Duloxetine for treating painful neuropathy or chronic pain
Abstract
Background
Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor licensed for the treatment of major depressive disorders, urinary stress incontinence and the management of neuropathic pain associated with diabetic peripheral neuropathy. A number of trials have been conducted to investigate the use of duloxetine in neuropathic and nociceptive painful conditions.
Objectives
To assess the benefits and harms of duloxetine for treating painful neuropathy and different types of chronic pain.
Search methods
We searched The Cochrane Neuromuscular Group Specialized Register (10 March 2009), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2009), MEDLINE (January 1966 to March 2009), EMBASE (January 1980 to March 2009), and www.clinicaltrials.gov to March 2009 and the reference lists of identified publications for trials of duloxetine used for the treatment of painful peripheral neuropathy or chronic pain.
Selection criteria
We selected all randomised or quasi‐randomised trials of any formulation of duloxetine, used for the treatment of painful peripheral neuropathy or chronic pain in adult participants.
Data collection and analysis
Two authors extracted data independently onto a specially designed proforma and cross checked them.
Main results
Six trials were identified including 2220 participants. Three studies included participants with painful diabetic neuropathy and three treated participants with fibromyalgia. Duloxetine at 60 mg daily is effective in treating painful diabetic peripheral neuropathy in the short‐term to 12 weeks with a risk ratio (RR) for 50% pain reduction at 12 weeks of 1.65 (95% confidence interval (CI) 1.34 to 2.03), number needed to treat (NNT) 6 (95% CI 5 to 10). Duloxetine at 60 mg daily is also effective in fibromyalgia over 12 weeks (RR 50% reduction in pain 1.57, 95% CI 1.20 to 2.06; NNT 8, 95% CI 5 to 17) and 28 weeks (RR 1.58, 95% CI 1.10 to 2.27). Adverse events were common in both treatment and placebo arms but more common in the treatment arm with a dose dependent effect. Most side effects were minor, but 16% of participants stopped the drug due to side effects. Serious adverse events were rare.
Authors' conclusions
There is moderately strong evidence that duloxetine 60 mg and 120 mg daily are efficacious for treating pain in diabetic peripheral neuropathy and fibromyalgia but 20 mg daily is not. Minor side effects are common at therapeutic doses but serious side effects are rare. Direct comparisons of duloxetine with other antidepressants and with other drugs already shown to be efficacious in neuropathic pain would be appropriate and should include unbiased economic analyses.
PICOs
Plain language summary
Duloxetine for neuropathic pain
Duloxetine is a drug used to treat depression and incontinence and it can be also be useful in treating certain types of pain. Pain can be produced spontaneously from damaged parts of the nervous system used to transmit pain information to the brain (neuropathic pain). When this damage is to nerves outside the spinal cord it is called a neuropathy. Pain is also produced when the nerves sense damage to another tissue (for example a pin being pressed into the skin) and this is called nociceptive pain. Some pain is of unclear origin, as no damage to the nervous system or to the tissues to which the nerves connect can be identified. This sort of pain happens, for example, in fibromyalgia. Duloxetine is also used to treat depression and problems with bladder function but the objective of this review was to consider all the evidence from double‐blind randomised controlled trials relating to the use of duloxetine to treat painful neuropathy and chronic pains of all sorts.
We looked at all the published scientific literature and identified six drug trials involving a total of 2220 participants that were of sufficient quality and reliability to include. Three tested the effect of duloxetine on painful diabetic neuropathy and three on the pain of fibromyalgia.
The usual dose of duloxetine is 60 mg. At this dose, there was moderately strong evidence that duloxetine reduced pain in both painful diabetic peripheral neuropathy and fibromyalgia. In diabetic peripheral neuropathic pain the relative rate of 50% improvement with duloxetine 60 mg per day was just over one and a half times more than with placebo. This equates to needing to treat 6 people with diabetic peripheral neuropathic pain with duloxetine to achieve a 50% response in one person. The effect on fibromyalgia was similar. A dose of 20 mg was not effective and a higher dose of 120 mg was no more effective than 60 mg.
Most people taking duloxetine will have at least one side effect. These are mostly minor and are commonly feeling sick, being too awake or too sleepy, developing a headache, having a dry mouth or becoming constipated or dizzy. About one in six people stop duloxetine because of side effects but serious problems caused by duloxetine are very rare.
Duloxetine may be about as good at reducing these sorts of pain as some of the other antidepressant drugs on the market but the evidence supporting this comparison is not strong.
We have concluded that duloxetine is useful for treating pain caused by fibromyalgia and diabetic neuropathy and it seems to be about as effective as other similar drugs already on the market. No direct comparison has been performed between duloxetine and any of these other drugs. As yet it is not clear whether the use of duloxetine is cost effective when compared to the other drugs already in use.
