Bennett, M.I. (2011). Effectiveness of antiepileptic or antidepressant drugs when added to opioids for cancer pain: Systematic review. Palliative Medicine, 25, 553–559. 

DOI Link

Purpose

STUDY PURPOSE: To determine the efficacy of antiepileptics and antidepressants as adjuvant medications for pain
 
TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED: MEDLINE, CINAHL, and EMBASE till July 2009, and the NICE website, Cochrane Collaboration, and DARE website; hand-search from reference lists retrieved
 
KEYWORDS: Not stated
 
INCLUSION CRITERIA: Adult patients; compared adjuvant drugs added to opioids to opioid alone or the use of another adjuvant medication; randomized or nonrandomized pre-post design; and assessed outcomes on pain relief
 
EXCLUSION CRITERIA: None specified

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 27
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The author evaluated the study design and identified confounding factors, allocation concealment, losses to follow-up, and intention to treat analyses. No specific tool was mentioned.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 8  
  • TOTAL PATIENTS INCLUDED IN REVIEW = 370
  • SAMPLE RANGE ACROSS STUDIES: 16–121 patients
  • KEY SAMPLE CHARACTERISTICS: All had neuropathic cancer pain

Phase of Care and Clinical Applications

PHASE OF CARE: Not specified
 
APPLICATIONS: Palliative care

Results

Six studies examined gabapentin, sodium valproate, or phenytoin, and two studies examined amitriptyline or imipramine. In two randomized, controlled trials, (RCTs) opioid doses were varied according to pain intensity, and in five trials, the opioid doses remained stable. The studies of phenytoin and valproate did not report pain intensities. For gabapentin, two RCTs and two observational studies reported an average benefit of 0.8 points (10-point scale, p = 0.025), but the reports of the percent of patients achieving at least a 30% pain relief were mixed. For amitriptyline, one study reported a benefit of 0.9 points of worst pain (p = 0.035), and one abstract did not report results. For gabapentin, adverse event outcomes were inconsistent; one RCT reported withdrawals caused by the medication, including one death. Respiratory depression was reported in two RCTs. Amitriptyline was associated with increased confusion, dry mouth, and drowsiness. The most common side effects were somnolence and dizziness.

Conclusions

The findings of this analysis suggest that the addition of antiepileptics and antidepressants to opioids for cancer-related neuropathic pain management may result in a small improvement in pain intensity at the risk of more adverse events.

Limitations

  • Relatively small number of studies
  • Some study designs associated with a high risk of bias

Nursing Implications

Adjuvant medications in addition to opioids for cancer-related neuropathic pain may be helpful for some patients; however, there is a need for skillful use and follow-up to evaluate the effect of adverse events. In some patients, these adverse events were severe. At the same time, the small changes in pain intensity reported here raise the question of whether these differences are clinically relevant and sufficient to warrant the risk of adverse events. Pain management needs to be highly individualized.

Legacy ID

5192