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Non-antiepileptic drugs for trigeminal neuralgia

  1. Jingjing Zhang1,
  2. Mi Yang1,
  3. Muke Zhou1,
  4. Li He1,*,
  5. Ning Chen1,
  6. Joanna M Zakrzewska2

Editorial Group: Cochrane Neuromuscular Disease Group

Published Online: 3 DEC 2013

Assessed as up-to-date: 20 MAY 2013

DOI: 10.1002/14651858.CD004029.pub4


How to Cite

Zhang J, Yang M, Zhou M, He L, Chen N, Zakrzewska JM. Non-antiepileptic drugs for trigeminal neuralgia. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD004029. DOI: 10.1002/14651858.CD004029.pub4.

Author Information

  1. 1

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

  2. 2

    Eastman Dental Institute, Oral Medicine, London, UK

*Li He, Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Xiang 37#, Chengdu, Sichuan, 610041, China. heli2003new@126.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 3 DEC 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 
Summary of findings for the main comparison. Tizanidine versus carbamazepine for trigeminal neuralgia

Tizanidine versus carbamazepine for trigeminal neuralgia

Patient or population: patients with trigeminal neuralgia
Settings: unclear, Norway
Intervention: tizanidine versus carbamazepine

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

Assumed riskCorresponding risk

CarbamazepineTizanidine

Immediate improvement in pain relief

Number of participants improved (good/very good efficacy) on a self assessed categorical 'overall efficacy score' (0 = no efficacy to 4 = very good)
Follow-up: 21 days (end of treatment)
667 per 1000200 per 1000
(33 to 1000)
RR 0.3
(0.05 to 1.89)
11
(1 study)
⊕⊕⊝⊝
low1,2
-

50% pain reduction 12 weeks after the start of treatment

Not measured
See commentSee commentNot estimable-See commentOnly trial of this intervention was of short (21 days) duration

Quality of life assessment 12 weeks after the start of treatment

Not measured
See commentSee commentNot estimable-See commentOnly trial of this intervention was of short (21 days) duration

Adverse effects (not reported)See commentSee commentNot estimable11

(1 study)
See commentAdverse event data collected but no details provided. "Tizanidine was generally better tolerated than carbamazepine, and few side effects were noted"2

*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

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.

 1Quality of the evidence downgraded for imprecision. This trial had relatively few patients and thus the measure of effect has wide CIs.
2Further downgrading for risk of bias and potential indirectness. Three participants taking tizanidine discontinued taking the optimal dose: two because of lack of efficacy, one due to unrelated disease. Other potential risks of bias were from unclear randomisation, allocation concealment and blinding procedures. Investigators used a non-validated outcome scale.

 Summary of findings 2 Tocainide versus carbamazepine for trigeminal neuralgia

 Summary of findings 3 Proparacaine hydrochloride 0.5% eye drops versus placebo for trigeminal neuralgia

 Summary of findings 4 Pimozide versus carbamazepine for trigeminal neuralgia

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Trigeminal neuralgia was defined by the International Association for the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve (Merskey 1994). The International Headache Society (Anonymous 2004) set the following criteria for trigeminal neuralgia.

A. Paroxysmal attacks of pain lasting from a fraction of a second to two minutes, affecting one or more divisions of the trigeminal nerve and fulfilling criteria B and C.
B. Pain that has at least one of the following characteristics:

  1. intense, sharp, superficial or stabbing;
  2. precipitated from trigger areas or by trigger factors.

C. Attacks are stereotyped in the individual patient.
D. There is no clinically evident neurological deficit.
E. Not attributed to another disorder.

The diagnosis of trigeminal neuralgia is based on clinical findings and there have not been any case controlled studies to validate diagnostic methods. A careful clinical history and examination can distinguish between trigeminal neuralgia and other disorders that cause facial pain (Zakrzewska 2002a).

Trigeminal neuralgia has an annual incidence of three to five per 100,000 people. It is more common in women than men (age-adjusted ratio: 1.74:1) and is most widespread in people aged 50 to 69 years. Attacks are commonly on the right side (Katusic 1990; Yoshimasu 1972). More recent data from primary care practices suggest that the incidence may be around 12.7 per 100,000 (Koopman 2009).

The aetiology is not clear. Compression of the trigeminal nerve root, at or near the dorsal root entry zone, by a blood vessel is a major causative or contributing factor (Devor 2002). Compression is not always found and it is then necessary to look for other causes. In a few cases trigeminal neuralgia is due to multiple sclerosis. Other rare causes include infiltration of the nerve root, trigeminal ganglion or nerve by a tumour or amyloid, and small infarcts or angiomas in the pons or medulla (Cheng 1993). Once all of these possibilities have been excluded, there remain a small proportion of patients in whom the aetiology is undetermined (Nurmikko 2001). Obermann has shown that atypical type trigeminal neuralgia may be the result of central changes (Obermann 2007). The pain of idiopathic trigeminal neuralgia is indistinguishable from that caused by a demonstrable structural lesion other than vascular compression.

Spontaneous remission of trigeminal neuralgia is common but the disorder is often progressive. Remission may last for months or even years but as the attacks become more frequent, the patient may develop persistent pain between episodes. Attacks may come in clusters and can completely disrupt activities of daily living if left untreated (Katusic 1990; Zakrzewska 2002b).

Antiepileptic drugs have been used in pain management since the 1960s. The clinical impression is that they are useful for neuropathic pain, especially when the pain is lancinating or burning (Jacox 1994). Based on two placebo-controlled studies of carbamazepine in trigeminal neuralgia, a Cochrane systematic review deduced a number needed to treat to benefit of 1.9 (95% confidence interval (CI) 1.4 to 2.8) (Wiffen 2011). In one randomised controlled trial (RCT), lamotrigine was effective as an add-on therapy (Zakrzewska 1997). Little evidence supports a beneficial role of other antiepileptic drugs such as clonazepam, phenytoin and sodium valproate (Sindrup 2002). Gabapentin has been evaluated in a small RCT (Lemos 2008) and pregabalin in a cohort study (Obermann 2008). The long-term effects of carbamazepine have been evaluated in only one study, which showed either loss of effect or poor tolerability in half the participants after 10 years (Taylor 1981). In a long-term cohort study of oxcarbazepine, pain increased with progression of disease severity and the drug became less effective in long-term pain control (Zakrzewska 2002b).

Non-antiepileptic drugs have been used to treat trigeminal neuralgia since the 1970s. Conventional analgesics such as aspirin, codeine and non-steroidal anti-inflammatory drugs are not used since experience suggests that they are not helpful. There has been a reported RCT on the use of dextromethorphan, an antitussive (cough suppressant) drug with analgesic effects, in patients with mixed facial neuralgias (Gilron 2000). Other drugs that are used include baclofen, pimozide, racemic ketamine, proparacaine, tocainide, misoprostol and capsaicin. Baclofen is a gamma-aminobutyric acid receptor agonist that has the least serious adverse effects (Steardo 1984). Pimozide is a neuroleptic that has shown significant relief of pain when compared with carbamazepine in a double-blind, cross-over trial. Racemic ketamine is an anaesthetic which showed some benefit when treating acute pain but was ineffective for pain lasting more than five years (Mathisen 1995). Topical ophthalmic anaesthetics, such as proparacaine, have been reported to relieve trigeminal neuralgia pain in some patients but not in a randomised trial (Kondziolka 1994). Tocainide is a drug used to prevent cardiac arrhythmias. It has been withdrawn from the market because of bone marrow suppression (Rawson 1998) but was tried in trigeminal neuralgia. Misoprostol is a long-acting prostaglandin E1 analogue which, in an open-label study, relieved trigeminal neuralgia in six of seven participants with definite multiple sclerosis who had failed to respond to conventional pharmacologic therapy (Reder 1995). Use of capsaicin, the pungent component of red pepper, has been reported in two case studies (Fusco 1992). There have been previous systematic reviews of all drugs for trigeminal neuralgia (Sindrup 1999; Zakrzewska 2009). The review in Clinical Evidence (Zakrzewska 2009) is updated every 18 months. International guidelines which used systematic review methodology have also been published (Cruccu 2008; Gronseth 2008). The aim of this review is to systematically review all double-blind RCTs of non-antiepileptic drugs for trigeminal neuralgia. Antiepileptic drugs for trigeminal neuralgia have been included in other Cochrane reviews (Moore 2009; Wiffen 2010a; Wiffen 2010b; Wiffen 2011).

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

To systematically review the efficacy and tolerability of non-antiepileptic drugs for trigeminal neuralgia.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We searched for all double-blinded, randomised controlled trials (RCTs) which lasted for at least two weeks and involved non-antiepileptic drugs in the treatment of trigeminal neuralgia.

 

Types of participants

We included all causes of trigeminal neuralgia, both idiopathic and symptomatic, where the diagnostic criteria were clearly defined.

 

Types of interventions

We included all non-antiepileptic drugs used to achieve analgesia. Non-antiepileptic drugs include: baclofen, pimozide, racemic ketamine, proparacaine, dextromethorphan, tocainide or any other single non-antiepileptic drug in any dose or combination. Comparison interventions were placebo, no treatment or carbamazepine.

The hypotheses below were to be tested.

  1. Therapy A* is more effective in controlling trigeminal neuralgia than placebo treatment.
  2. Therapy A* is more effective in controlling trigeminal neuralgia than no treatment.
  3. Therapy A* is more effective in controlling trigeminal neuralgia than carbamazepine.
  4. Therapy B** is more effective in controlling trigeminal neuralgia than placebo treatment.
  5. Therapy B** is more effective in controlling trigeminal neuralgia than no treatment.
  6. Therapy B** is more effective in controlling trigeminal neuralgia than therapy A.
  7. Therapy B** is more effective in controlling trigeminal neuralgia than carbamazepine.

*Therapy A = baclofen, pimozide, racemic ketamine, proparacaine, tocainide or any other single non-antiepileptic drug.
**Therapy B = combination of any two drugs in therapy A.

 

Types of outcome measures

 

Primary outcomes

The primary outcome was immediate improvement in pain relief evaluated as decreased pain intensity or trigeminal neuralgia score, that is number of attacks per day and their intensity.

 

Secondary outcomes

Secondary outcomes were:

  1. improvement in pain intensity or trigeminal neuralgia score at least 12 weeks after the start of treatment;
  2. the number of participants with 50% pain reduction at least 12 weeks after the start of treatment;
  3. quality of life measured with a validated scale, such as the Short Form 36 Health Survey questionnaire (SF-36) (Ware 1992) at least 12 weeks after the start of treatment; and
  4. adverse effects that were attributable to treatment by two weeks from the start of treatment.

 

Outcomes for inclusion in a 'Summary of findings' table

We included a 'Summary of findings' table to illustrate the findings of the review and our assessment of the quality of evidence for key outcomes:

  • immediate improvement in pain relief;
  • improvement in pain intensity or trigeminal neuralgia score at least 12 weeks after the start of treatment;
  • the number of participants with 50% pain reduction at least 12 weeks after the start of treatment;
  • quality of life measured with a validated scale, such as the Short Form 36 Health Survey questionnaire (SF-36) (Ware 1992) at least 12 weeks after the start of treatment; and
  • adverse effects.

We graded the quality of the evidence from included RCTs as high, moderate, low or very low based on the GRADE criteria. These start from a grading of high for RCTs and reasons for downgrading are: study limitations, consistency of effect, imprecision, indirectness and publication bias. Also, evidence from downgraded RCTs can be upgraded for a large effect size, when all plausible confounding would tend to underestimate the size of the effect or when there is a dose-response gradient (GRADE working group 2004; Schünemann 2011a; Schünemann 2011b).

 

Search methods for identification of studies

 

Electronic searches

We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 May 2013), CENTRAL (2013, Issue 4 in The Cochrane Library), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), LILACS (January 1982 to May 2013), the Chinese Biomedical Retrieval System (1978 to May 2013), ClinicalTrials.gov (http://www.clinicaltrials.gov/) (May 2013) and the World Health Organization International Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/). There were no restrictions on the basis of language. We reviewed the bibliographies of the randomised trials found and contacted the authors and known experts in the field to identify additional published or unpublished data. For the detailed search strategies see Appendix 1 (MEDLINE), Appendix 2 (EMBASE), Appendix 3 (CENTRAL), Appendix 4 (LILACS), Appendix 5 (Chinese Biomedical Retrieval System), Appendix 6 (ClinicalTrials.gov) and Appendix 7 (ICTRP).

 

Searching other resources

In this 2013 update, we searched the following 10 journals in electronic database of Chinese Biomedical Retrieval System rather than by handsearching:

  • Chinese Journal of Neurology;
  • Chinese Journal of Neuroscience;
  • Journal of Apoplexy and Nervous Diseases;
  • Journal of Brain and Nervous Diseases;
  • Journal of Clinical Neurology;
  • Chinese Journal of Nervous and Mental Diseases;
  • Chinese Journal of Clinical Neurosciences;
  • Chinese Journal of Pain Medicine;
  • Chinese Journal of New Drugs and Clinical Remedies;
  • Chinese Journal of Neuromedicine.

We also searched the retrieved articles for any other potentially missing studies and a personal reference database collected over 20 years (JZ).

 

Data collection and analysis

 

Selection of studies

Two review authors (JZ and NC) scrutinised the titles and abstracts identified from the updated searches. We obtained the full text of any study of possible relevance for independent assessment. The authors decided which trials fitted the inclusion criteria and graded their risk of bias. The authors resolved disagreements about inclusion by discussion. Two review authors (LH and JZ) arbitrated if there was a failure in resolving disagreement. If necessary and if possible we contacted the trial authors for clarification.

 

Data extraction and management

We collected information from each study about diagnostic criteria, comparability of groups at baseline, pain condition and number of patients studied, non-antiepileptic drug type and dose regimen, study design, study duration and follow-up, length of washout, analgesic outcome measures and results, withdrawals and adverse effects (minor and major).

Two review authors (JZ and MY) independently extracted and checked data on participants, methods, interventions, outcomes and results using a data extraction form. We obtained missing data from the authors whenever possible. One author (MY) entered data into the Cochrane software Review Manager, currently RevMan 5.2 (RevMan 2012). A second author (MZ) checked the data entry and a third author (JZ) did another independent assessment.

 

Assessment of risk of bias in included studies

We assessed the risk of bias of each trial. The assessment took into account the security of randomisation, allocation concealment, blinding of participants and personnel and blinding of outcome assessors, completeness of outcome data, selective reporting and any other potential bias, as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors assessed these items independently and subdivided trials.

 

Measures of treatment effect

We calculated a treatment effect with the Cochrane statistical package RevMan. We expressed results as risk ratios (RRs) or risk differences (RDs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. According to the method of assessing risk of bias in cross-over trials (Higgins 2011), we evaluated the following items for cross-over trials: (i) whether the cross-over design was suitable; (ii) whether there was a carry-over effect; (iii) whether the first period data were available; (iv) incorrect analysis; and (v) comparability of results with those from parallel-group trials. We planned to analyse all outcomes under consideration.

 

Dealing with missing data

We analysed data on an intention-to-treat basis. Therefore, we included all participants with available data in the analysis in the group to which they were allocated, regardless of whether or not they received the allocated intervention. If in the original reports participants were not analysed in the group to which they were randomised, and there was sufficient information in the trial report, we attempted to restore them to the correct group. We obtained missing data from the study authors whenever possible.

 

Assessment of reporting biases

As there were insufficient studies, we did not use a funnel plot to investigate the possibility of publication bias but used a descriptive analysis to evaluate the possible reporting bias.

 

Data synthesis

As the non-antiepileptic and control group interventions tested in the included studies were different, we did not use RevMan to perform meta-analyses of the studies. Instead, we described the results of each trial as reported by the authors.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of studies

 

Results of the search

In this 2013 update, we performed electronic searches and retrieved 71 references from the Cochrane Neuromuscular Disease Group Specialized Register, 185 from CENTRAL, 1571 from MEDLINE, 314 from EMBASE, 17 from LILACS, 156 from the Chinese Biomedical Retrieval System, 54 from Clinicaltrials.gov and 24 from WHO ICTRP. We have identified two new ongoing studies since the original review in 2005. In total 29 reports potentially met our inclusion criteria.

We included four trials with 139 participants (Kondziolka 1994; Lechin 1989; Lindström 1987; Vilming 1986) (see Characteristics of included studies). We excluded 23 studies and there were two ongoing studies.

 

Included studies

The review includes four trials. Three studies compared an oral non-antiepileptic drug with carbamazepine; the drugs used were tizanidine (Vilming 1986), tocainide (Lindström 1987), and pimozide (Lechin 1989). The duration of treatments was generally short: two weeks (Lindström 1987), 21 days (Vilming 1986) and eight weeks per treatment period in Lechin 1989. The trials took place in Norway (Vilming 1986), Sweden (Lindström 1987), and Venezuela (Lechin 1989).

The fourth study, Kondziolka 1994 (47 participants), was conducted in the US and compared a single application of 0.5% proparacaine hydrochloride eye drops with buffered saline placebo.

Two studies had a parallel-group design (Kondziolka 1994; Vilming 1986), the other two were cross-over trials.

Outcome measures in Vilming 1986 (12 participants) were VAS pain and overall efficacy of medication (no efficacy, slight, moderate, good, very good) daily. Lindström 1987 (12 participants) used a zero to 10-point scale to measure the frequency and severity (duration and intensity) of attacks; Lechin 1989 (68 participants) used a TN symptom score (1 to 100); and Kondziolka 1994 reported a zero to 10-point verbal pain rating scale and a descriptive scale (unchanged, moderately better, markedly better, or worse) to grade outcome.

None of the study reports stated the investigators' conflicts of interest and only Lindström 1987 and Lechin 1989 provided information on funding, which came from an institute or foundation.

 

Excluded studies

We excluded 23 studies (Carasso 1979; Fromm 1984; Fromm 1987; Fromm 1993; Gazerani 2009; Gilron 2000; Jiang 2007; Jiang 2008; Kanai 2006a; Kanai 2006b; Kanai 2006c; Laurinda 2008; Liu 1999; Luo 1995; Parekh 1989; Shao 1999; Shao 2011; Silver 2007; Stajcic 1990; Wang 2007; Xu 1998; Yan 2011; Zhao 2011) as: they were not RCTs (Kanai 2006b; Liu 1999; Luo 1995; Xu 1998; Shao 2011; Yan 2011; Zhao 2011), not double-blind (Carasso 1979; Wang 2007), were of a combination of treatments rather than a single non-antiepileptic drug (Laurinda 2008; Shao 1999; Silver 2007), were repeated (Jiang 2007), the participants enrolled did not correspond with the protocol (Jiang 2008) or their characteristics were not described (Gilron 2000), the duration of treatment was less than two weeks (Fromm 1984; Fromm 1987; Fromm 1993; Parekh 1989), loss to follow-up was more than 20% (Stajcic 1990) or the study objective did not correspond to the protocol (Kanai 2006a; Kanai 2006c). (See Characteristics of excluded studies).

 

Risk of bias in included studies

The 'Risk of bias' summary (Figure 1) shows the review authors' judgements about each 'Risk of bias' item for the included studies. One study had an overall low risk of bias (Kondziolka 1994). For the other three the risk of bias was generally unclear and in particular there was not enough information to assess the adequacy of randomisation and blinding.

 FigureFigure 1. 'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study. Red = high risk of bias; yellow = unclear risk of bias; green = low risk of bias

 

Allocation

Four trials (Kondziolka 1994; Lechin 1989; Lindström 1987; Vilming 1986) stated that they were randomised. Only one trial (Kondziolka 1994) described an adequate method of randomisation; the participants were randomly assigned by the tossing of a coin. This trial also compared the characteristics of the two groups, which showed that the randomisation had been effective. The report states that "The code was not broken until the study was completed". The other three trials did not describe their method of 'random allocation' or allocation concealment.

 

Blinding

Most trial reports described the method of blinding only in broad terms such as 'double-blind', which made it impossible to know exactly who was blinded (Higgins 2011). All four trials (Kondziolka 1994; Lechin 1989; Lindström 1987; Vilming 1986) claimed that they were double-blind; one trial (Kondziolka 1994) described this in detail. Lechin 1989 stated that trial and placebo medications were identical.

 

Incomplete outcome data

Two trials reported that there were dropouts or withdrawals (Lechin 1989; Vilming 1986) and they reported the reason but did not use intention-to-treat analysis to analyse the results.

 

Selective reporting

We considered the risk of selective reporting bias introduced by the trial investigators to be high in two trials (Lechin 1989; Vilming 1986). In Vilming 1986, the trial authors did not report visual analogue scale (VAS) measurements, one of the prespecified outcomes, in a suitable way. Lechin 1989 reported data primarily in graphs. The first period data for reduction in trigeminal neuralgia score were reported in the text after six weeks of treatment, which the trial authors describe as the point of "maximal improvement" for both pimozide and carbamazepine. This outcome is therefore at high risk of bias owing to selective reporting. We considered the risk of reporting bias in Lindström 1987 and Kondziolka 1994 to be low.

 

Other potential sources of bias

Only one trial (Kondziolka 1994) claimed that the treatment groups were the same with regard to gender, age, duration of disease and pain scores. The others did not compare the baseline characteristics of the groups in detail. Many of the trials lacked clear diagnostic criteria and referred to typical trigeminal neuralgia but did not define it and they did not report whether participants had idiopathic trigeminal neuralgia. One cross-over trial (Lindström 1987) did not report a washout period, so there is a high risk of a carry-over effect in this study. Vilming 1986 did not report whether there was a washout period prior to the start of the trial.

 

Effects of interventions

See:  Summary of findings for the main comparison Tizanidine versus carbamazepine for trigeminal neuralgia;  Summary of findings 2 Tocainide versus carbamazepine for trigeminal neuralgia;  Summary of findings 3 Proparacaine hydrochloride 0.5% eye drops versus placebo for trigeminal neuralgia;  Summary of findings 4 Pimozide versus carbamazepine for trigeminal neuralgia

As the non-antiepileptic and control group interventions tested in the included studies were different, we did not combine the results. Instead, we describe the results of each trial as reported by the authors.

Three trials reported the proportion of participants with a good initial effect evaluated by pain intensity or trigeminal neuralgia scores two weeks after treatment.

 

Tizanidine versus carbamazepine

This comparison was reported in Vilming 1986, a very small parallel-group trial (12 participants, with six in each group).

The duration of treatment was 21 days. Three participants taking tizanidine discontinued taking the optimal dose, one because of unrelated disease and two as a result of intolerable pain. The report provides results for 11 participants.

 

Primary outcome: immediate improvement in pain relief

A visual analogue scale (VAS) was used to evaluate pain but the report does not include the results. The investigators reported overall efficacy assessed by participants and investigators on a four-point scale (no efficacy, slight, moderate, good or very good) but provide no other details of the measure. At the end of treatment, one of five participants improved with tizanidine and four of six with carbamazepine (RR 0.30, 95% CI 0.05 to 1.89) ( Analysis 1.1). The difference was not statistically significant.

 

Secondary outcomes

The duration of treatment was 21 days, which was too short for the measurement of our secondary efficacy outcomes at 12 weeks.

Side effects were not specifically reported, other than, "Tizanidine was generally better tolerated than carbamazepine, and few side effects were noted. Laboratory tests did not show any deviations that could be related to the test medication."

 

Tocainide versus carbamazepine

One double-blind, cross-over RCT (Lindström 1987) in 12 participants compared tocainide with carbamazepine.

The duration of each phase was two weeks. However, the authors did not report the washout period or data from the end of the first arm in this trial. Since there is a high risk of carry-over effects, we have not reported the quantitative data from this trial.

For adverse effects, the authors reported that tocainide produced nausea, distal paraesthesias and skin rash which led to withdrawal from the study, but non-randomised studies showed an unacceptable rate of serious haematological side effects and deaths (see Discussion). The Lindstrom study did not report whether the adverse effects of tocainide were dose-dependent.

 

Proparacaine hydrochloride 0.5% versus placebo

In a parallel-group RCT (Kondziolka 1994), investigators assigned 47 participants to receive a single dose of proparacaine hydrochloride 0.5% or placebo eye drops. Each participant was treated only once.

 

Primary outcome: immediate improvement in pain relief

A verbal pain rating scale (VRS) was used to assess the effect. There was no significant reduction of pain after 3, 10 or 30 days. At 30 days, six of 25 participants improved (i.e. had a 2 or more level decrease in pain on 10-point scale, or pain was gone or rare) with proparacaine hydrochloride 0.5%, and five of 22 improved with placebo (RR 1.06, 95% CI 0.37 to 2.99) ( Analysis 2.1). Eleven participants in the treatment group and 14 participants in the control group underwent surgery during follow-up. Two participants in the control group required medication.

 

Secondary outcomes

The study duration was too short to report secondary efficacy outcomes at 12 weeks. For adverse events, the authors state "We observed no morbidity related to placement of either proparacaine or saline eyedrops."

 

Pimozide versus carbamazepine

One double-blind, cross-over RCT (Lechin 1989) compared pimozide and carbamazepine in 68 people but nine were not admitted to the treatment phase. Eleven participants did not contribute data to the statistical analysis: 10 because of protocol deviations and one dropped out. The trial lasted 24 weeks: four weeks of placebo washout, eight weeks of treatment following random assignment to carbamazepine or pimozide, four weeks of abrupt withdrawal with placebo substitution and eight weeks of cross-over treatment.

 

Primary outcome: immediate improvement in pain relief

A trigeminal neuralgia score ranging from 0 to 100 was used to assess the effect. However, the authors did not state how they defined 'improvement', other than stating that all of the 48 participants on pimozide and 27 out of 48 participants on carbamazepine "showed improvement". They do give a percentage improvement score for each group after six weeks' treatment (when the authors state that there was "maximal improvement"); they also report that "similar differences were obtained" at weeks seven and eight, week eight being the end of the first treatment period. Week seven and eight results are provided in graph form in the study report as are second period results. In the first period, the reduction in total trigeminal neuralgia score was 78.4% with pimozide and 49.7% with carbamazepine, six weeks after starting treatment (MD 28.70%, 95% CI 20.88% to 36.52%) (see  Analysis 3.1).

 

Secondary outcomes

The study duration was too short (eight-week treatment phases) to report secondary efficacy outcomes at 12 weeks.

Adverse effects were recorded in 40 (83.3%) participants with pimozide. These were physical and mental retardation, hand tremors, memory impairment, involuntary movements during sleep and slight Parkinson's disease manifestations. In the carbamazepine period, 22 serious adverse effects occurred (one abnormal full blood count, one abnormal liver function, 18 lethargy, one inappropriate secretion of vasopressin and one erythematous exanthem that disappeared after the trial. However, the report does not provide the total number of participants with adverse effects in each group. Since some participants might have had more than one adverse effect with carbamazepine, we could not calculate the incidence of adverse effects between the two drugs. For pimozide, the adverse effects could be attenuated by reducing the dose, so may be dose-dependent.

No studies were alike, therefore we did not perform a meta-analysis.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

We did not identify any new randomised controlled trials (RCTs) for this update. In a previous update, we re-evaluated the nine trials in the original review in the light of changed inclusion criteria. Since most drugs used in trigeminal neuralgia need to be escalated slowly in dose, and a steady state reached at the maximum dose, we considered it important that a trial should report the results from at least two weeks at the maximum steady state dose. Trigeminal neuralgia is a chronic condition and drugs need to provide pain relief for long periods. Our inclusion criteria therefore stated that the trial had last at least two weeks using the maximum steady dose. After reassessment of the trials, four clinical trials investigating non-antiepileptic drugs in the treatment of trigeminal neuralgia, with a total of 139 participants, met the inclusion criteria. The drugs tested were tizanidine, tocainide, proparacaine hydrochloride (0.5% eye drops) and pimozide. We were unable to pool the results because of heterogeneity between the studies. The results of these trials can be summarised as follows.

  1. There was no significant difference in effect between carbamazepine and tizanidine measured using the selected outcomes. Larger and better studies are required to draw any conclusions (Vilming 1986) ( Summary of findings for the main comparison).
  2. The efficacy of tocainide was not analysed because of the high risk of a carry-over effect and no separate first phase data were presented that would have enabled us to analyse these separately ( Summary of findings 2). In non-randomised studies, tocainide produced serious haematological side effects limiting its use (Rawson 1998).
  3. Proparacaine hydrochloride 0.5% instilled into the eyes was simple and safe but no significant effect was observed when compared with placebo (Kondziolka 1994) ( Summary of findings 3). In this trial three participants had first division (V1) pain only and a further four had V1 as well as other division involvement. The rest of the participants did not have V1 involvement, therefore they were looking for a systemic effect of the drug. The authors did not report the results separately for the V1 participants but presumably if the drug had worked better in that group they would have reported it. We therefore assume that the trial showed that the drug neither works centrally nor peripherally.
  4. The effect of pimozide was evaluated in one double-blind, cross-over RCT ( Summary of findings 4). Adverse effects were common and the authors suggested it should not be chosen as a first-line treatment option (Lechin 1989).

These conclusions are limited by methodological considerations such as the method of randomisation, quality of double-blinding, allocation concealment, study duration and selection of outcome measures. All of the included trials were either inadequately reported or had methodological flaws. The quality problems were as follows:

  1. the method of randomisation and allocation concealment, diagnostic criteria and comparability of the baseline groups were not reported;
  2. the washout period was not reported in a cross-over trial;
  3. the blinding methods were unclear;
  4. dropouts were high and not reported in detail and intention-to-treat analysis was not carried out;
  5. the follow-up time was short;
  6. the selection of assessment tools was not consistent and adverse effects were not reported in some trials;
  7. the participants recruited in some trials were not typical and did not meet the diagnostic criteria for trigeminal neuralgia.

At present we cannot draw any definitive conclusions about the effect and reliability of any non-antiepileptic drug in trigeminal neuralgia.

All these trials were carried out before more rigorous methods were introduced for the conduct of RCTs. No study included a power calculation and the primary and secondary outcome measures were not clearly stated. One of the studies (Kondziolka 1994) had a low risk of bias; the other three had an unclear risk of bias.The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has provided some guidelines on the use of outcome measures which need to be considered when designing future trials in this field (Dworkin 2005). Trials in patients with trigeminal neuralgia are difficult to conduct due to the lack of knowledge about the natural history of the condition. Patients can go into a natural period of complete pain remission, as is reported to have potentially occurred in one participant in the tizanidine study (Vilming 1986). The following outcomes need to be measured: the frequency of attacks of pain, the duration of each attack and the severity of attack. Evoked or spontaneous pain could also be measured as there is a suggestion that this can be altered differently (Beydoun 2002). A 50% pain reduction is considered a good outcome in all chronic pain studies of other conditions but a higher target is possible in patients with trigeminal neuralgia. Quality of life assessment is important because patients may be unable to eat or socialise and if rendered pain-free with drugs they may be unable to walk due to ataxia, diplopia and drowsiness. In the current update of the review we revised our outcomes to include 50% pain reduction and quality of life assessment.

The results of our review are consistent with the previous studies described in the Background section.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 

Implications for practice

There is low-quality evidence that the effect of tizanidine is not significantly different than that of carbamazepine in treating trigeminal neuralgia. Pimozide is more effective than carbamazepine, although the evidence is low-quality and the data did not allow comparison of adverse event rates. There is also low-quality evidence that 0.5% proparacaine hydrochloride eye drops have no benefit over placebo. Limitations in the data for tocainide prevent any conclusions being drawn.

 
Implications for research

More research is needed to determine whether non-antiepileptic drugs are beneficial in trigeminal neuralgia. Future trials should describe their methods adequately and use clear inclusion criteria, allocation concealment, randomisation, double-blind assessment, intention-to-treat analysis and long-term follow-up. The length of washout period before interventions, and between periods in cross-over trials, must be adequate. Outcome measures should include the frequency, duration and severity of attacks of pain, and quality of life. Adverse events and the number of and explanation for dropouts must be reported. Trials should be adequately powered.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

The authors would like to thank the Cochrane Neuromuscular Disease Group staff, in particular Kate Jewitt, Carolyn Reid, Ruth Brassington and Professor Hughes for their advice and support through the review process.

The Cochrane Neuromuscular Disease Group Trials Search Co-ordinator (Angela Gunn for this update) conducted searches of the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and LILACS.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
Download statistical data

 
Comparison 1. Tizanidine versus carbamazepine

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

 1 Number improved (reported by participant on global efficacy scale)111Risk Ratio (M-H, Fixed, 95% CI)0.3 [0.05, 1.89]

 
Comparison 2. Proparacaine hydrochloride 0.5% versus placebo

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

 1 Number improved (reported by participant on verbal pain rating scale)147Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.37, 2.99]

 
Comparison 3. Pimozide versus carbamazepine

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

 1 Improvement (reduction in total TN score)148Mean Difference (IV, Fixed, 95% CI)28.70 [20.88, 36.52]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Appendix 1. MEDLINE (Ovid SP) search strategy

Database: Ovid MEDLINE(R) <1946 to May Week 2 2013>
Search strategy:
--------------------------------------------------------------------------------
1 randomized controlled trial.pt. (351508)
2 controlled clinical trial.pt. (86242)
3 randomized.ab. (253157)
4 placebo.ab. (138957)
5 drug therapy.fs. (1619317)
6 randomly.ab. (181024)
7 trial.ab. (261494)
8 groups.ab. (1175082)
9 or/1-8 (3026869)
10 exp animals/ not humans.sh. (3847813)
11 9 not 10 (2571885)
12 exp Trigeminal Nerve/ (13968)
13 Facial Neuralgia/ (1113)
14 exp Trigeminal Nerve Diseases/ (7128)
15 (trigeminal or trigeminus).tw. (18945)
16 tic douloureux.mp. (250)
17 (cranial or face or facial or oro?facial or tri?facial or cranio?facial or maxillo?facial).tw. (231226)
18 or/12-17 (252495)
19 neuralgia$.mp. (15849)
20 18 and 19 (7506)
21 trigeminal neuralgia/ (5383)
22 20 or 21 (7506)
23 11 and 22 (1591)
24 remove duplicates from 23 (1571)
25 randomized controlled trial.pt. (351508)
26 controlled clinical trial.pt. (86242)
27 randomized.ab. (253157)
28 placebo.ab. (138957)
29 drug therapy.fs. (1619317)
30 randomly.ab. (181024)
31 trial.ab. (261494)
32 groups.ab. (1175082)
33 or/25-32 (3026869)
34 exp animals/ not humans.sh. (3847813)
35 33 not 34 (2571885)
36 exp Trigeminal Nerve/ (13968)
37 Facial Neuralgia/ (1113)
38 exp Trigeminal Nerve Diseases/ (7128)
39 (trigeminal or trigeminus).tw. (18945)
40 tic douloureux.mp. (250)
41 (cranial or face or facial or oro?facial or tri?facial or cranio?facial or maxillo?facial).tw. (231226)
42 or/36-41 (252495)
43 neuralgia$.mp. (15849)
44 42 and 43 (7506)
45 trigeminal neuralgia/ (5383)
46 44 or 45 (7506)
47 35 and 46 (1591)
48 remove duplicates from 47 (1571)
49 randomized controlled trial.pt. (351508)
50 controlled clinical trial.pt. (86242)
51 randomized.ab. (253157)
52 placebo.ab. (138957)
53 drug therapy.fs. (1619317)
54 randomly.ab. (181024)
55 trial.ab. (261494)
56 groups.ab. (1175082)
57 or/49-56 (3026869)
58 exp animals/ not humans.sh. (3847813)
59 57 not 58 (2571885)
60 exp Trigeminal Nerve/ (13968)
61 Facial Neuralgia/ (1113)
62 exp Trigeminal Nerve Diseases/ (7128)
63 (trigeminal or trigeminus).tw. (18945)
64 tic douloureux.mp. (250)
65 (cranial or face or facial or oro?facial or tri?facial or cranio?facial or maxillo?facial).tw. (231226)
66 or/60-65 (252495)
67 neuralgia$.mp. (15849)
68 66 and 67 (7506)
69 trigeminal neuralgia/ (5383)
70 68 or 69 (7506)
71 59 and 70 (1591)
72 remove duplicates from 71 (1571)

 

Appendix 2. EMBASE (Ovid SP) search strategy

Database: EMBASE <1980 to 2013 Week 20>
Search strategy:
--------------------------------------------------------------------------------
1 crossover-procedure.sh. (36896)
2 double-blind procedure.sh. (114620)
3 single-blind procedure.sh. (17374)
4 randomized controlled trial.sh. (342470)
5 (random$ or crossover$ or cross over$ or placebo$ or (doubl$ adj blind$) or allocat$).tw,ot. (953986)
6 trial.ti. (144904)
7 or/1-6 (1086574)
8 (animal/ or nonhuman/ or animal experiment/) and human/ (1260257)
9 animal/ or nonanimal/ or animal experiment/ (3386195)
10 9 not 8 (2801568)
11 7 not 10 (996670)
12 limit 11 to embase (780448)
13 trigeminal nerve/ (9260)
14 facial nerve/ (9155)
15 trigeminal nerve disease/ (672)
16 (trigeminal or trigeminus).tw. (22066)
17 (cranial or face or facial or oro?facial or tri?facial or cranio?facial or maxillo?facial).tw. (293660)
18 (tic douloureux or tic doloureux or tic doloreux or tic douloreux).mp. (325)
19 or/13-18 (314032)
20 neuralgia$.mp. (20949)
21 19 and 20 (7928)
22 trigeminus neuralgia/ (8062)
23 21 or 22 (9729)
24 12 and 23 (314)
25 remove duplicates from 24 (314)

 

Appendix 3. Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library

#1 MeSH descriptor Trigeminal Neuralgia, this term only
#2 MeSH descriptor Trigeminal Nerve explode all trees
#3 MeSH descriptor Facial Nerve, this term only
#4 MeSH descriptor Trigeminal Nerve Diseases explode all trees
#5 trigeminal OR trigeminus
#6 "tic douloureux" OR "tic doloureux" OR "tic doloreux" OR "tic douloreux"
#7 cranial OR face OR facial OR orofacial OR trifacial OR craniofacial OR maxillofacial
#8 (#2 OR #3 OR #4 OR #5 OR #6 OR #7)
#9 neuralgia*
#10 (#8 AND #9)
#11 (#1 OR #10)

 

Appendix 4. LILACS search strategy

(((MH: A08.800.800.120.760$ or "facial neuralgia" or "neuralgia facial" or MH:C10.292.775$ or trigeminal or trigemino or trigemeo or trigeminus or "tic douloureux" or cranial or craneal or craniana or face or cara or facial or faciales or faciais or orofacial or orofaciales or orofaciais or craniofacial or cranio-facial or craniofaciales or craniofaciais or cranio-faciales or cranio-faciais or maxillofacial or maxilofacial or maxillofaciales or maxilofaciales or maxillofaciais or maxilofaciais or maxillo-faciales or maxilo-facialis or maxillo-faciais or maxilo-faciais) and neuralgia) or "trigeminal neuralgia" or "neuralgia del trigemino" or "neuralgia do trigemeo") and ((PT:"Randomized Controlled Trial" or "Randomized Controlled trial" or "Ensayo Clínico Controlado Aleatorio" or "Ensaio Clínico Controlado Aleatório" or PT:"Controlled Clinical Trial" or "Ensayo Clínico Controlado" or "Ensaio Clínico Controlado" or "Random allocation" or "Distribución Aleatoria" or "Distribuição Aleatória" or randon$ or Randomized or randomly or "double blind" or "duplo-cego" or "duplo-cego" or "single blind" or "simples-cego" or "simples cego" or placebo$ or trial or groups) AND NOT (B01.050$ AND NOT (humans or humanos or humanos)))

 

Appendix 5. Chinese Biomedical Retrieval System search strategy

1 suijiduizhaoshiyan

2 linchuanduizhaoshiyan

3 suijifenpei

4 mangfa

5 danmang

6 sanmang

7 *mang

8 zhutici="suijiduizhaoshiyan/quanbufuzhitici"

9 zhutici="lichuangshiyan, 1qi/quanbufuzhutici"

10 zhutici="lichuangshiyan, 2qi/quanbufuzhutici"

11 zhutici="lichuangshiyan, 3qi/quanbufuzhutici"

12 zhutici="lichuangshiyan, 4qi/quanbufuzhutici"

13 zhutici="lichuangshiyan/quanbufuzhutici/quanbushu"

14 duizhao

15 kongbaiduizhao

16 anweiji

17 1 or 2 or 3 or 4 or 5 or 6 or 7 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16

18 zhutici="sanchashenjingtong/quanbufuzhutici"

19 zhutici="sanchashenjingjibing/quanbufuzhutici/quanbushu"

20 sanchashenjing*

21 mianbutengtong

22 zhutici="mianbutengtong/quanbufuzhutici/quanbushu"

23 mian*tong

24 mian*teng

25 toumian*tong

26 toumian*teng

27 sancha*teng

28 sancha*tong

29 sancha*jibing

30 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29

31 17 and 30

 

Appendix 6. Clinicaltrials.gov

randomized controlled trial OR controlled clinical trial OR randomized OR randomized OR placebo OR drug therapy OR randomly OR trial AND double-blind | Trigeminal Nerve OR TN OR Facial Neuralgia OR Trigeminal Nerve Diseases OR (trigeminal or trigeminus) OR douloureux OR trigeminal neuralgia

 

Appendix 7. WHO international Clinical trials Registry

Trigeminal Nerve OR TN OR Facial Neuralgia OR Trigeminal Nerve Diseases OR (trigeminal or trigeminus) OR douloureux OR trigeminal neuralgia

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Last assessed as up-to-date: 20 May 2013.


DateEventDescription

17 April 2013New citation required but conclusions have not changedSearches updated. A new author has joined the review update team: Jingjing Zhang

10 March 2013New search has been performedWe added new references and updated the searches but identified no new trials. We revised some 'Risk of bias' assessments and removed some data from the results upon re-examination of trial reports.



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Protocol first published: Issue 1, 2003
Review first published: Issue 3, 2006


DateEventDescription

7 December 2010New citation required but conclusions have not changedAdditional authors: Mi Yang, Ning Chen and Joanna M Zakrzewska. Bo Wu withdrew.

30 April 2010New search has been performedWe updated the database searches in April 2010. No new randomised controlled trial was identified. We re-evaluated the nine trials included, and five were excluded for reasons listed in the text. The overall review conclusions remain unchanged in the update.

2 July 2008AmendedConverted to new review format.

24 April 2006New citation required and conclusions have changedSubstantive amendment.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

JZ: wrote the first draft of this (2013) update.

LH: wrote the first draft of the review and instructed the other authors.

MY: wrote the 2011 update of this review.

NC, MZ and JZ commented on each draft.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Internal sources

  • Chinese Cochrane Center, China.
  • Joanna Zakrzewska undertook this work at University College London/University College London Hospitals Trust, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centre funding scheme, UK.

 

External sources

  • Chinese Medical Board of New York (CMB), USA.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

In the 2011 update, we modified the original protocol. We edited the methods section Assessment of risk of bias in included studies according to Higgins 2008 and completed a 'Risk of bias' assessment and table for each of the included studies. In Types of participants we included all causes of trigeminal neuralgia in which the diagnostic criteria were clearly defined. We also specified that the trials needed to have lasted at least two weeks in total.

In this 2013 update, we excluded quasi-RCTs; the protocol stated that we would include quasi-RCTs (He 2006) (we found no quasi-RCTs). According to the latest version of Cochrane Handbook for Systematic Reviews of Interventions, only RCTs can prevent systematic differences in general characteristics between different intervention groups. We searched the 10 journals that we previously handsearched in the electronic Chinese Biomedical Retrieval System database. We also updated the 'blinding' assessments, and split blinding into blinding of participants and personnel (performance bias) and blinding of outcome assessors (assessment bias) (Higgins 2011). In addition, we added a 'Summary of findings' table in this update.

We revised our outcomes in this update to include 50% pain reduction and quality of life measures.

Changes to the team of authors have taken place. See Other published versions of this review.

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Kondziolka 1994 {published data only}
  • Kondziolka D, Lemley T, Kestle JR, Lunsford LD, Fromm GH, Jannetta PJ. The effect of single-application topical ophthalmic anesthesia in patients with trigeminal neuralgia. A randomized double-blind placebo-controlled trial. Journal of Neurosurgery 1994;80(6):993-7. [PUBMED: 8189280]
Lechin 1989 {published data only}
Lindström 1987 {published data only}
Vilming 1986 {published data only}

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Carasso 1979 {published data only}
Fromm 1984 {published data only}
Fromm 1987 {published data only}
Fromm 1993 {published data only}
Gazerani 2009 {published data only}
  • Gazerani P, Pedersen NS, Staahl C, Drewes AM, Arendt-Nielsen L. Subcutaneous botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin. Pain 2009;141(1-2):60-9. [PUBMED: 19004549]
Gilron 2000 {published data only}
Jiang 2007 {published data only}
  • Jiang L, Niu G. Therapeutic effect observation of neurotropin in the treatment of senile essential trigeminal neuralgia. Chinese Journal of Practical Nervous Diseases 2007;10(7):25-6.
Jiang 2008 {published data only}
  • Jiang L, Niu G. The effect of neurotropin on idiopathic trigeminal neuralgia. Zhejiang Medical Journal 2008;30(6):644-5.
Kanai 2006a {published data only}
Kanai 2006b {published data only}
Kanai 2006c {published data only}
Laurinda 2008 {published data only}
  • Lemos L, Flores S, Oliveira P, Almeida A. Gabapentin supplemented with ropivacain block of trigger points improves pain control and quality of life in trigeminal neuralgia patients when compared with gabapentin alone. Clinical Journal of Pain 2008;24(1):64-75. [PUBMED: 18180639]
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References to ongoing studies

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
NCT00004431 {published data only}
  • NCT00004431. Randomized study of L-baclofen in patients with refractory trigeminal neuralgia. clinicaltrials.gov/show/NCT00004431 (accessed 5 November 2013).
NCT01540630 {published data only}
  • NCT01540630. A phase IIa withdrawal study of CNV1014802 in patients with trigeminal neuralgia. http://clinicaltrials.gov/show/NCT01540630 (accessed 5 November 2013).

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
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