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Anticonvulsants in SCI Pain

Anticonvulsant medications are often utilized in treating neurogenic or deafferent pain following SCI based on the theory that these drugs alter sodium conduction in uncontrolled hyperactive neurons (“convulsive environment”) in the spinal cord. Carbamazepine has been reported as being somewhat effective in the paroxysmal, sharp, shooting pain of trigeminal neuralgia (Swerdlow 1984). Gibson and White (1971) described relief resulting from carbamazepine treatment in two cases of L2 and T8 SCI with intractable pain below the level of SCI. A similar effect of Carbamazepine (200 mg 2x daily in combination with Amitriptyline 50 mg 3x daily) was reported in a complete C8 patient with dysesthesia below the level of the injury (Sandford et al. 1992). Again, controlled studies utilizing these drugs in SCI pain are lacking with the exception of gabapentin and pregabalin.

Gabapentin and pregabalin are now regarded as first-line treatments of neuropathic pain (Ahn et al. 2003; Moulin et al. 2007). Gabapentin and pregabalin have been recommended as first line treatments for neuropathic pain in Canadian and international guidelines (Gajraj 2007). The mechanism of action for Pregabalin and Gabapentin is through binding the alpha-2 delta receptors in the central nervous system. These receptors are present on the presynaptic nerve terminals. When bound by gabapentin or pregabalin they decrease the influx of calcium into the presynaptic terminal there by decreasing the release of excitatory neurotransmitters. Gabapentin and pregabalin appear to potentiate GABA effects centrally through enhancement of GABA synthesis and release. Levendoglu et al. (2004) noted that neuropathic pain is ultimately generated by excessive firing of pain-mediating nerve cells, insufficiently controlled by segmental and non-sequential inhibitory circuits. Gabapentin and pregabalin work by increasing GABA and reducing the release of glutamate thereby suppressing the sensitivity of N-methyl-D-asparate (NMDA) receptor. This has been shown to reduce neuronal hyper-excitability recorded at the spinal dorsal horn near the level of injury (Ahn et al. 2003). Gabapentin and pregabalin are relatively well tolerated with only a few transient side effects, lack of organ toxicity, and no evidence of significant interaction with other medications (Levendoghu et al. 2004; Gajraj 2007).

Table 23 Anticonvulsants for SCI Pain

Author Year

Country
PEDro Score
Research Design
Total Sample Size

MethodsOutcome
Gabapentin
Kaydok et al. 2014

Turkey

RCT

PEDro=7

N=28

Population: Age=42.8yrs’ Time since SCI=35.3 mons; Duration of pain=29.3 mons; Type of pain=neuropathic.

Treatment: Participants were randomly allocated to the gabapentin or pregabalin group. Those in the gapapentin group received an initial dose of 300 mg/day which was titrated to a max dose of 3600 mg/day by the 4th week. Those in the pregabalin group received an initial dose of 150mg/day which was titrated to a max of 600mg/day by the 4th week. These dosages were maintained for 8 weeks. Patients then underwent a 2 week washout period and were crossed over to the alternative group.

Outcome Measures: VAS

1.     No significant difference in VAS between gabapentin and pregabalin.

 

Rintala et al. 2007

USA

RCT

PEDro=10

N=38

Population: SCI: Mean age=42.6 yr; 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 yr; Duration of pain=7.3 yr. Type of pain=neuropathic.

Treatment: Patients were randomized into one of six 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 wk with one washout week before and after each drug treatment, for a total of 31 wk. The maximum doses were 50mg 3x/day for amitriptyline, 1200mg 3x/day for gabapentin, and 25mg 3x/day for diphenhydramine (control).

Outcome Measures: Center of Epidemiologic Studies Depression Scale-Short Form  (CESD-SF)

1.     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).

2.     Subjects with low (<10) baseline CESD-SF scores showed no significant difference among the medications.

Levendoglu et al. 2004

Turkey

RCT

PEDro=9

N=20

Population: Age=23-62 yr; Gender: males=13, females=7; Onset of pain post injury=1-8 mo; Duration of pain=6-45 mo. Type of pain=neuropathic.

Treatment: Subjects were randomized to gabapentin or placebo for a 4 wk titration period. Following this 4 wk period subjects continued to receive max tolerated doses. After a 2 wk 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.

 

 

1.     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 week 4 and 8 of administration.

2.     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).

3.     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).

4.     More experienced side effects in the treatment group then in the placebo group (p<0.05).

Tai et al. 2002

USA

RCT

PEDro=6

N=7

Population: Age=27-47 yr; Gender: males=6, females=1; Level of injury=C2-T7; Time since injury=1 mo-20 yr. Type of pain=neuropathic.

Treatment: Subjects with neuropathic pain were treated with gabapentin or placebo.

Outcome Measures: Neuropathic Pain Scale, which has 10 categories of pain types.

1.     Significant reduction of “unpleasant feeling” with gabapentin vs. placebo (p=0.028).

2.     Trends of reductions with gabapentin vs. placebo for “pain intensity” (p=0.094) and “burning feeling” (p=0.065).

3.     No other differences for any other pain descriptors including “sharp,” “dull,” “cold,” “sensitive,” “itchy,” “deep,” and “surface.”

Ahn et al. 2003

Korea

Pre-post

N=31

Population: Mean age=45 yr; Gender: males=19, females=12; Level of injury: paraplegia, tetraplegia; Severity of injury: complete, incomplete; Duration of pain=10 yr. Type of pain=neuropathic.

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 mg/day and 3600 mg/day. Group 1 had <6 mo of pain and group 2 >6 mo.

Outcome Measures: Pain and sleep interference scores of the two groups were compared.

1.     At the end of the study, both groups showed they had lower mean scores for pain and sleep interference score (p<0.05).

2.     Mean pain score for Group 1 decreased more than it did for Group 2 (p<0.05).

3.     This score decreased more for Group 1 during wk 2-8 than it did for Group 2 (p<0.05).

4.     Mean sleep interference score for Group 1 decreased more than it did for Group 2 (p<0.05).

 

 

To et al. 2002

Australia

Case Series

N=44

Population: Age=15-75 yr; Gender: males=28, females=10; Level of injury: paraplegia, tetraplegia. Type of pain=neuropathic.

Treatment: Neuropathic pain was treated with gabapentin.

Outcome Measures: Level of pain experienced by subjects.

 

1.     76% of subjects reported some improvement in pain after taking gabapentin.

2.     Visual Analogue Scores decreased from 8.86 pre-treatment to 4.13 post-treatment (6 mo later) (p<0.001), with a significant curvilinear trend (p=0.001).

Pregabalin
Min et al. 2016

South Korea

RCT Crossover

PEDro=6

N=55

Population: Mean age=51.7yr; Gender: males=44, females=11; Level of injury: paraplegia=29, quadriplegia=26; Severity of injury: incomplete=45, complete=10; Mean time post injury=2458d; Type of pain=neuropathic.

Treatment: Participants received pregabalin (300mg/d) and oxcarbazepine (300mg, 2x/d), each for 1-2wk, provided in a randomized sequence. Participants were divided according presence or absence of evoked pain. Outcomes were assessed before and after each trial.

Outcome Measures: Visual Analogue Scale – Pain Intensity (electrical pain, burning pain, pricking pain, numbness, allodynia, hyperalgesia).

1.      Overall, both pregabalin and oxcarbazepine were effective in relieving all types of pain (p<0.05), and there were no significant differences between medications in effectiveness.

2.      Oxacarbazepine was significantly more effective in relieving electrical, burning, and numbness pain in those without evoked pain than those with it (p<0.05).

3.      Pregabalin was significantly more effective in relieving burning pain in those without evoked pain than those with it (p<0.05).

4.      In those with evoked pain present, pregabalin was significantly more effective than oxcarbazepine in relieving allodynia and hyperalgesia than pregabalin (p<0.001).

5.      In those with evoked pain absent, there was no significant difference between medications in effectiveness.

Kaydok et al. 2014

Turkey

RCT

PEDro=7

N=28

Population: Age=42.8yrs’ Time since SCI=35.3 mons; Duration of pain=29.3 mons; Type of pain=neuropathic.

Treatment: Participants were randomly allocated to the gabapentin or pregabalin group. Those in the gapapentin group received an initial dose of 300 mg/day which was titrated to a max dose of 3600 mg/day by the 4th week. Those in the pregabalin group received an initial dose of 150mg/day which was titrated to a max of 600mg/day by the 4th week. These dosages were maintained for 8 weeks. Patients then underwent a 2 week washout period and were crossed over to the alternative group.

Outcome Measures: Visual analog pain scale (VAS), neuropathic pain scale (NPS), Lattinen test (LT) and Beck depression inventory (BDI) pain diary.

1.     No significant difference in VAS between gabapentin and pregabalin.
Cardenas et al. 2013

USA

RCT

PEDro=10

N=219

Population: Mean age=45.7yrs; Gender: Male=176; Female=43; Type of pain=neuropathic.

Treatment: SCI individuals with neuropathic below level pain for greater than 3 months were randomized to a twice daily pregabalin group (up to 600mg/d) or placebo for 12 weeks.

Outcome Measures: Duration-adjusted average change in pain,

1.     Significant improvement in pain was seen in the treatment group compared to placebo, p=0.0003.

2.     Significant improvement in pain related sleep interference scores were seen post treatment in the pregabalin group compared to placebo, p<0.05.

Arienti et al. 2011

Italy

RCT

PEDro=6

N=47

Population: Severity of injury: AIS A=33; B, C and D=14. Level of injury: paraplegia=19, tetraplegia=7. Type of pain=neuropathic.

Intervention: Patients were randomly placed into three groups: pharmacological group received 600 mg per day of pregabalin. The pharmacological and osteopathic group received 600mg per day of pregabalin and osteopathical treatment once a week for the first month, once every fortnight for the second month, once during the third month all for 45 min each by an osteopathic physician. The osteopathic group received on the osteopathic treatment described above.

Outcome Measures: Verbal numeric scale (VNS)

1.     Rates of improvement based on the VNS scores were similar across the two treatments (p=0.26).

2.     The highest pain relief was seen in the combined pharmacological and osteopathic group compared to the pharmacological alone (p=0.05) and the osteopathic alone (p=0.001).

Vranken et al. 2008

Netherlands

RCT

PEDro=9

N=40

 

Population: Treatment group: Mean age=54.2 yr; Gender: males=11, females=9; Control group: Mean age=54.7 yr; males=10, females=10. Type of pain=neuropathic.

Treatment: Those in treatment group received escalating doses of pregabalin (150 mg, 300 mg, or 600 mg daily), while the control group received placebo.

Outcome Measures: Visual Analogue Scale (VAS)

1.     82.5% of subjects completed the study.

2.     Those in the treatment group experienced a decrease in pain (p<0.01) compared to control group.

3.     With respect to health status and quality of life, treatment group experienced a statistically significant improvement on the EQ-5D VAS and EQ-5D utility scores (p<0.01).

4.     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.

Sidall et al. 2006

Australia

RCT

PEDro=9

N=137

Population: Mean age=45 yr; Gender: males=19, females=12; Level of injury: paraplegia, tetraplegia; Severity of injury: complete, incomplete; Duration of pain=10 yr. Type of pain=neuropathic.

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.

 

1.     The mean baseline pain score was 6.54 in the pregabalin group and 6.73 in the placebo group.

2.     The mean endpoint pain score was lower in the pregabalin group (4.62) than the placebo group (6.27; p<0.001).

3.     Efficacy observed as early as wk 1 and maintained for the duration of the study.

4.     The average pregabalin dose after the 3 wk stabilization phase was 460 mg/day.

5.     Pregabalin was associated with improvements in disturbed sleep (p<0.001) and anxiety (p<0.05)

6.     Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events.

Carbamazepine
Min et al. 2016

South Korea

RCT Crossover

PEDro=6

N=55

Population: Mean age=51.7yr; Gender: males=44, females=11; Level of injury: paraplegia=29, quadriplegia=26; Severity of injury: incomplete=45, complete=10; Mean time post injury=2458d; Type of pain=neuropathic.

Treatment: Participants received pregabalin (300mg/d) and oxcarbazepine (300mg, 2x/d), each for 1-2wk, provided in a randomized sequence. Participants were divided according presence or absence of evoked pain. Outcomes were assessed before and after each trial.

Outcome Measures: Visual Analogue Scale – Pain Intensity (electrical pain, burning pain, pricking pain, numbness, allodynia, hyperalgesia).

1.     Overall, both pregabalin and oxcarbazepine were effective in relieving all types of pain (p<0.05), and there were no significant differences between medications in effectiveness.

2.     Oxacarbazepine was significantly more effective in relieving electrical, burning, and numbness pain in those without evoked pain than those with it (p<0.05).

3.     Pregabalin was significantly more effective in relieving burning pain in those without evoked pain than those with it (p<0.05).

4.     In those with evoked pain present, pregabalin was significantly more effective than oxcarbazepine in relieving allodynia and hyperalgesia than pregabalin (p<0.001).

5.     In those with evoked pain absent, there was no significant difference between medications in effectiveness.

Salinas et al. 2012

Colombia

RCT

PEDro=9
NInitial=46; NFinal=44

Population: Mean age=36yr; Gender: males=42, females=4; Level of injury: paraplegia=28, quadriplegia=18; Severity of injury: incomplete=13, complete=33; Time post injury <2wk; Type of pain=neuropathic.

Treatment: Individuals without neuropathic pain were randomized to receive carbamazepine (600mg/d, n=24) or placebo (control, n=22) for 1mo. Outcomes were assessed pre and post treatment, and at 3 and 6mo follow-up.

Outcome Measures: Visual Analogue Scale – Pain Intensity (VAS-PI), Short Form 36 Scale (SF-36).

1.     At 1mo, significantly less of the treatment group reported moderate/intense pain (VAS-PI>4) than the control group (2 vs 8, p=0.024).

2.     At 3mo, more of the treatment group reported moderate/intense pain than the control group, but the difference was not significant (8 vs 6, p=0.498).

3.     At 6mo, less of the treatment group reported moderate/intense pain than the control group, but the difference was not significant (6 vs 8, p=0.298).

4.     There was no significant difference between groups in SF-36 scores.

Chen et al. 2018

China

PCT

N=54

Population: NMES+carbamazepine group: Mean age=41.8±12.6 yr; Gender: males=25, females=2; Time since injury=31.2±11.5 mo; Level of injury: C=12, T=13, L=2; Severity of injury: AIS A=16, B=3, C=5, D=3; Type of pain=neuropathic.

Carbamazepine group: Mean age=43.5±13.7 yr; Gender: males=23, females=4; Time since injury=29.7±10.8 mo; Level of injury: C=14, T=10, L=3; Severity of injury: AIS A=18, B=2, C=3, D=4; Type of pain=neuropathic.

Intervention: Participants were assigned to either an NMES + carbamazepine group or a carbamazepine only group for 3 mo of treatment with outcomes measures at baseline and post-intervention.

Outcome Measures: Pain intensity numerical rating scale (NRS), quality of life (QOL) sort form 36 (SF-36) scale, and adverse events.

*Neuromuscular electrical stimulation (NMES), neuropathic pain (NPP)

1.     No significant difference in NRS for NPP or the QOL in SF-36 in the NMES group (p>0.05).

2.     No serious adverse events in either group.

Lamotrigine
Agarwal & Joshi, 2017

India

RCT

PEDro=6

N=147

Population: Age=18+ yr; Gender: males=136, females=11; Level of injury: paraplegia=64, tetraplegia=83; Severity of injury: AIS A=112. B/C/D=35; Type of pain=neuropathic.

Intervention: Participants with neuropathic pain (NP) were randomized to either amitriptyline or lamotrigine for 3 wk trials to compare the effects of pain suppression.

Outcome Measures: Short-form MC Gill Pain Questionnaire (SFMPQ2) score on pain, adverse events and withdrawn patients.

1.     No significant differences between reduction of pain scores between the amitriptyline and lamotrigine groups (p>0.05).

2.     Only notable adverse events were dry mouth and drowsiness, and patients reported exceeding the 50 mg dose recommendation in the amitriptyline group with no adverse events in the lamotrigine group.

3.     140 of the 147 subjects completed the study, 5 dropped out and two passed away.

Finnerup et al. 2002

Denmark

RCT

PEDro=10

N=30

Population: SCI patients with pain at or below the level of injury. Type of pain=neuropathic.

Treatment: A 1 wk baseline period was followed by two treatment periods of 9 wk. Lamotrigine slowly increased to a maximum of 400 mg or placebo separated by a 2 wk 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.

1.     Twenty-two patients completed the trial.

2.     No statistically significant effect of lamotrigine as evaluated in the total sample

3.     In patients with incomplete SCI, lamotrigine significantly reduced pain at or below SCI level.

4.     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

RCT

PEDro=7

N=36

Population: Mean age=52.8 yr; 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; Type of pain=neuropathic.

Treatment: Patients were randomized into two 5 week treatment groups receiving either levetiracetam or placebo tablets. After a 1 wk washout period, individuals were crossed over to the 2nd group. Patients received 500 mg x2 for the first week, 1000mg x2 in the second week, and 1500 mg x2 in wk 3-5. Patients were assessed at baseline, end of each treatment and 6 mo follow-up.

Outcome Measures: Neuropathic pain symptom inventory

1.     Levitiracetam treatment showed no significant improvement in median pain intensity compared to placebo treatment (p=0.46).

2.     No difference was seen in pain relief between the patients treated with levitiracetam alone and those with concomitant main medication.

3.     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

RCT

PEDro=5

N=20

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

Treatment: Subjects were administered 600 mg of valproate or placebo 2x 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 wk, followed by a 2 wk washout period, followed by 3 wk of cross-over treatment.

Outcome Measures: McGill Pain Questionnaire (MPQ)

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

Discussion

Gabapentin

Three studies found that gabapentin was no better than placebo in improving pain intensity post SCI (Rintala et al. 2007; Kaydok et al. 2014; Tai et al. 2002). While, Levendoglu et al. (2004) found gabapentin significantly reduced post SCI neuropathic pain compared to placebo. Three pre-post studies found gabapentin had a time effect in reducing pain post SCI (To et al. 2002; Ahn et al. 2003; Putzke et al. 2002).

Pregabalin

Six studies examined the efficacy of pregabalin on pain post SCI. Min et al. (2016) found pregabalin and oxcarbazepine were equally effective in relieving pain overall. However, was more effective in relieving burning pain, allodynia, and hyperalgesia. Kaydok et al. (2014) found no significant difference in pain reducing between gabapentin and pregabalin. Siddall et al. (2006) published the results of a double blind randomized control trial evaluating the use of flexible dose pregabalin in the treatment of neuropathic pain in spinal cord injury. A total of 137 subjects with central neuropathic pain post spinal cord injury participated. The primary outcome was the VAS pain scale and secondary outcomes included sleep interference and anxiety scales. Seventy patients were randomized to receive pregabalin and 67 patients received placebo. At the end of the trial the pregabalin treated patients had significantly more pain relief. The pregabalin treated subjects also reported significantly improved sleep and anxiety. Side effects were mild and transient and included dizziness, drowsiness and edema (similar to gabapentin).

Arienti et al. (2011) compared treatment of pain in three groups: 1) pregabalin only group; 2) pregabalin and osteopathy group; 3) osteopathy group. The study found significant improvement in pain perception and pain relief in the combined pregabalin and osteopathy group compared to the other two groups (p<0.01). Further, relief of pain was faster in the combined group compared to the pregabalin and osteopathy only groups.

In a RCT conducted by Vranken et al. (2008) patients in the treatment group received escalating doses of pregabalin (150-600 mg daily), while those in the control group received a placebo. Subjects in the treatment group reported a significant decrease in pain (p<0.01), along with improvements in the EQ-5D VAS and utility scores (p<0.01), as well as the Bodily Pain subscale of the SF-36 (p<0.05), relative to the control group.

Cardenas et al. (2013) studied 220 patients with neuropathic pain post SCI they were randomized to 150-600mg of pregabalin (108 patients) vs Placebo (112) patients. The patients in the treatment group experienced significant improvements in all primary and key secondary outcomes including duration adjusted average change in pain, change in mean pain scores,percentage of patients with greater that 30% reduction in pain and reduction in pain related sleep interference scores compared to placebo. The improvements were seen as early as one week after initiation of treatment and lasted for the duration of the 17 week study. As with previous studies the medication was generally well tolerated, somnolence and dizziness were the most common side effects. This study provided class 1 evidence for the effectiveness of pregabalin 150mg to 600mg in the treatment of neuropathic pain post spinal cord injury.

Lamotrigine

Two studies evaluated the effectiveness of lamotrigine in reducing pain post SCI. Agarwal and Joshi (2017) found lamotrigine resulted in similar reduction in pain compared to amitriptyline. Finnerup et al. (2002) studied the effects of lamotrigine on post SCI pain. Although the overall result showed no difference between placebo and lamotrigine, there was a significant reduction in pain in the incomplete spinal cord group.

Levetiracetam

Finnerup et al. (2009) conducted a randomized, double blind, crossover trial of levetiracetam in SCI individuals with pain. Participants were placed in either the levetiracetam or placebo group for five weeks and then crossed over after a one week washout period. This study found no significant difference between the levetiracetam and the placebo treatment group in improving pain intensity (p=0.46).

Valproate

In a double-blind cross-over study (n=20), Drewes et al. (1994) examined the effects of a three week treatment course of valoproic acid on chronic central pain in individuals who had sustained a SCI. Overall, they found no significant differences between the control and treatment groups; however, there was a trend towards improvement in the treatment group.

Table 24 Summary of Anticonvulsant Pain Treatment Post SCI

StudyStudy TypeNInterventionOutcome
Rintala et al. 2007RCT22Gabapentin
Levendoglu et al. 2004RCT20Gabapentin+
Tai et al. 2002RCT7Gabapentin+
To et al. 2002Non-RCT44Gabapentin+
Ahn et al. 2003Non-RCT31Gabapentin+
Putzke et al. 2002Non-RCT21Gabapentin+
Cardenas et al. 2013RCT219Pregabalin+
Siddall et al. 2006RCT137Pregabalin+
Vranken et al. 2008RCT40Pregabalin+
Finnerup et al. 2002RCT30Lamotrigine+*
Finnerup et al. 2009RCT36Levetiracetam
Drewes et al. 1994RCT20Valproate

Note: *=in individuals with incomplete SCI

Conclusion

There is level 1b evidence (Levendoglu et al. 2004) that the gabapentin improves neuropathic pain post SCI compared to placebo.

There is level 1b evidence (Rintala et al. 2007) that gabapentin is no more effective as an active placebo in improving neuropathic pain post SCI.

There is level 1b evidence (Kaydok et al. 2014) that gabapentin and pregabalin are equally effective at reducing neuropathic pain post SCI.

There is level 1b evidence (from one randomized controlled trial; Arienti et al. 2011) that combined pregabalin and osteopathy treatment improves pain post SCI.

There is level 4 evidence (from one pre-post study; Ahn et al. 2003) that the anticonvulsant Gabapentin is more effective when SCI pain is<6 months than >6 months.

There is level 1b evidence (from one randomized controlled trial; Finnerup et al. 2002) that lamotrigine improves neuropathic pain in incomplete spinal cord injury

There is level 1b evidence (from one randomized controlled trial; Finnerup et al. 2009) that Levetiracetam is not effective in reducing neuropathic pain post SCI.

There is level 2 evidence (from one randomized controlled trial; Drewes et al. 1994) that valproic acid does not significantly relieve neuropathic pain post SCI.

Gabapentin and pregabalin improve neuropathic pain post SCI.

Combined osteopathy and pregabalin may improve pain post SCI.

Lamotrigine may improve neuropathic pain in incomplete spinal cord injury

Levetiracetam is not effective in reducing neuropathic pain post SCI.

Valproic acid does not reduce neuropathic pain post SCI.