Table 2.

Anticonvulsants for SCI Pain

Author Year Country Score (PEDro/D&B)	Population	Intervention	Results
Gabapentin/Pregabalin
Rintala et al. 200735 USA RCT PEDro=10	N:22 Type of pain: Individuals with neuropathic pain	Treatment: Patients were randomized into 1 of 6 groups: 1) gabapentin-amitriptyline-diphenhydramine (n=7), 2) gabapentin-diphenhydramine-amitriptyline (n=6), 3) amitriptyline-gabapentin-diphenhydramine (n=6), 4) amitriptyline-diphenhydramine-gabapentin (n=6), 5) dephenhydramine-gabapentin-amitriptyline (n=7), 6) diphenhydramine-amitriptyline-gabapentin (n=6). Each drug was administered for 9 wks with 1 washout week before and after each drug treatment, for a total of 31 weeks. The maximum doses were 50mg, 3x/day for amitriptyline; 1200mg, 3x/day for gabapentin; 25mg, 3x/day, diphenhydramine (control). Pain Scale: VAS, NRS.	In subjects with high (≥ 10) baseline Center for Epidemiologic Studies Depression Scale-Short Form (CESD-SF) scores at 8 weeks: Amitriptyline was significantly more effective in reducing pain intensity than diphenhydramine (p=0.035); but not gapapentin (p=0.61). No significant difference in pain intensity was seen in effectiveness of gabapentin over diphenhydramine (p=0.97). Subjects with low (< 10) baseline CESD-SF scores showed no significant difference among the medications. rd
Siddall et al. 200636 Australia RCT PEDro=9	N:137 Type of pain: Individuals with neuropathic pain	Treatment: Those in treatment group (n=70) received 150 to 600 mg/daily of pregabalin, while those in control group (n=67) received a placebo. Pain Scale: VAS, SFMPQ	Those in treatment group, once dose stabilized, averaged 460 mg/d at end of 3 week. Pregabalin more effective than placebo at reducing pain by end of study (p<0.001). Pain reduction noted both with incomplete ( p<0.001) and complete SCI (p<0.05). The number who reported either a ≥ 30% or ≥ 50% reduction in pain from baseline to final assessment were more likely to be in the pregabalin group (p<0.001 and p<0.05, respectively). Those in pregabalin group also noted reduction in sleep problems (p<0.021), and an improvement in sleep quality (p<0.05) compared to the control group.
Vranken et al. 200737 Netherlands RCT PEDro=9	N:40 Type of pain: Individuals with neuropathic pain	Treatment: Those in treatment group received escalating doses of pregabalin (150, 300, or 600 mg/daily), while control group received placebo. Pain Scale: VAS, PDI	82.5% of subjects completed the study. Those in the treatment group experienced a decrease in pain (p<0.01) compared to control group. With respect to health status and quality of life, treatment group experienced a statistically-significant improvement, in particular on the EQ-5D VAS and EQ-5D utility scores (p<0.01). Scores on the SF-36 showed significant improvement in the bodily pain domain (p<0.009) for the treatment group, but not in other domains.
Levendoglu et al., 200438 Turkey RCT PEDro=9	N:20 Type of pain: Individuals with neuropathic pain	Treatment: Subjects randomized to gabapentin or placebo for a 4-week titration period. Following this 4-week period, subjects continued to receive max tolerated doses. After 2-week washout period, treatments were switched in a crossover design. Pain Scale: VAS, NPS	Placebo and gabapentin improved pain scores for the following: intensity (p<0.000), shape (p<0.000), hot (p<0.001), unpleasantness (p<0.000), deep and surface pain (p<0.001), at 4th week and again at 8th week of administration. Intensity of pain decreased significantly for gabapentin groups during treatment (p<0.001) and intensity of pain differed between two groups at all time points (p<0.001). VAS scores indicated significant pain relief, which began at week 2 and continued until week 6 (p<0.001). There was a significant difference between the VAS scores for the two groups at the end of the stable dosing periods (p<0.001). More subjects had side effects in the treatment group than in the placebo group (p<0.05).
Tai et al., 200239 USA RCT PEDro=6	N:7 Type of pain: Individuals with neuropathic pain	Treatment: SCI subjects with neuropathic pain were treated with gabapentin or placebo. Pain Scale: NPS	Significant reduction in ‘unpleasant feeling’ with gabapentin vs. placebo (p=0.028). Trend towards reductions with gabapentin vs. placebo for ‘pain intensity’ (p=0.094) and ‘burning sensation’ (p=0.065). No other differences for any other pain descriptors, including ‘"sharp’, ’dull’, ’cold’, ’sensitive’, ’itchy’, ‘deep’, ’surface’.
To et al., 200240 Australia Case Series D&B=18	N:38 Type of pain: Individuals with neuropathic pain	Treatment: SCI patients were treated with gabapentin for neuropathic pain. Pain Scale: VAS	76% of subjects reported improvement in pain after taking gabapentin. The VAS decreased from 8.86 pre-treatment to 4.13 post-treatment (6mo later) (p<0.001), with a significant curvilinear trend (p=0.001).
Ahn et al., 200332 Korea Case cohort D&B=17	N:31 Type of pain: Individuals with neuropathic pain	Treatment: SCI patients were started on 300 mg of gabapentin, which was increased over 18 days to 1500 mg, followed by a 5-week maintenance period. If pain score did not decrease over this time period, meds were increased to 2400–3600 mg/day. Group 1 had <6 mo of pain; group 2 > 6 mo. Pain Scale: VAS	Both groups (1 & 2) experienced lower mean scores for pain and sleep interference (p<0.05). Mean pain score decreased more for Group 1 than Group 2 (p<0.05). Mean pain score decreased more for Group 1 during weeks 2–8 than for Group 2 (p<0.05). Mean sleep interference score decreased more for Group 1 than Group 2 (p<0.05).
Putzke et al. 200241 USA Observational D&B=8	N:21 Type of pain: Not stated	Treatment: Participants were asked to complete a survey (or interview). Pain Scale: NRS	67% of patients reported having had a favorable response to gabapentin. Among those reporting a favorable response, side effects were forgetfulness & sedation. Among those interviewed a second time, most who reported a favorable response were using other medications and gabapentin for pain. Side effects like sedation and forgetfulness were common.
Lamotrigine
Finnerup et al. 200242 Denmark RCT PEDro=9	N:22 Type of pain: Individuals with neuropathic pain	Treatment: Following a 1-week baseline period, two 9-week treatment periods, consisting of either lamotrigine or placebo. Once the first 9-week period ended, a 2-week wash-out period began, followed by a second 9-week treatment phase. For those on lamotrigine, subjects were started on 25 or 100 mg and this was increased gradually to 400 mg/day. Dose was decreased if the patient could not tolerate the 400 mg/day; dose not allowed to drop below 200 mg/day. Pain Scale: MPQ.	No significant effect on pain intensity across total sample (p=0.11). For incomplete lesions, lamotrigine reduced pain (p=0.002) when compared to placebo; however, medication had no effect on those with a complete injury. Lamotrigine did not change any of the secondary endpoints. No differences were noted on the SF-36 or MPQ.
Levetiracetam
Finnerup et al. 200945 Denmark RCT PEDro=7	N=24 Type of pain: Individuals with neuropathic pain	Treatment: Patients were randomized and blinded into two 5 week treatment groups receiving either levetiracetam or placebo tablets. After a 1 week washout period, individuals were crossed over to the 2nd group. Patients received 500mg × 2 for the first week to 1000mg × 2 for the second week, 1500mg × 2 for the 3rd-5th week. Patients were assessed at baseline, end of each treatment and 6 months follow-up. Pain Scale: NPSI, NRS.	No significant difference was seen between levetiracetam and placebo treatment in the median pain intensity (p=0.46) or in secondary outcome measures. Patients treated with concomitant pain medication and patients without concomitant pain medication found no difference in pain reduction. No difference in pain reduction was seen between patients treated with gabapentin and/or pregabalin and patients without gabapentin/pregabalin treatment (p=0.95). There was a trend towards greater adverse events in patients during levetiracetam treatment rather than the placebo treatment; however no significant difference was seen (p>0.075).
Valproate
Drewes et al.,199444 Denmark RCT PEDro =5	N:20 Type of pain: Individuals with neuropathic pain	Treatment: Subjects were administered 600mg of valproate or placebo twice daily. Daily dose of valproate was increased (on an individual basis) if pain persisted and no side effects were reported. First treatment phase lasted 3 weeks, followed by a 2-week washout period, followed by 3 weeks of cross-over treatment. Pain Scale: MPQ	A trend toward improvement was noted among those in the valproate group; however, differences between the two groups were not significant.

Abbreviations: CESD-SF = Center for Epidemiologic Studies Depression Scale-Short Form; D&B = Downs and Black quality assessment scale score²⁷; EQ = EuroQoL; MPQ = McGill Pain Questionnaire; NPS = Neuropathic Pain Scale; NPSI = Neuropathic Pain Symptom Inventory; NRS = 11 Point Numeric Rating Scale; PDI = Pain Disability Index; PEDro = Physiotherapy Evidence Database rating scale score²⁶; SF-36 = Short Form 36 Health Survey; SFMPQ = Short Form McGill Pain Questionnaire; VAS = Visual Analogue Scale