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Oxcarbazepine for neuropathic pain

  1. Muke Zhou1,
  2. Ning Chen1,
  3. Li He1,*,
  4. Mi Yang1,
  5. Cairong Zhu2,
  6. Fengbo Wu3

Editorial Group: Cochrane Neuromuscular Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 30 OCT 2012

DOI: 10.1002/14651858.CD007963.pub2


How to Cite

Zhou M, Chen N, He L, Yang M, Zhu C, Wu F. Oxcarbazepine for neuropathic pain. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD007963. DOI: 10.1002/14651858.CD007963.pub2.

Author Information

  1. 1

    West China Hospital, Sichuan University, Department of Neurology, Chengdu, Sichuan, China

  2. 2

    School of Public Health, Sichuan University, Epidemic Disease & Health Statistics Department, Sichuan, Chengdu, China

  3. 3

    West China Hospital, Sichuan University, Department of Pharmacy, Chengdu, Sichuan, China

*Li He, Department of Neurology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, China. heli2003new@126.com.

Publication History

  1. Publication Status: New
  2. Published Online: 28 MAR 2013

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Characteristics of included studies [ordered by study ID]
Beydoun 2006

MethodsA multicentre, double-blind, placebo-controlled, randomised, parallel-group, dose-ranging study to evaluate the efficacy and safety of three daily doses of oral oxcarbazepine (600, 1200, and 1800 mg) as monotherapy for painful diabetic neuropathy. It consisted of a 2-week pre-randomisation screening phase and a 16-week double-blind phase (including a 4-week titration period and a 12-week maintenance period).


ParticipantsA total of 347 participants with painful diabetic neuropathy were included and randomised in a 1:1:1:1 ratio to oxcarbazepine 600 mg/day (300 mg bid; n = 83), 1200 mg/day (600 mg bid; n = 87), 1800 mg/day (900 mg bid; n = 88), or placebo (n = 89).

Gender (% male) 600 mg, 900 mg, 1200 mg oxcarbazepine and placebo: 60%; 52%; 53%; 56%. Mean age, years (SD) 600 mg, 900 mg, 1200 mg oxcarbazepine and placebo: 61.1 (10.7); 60.3 (10.3); 59.3 (9.3); 62.1 (10.3).

Inclusion criteria: men and non-pregnant women; 18 years of age or older; with a diagnosis of diabetes mellitus (type 1 or 2) and pain attributed to diabetic neuropathy for 6 months to 5 years; with a pain rating score of at least 50 units on a 100-unit VAS at the screening visit, stable glycaemic control (as evidenced by a HbA1c level of ≤11% at baseline), and baseline serum sodium levels of 35 mmol/L or higher; the VAS must have averaged at least 40 units during the pre-randomisation phase, with < 25% variability in the last 7 days prior to randomisation.

Exclusion criteria included: people with other types of pain; clinically significant medical or psychiatric illnesses; a prior history of hyponatraemia or non-compliance; drug or alcohol abuse in the preceding year; amputations other than the toes; treatment with lithium or monoamine oxidase inhibitors; previous treatment with oxcarbazepine; a history of sensitivity to carbamazepine or its metabolites.


InterventionsParticipants received the initiated dose of 300 mg oxcarbazepine (one tablet) or matching placebo daily for three days, then one tablet bid from the fourth day. Thereafter, the dose was increased by one tablet every 5 days until the target dose of 600 mg/day, 1200 mg/day or 1800 mg/day for each group was reached. Dose reductions due to tolerability problems were allowed at any time during the study.


OutcomesThe primary outcome was change in mean VAS score from baseline to the end of the study (16 weeks).

Secondary outcomes included participants' Global Assessment of the Therapeutic Effect, onset of therapeutic effect, durability of treatment effect, sleep disturbances, and quality of life.

Safety was also assessed during the screening and double-blind treatment phases, consisting of monitoring vital signs, neurological and physical examinations, laboratory parameters, spontaneous reports of adverse events, and serious adverse events.


NotesTrial conducted between November 2001 and September 2003 at 37 centres across the United States. This study was funded by Novartis Pharmaceuticals Inc.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskThe study is similar to the Dogra study so it is likely that randomisation was adequate.

Allocation concealment (selection bias)Low riskThe study is similar to the Dogra study so it is likely allocation concealment have been performed.

Blinding (performance bias and detection bias)
All outcomes
Low riskIt was stated that there was a double-blind phase, and matching placebos were used.

Incomplete outcome data (attrition bias)
All outcomes
High riskMissing data of both groups were clearly described and an ITT analysis was performed. The number of withdrawals was not balanced across different doses of oxcarbazepine and placebo groups (respectively 16/83 at 600 mg/day oxcarbazepine, 34/87 at 1200 mg/day, 48/88 at 1800 mg/day, and 17/89 of participants on placebo), especially those due to adverse events (respectively 9/83, 20/87, 36/88, and 6/89 in each group).

Selective reporting (reporting bias)Low riskOutcomes listed in the methods section were all reported.

Other biasLow riskNo other potential bias was found.

Dogra 2005

MethodsA multicentre, placebo-controlled, double-blind, parallel-group study. It consisted of three phases: a 2-week pre-randomisation screening phase, a 18-week double-blind treatment phase (including a 4-week titration period, a 12-week maintenance period and a 2-week follow-up period), and a 52-week open-label extension phase. The primary efficacy analysis was performed on the ITT population.


ParticipantsA total of 289 patients were screened for the study, and 146 participants were included to be randomised to either oxcarbazepine (69 participants) or placebo (77 participants).

Gender (% male): oxcarbazepine 54%; placebo 62%.

Mean age (SD), years: oxcarbazepine 59.7 (10.4); placebo 60.5 (8.1).

The inclusion criteria were: male or female outpatients; 18 years of age or older; an established clinical diagnosis of diabetes mellitus (type 1 or 2); stable diabetic control as evidenced by (a) HbA1c level 11% or less at baseline, (b) average HbA1c over the 6 months prior to study entry within 1 unit (%) of baseline; a history of neuropathic pain between 6 months and 5 years in duration; pain rating of ≥ 50 units on the VAS at the first screening visit; average pain score of 50 units over 4 of the last 7 days prior to randomisation; 25% or less variation in the severity of the pain in the 7 days prior to randomisation, as assessed from the electronic diary information recorded daily during the screening phase.

The exclusion criteria were: presence of other pain that could confound assessment of neuropathic pain of diabetic origin; currently or had previously taken oxcarbazepine; presence of skin lesions that could affect the ability to assess their neuropathic pain, or if they had undergone amputations (other than toes); history of renal insufficiency (creatinine clearance < 30 mL/min); hyponatraemia (serum sodium levels < 135 mmol/L); chronic infectious disease; known hypersensitivity to oxcarbazepine or carbamazepine.

A total of 40 participants were withdrawn during the double-blind phase, for the following reasons: adverse effects, protocol violation, unsatisfactory effect, patient withdrew consent, lost to follow-up or administrative reasons. However, all of them were included in the ITT analyses.


InterventionsOral oxcarbazepine was initiated at 300 mg/day, increased 3 days later to 300 mg twice a day, and then titrated in 300 mg increments every 5 days as tolerated up to a maximum dose of 900 mg twice a day (1800 mg/day) over the 4-week titration period. There followed a 12-week maintenance period. The mean oxcarbazepine dose during the maintenance period was 1445 mg/day. In the control group, matched placebos were administered in the same way.


OutcomesThe primary outcome was the average daily VAS score for pain severity during the last week of double-blind treatment compared with baseline.

The secondary outcomes were the patient's global assessment of therapeutic effect, onset of therapeutic effect, durability of treatment effect, sleep disturbances and quality of life.

Safety assessments during the screening and double-blind treatment phases were also performed, including monitoring vital signs, neurological and physical status, laboratory parameters, spontaneous reports of adverse events and serious adverse events.


NotesConducted in 22 diabetes and neurology pain clinics and research centres in the USA and Canada. This study was funded by Novartis Pharmaceuticals Inc.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants were randomised in a 1:1 ratio to each group; "the randomisation scheme was created by Novartis Drug Supply Management using a validated system that automates the random assignment of treatment groups to randomisation numbers".

Allocation concealment (selection bias)Low riskIt was stated in the article that "the randomization scheme was created by Novartis Drug Supply Management using a validated system that automates the random assignment of treatment groups to randomization numbers. The randomization numbers were assigned to centres in blocks", so allocation concealment was likely to have been performed.

Blinding (performance bias and detection bias)
All outcomes
Low riskIn the double-blind phase, matched placebos were used and administered in the same way with the same initiated doses and increments.

Incomplete outcome data (attrition bias)
All outcomes
High riskThe numbers of withdrawals were not balanced across groups (25/69 of oxcarbazepine participants versus 15/77 of placebo participants), especially those due to adverse events (19/69 versus 6/77).

Selective reporting (reporting bias)Low riskOutcomes listed in the methods section were all reported.

Other biasLow riskNo other potential bias was found.

Grosskopf 2006

MethodsMulticentre, double-blind, placebo-controlled study, with a 2-week pre-randomisation screening phase and a 16-week double-blind treatment phase (including a 4-week titration period and a 12-week maintenance period).


ParticipantsA total of 141 participants were randomised to oxcarbazepine (n = 71) or placebo (n = 70).

Gender (% male): oxcarbazepine 40 (56); placebo 38 (54); all 78 (55). Mean age, years (SD): oxcarbazepine 60.8 (10.6); placebo 61.4 (10.6); all 61.1 (10.5).

The inclusion criteria included: males and non-pregnant, non-lactating females aged 18 years or older with established clinical diagnosis of diabetes mellitus type 1 or 2; with a history of neuropathic pain for 6 months to 5 years prior to study entry; stable diabetic control defined as HbA1c ≤ 11% at baseline and an average HbA1c within 1% of baseline over the 6 months prior to study entry; with a pain rating of 50 units or more on the 100-unit VAS at the first screening visit, and a mean VAS score of 40 units or more over 4 of the last 7 days prior to randomisation and with < 25% variability during the last 7 days prior to randomisation.
Exclusion criteria included: patients with pain that could confound assessment of neuropathic pain of diabetic origin; previous or current oxcarbazepine treatment; skin conditions that could affect assessment of pain; amputations (other than toes); renal insufficiency; serum sodium levels < 135 mmol/L; chronic infectious disease and known hypersensitivity to oxcarbazepine or carbamazepine.


InterventionsIn the treatment group, oral oxcarbazepine was initiated at 300 mg daily and titrated over 4 weeks to tolerability or maximum dose of 600 mg twice per day (1200 mg/day), and the dose remained unchanged throughout the maintenance period, except for dose reductions in the event of poor tolerability. Mean oxcarbazepine dose during the maintenance period was 1091 mg/day. In the control group, matched placebos were administered in the same way with the same initiated doses and increments.


OutcomesThe primary outcome was the average VAS score for pain severity for the final week of double-blind treatment compared with baseline. Secondary efficacy variables were participants' global assessment of therapeutic effect, onset of therapeutic effect, durability of therapeutic effect, sleep disturbances and quality of life.


NotesConducted in 22 centres in the USA, Germany and the UK. This study was funded by Novartis Pharmaceuticals Inc.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskIt was stated that participants were randomly assigned in a 1:1 ratio to each group; the detailed method of sequence generation was not specified in this article, but it was said that design of this study was similar to the Dogra study (Dogra 2005), so randomisation numbers were likely to have been used as well.

Allocation concealment (selection bias)Unclear riskThe method of allocation concealment was not described, but it was said that design of this study was similar to the Dogra study (Dogra 2005), so allocation concealment was likely to have been performed.

Blinding (performance bias and detection bias)
All outcomes
Low riskIt was stated to be a double-blind study, and matched placebos were used.

Incomplete outcome data (attrition bias)
All outcomes
High riskMissing data in both groups were clearly described and an ITT analysis was performed. But the numbers of withdrawals were not balanced across groups (29/71 of oxcarbazepine participants versus 17/70 of placebo participants), especially those due to adverse events (18/71 versus 4/70).

Selective reporting (reporting bias)Low riskOutcomes listed in the methods section were all reported.

Other biasLow riskNo other potential bias was found.

Novartis 2004

MethodsMulticentre, double-blind, randomised, placebo-control study, with a 2-week pre-randomisation screening phase and a 16-week double-blind treatment phase (including a 4-week titration period and a 12-week maintenance period).


ParticipantsA total of 145 participants were randomised to oxcarbazepine (n = 71) or placebo (n = 74).

Gender (F:M): oxcarbazepine 43:28; placebo 36:38.
Mean age, years (SD): oxcarbazepine 53.8 (13.67); placebo 55.1 (12.33).

The inclusion criteria included: males or females aged 18 years or more with a diagnosis of radiculopathy and evidence of motor deficit or reflex loss on examination, a history of neuropathic pain for at least 6 months and a VAS score of 50 or more.

Exclusion criteria included: patients with prior oxcarbazepine experience, history of hyponatraemia or renal insufficiency (creatinine clearance < 30 mL/min), a known sensitivity to carbamazepine, or were being treated with lithium or monoamine oxidase inhibitors.


InterventionsIn the treatment group, oral oxcarbazepine was initiated at 300 mg daily and titrated over 4 weeks to a maximum target dose of 1800 mg daily, and the final dose remained unchanged throughout the maintenance period.

In the control group, matching placebo tablets were administered in the same way.


OutcomesThe primary outcome was the average VAS score for pain severity during the last week of double-blind treatment. Secondary efficacy variables were participants' global assessment of therapeutic effect, durability of treatment effect, onset of therapeutic effect, proportion of days rescue medication administered during the double-blind phase, average daily dose of rescue medication administered during the double-blind phase.


NotesConducted in 40 centres: 3 in Great Britain and 37 in the US. This study was funded by Novartis Pharmaceuticals Inc. Study number CTRI476G2304.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRelevant information could not be obtained.

Allocation concealment (selection bias)Unclear riskRelevant information could not be obtained.

Blinding (performance bias and detection bias)
All outcomes
Low riskStated to be a double-blind study, and matched placebos were used.

Incomplete outcome data (attrition bias)
All outcomes
High riskMissing data in both groups were clearly described and an ITT analysis was performed, but data of one participant in the oxcarbazepine group was not included in the ITT analysis and the reason for this was not clarified. Additionally, the numbers of withdrawals were not balanced across groups (40/71 of oxcarbazepine participants versus 33/74 of placebo participants), especially those due to adverse events (30/71 versus 11/74) or lack of efficacy (4/71 versus 15/74).

Selective reporting (reporting bias)Low riskNo data from this trial were published, but all outcomes listed in the methods section were reported on the Novartis website (Novartis database).

Other biasLow riskNo other potential bias was found.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Beydoun 2002Available only as an abstract of a double-blind RCT, comparing efficacy and safety of oxcarbazepine versus carbamazepine for the treatment of 46 participants with new-onset trigeminal neuralgia. However, we were unable to obtain data for our prespecified outcomes from the published abstract. We could not find the full text of this article or retrieve any useful data from the authors and pharmaceutical company although we have attempted to.

Beydoun 2007A report of two open-label studies (involving 497 and 97 participants, respectively) to evaluate the long-term safety and tolerability of oxcarbazepine for diabetic neuropathy, without a control group.

Gong 2010A non-blind trial investigating 99 participants with trigeminal neuralgia, aiming to compare the efficacy and safety of oxcarbazepine with carbamazepine and topiramate.

Hu 2010A non-blind trial investigating 369 participants with trigeminal neuralgia, aiming to compare the efficacy and safety of oxcarbazepine to carbamazepine.

Li 2011A non-blind trial investigating 78 participants with trigeminal neuralgia, aiming to compare the efficacy and safety of oxcarbazepine to carbamazepine.

Lindström 1987Double-blind cross-over trial in which 15 participants with trigeminal neuralgia received oxcarbazepine or carbamazepine for only 3 weeks. The trial had a short follow-up duration, less than the minimum (six weeks) we specified in the protocol.

Rémillard 1994An open-label study with 20 participants investigating efficacy of oxcarbazepine for intractable trigeminal neuralgia, without a control group.

Venancio-Ramirez 2004Randomised trial of gabapentin and oxcarbazepine in 60 participants with postherpetic neuropathy. Four-week observation period too short to meet our inclusion criteria.

Zhou 2010A non-blind trial investigating 64 participants with trigeminal neuralgia, aiming to compare the efficacy of oxcarbazepine to carbamazepine.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Brainer-Lima 2003

MethodsRandomised assignment to either oxcarbazepine or amitriptyline.

ParticipantsTwenty participants (12 women, 8 men, aged 28 to 85 years) with cancer-related neuropathic pain (neoplastic compression or infiltration of the nerves) treated with opiates.

InterventionsParticipants were randomly assigned to either oxcarbazepine (10) or amitriptyline (10) and opioids were discontinued gradually. The opiate reduction was initiated at the end of radiotherapy/chemotherapy protocols. Opiate reduction was a rate of 10% less total opiate dose each other day or as tolerability allowed.

OutcomesPain relief measured using a 100 mm Visual Analogue Scale (VAS)

Presence and severity of opioid withdrawal symptoms

NotesFurther information required. Unclear from the abstract whether opiate dosage was the same in each group.

Liebel 2001

MethodsDouble-blind multicentre randomised trial.

ParticipantsForty-eight participants aged 40 years or older with newly diagnosed untreated trigeminal neuralgia.

InterventionsParticipants were randomly allocated to either oxcarbazepine or carbamazepine group. The starting dose was 300 mg twice daily for oxcarbazepine and 200 mg twice daily for carbamazepine. Dosage was increased gradually up to achieve the best therapeutic effect combined with satisfactory tolerability.

OutcomesNumber of days with pain since the last visit

Change in nature of pain

Mean number of attacks of pain per day

Mean number of attacks of pain per week

Severity of pain

Global assessment of therapeutic efficacy

NotesOnly available as an abstract, which is not sufficiently detailed for assessment. Further information required.

 
Characteristics of ongoing studies [ordered by study ID]
NCT01302275

Trial name or titleOxcarbazepine for the treatment of chronic peripheral neuropathic pain (IMIOXC)

MethodsA randomised, double-blind, placebo-controlled trial.

ParticipantsThe estimated number enrolled participants is 120.

Inclusion criteria: aged 18 years or older; both genders; definite or probable neuropathic pain; diagnosis of polyneuropathy, postherpetic neuralgia or peripheral nerve injury; pain duration > 3 months; pain rating at baseline ≥ 4 point NRS; informed consent obtained.

Exclusion criteria: other non-neuropathic pain condition; allergy to oxcarbazepine; renal or hepatic impairment; epilepsy; depression and other serious psychiatric disorders; serious medical condition; previous treatment for neuropathic that cannot be stopped; pregnancy; patients expected not to be able to comply with study protocol; treatment with anticonvulsants, antidepressants or opioids.

InterventionsIn the experimental group, oxcarbazepine capsules (300 mg) are gradually increased during 21 days from 300 mg daily to 2400 mg, and kept on that dose (2400 mg) for three weeks. In the control group, identical placebo capsules are increased gradually from 1 daily to 8 daily.

OutcomesPrimary outcome measures: total pain rated on numeric rating scale.

Secondary outcome measures: response defined as at least 50% reduction in pain score; Neuropathic Pain Symptom Inventory; Patient Global Impression of Change; rating of evoked pain; sleep disturbance; quality of life; use of escape medication

Starting dateFebruary 2011

Contact informationDanish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark, 8000. Contact person: Nanna B Finnerup, MD. +45 89493455 finnerup@ki.au.dk; Troels S Jensen, MD. +45 89494137 tsjensen@ki.au.dk.

Department of Neurology, Odense University Hospital. Odense, Denmark, DK-5000. Contact person: Søren H Sindrup, MD. +45 65412471 soeren.sindrup@ouh.regionsyddanmark.dk; Dyveke T Demant, MD. +45 65412485 dyveke.demant@gmail.com

NotesSponsored by Odense University Hospital.

 
Comparison 1. Oxcarbazepine versus placebo for painful diabetic neuropathy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Reduction in patient-reported pain scores by 50% from the baseline1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 16 weeks after starting the treatment
1146Risk Ratio (M-H, Fixed, 95% CI)1.91 [1.08, 3.39]

 2 Reduction in patient-reported pain scores by 30% from the baseline1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 16 weeks after starting the treatment
1146Risk Ratio (M-H, Fixed, 95% CI)1.57 [1.01, 2.44]

 3 Patients' global impression of their change in pain2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 All improved patients after 16-week treatment
1146Risk Ratio (M-H, Fixed, 95% CI)1.80 [1.32, 2.45]

    3.2 Patients with obvious or significant improvement after 16-week treatment
2493Risk Ratio (M-H, Fixed, 95% CI)1.46 [1.13, 1.88]

 4 Adverse effects3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 Adverse events leading to withdrawals
3634Risk Ratio (M-H, Fixed, 95% CI)3.83 [2.29, 6.40]

    4.2 Serious adverse events
3634Risk Ratio (M-H, Fixed, 95% CI)3.65 [1.45, 9.20]

 
Comparison 2. Oxcarbazepine versus placebo for neuropathic pain due to radiculopathy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Reduction in patient-reported pain scores by 50% from baseline1145Risk Ratio (M-H, Fixed, 95% CI)0.52 [0.22, 1.22]

 2 Patients' global impression of therapeutic effect1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 All improved patients after 16-week treatment
1145Risk Ratio (M-H, Fixed, 95% CI)1.35 [0.92, 1.98]

    2.2 Patients with obvious or significant improvement after 16-week treatment
1145Risk Ratio (M-H, Fixed, 95% CI)1.61 [0.81, 3.20]

 3 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 All kinds of adverse events
1145Risk Ratio (M-H, Fixed, 95% CI)1.22 [1.07, 1.39]

    3.2 Adverse events leading to withdrawals
1145Risk Ratio (M-H, Fixed, 95% CI)2.84 [1.55, 5.23]

    3.3 Serious adverse events
1145Risk Ratio (M-H, Fixed, 95% CI)3.13 [0.65, 14.98]

 
Comparison 3. Subgroup analysis: different daily doses of oxcarbazepine versus placebo for painful diabetic neuropathy

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Patients with obvious or significant improvement after 16-week treatment2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 600 mg oxcarbazepine daily
1172Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.66, 1.45]

    1.2 1200 mg oxcarbazepine daily
1176Risk Ratio (M-H, Fixed, 95% CI)1.36 [0.97, 1.92]

    1.3 1800 mg oxcarbazepine daily
2323Risk Ratio (M-H, Fixed, 95% CI)1.60 [1.21, 2.11]

 2 Adverse effects leading to withdrawals3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 600 mg oxcarbazepine daily
1172Risk Ratio (M-H, Fixed, 95% CI)1.61 [0.60, 4.32]

    2.2 1200 mg oxcarbazepine daily
2317Risk Ratio (M-H, Fixed, 95% CI)3.83 [1.97, 7.41]

    2.3 1800 mg oxcarbazepine daily
2323Risk Ratio (M-H, Fixed, 95% CI)4.83 [2.68, 8.70]

 3 Serious adverse effects3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 600 mg oxcarbazepine daily
1172Risk Ratio (M-H, Fixed, 95% CI)2.14 [0.20, 23.21]

    3.2 1200 mg oxcarbazepine daily
2317Risk Ratio (M-H, Fixed, 95% CI)4.68 [1.38, 15.95]

    3.3 1800 mg oxcarbazepine daily
2323Risk Ratio (M-H, Fixed, 95% CI)4.55 [1.55, 13.37]

 
Summary of findings for the main comparison. Oxcarbazepine versus placebo for painful diabetic neuropathy

Oxcarbazepine versus placebo for painful diabetic neuropathy

Patient or population: people with painful diabetic neuropathy
Settings: hospitals and clinics
Intervention: oxcarbazepine

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Placebooxcarbazepine

Reduction in patient-reported pain scores by 50% from the baseline
Visual Analogue Scale
Follow-up: mean 16 weeks
182 per 1000348 per 1000
(197 to 617)
RR 1.91
(1.08 to 3.39)
146
(1 study)
⊕⊕⊕⊝
moderate1
NNTB 6.0 (95% CI 3.3 to 41.0)

Reduction in patient-reported pain scores by 30% from the baseline
Visual Analogue Scale
Follow-up: mean 16 weeks
286 per 1000449 per 1000
(289 to 698)
RR 1.57
(1.01 to 2.44)
146
(1 study)
⊕⊕⊕⊝
moderate1
NNTB 6.1 (95% CI 3.1 to 113.6)

Patients with obvious or significant improvement after 16 weeks treatment
the patient's global assessment of therapeutic effect
Follow-up: mean 16 weeks
301 per 1000439 per 1000
(340 to 566)
RR 1.46
(1.13 to 1.88)
493
(2 studies)
⊕⊕⊕⊝
moderate1,2,3
NNTB 6.4 (95% CI 4.1to 14.4)

Serious adverse events
clinical manifestation
Follow-up: mean 16 weeks
25 per 100091 per 1000
(36 to 230)
RR 3.65
(1.45 to 9.2)
634
(3 studies)
⊕⊕⊕⊝
moderate1,2,3
NNTH 17.4 (95% CI 11.0 to 42.0).

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio; NNTB: number needed to treat for an additional beneficial outcome; NNTH: number needed to treat for an additional harmful outcome.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 The numbers of withdrawal were not balanced across groups, especially those due to adverse events.
2 The placebo responses of included trials showed considerable inconsistency.
3 Results of each daily dose group suggested trends of dose-effect relationships both for global recovery and adverse events: the highest daily dose (1800 mg/day) of oxcarbazepine had the best effect on pain relief but also led to the most adverse events, especially serious ones.