix, liver, lung, colon, pancreas, bladder, rectum, histiocytoma, and uterus. The first study included 20 patients whose pain had been treated successfully with opioids. The second study included 10 patients whose pain had been unrelieved by their dose of morphine. In the second study, pain was defined as “neuropathic,” and the patients had a Karnofsky score of 50 or more.

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

The following treatments were 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)

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.

The objective of the systematic review was to assess the effectiveness of ketamine as an adjuvant therapy in treating cancer pain. Because of the small number of RCTs, small sample sizes, and lack of other acceptable research, evidence is insufficient to make the use of ketamine as an adjuvant to opioids 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.