Fibromyalgia

PaPaS reviews: interventions for fibromyalgia
Correct at September 2017

Amitriptyline for fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011824/abstract

Citation: Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for fibromyalgia in adults. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.: CD011824. DOI: 10.1002/14651858.CD011824

Plain Language Summary

Our understanding of fibromyalgia (a condition of persistent, widespread pain and tenderness, sleep problems, and fatigue) is poor. Common pain relieving medicines such as paracetamol and ibuprofen are not usually considered effective in fibromyalgia. Medicines that are sometimes used to treat epilepsy or depression can be very effective in some people with fibromyalgia, as they are in some other forms of chronic pain where there may be nerve damage (neuropathic pain).

Amitriptyline is an antidepressant, and antidepressants are recommended for treating fibromyalgia. Although amitriptyline is commonly used to treat fibromyalgia, a review in 2012 found no good quality evidence to support its use. Most studies were small, old, and used methods or reported results that we now recognise as making benefits seem better than they are.

This review is an update of the 2012 review, which considered both fibromyalgia and neuropathic pain conditions. Neuropathic pain is now considered in a separate review. Here we examine how well amitriptyline worked in treating fibromyalgia, using a definition of what worked that involved both a high level of pain relief and the ability to take the tablets over a longer time without side effects being intolerable.

In March 2015 we performed searches to look for new studies, and found only two additional small studies to include. Neither provided any good quality evidence for benefit or harm. There were still no studies that could provide an answer that was trustworthy or reliable, because most were relatively old, and used methods or reported results that we now recognise as making benefits seem better than they are. This is disappointing, but we can still make useful comments about the drug.

Amitriptyline probably does provide good levels of pain relief for some people with fibromyalgia, although we cannot be certain of this. Our best guess is that amitriptyline provides good pain relief in about 1 in 4 (25%) more people than does placebo. About 1 in 3 (31%) more people than with placebo report having one or more adverse events, which are usually not serious but may be troublesome and interfere with taking the treatment. We cannot trust either figure based on the information available.

The most important message is that amitriptyline probably does give really good pain relief to some patients with fibromyalgia, but only a minority of them; amitriptyline will not work for most people.

Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010567.pub2/abstract

Citation: Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice ASC, Lunn MPT, Hamunen K, Haanpaa M, Kalso EA. Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD010567. DOI: 10.1002/14651858.CD010567.pub2

Plain Language Summary

Neuropathic pain is pain coming from damaged nerves. It is different from pain messages carried along healthy nerves from damaged tissue (eg a fall, cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines such as paracetamol or ibuprofen are probably 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.

Antiepileptic drugs (previously called anticonvulsants) are used for treating epilepsy, but have also been used for treating neuropathic pain and fibromyalgia. Many of the drugs have been the subject of individual Cochrane reviews. In August 2013 we collected all these Cochrane reviews on antiepileptic drugs together to provide an overview. Individual antiepileptic drugs work in different ways, and there is no expectation that they are equally effective.

We found that only for gabapentin and pregabalin was there some evidence that they worked in long-term nerve pain with diabetes (painful diabetic neuropathy) and pain after shingles (postherpetic neuralgia). Pregabalin also had evidence of efficacy in central neuropathic pain (typically pain after stroke) and in fibromyalgia. The drugs work very well in some people with these painful conditions, with pain reduced by half. However, only between 1 in 10 and 1 in 4 people will get this level of benefit, depending on the pain condition and the drug. Most people will get no pain relief.

The antiepileptic drugs produced side effects in most people taking them, and for about 1 in 4 these could not be tolerated so they stopped taking the drug. Serious side effects were no more common with antiepileptic drugs than with a harmless placebo.

The evidence we found did not meet current best standards, and as a result it may overestimate benefit. The biggest concern is a lack of any evidence for most drugs in most types of neuropathic pain and fibromyalgia. For lacosamide and lamotrigine there is evidence of a lack of effect; for other antiepileptic drugs (including carbamazepine, clonazepam, phenytoin, valproate) there is no evidence of effect or insufficient evidence of effect.

Antipsychotics for fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011804.pub2/abstract

Citation: Walitt B, Klose P, Üçeyler N, Phillips T, Häuser W. Antipsychotics for fibromyalgia in adults. Cochrane Database of Systematic Reviews 2016, Issue 6. Art. No.: CD011804. DOI: 10.1002/14651858.CD011804.pub2

Plain Language Summary

Bottom line

Quetiapine may be considered for 4 to 12 weeks to reduce pain, sleep problems, depression and anxiety in fibromyalgia patients with major depression. Potential side effects such as weight gain should be balanced against the potential benefits.

Background

People with fibromyalgia often have chronic (longer than three months) widespread pain, as well as sleep problems, problems with thinking and exhaustion. They often report severe limitations of daily functioning and poor quality of life. Therapies focus on reducing key symptoms and disability, and improving health-related quality of life. In addition, many patients with fibromyalgia suffer from depression. Medicines used to treat depression can reduce the main symptoms in some people with fibromyalgia. Quetiapine is a drug for the treatment of psychosis (an abnormal condition of the mind described as involving a loss of contact with reality), which is also licensed for the treatment of major depression in some countries.

Study characteristics

In May 2016, we searched for clinical trials in which antipsychotics were used to treat symptoms of fibromyalgia in adults. We found a total of four studies with 298 participants. We found three studies with 208 participants, which were eight and 12 weeks long and compared quetiapine, an antipsychotic, against a fake medication (placebo). One hundred and sixty-six participants were diagnosed with major depression. We also found one study comprising 90 patients that compared quetiapine to an antidepressant named amitriptyline, which is frequently used in the treatment of fibromyalgia. Five people in this study were diagnosed with major depression.

Key results and quality of the evidence

Quetiapine was not better than a fake medication in achieving a pain reduction of 50% or more (very low quality evidence). Quetiapine was better than the fake medication in achieving a pain reduction of 30% or more, reducing sleep problems, and improving depressed mood and anxiety (very low quality evidence). Quetiapine was better than the fake medication in improving health-related quality of life. Fewer participants dropped out of the trial due to lack of efficacy with quetiapine than with fake medication (very low quality evidence). There was no difference in tolerability and safety between quetiapine and a fake medication (very low quality evidence). For some people, quetiapine led to substantial weight gain and somnolence (sleepiness).

Quetiapine and amitriptyline (an antidepressant which is frequently used to improve sleep and reduce pain in people with fibromyalgia) did not differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life. Both drugs did not differ in the proportion of patients reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared with amitriptyline, more people experienced side effects and left the study due to side effects with quetiapine (low quality evidence). No serious side effects with either drug were reported (low quality evidence).

We found no relevant study with other antipsychotics than quetiapine in fibromyalgia.

Cannabinoids for fibromyalgia

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011694.pub2/abstract

Citation: Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W. Cannabinoids for fibromyalgia. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD011694. DOI: 10.1002/14651858.CD011694.pub2

Plain Language Summary

Background

Fibromyalgia is characterised by chronic (longer than three months) widespread pain that often co-exists with sleep problems, problems with thinking and fatigue (exhaustion). People often report severe limitations of daily functioning and poor health-related quality of life. Therapies focus on reducing key symptoms and disability, and improving health-related quality of life. Cannabis has been used for 3000 years to reduce pain and other symptoms, such as loss of appetite and anxiety.

Key results and quality of the evidence

In April 2016 we searched for reports of clinical trials that used cannabis products to treat symptoms in adults with fibromyalgia. We found two small, moderate quality studies, of four and six weeks long, including 72 participants. Both studies tested nabilone, a synthetic (man-made) cannabis product, comparing it with placebo (a dummy pill) or amitriptyline (an antidepressant frequently used in the treatment of fibromyalgia).

Nabilone did not convincingly relieve fibromyalgia symptoms (pain, sleep, fatigue) better than placebo or amitriptyline (very low quality evidence). Compared with placebo and amitriptyline, more people experienced side effects and left the study due to side effects (very low quality evidence). There were no serious side effects reported. We found no relevant study with herbal cannabis, plant-based cannabinoids or other synthetic cannabinoids than nabilone in fibromyalgia.

There was not enough high quality evidence available to draw any robust conclusions. We found no studies on medical cannabis in fibromyalgia.

Carbamazepine for chronic neuropathic pain and fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005451.pub3/abstract

Citation: Wiffen PJ, Derry S, Moore RA, Kalso EA. Carbamazepine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD005451. DOI: 10.1002/14651858.CD005451.pub3

Plain Language Summary

Background

Fibromyalgia is characterised by chronic (longer than three months) widespread pain that often co-exists with sleep problems, problems with thinking and fatigue (exhaustion). People often report severe limitations of daily functioning and poor health-related quality of life. Therapies focus on reducing key symptoms and disability, and improving health-related quality of life. Cannabis has been used for 3000 years to reduce pain and other symptoms, such as loss of appetite and anxiety.

Key results and quality of the evidence

In April 2016 we searched for reports of clinical trials that used cannabis products to treat symptoms in adults with fibromyalgia. We found two small, moderate quality studies, of four and six weeks long, including 72 participants. Both studies tested nabilone, a synthetic (man-made) cannabis product, comparing it with placebo (a dummy pill) or amitriptyline (an antidepressant frequently used in the treatment of fibromyalgia).

Nabilone did not convincingly relieve fibromyalgia symptoms (pain, sleep, fatigue) better than placebo or amitriptyline (very low quality evidence). Compared with placebo and amitriptyline, more people experienced side effects and left the study due to side effects (very low quality evidence). There were no serious side effects reported. We found no relevant study with herbal cannabis, plant-based cannabinoids or other synthetic cannabinoids than nabilone in fibromyalgia.

There was not enough high quality evidence available to draw any robust conclusions. We found no studies on medical cannabis in fibromyalgia.

Clonazepam for neuropathic pain and fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009486.pub2/abstract

Citation: Corrigan R, Derry S, Wiffen PJ, Moore RA. Clonazepam for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2012, Issue 5. Art. No.: CD009486. DOI: 10.1002/14651858.CD009486.pub2

Plain Language Summary

Nerves which have been damaged by injury or disease can continue to produce pain. This type of pain is called neuropathic pain. Some antiepileptic medications can help neuropathic pain. Clonazepam is an antiepileptic medication, and the aim of this review was to assess how effective clonazepam is for neuropathic pain and fibromyalgia. We identified no good quality studies of clonazepam used in this situation. Dependence and tolerance may occur with prolonged use, although it is less of a problem with clonazepam than many other drugs from the same class (benzodiazepines), and behavioural disinhibition has been reported in a few patients with psychiatric problems. Based on current evidence, clonazepam cannot be recommended for treating neuropathic pain. Other antiepileptic drugs such as pregabalin, gabapentin, and carbamazepine have been shown to be of value in neuropathic pain.

Gabapentin for fibromyalgia pain in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012188.pub2/abstract

Citation: Cooper TE, Derry S, Wiffen PJ, Moore RA. Gabapentin for fibromyalgia pain in adults. Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD012188. DOI: 10.1002/14651858.CD012188.pub2

Plain Language Summary

Bottom Line

There is no good evidence to support or contradict the suggestion that gabapentin at daily doses of 1200 to 2400 mg reduces pain in fibromyalgia.

Background

Fibromyalgia is a complex disorder characterised by widespread pain, fatigue, poor sleep, low mood, and other bodily symptoms. Common pain-relieving medicines such as paracetamol and ibuprofen are not usually considered effective. Antiepileptic drugs are commonly used to treat fibromyalgia, but there is uncertainty about how good they are.

Gabapentin is a medicine used to treat pain caused by nerves that are not working properly. Gabapentin changes the way that the nerves send messages to the brain. It can be taken in a tablet or a liquid, with or without food. Doses are usually 1200 mg to 2400 mg each day. At the start of treatment low doses are used to minimise side effects, but the dose is usually increased after a few weeks.

Study characteristics

In May 2016 we searched for clinical trials where gabapentin was used to treat pain due to fibromyalgia in adults. We found one study that met the requirements for this review. The study tested 1200 to 2400 mg/day of gabapentin compared with a placebo over 12 weeks, in 150 people.

Key results

The study did not report the number of people with pain reduced by half at the end of week 12. At that time 5 in 10 people taking gabapentin and 3 in 10 taking the placebo had their pain reduced by at least one third. A report of feeling better to any degree was reported by 9 in 10 taking gabapentin and 5 in 10 taking placebo.

About 2 in 10 people taking gabapentin stopped taking the medicine because of side effects, compared with 1 in 10 taking the placebo. The study did not report the number of people with serious side effects, but did report that there were no deaths.

Quality of the evidence

We rated the quality of the evidence as very low because there was only a single small study with important study limitations. Several factors reduced our confidence in the result. Very low quality evidence means that we are very uncertain about the results.

Lamotrigine for chronic neuropathic pain and fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006044.pub4/abstract

Citation: Wiffen PJ, Derry S, Moore RA. Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD006044. DOI: 10.1002/14651858.CD006044.pub4

Plain Language Summary

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.

Milnacipran for pain in fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008244.pub3/abstract

Citation: Cording M, Derry S, Phillips T, Moore RA, Wiffen PJ. Milnacipran for pain in fibromyalgia in adults. Cochrane Database of Systematic Reviews 2015, Issue 10. Art. No.: CD008244. DOI: 10.1002/14651858.CD008244.pub3

Plain Language Summary

Fibromyalgia is characterised by persistent, widespread pain and tenderness, sleep problems, and fatigue. Common pain-relieving medicines such as paracetamol and ibuprofen are not usually considered effective. Medicines used to treat epilepsy or depression can be effective in some people with fibromyalgia and other forms of chronic (persistent, long-lasting) pain where there may be nerve damage. Milnacipran is an antidepressant, and antidepressants are widely recommended for treating fibromyalgia. Milnacipran is licensed to treat fibromyalgia only in some parts of the world, particularly the USA.

This review is an update of one originally published in 2012, which examined how well milnacipran worked in both fibromyalgia and neuropathic pain conditions (pain from damage to nerves or disease affecting the nerves). Here we examine only fibromyalgia. The earlier review showed that milnacipran worked, but only in a small proportion of people with fibromyalgia. This is the same as all other fibromyalgia treatments to date, and for chronic pain conditions generally. We use a definition of 'worked' that involved both a high level of pain relief and the ability to take the tablets over a longer time without side effects being intolerable.

We searched scientific databases for studies that looked at the effects of milnacipran in adults with fibromyalgia who had moderate or severe pain. The treatment had to last at least eight weeks. The evidence is current to May 2015.

We identified six studies that satisfied the inclusion criteria, including one new study for this update. Over 4000 participants were treated with milnacipran 100 or 200 mg, or placebo, for 8 to 24 weeks at the target dose. Overall study quality was good, although the method of analysis for our primary outcomes of pain relief could overestimate treatment effect.

Milnacipran at either dose provided moderate pain relief (at least 30% reduction in pain intensity) to 1 in 10 (10%) more people than did placebo (high quality evidence). This relatively modest effect may be clinically important in this difficult-to-treat condition. Adverse events were reported by most participants in all treatment groups, but were more common with milnacipran than placebo (high quality evidence), with nausea (feeling sick) and constipation showing the greatest differences (moderate quality evidence). Serious adverse events were uncommon, fewer than 1 in 50 (2%) participants, and did not differ between treatment groups (low quality evidence). The numbers of participants dropping out of the studies (withdrawals) because of adverse events were also more common with milnacipran than placebo, and were more common with 200 mg than 100 mg (high quality evidence), while withdrawals due to lack of effect were less common with milnacipran, with no difference between doses (moderate quality evidence).

Milnacipran gives good pain relief to some people with fibromyalgia, but only a minority; it will not work for most people.

Oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012332.pub2/abstract

Citation: Derry S, Wiffen PJ, Häuser W, Mücke M, Tölle TR, Bell RF, Moore RA. Oral nonsteroidal anti-inflammatory drugs for fibromyalgia in adults. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD012332. DOI: 10.1002/14651858.CD012332.pub2

Plain Language Summary

Bottom line

We found very low-quality evidence that oral non-steroidal anti-inflammatory drugs (NSAIDs) have no effect on pain or other symptoms in people with moderate or severe pain from fibromyalgia. Ibuprofen and diclofenac are common NSAIDs.

Background

Fibromyalgia is characterised by persistent, widespread pain, sleep problems, and fatigue. NSAIDs are drugs with analgesic (pain-killing), antipyretic (fever-reducing) effects, and also with anti-inflammatory effects at higher doses. NSAIDs are frequently used to treat rheumatic diseases.

Our definition of a good result was someone who had a high level of pain relief and was able to keep taking the medicine without side effects that made them want to stop.

Study characteristics

We searched for clinical trials in which NSAIDs were used to treat symptoms of fibromyalgia in adults. The latest search was in January 2017. Six studies satisfied the inclusion criteria, randomising 292 participants to treatment with NSAID or placebo. NSAIDs tested were etoricoxib 90 mg daily, ibuprofen 2400 mg daily, naproxen 1000 mg daily, and tenoxicam 20 mg daily; 146 participants received NSAID and 146 placebo. Study duration was between three and eight weeks. Not all studies reported the outcomes of interest.

Key results

We found no difference between NSAID or placebo for a range of outcomes. Pain reduction by half or better was experienced by 1 in 10 with NSAID and 2 in 10 with placebo. Pain reduction by a third or better was experienced by about 2 in 10 with both NSAID and placebo. Side effects were experienced by 3 in 10 with NSAID and 2 in 10 with placebo.

Quality of the evidence

The evidence was of very low quality. This means that the research does not provide a reliable indication of the likely effect. The chance that the real effect of NSAIDs could be substantially different is very high. Small studies like those in this review tend to overestimate results of treatment compared to the effects found in larger, better studies. The very low-quality evidence and the lack of any obvious benefit mean that NSAIDs cannot be regarded as useful for the management of fibromyalgia.

Oxycodone for pain in fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD012329/abstract

Citation: Gaskell H, Moore RA, Derry S, Stannard C. Oxycodone for pain in fibromyalgia in adults. Cochrane Database of Systematic Reviews 2016, Issue 9. Art. No.: CD012329. DOI: 10.1002/14651858.CD012329

Plain Language Summary

Bottom line

There is no good evidence to support or refute the suggestion that oxycodone, alone or in combination with naloxone, reduces pain in fibromyalgia.

Background

Fibromyalgia is a complex disorder characterised by widespread pain, fatigue, poor sleep, low mood, and other bodily symptoms. Common pain-relieving medicines such as paracetamol and ibuprofen are not usually considered effective. Opioid painkillers are commonly used to treat fibromyalgia, but there is uncertainty over how good they are.

Opioid painkillers are drugs like morphine. Morphine is derived from plants, but many opioids are also made by chemical synthesis rather than being extracted from plants. Oxycodone is a semi-synthetic opioid, manufactured from the opioid alkaloid thebaine, and is widely available.

This review replaces part of a review originally published in 2014, which examined how well oxycodone worked in pain in fibromyalgia and some other medical conditions. In this review, we examined only pain in fibromyalgia. In the previous review, we did not find any evidence that oxycodone is, or is not, of value in treating pain in fibromyalgia.

Study characteristics

In July 2016, we searched for clinical trials where oxycodone, either alone or in a fixed-dose combination with naloxone, was used to treat pain due to fibromyalgia in adults. We did not find any studies that met the requirements for this review.

Key results

There was no information from randomised controlled trials on the benefits or harms of oxycodone when used to treat pain in fibromyalgia.

Quality of the evidence

We rated the quality of the evidence as very low because there were no studies. Very low quality evidence means that we are very uncertain about the results.

Phenytoin for neuropathic pain and fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009485.pub2/abstract

Citation: Birse F, Derry S, Moore RA. Phenytoin for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2012, Issue 5. Art. No.: CD009485. DOI: 10.1002/14651858.CD009485.pub2

Plain Language Summary

Nerves which have been damaged by injury or disease can continue to produce pain. This type of pain is called neuropathic pain. Some antiepileptic medications can help neuropathic pain. Phenytoin is an antiepileptic medication, and the aim of this review was to assess how effective phenytoin is for neuropathic pain and fibromyalgia. We identified no good quality studies of phenytoin used in this situation. When used to treat epilepsy, phenytoin can cause potentially troublesome adverse events, affecting nervous tissue, the blood, and unborn children. Based on current evidence, phenytoin cannot be recommended for treating neuropathic pain. Other antiepileptic drugs such as pregabalin, gabapentin, and carbamazepine have been shown to be of value in neuropathic pain.

Pregabalin for pain in fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011790.pub2/abstract

Citation: Derry S, Cording M, Wiffen PJ, Law S, Phillips T, Moore RA. Pregabalin for pain in fibromyalgia in adults. Cochrane Database of Systematic Reviews 2016, Issue 9. Art. No.: CD011790. DOI: 10.1002/14651858.CD011790.pub2

Plain Language Summary

Bottom line

We found high quality evidence that pregabalin at daily doses of 300 to 600 mg produces a large fall in pain in about 1 in 10 people with moderate or severe pain from fibromyalgia. Pain reduction comes with improvements in other symptoms, in quality of life, and in ability to function.

Background

Fibromyalgia is characterised by persistent, widespread pain and tenderness, sleep problems, and fatigue. Common pain-relieving medicines such as paracetamol and ibuprofen are not usually considered effective. Medicines used to treat epilepsy or depression can be effective in some people with fibromyalgia and other forms of chronic (persistent, long-lasting) pain where there may be nerve damage. Pregabalin is an antiepileptic licensed to treat fibromyalgia in some parts of the world, in particular the USA.

This review is an update of one originally published in 2009, which examined the effects of pregabalin on all types of pain. In this review we have only examined fibromyalgia pain. The earlier review showed that pregabalin worked in a small proportion of people with fibromyalgia. This is the same as all other fibromyalgia treatments to date, and for chronic pain conditions generally. Our definition of 'worked' involved both a high level of pain relief and being able to take the medication over a longer period without intolerable side effects.

Study characteristics

We searched scientific databases for studies that looked at the effects of pregabalin in adults with fibromyalgia who had moderate or severe pain. The treatment had to last at least eight weeks. The evidence is current to March 2016.

Eight studies satisfied the inclusion criteria, including three new studies for this update. Five studies randomised 3283 participants to immediate treatment with pregabalin or placebo. Two studies identified 687 out of 1492 participants who had a good pain response and could take the medicine, and then randomised them to continued treatment with pregabalin or placebo. Study quality was good. One other had no useful data.

Key results

High quality evidence showed that 1 in 10 people with moderate or severe fibromyalgia pain reported a large fall in pain by a third to a half over 12 to 26 weeks. This is an outcome that people with fibromyalgia consider to be useful. The dose of pregabalin was 300 to 600 mg daily.

Side effects occurred in 8 or 9 people in 10, often while adjusting to the medicine. Particular side effects were dizziness (affecting 1 in 4 participants), drowsiness (1 in 7), weight gain (1 in 18), and peripheral oedema (1 in 19) (high quality evidence). Serious side effects were no more common with pregabalin than with placebo, affecting 1 or 2 in 100. About 1 in 10 more participants taking pregabalin withdrew from the study because of side effects, and 1 in 17 fewer withdrew because the medicine was not working.

Quality of the evidence

The evidence was mostly of high quality, which means we are very confident that the true effect lies close to that of the estimate of the effect in this review. Concern about how information was handled when people left the studies was offset by other information showing that results were not impacted by this to any important degree.

Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults

Link to Cochrane Libraryhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009183.pub2/abstract

Citation: Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD009183. DOI: 10.1002/14651858.CD009183.pub2

Plain Language Summary

Valproic acid and sodium valproate for neuropathic pain and fibromyalgia

Neuropathic pain is caused by nerve damage, often accompanied by changes in the central nervous sytem, and fibromyalgia is a related complex pain syndrome. Many people with these conditions are disabled with moderate or severe pain for many years. Conventional analgesics are usually not effective treatment options. In light of the fact that there are similarities between the pathophysiologic and biochemical mechanisms observed in epilepsy and in neuropathic pain, it is not surprising that antiepileptic agents can be used to treat neuropathic pain. The aim of this review was to investigate the efficacy and adverse events associated with use of sodium valproate and valproic acid for the treatment of chronic neuropathic pain and fibromyalgia. We identified three relevant studies, two in diabetic neuropathy and a third in post-herpetic neuralgia. Two of the three studies report significantly greater reduction in pain for valproate than placebo, but studies were small (≤ 45 participants) and provided insufficient data for pooled analysis, and the methods of analysis used may have overestimated treatment effect. Adverse events such as nausea, sedation, drowsiness, vertigo, and abnormal liver function are more common with valproate than placebo, but these studies were unsuitable to allow for a comprehensive assessment of harm.

There is insufficient evidence to support the use of valproic acid or sodium valproate as a first-line treatment for neuropathic pain.