Is Lamotrigine Any Use For Neuropathic Pain

Today's post from onlinelibrary.wiley.com (see link below) talks about Lamotrigine (Lamictal in Europe) as a treatment for neuropathic pain. Lamotrigine is another anti-epilepsy drug used to combat nerve pain and is becoming more and more popular as doctors run out of options for patients with stubborn symptoms. However, this study is pretty damning in its conclusions and views Lamotrigine as being no better than a placebo. This puts the patient in a difficult position, as the doctor  or specialist has prescribed it, often based on so-called 'other patient experiences'. However, drug company representatives are often the driving force behind its prescription and you need to really talk it over with your doctor before accepting it as a treatment. Using research conclusions such as this one may strengthen your argument. After that, you have to make a decision as to whether to take it or not and run the risk of your doctor feeling offended that you're rejecting his or her suggestions. However, it's your health at issue here and you deserve the best treatment. The potential side effects are also an issue to think about. May be worth asking for an alternative.

Lamotrigine for chronic neuropathic pain and fibromyalgia in adults

Philip J Wiffen*,
Sheena Derry,
R Andrew Moore

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 3 DEC 2013

Assessed as up-to-date: 26 NOV 2013

DOI: 10.1002/14651858.CD006044.pub4

Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


Abstract

Background

This is an update of the original Cochrane review entitled Lamotrigine for acute and chronic pain published in Issue 2, 2007, and updated in Issue 2, 2011. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review adds no new additional studies looking at evidence for lamotrigine as an effective treatment for chronic neuropathic pain or fibromyalgia. The update uses higher standards of evidence than previously.

Objectives

To assess the analgesic efficacy of lamotrigine in the treatment of chronic neuropathic pain and fibromyalgia, and to evaluate adverse effects reported in the studies.

Search methods

We identified randomised controlled trials (RCTs) of lamotrigine for chronic neuropathic pain and fibromyalgia (including cancer pain) from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). We ran searches for the original review in 2006, in 2011 for the first update, and subsequent searches in August 2013 for this update. We sought additional studies from the reference lists of the retrieved papers. The original review and first update included acute pain, but no acute pain studies were identified.

Selection criteria

RCTs investigating the use of lamotrigine (any dose, by any route, and for any study duration) for the treatment of chronic neuropathic pain or fibromyalgia. Assessment of pain intensity or pain relief, or both, using validated scales. Participants were adults aged 18 and over. We included only full journal publication articles.

Data collection and analysis

Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. The first tier used data where studies reported the outcome of at least 50% pain reduction from baseline, lasted at least eight weeks, had a parallel group design, included 200 or more participants in the comparison, and reported an intention-to-treat analysis. First-tier studies did not use last observation carried forward (LOCF) or other imputational methods for dropouts. The second tier used data that failed to meet this standard and second-tier results were therefore subject to potential bias.

Main results

Twelve included studies in 11 publications (1511 participants), all with chronic neuropathic pain: central post-stroke pain (1), chemotherapy-induced neuropathic pain (1), diabetic neuropathy (4), HIV-related neuropathy (2), mixed neuropathic pain (2), spinal cord injury-related pain (1), and trigeminal neuralgia (1). We did not identify any additional studies. Participants were aged between 26 and 77 years. Study duration was two weeks in one study and at least six weeks in the remainder; eight were of eight-week duration or longer.

No study provided first-tier evidence for an efficacy outcome. There was no convincing evidence that lamotrigine is effective in treating neuropathic pain and fibromyalgia at doses of 200 mg to 400 mg daily. Almost 10% of participants taking lamotrigine reported a skin rash.

Authors' conclusions

Large, high-quality, long-duration studies reporting clinically useful levels of pain relief for individual participants provided no convincing evidence that lamotrigine is effective in treating neuropathic pain and fibromyalgia at doses of about 200 to 400 mg daily. Given the availability of more effective treatments including antiepileptics and antidepressant medicines, lamotrigine does not have a significant place in therapy based on the available evidence. The adverse effect profile of lamotrigine is also of concern.

Plain language summary

Lamotrigine (an antiepileptic drug) for chronic neuropathic pain or fibromyalgia

Neuropathic pain is pain coming from damaged nerves. It is different from pain messages carried along healthy nerves from damaged tissue (a fall, or cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines like paracetamol or ibuprofen are not effective in neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain. Our understanding of fibromyalgia (a condition of persistent, widespread pain and tenderness, sleep problems, and fatigue) is lacking, but fibromyalgia can respond to the same medicines as neuropathic pain.

Lamotrigine is a medicine used to treat epilepsy, and so might be a useful medicine for neuropathic pain or fibromyalgia.

On 26 November 2013 we performed searches to look for clinical trials where lamotrigine was used to treat neuropathic pain or fibromyalgia. We found 12 studies of reasonable quality that tested lamotrigine against placebo for a number of weeks. Almost half of the 1511 people in the studies had painful limbs because of damaged nerves caused by diabetes, and seven different painful neuropathic conditions were examined. No studies looked at fibromyalgia.

Lamotrigine did not help the pain, and was no different from placebo except in causing more side effects. Adverse events were more frequent with lamotrigine than placebo, with rash in 1 person in 27.

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006044.pub4/abstract

Fibromyalgia Or Small Fibre Neuropathy Are We Any Nearer To The Truth

Today's fairly technical post from bodyinmind.org (see link below) looks at the ongoing discussion as to whether fibromyalgia is caused by, causes, or is linked to, small fibre neuropathy. The article looks in detail at the studies and seems to conclude that while the relentless pain of fibromyalgia is clearly a disturbance of the central nervous system, it's not necessarily directly associated with the peripheral nerve system. I wonder how many fibromyalgia and small fibre neuropathy patients actually care and whether it's more a question of semantics that hard scientific fact. That said, for doctors and their subsequent treatment it probably is important to know what the root causes are because that affects how the patient is treated. One thing is sure, if you have either condition, you're probably suffering considerably.

Small fibre neuropathy in Fibromyalgia: cause or consequence?
March 8, 2016 by BiM 

Dan Clauw recently wrote an insightful editorial for Pain[1], in which he highlighted an important finding about the idea that people with fibromyalgia show signs of ‘small fibre neuropathy’. Changes in intra-epidermal nerve fibres (‘small fibres’) have been shown in many clinical conditions, including conditions that are characterised by chronic pain. So the idea that people with fibromyalgia show such changes is not revolutionary. However, the study Clauw refers to also examined the nature of the changes, comparing small fibre biopsies in people with fibromyalgia to healthy controls and to people with the classic signs and symptoms of ‘small fibre neuropathy’[2]. Unsurprisingly, the nature of the changes in fibromyalgia differ from those in classic small fibre neuropathy, which the authors interpreted as suggesting that the mechanisms driving the changes probably differ, too.

Clauw uses this as a springboard to point out that naming these differences in intra-epidermal nerve density as ‘small fibre neuropathy’ in those that don’t have the classic set of signs and symptoms of small fibre neuropathy is likely to cause confusion, because (a) it implies a causative link and (b) it ignores the subtle, but relevant, heterogeneity in morphology. There is sufficient evidence to firmly support the view that chronic pain conditions like fibromyalgia cannot be caused exclusively by peripheral disease: the central nervous system appears to be a major player. Indeed, it is far more likely that the central nervous system drives the changes in intra-epidermal nerve fibres (concomitant with probable changes in many other peripheral structures) that are seen in people with fibromyalgia and in other chronic pain conditions.

So what words should we use to describe these small fibre changes that seem nearly ubiquitous in chronic pain conditions? If we view the many central changes that are seen in chronic pain conditions as evidence of ‘neuroplasticity’, why do we not take the same view for peripheral changes? After all, Clauw argues, it is plausible that the changes in small fibres could be a response to a myriad of drivers. Whatever term we use ought to allow for the possibility that morphological changes in intra-epidermal nerve fibres are a side event to the main show; they may only be relevant if and when they match up with a patient’s history and clinical findings.

About Tory Madden

Tory arrived from South Africa to start her PhD at BiM. She is a physiotherapist who worked clinically before turning her focus toward research. She is interested in pretty much anything related to pain and neuroscience, thanks to some particularly inspirational teaching by Romy Parker during her undergraduate training at the University of Cape Town.

Tory’s research looks at classical conditioning and pain. She is also an associate editor for BiM. She tries to spend much of her spare time exercising to compensate for the vast quantity of chocolate that lives in her bottom desk drawer. Luckily, she loves trail running as much as she does food.
References

[1] Clauw, Daniel J. (2015) What is the meaning of “small fiber neuropathy” in fibromyalgia? Pain 156:2115-16.

[2] Doppler, Kathrin; Rittner, Heike L.; Deckart, Maximiliane; Sommer, Claudia (2015) Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia. Pain 156:2319-25.

http://www.bodyinmind.org/small-fibre-neuropathy-fibromyalgia/