The Efficacy of Selective Serotonin Reuptake Inhibitors for the Management of Chronic Pain

Abstract

OBJECTIVE: To assess the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the management of chronic pain. METHODS:Randomized, controlled trials of SSRIs in the management of chronic pain were identified by searching MEDLINE from 1966 to 1997 and by contacting the manufacturers of SSRIs available in the United States.MAIN RESULTS: Nineteen studies were identified, including 10 on the treatment of headache, 3 on diabetic neuropathy, 3 on fibromyalgia, and 3 on mixed-chronic pain. SSRIs were consistently helpful for mixed-chronic pain. Results were conflicting for migraine headache, tension headache, diabetic neuropathy, and fibromyalgia.CONCLUSIONS: SSRIs appear to be beneficial for mixedchronic pain. It is unclear, from the available evidence, whether SSRIs are beneficial for migraine headaches, tension headaches, diabetic neuropathy, or fibromyalgia. For those patients it may be reasonable to reserve SSRIs for those who fail to respond to other medications or who are intolerant of their side effects. KEY WORDS: chronic pain, management of; selective serotonin reuptake inhibitors. J GEN INTERN MED 1997;12:384-389.T he clinical management of chronic pain remains a challenge. Despite advances in pain research and clinical treatment, rates of disability due to chronic pain continue to climb worldwide. 1 Although chronic pain is treated with many medications, such as tricyclic antidepressants, nonsteroidal anti-inflammatory drugs, anticonvulsants, and opioids, none has shown outstanding efficacy. Narcotics are usually avoided because of the risk of developing tolerance, dependence, and functional deterioration. 2 Tricyclic antidepressants have proven efficacy in the treatment of chronic pain conditions such as diabetic neuropathy, fibromyalgia, chronic headaches, and post-herpetic neuralgia. 3 Their ability to relieve pain in these conditions appears to be independent of their antidepressant effect and may be related to their effect on neuronal reuptake of serotonin and norepinephrine. Unfortunately, side effects including dry mouth, constipation, orthostatic hypotension, and urinary retention often limit their use.Fluoxetine was introduced as the first selective serotonin reuptake inhibitor (SSRI) in the United States in 1988. Since then, SSRIs have become the most frequently prescribed antidepressant medications owing to their favorable side-effect profile. 4 More than half of antidepressant prescriptions written in the primary care setting are for conditions other than depression. 5 There is considerable interest in the use of SSRIs for the management of chronic pain, although they are not currently approved by the Food and Drug Administration for this purpose. This review summarizes available data on the value of these medications for pain control in several clinical situations. METHODSWe used the National Library of Medicine search engine to search MEDLINE from 1966 to 1997 using the medical subject heading (MeSH) term "pain," exploding it, and adding the following words in all fields: pain, ne...

The Pharmacotherapy of Chronic Pain: A Review

“…Of 10 controlled trials examining SSRIs in the treatment of chronic headache, three found SSRIs to be no better than placebo and two found them to be marginally superior to placebo. In the remainder, there was some improvement but the analgesic effect was not superior to the comparison drug (82). There are three placebo-controlled trials using SSRIs in diabetic neuropathy; the larger study (n=46) found no difference between fluoxetine and placebo (83), while the two smaller studies found that paroxetine (84) and citalopram (85) exhibited some analgesic effect compared with placebo.…”

Possible Involvement of Opioidergic and Serotonergic Mechanisms in Antinociceptive Effect of Paroxetine in Acute Pain

“…Paroxetine is the most potent inhibitor of serotonin re-uptake among SSRIs (6,7). In clinical practice, paroxetine is used in the treatment of depressive disorders and as an adjuvant drug in chronic pain (2,6).…”

Comparison of Antinociceptive activity of Fluoxetine with Morphine in Albino Rats

“…Recently, numerous open and controlled studies have shown that antidepressant drugs also have analgesic activity and particularly, selective serotonin reuptake inhibitors (SSRI) like Fluoxetine are effective in mixed, chronic pain [10] . It has also been shown that some antidepressants are superior to placebo in about 75% of studies [11] . A wide range of pain conditions are responsive to antidepressants, particularly diabetic neuropathy pain and probably rheumatoid arthritis [12] and migraine [13] , fibromyalgia [10] .…”