Primary outcome measure
None of the included studies reported results as the number of patients with self reported pain relief of 50% or greater.
Secondary outcome measures
1. The number of participants reporting pain relief of 30% or greater (derived using the same pain assessments as the primary outcome).
2. The number of participants reporting global impression of clinical change (PGIC) much or very much improved.
3. The number of participants reporting PGIC very much improved.
4. Mean changes in the score of validated quality of life scales (QOLs).
None of the included studies measured or reported outcomes recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), that is, secondary outcomes 1 through 4 above (Dworkin 2008). Therefore, we compared mean or median pain scores as measured by numerical pain rating scales (0 to 10: 0 = no pain, 10 = worst pain) and additional pain outcomes including number of participants developing pain, and analgesic consumption.
In Pandey 2002, participants had significantly lower mean pain scores at the endpoint of the gabapentin phase (day 7) compared to the endpoint of the placebo phase (MD -3.61, 95% CI -4.12 to -3.10, n = 18 in both phases). Of note, while within-group comparisons were not part of our analysis, pain was lower each day from day 1 to 7 versus baseline (day 0) during the gabapentin phase, decreasing from 7.22 ± 0.83 (mean ± standard deviation) at baseline to 2.06 ± 0.63 on day 7 (P < 0.001 for all comparisons). The decrease in pain scores during the placebo phase was not significant on any day versus baseline (day 0: 7.83 ± 0.78, day 7: 5.67 ± 0.91).
In Pandey 2005, participants in the gabapentin group (n = 12) had significantly lower median pain scores (3.5, 2.5, 2.0, 2.0, 2.0, 2.0, and 2.0; from day 1 to 7, respectively) on all treatment days in comparison to the placebo (6.0, 6.0, 6.0, 6.0, 6.0, 6.0, and 6.0) (n = 12) and carbamazepine (6.0, 6.0, 5.0, 4.0, 4.0, 3.5, and 3.0) (n = 12) groups (P < 0.05). There were no statistically significant differences in the median pain scores between the carbamazepine and placebo groups from day 1 to day 3 (3.0, 3.0, and 3.0 versus 4.0, 4.0, and 4.0), but from day 4 until the end of the study significantly lower median pain scores were noted in the carbamazepine group (4.0, 4.0, 3.5, and 3.0) compared with placebo (6.0, 6.0, 6.0, and 6.0) (P < 0.05).
Number of participants with pain
When intravenous immunoglobulin (IVIg) plus methylprednisolone (n = 111) was compared with IVIg plus placebo (n = 112), after four weeks no significant differences were found in the number of participants with pain (RR 0.89, 95% CI 0.68 to 1.16, P = 0.38), number of participants with decreased pain severity (RR 0.95, 95% CI 0.63 to 1.42, P = 0.80) and number of participants with increased pain severity (RR 0.85, 95% CI 0.52 to 1.41, P = 0.54) (Ruts 2007).
In Pandey 2002, significant reductions in fentanyl consumption were reported when comparing the gabapentin phase to the placebo phase (n = 18 in both phases) for each day from day 1 to day 7 (P < 0.001 for each day). At day 7 (endpoint) the mean difference in fentanyl consumption was -251 µg (95% CI -265 to -238 µg).
In Pandey 2005 on day one, mean fentanyl consumption was lower in both the gabapentin and carbamazepine groups compared to placebo but no difference was found between the gabapentin and carbamazepine groups (n = 12 in all groups). From day two, there were significant differences in fentanyl consumption amongst the three groups with the lowest consumption in the gabapentin group and the highest in the placebo group (n = 12 in all groups). At the endpoint, a reduction in fentanyl consumption of 225 µg (95% CI -249 to -200 µg) was found when comparing gabapentin versus placebo; 176 µg (95% CI -202 to -150 µg) when comparing carbamazepine and placebo; and 48 µg (95% CI -71 to -26 µg) when comparing gabapentin with carbamazepine (n = 12 in all groups).
5.The number of withdrawals due to lack of efficacy
No participants withdrew due to lack of efficacy (or for any other reason) in any of the included studies.
6. The number of participants experiencing any adverse event
Two trials (Pandey 2002; Pandey 2005) reported adverse events (or lack of). In Pandey 2002, no significant differences were found in the incidence of nausea (RR 0.50, 95% CI 0.05 to 5.04, P = 0.56) or constipation (RR 0.14, 95% CI 0.01 to 2.54, P = 0.19) between gabapentin and placebo. In Pandey 2005, other than sedation, no adverse events were reported. Ruts 2007 did not describe reporting of adverse events.
In Pandey 2002, there was a significant reduction in mean sedation scores (numerical rating scale of 1 to 6: 0 = anxious, agitated, or restless; 6 = asleep, no response) at the endpoint of the gabapentin phase versus the placebo phase (MD -1.19, 95% CI -1.52 to -0.86), which the authors attributed to reduced requirements for fentanyl in the gabapentin phase. Similarly, in Pandey 2005 a significant difference in median sedation scores was recorded during the study period in the gabapentin (2.0 on all days 1 to 7), carbamazepine (3.0, 3.0, 3.0, 3.5, 3.0, 3.0, and 3.0; days 1 to 7, respectively) and placebo (4.0, 4.0, 4.0, 4.0, 4.0, 4.0, and 4.0) groups, again attributed to differences in fentanyl consumption. Participants in the gabapentin and carbamazepine groups had significantly lower sedation scores compared with placebo (P < 0.05). When comparing active interventions, sedation scores were significantly lower in those receiving gabapentin versus those receiving carbamazepine for each day from days 1 to 7 (P < 0.05).
7. The number of participants experiencing any serious adverse event
In Pandey 2002 and Pandey 2005 no participant experienced a serious adverse event. As noted above, Ruts 2007 did not describe reporting of adverse events. There were no deaths reported in any of the studies.
8. The number of withdrawals due to adverse events
There were no withdrawals due to adverse events (or for any other reason) in any of the included studies.