Pain Management Table 21 Anticonvulsants for SCI Pain

Author Year
Country
PEDro Score
Research Design
Total Sample Size

Methods

Outcome

Gabapentin

Kaydok et al. 2014
Turkey
RCT
PEDro=7
N=28

Population: Mean age: 42.8 yr; Mean time since injury: 35.3 mo; Mean duration of pain: 29.3 mo; Type of pain: neuropathic.
Intervention:
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 wk. Those in the pregabalin group received an initial dose of 150mg/day which was titrated to a max of 600mg/day by the 4th wk. These dosages were maintained for 8 wk. Patients then underwent a 2 wk washout period and were crossed over to the alternative group.
Outcome Measures:
Visual Analog Scale (VAS), Neuropathic Pain Scale(NPS).
  1. No significant difference in VAS between gabapentin and pregabalin.
Effect Sizes

Rintala et al. 2007
USA
P
EDro=10
RCT
N=38

Population: Mean age: 42.6 yr; Gender: males=20, females=2; Injury etiology: SCI=22, other=16; Level of injury: paraplegia=7, tetraplegia=12; Level of severity: AIS A-C=19, AIS D=3; Mean time since injury: 12.6 yr; Mean duration of pain: 7.3 yr. Type of pain: neuropathic.
Intervention: 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 wk 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
PEDro=9
RCT Crossover
N=20

Population: Age range: 23-62 yr; Gender: males=13, females=7; Duration of pain range: 6-45 mo; Type of pain: neuropathic.
Intervention: 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 (NPS), Visual analog scale (VAS), 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).
Effect Sizes

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

Population: Age range: 27-47 yr; Gender: males=6, females=1; Level of injury: C2-T7; Time since injury range: 1 mo-20 yr. Type of pain: neuropathic.
Intervention: Subjects with neuropathic pain were treated with gabapentin or placebo.
Outcome Measures: Neuropathic Pain Scale (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; Level of severity: complete, incomplete; Mean duration of pain: 10 yr. Type of pain: neuropathic.

Intervention: 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).

Putzke et al. 2002
USA
Observational
N=21

Population: Gender: males=16, females=5; Level of injury: paraplegia=14, tetraplegia=7; Level of severity: incomplete=16, complete=5; Type of pain: neuropathic.

Intervention: Participants were asked to complete a survey (or interview).

Outcome Measures: Numeric Rating Scale (NRS).

  1. 67% of patients reported having had a favourable response to gabapentin.
  2. Among those reporting a favourable response, side effects were forgetfulness & sedation.
  3. Among those interviewed a second time, most who reported a favourable response were using other medications and gabapentin for pain.
  4. Side effects like sedation and forgetfulness were common.

Pregabalin

Min et al. 2016
South Korea
RCT Crossover
PEDro=6
N=55

Population: Mean age: 51.7 yr; Gender: males=44, females=11; Level of injury: paraplegia=29, quadriplegia=26; Level of severity: incomplete=45, complete=10; Mean time since injury: 2458 days; Type of pain: neuropathic.
Intervention: Participants received pregabalin (300mg/day) and oxcarbazepine (300mg, 2x/day), each for 1-2 wk, 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 (VAS-PI) (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.
Effect Sizes

Kaydok et al. 2014
Turkey
RCT
PEDro=7
N=28

Population: Mean age: 42.8 yr; Mean time since injury: 35.3 mo; Mean duration of pain: 29.3 mo; Type of pain: neuropathic.
Intervention: 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 wk. Those in the pregabalin group received an initial dose of 150mg/day which was titrated to a max of 600mg/day by the 4th wk. These dosages were maintained for 8 wk. Patients then underwent a 2 wk washout period and were crossed over to the alternative group.
Outcome Measures: Visual Analog Scale (VAS), Neuropathic Pain Scale(NPS).
  1.  No significant difference in VAS between gabapentin and pregabalin.
Effect Sizes

Cardenas et al. 2013
USA
PEDro=10
RCT
N=219

Population: Mean age=45.7yrs; Gender: Male=176; Female=43
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 (DAAC) 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: Level of injury: paraplegia=19, tetraplegia=7; Level of severity: AIS A=33, B, C and D=14; Type of pain: neuropathic.
Intervention: Patients were randomly placed into three groups: pharmacological group (Ph) received 600 mg/day of pregabalin. The pharmacological and osteopathic (PhO) group received 600 mg/day of pregabalin and osteopathical treatment once a wk for the first mo, once every fortnight for the second mo, once during the third month all for 45 min each by an osteopathic physician. The osteopathic group (OMT) 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).
Effect Sizes Effect Sizes

Vranken et al. 2008
Netherlands
PEDro=9
RCT
N=40

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

Sidall et al. 2006
Australia
P
EDro=9
RCT
N=137

PopulationMean 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.
Effect Sizes

Carbamazepine

Salinas et al. 2012
Colombia
RCT
PEDro=9
NInitial=46, NFinal=44

Population: Mean age: 36 yr; Gender: males=42, females=4; Level of injury: paraplegia=28, quadriplegia=18; Level of severity: incomplete=13, complete=33; Mean time since injury: <2wk.
Intervention: Individuals without neuropathic pain were randomized to receive carbamazepine (600mg/d, n=24) or placebo (control, n=22) for 1 mo. Outcomes were assessed pre-and post treatment, and at 3 and 6 mo 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 3 mo, 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 6 mo, 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.
Effect Sizes

Min et al. 2016
South Korea
RCT Crossover
PEDro=6
N=55

Population: Mean age: 51.7 yr; Gender: males=44, females=11; Level of injuryparaplegia=29, quadriplegia=26; Level of severity: incomplete=45, complete=10; Mean time since injury: 2458 days; Type of pain: neuropathic.
Intervention:
Participants received pregabalin (300mg/day) and oxcarbazepine (300mg, 2x/day), each for 1-2 wk, 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 (VAS-PI) (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.
Effect Sizes

Lamotrigine

Finnerup et al. 2002
Denmark
P
EDro=10
RCT
N=30

Population: SCI patients with pain at or below the level of injury; Type of pain: neuropathic.
Intervention: 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: Change in median pain score from baseline wk to the last wk of treatment, 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
PEDro=7
RCT
N=36

Population: Mean age: 52.8 yr; Gender: males=29, females=7; Level of injury: C=13, T=19, L=4; Level of severity: AIS A=13, AIS B=2, AIS C=3, AIS D=18; Type of pain: at level=17, below level=31.
Intervention: Patients were randomized into two 5 wk treatment groups receiving either levetiracetam or placebo tablets. After a 1 wk washout period, individuals were crossed over
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
PEDro=5
RCT
N=20

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

Note: AIS=ASIA Impairment Scale

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