Gabapentin

Rintala et al. 2007;
USA
PEDro=10
RCT
N=22

Population: SCI: Mean age = 42.6 yrs; Gender: males = 20, females = 2; Level of injury: paraplegia = 7, tetraplegia = 12; Severity of injury: AIS A-C = 19, D = 3; Time since injury = 12.6 yrs; Duration of pain = 7.3 yrs.
Treatment: Patients were randomized into 1 of 6 groups: 1) gabapentin-amitripyline-diphenhydramine (GAD)(n=7), 2) GDA (n=6), 3) AGD (n=6), 4) ADG (n=6), 5) DGA (n=7), 6) DAG (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).
Outcome Measures: Effectiveness of amitriptyline, diphenhydramine, gabapentin on pain management.

• Amitriptyline was significantly more effective than diphenhydramine at 8 weeks, in subjects with high (≥ 10) baseline CESD-SF scores (p=0.035).
• No significant difference was seen at 8 weeks in subjects with high (≥ 10) baseline CESD-SF scores in :
  • Effectiveness of amitriptyline over gabapentin (p=0.061).
  • Effectiveness of gabapentin over diphenhydramine (p=0.97).
• Subjects with low (< 10) baseline CESD-SF scores showed no significant difference among the medications.

Levendoglu et al. 2004;
Turkey
PEDro=9
RCT
N=20

Population: Age = 23-62 yrs; Gender: males = 13, females = 7; Onset of pain post injury = 1-8 mths; Duration of pain = 6-45 mths.
Treatment: Subjects were randomized to gabapentin or placebo for a 4 weeks titration period. Following this 4 week period subjects continued to receive max tolerated doses. After a 2 week washout period the treatments were switched in a crossover design.
Outcome Measures: Neuropathic pain scale, VAS, and Lattinen test were used to assess pain and quality of sleep.

• Both placebo and the gabapentin improved pain scores for the following: pain intensity (p<0.000), shape (p<0.000), hot (p<0.001), unpleasantness (p<0.000), deep and surface pain (p<0.001), at the 4th week and again at the 8th week of administration.
• Intensity of pain decreased significantly for the gabapentin groups during treatment p<0.001) and the intensity of pain differed between the two groups at all time periods (p<0.001).
• VAS scores indicated that there was significant pain relief, which began at week 2 and continued until week 6 (p<0.05) and pain relief between the two groups at the end of the stable dosing periods was significantly different p<0.000.
• More experienced side effects in the EX group then in the placebo gr (p<0.05).

Tai et al. 2002;
USA
PEDro=6
RCT
N=7

Population: Age = 27-47 yrs; Gender: males = 6, females = 1; Level of injury = C2-T7; Time since injury = 1mth-20 yrs.
Treatment: Subjects with neuropathic pain were treated with gabapentin or placebo.
Outcome Measures: Neuropathic Pain Scale, which has 10 categories of pain types.

• Significant reduction of "unpleasant feeling" with gabapentin vs. placebo (p=0.028).
• Trends of reductions with gabapentin vs. placebo for "pain intensity" (p=0.094) and "burning feeling" (p=0.065).
• No other differences for any other pain descriptors including "sharp", "dull", "cold", "sensitive", "itchy", "deep", "surface".

To et al. 2002;
Australia
Downs & Black score=18
Case Series
N=44

Population: Age = 15-75 yrs; Gender: males = 28, females = 10; Level of injury: paraplegia, tetraplegia.
Treatment: Neuropathic pain was treated with gabapentin.
Outcome Measures: Level of pain experienced by subjects.

• 76% of subjects reported some improvement in pain after taking gabapentin.
• The visual analogue score (VAS) decreased from 8.86 pre-treatment to 4.13 post-treatment (6mths later) (p<0.001), with a significant curvilinear trend (p=0.001).

Ahn et al. 2003;
Korea
Downs & Black score=17
Pre-post
N=31

Population: Mean age = 45 yrs; Gender: males = 19, females = 12; Level of injury: paraplegia, tetraplegia; Severity of injury: complete, incomplete; Duration of pain = 10 yrs.
Treatment: Subjects were started on 300 mg of gabapentin, which was increased over 18 days to 1500 mg, followed by a 5 wk maintenance period. If pain score did not decrease during this time period, meds were increased to 2400 and 3600 mg/day. Group1 had <6 mo of pain; Group2 >6 mo.
Outcome Measures: Pain and sleep interference scores of the 2 groups were compared.

• At the end of the study, both groups (1 & 2) showed they had lower mean scores for pain and sleep interference score (p<0.05).
• Mean pain score for Group 1 decreased more than it did for Group 2 (p<0.05).
• This score decreased more for Group 1 during weeks 2-8 than it did for Group 2 (p<0.05).
• Mean sleep interference score for Group 1 decreased more than it did for Group 2 (p<0.05).

Putzke et al. 2002
USA
D&B=8
Observational
N=21

Population: Gender: males=76%, females=24%; Level of injury: paraplegia=67%, tetraplegia=33%; Severity of injury: incomplete=76%, complete=33%; Type of pain=neuropathic pain.
Treatment: Participants were asked to complete a survey (or interview).
Outcome Measures: NRS

• 67% of patients reported having had a favourable response to gabapentin.
• Among those reporting a favourable response, side effects were forgetfulness & sedation.
• Among those interviewed a second time, most who reported a favourable response were using other medications and gabapentin for pain.
• Side effects like sedation and forgetfulness were common.

Pregabalin

Sidall et al. 2006;
Australia
PEDro=9
RCT
N=137

Population: Mean age = 45 yrs; Gender: males = 19, females = 12; Level of injury: paraplegia, tetraplegia; Severity of injury: complete, incomplete; Duration of pain = 10 yrs.
Treatment: Patients were randomized to either flexible-dose pregabalin 150 to 600 mg/day (n = 70) or placebo (n = 67), administered BID
Outcome Measures: Pain scores, sleep interference and anxiety scores of the two groups were compared.

• A 12-week, multicenter study of patients randomized to either flexible-dose pregabalin 150 to 600 mg/day (n = 70) or placebo (n = 67), administered BID.
• The primary efficacy variable was the endpoint mean pain score, derived from patients’ last 7 days daily pain diary entries.
• The mean baseline pain score was 6.54 in the pregabalin group and 6.73 in the placebo group.
• The mean endpoint pain score was lower in the pregabalin group (4.62) than the placebo group (6.27; p < 0.001).
• Efficacy observed as early as week 1 and maintained for the duration of the study.
• The average pregabalin dose after the 3-week stabilization phase was 460 mg/day.
• Pregabalin was associated with improvements in disturbed sleep (p < 0.001) and anxiety (p < 0.05)
• Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events.

Vranken et al. 2007
Netherlands
PEDro=9
RCT
N=40

Population: Treatment group: Mean age=54.2yrs; Gender: males=11, females=9; Control group: Mean age=54.7yrs; males=10, females=10.
Treatment: Those in treatment group received escalating doses of pregabalin (150, 300, or 600 mg/daily), while control group received placebo.
Outcome Measures: VAS

• 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.

Lamotrigine

Finnerup et al. 2002
Denmark
PEDro=10
RCT
N=30

Population: Thirty patients with spinal cord injury (SCI) and at or below level neuropathic pain
Treatment: A 1-week baseline period was followed by two treatment periods of 9 weeks. Lamotrigine slowly increased to a maximum of 400 mg or placebo separated by a 2-week washout period.
Outcome Measures: The primary outcome measure was the change in median pain score from baseline week to the last week of treatment. Secondary outcome measures included thresholds to standardized sensory stimuli using quantitative sensory testing.

• Twenty-two patients completed the trial.
• No statistically significant effect of lamotrigine as evaluated in the total sample
• In patients with incomplete SCI, lamotrigine significantly reduced pain at or below SCI level.
• Patients with brush evoked allodynia and wind-up-like pain in the area of maximal pain were more likely to have a positive effect to lamotrigine than patients without these evoked pains.

Levetiracetam

Finnerup et al. 2009
Denmark
PEDro=7
RCT
N=36

Population: Mean age=52.8yrs; Gender: males=29, females=7; Level of injury: C=13, T=19, L=4; Severity of injury: AIS A=13, B=2, C=3, D=18; Type of pain: at level=17, below level=31
Treatment: Patients were randomized 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 x 2 for the first week to 1000mg x 2 for the second week, 1500mg x 2 for the 3rd-5th week. Patients were assessed at baseline, end of each treatment and 6 months follow-up.
Outcome Measures: Neuropathic pain symptom inventory

• Levitiracetam treatment showed no significant improvement in median pain intensity compared to placebo treatment (p=0.46).
• No difference was seen in pain relief between the patients treated with levitiracetam alone and those with concomitant main medication.
• Side effects due to levetiracetam included incoordination, dizziness, somnolence, constipation and confusion; however these effects were not statistically different from those in the placebo group.

Valproate

Drewes et al. 1994
Denmark
PEDro =5
RCT
N=20

Population: Mean age=32.5yrs; Gender: males=15, females=5; Level of injury: paraplegia=16, tetraplegia=4; Type of pain=neuropathic.
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.
Outcome Measures: MPQ

• A trend toward improvement was noted among those in the valproate group; however, differences between the two groups were not significant.