Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Selective serotonin reuptake inhibitors are effective for mixed chronic pain

ACP J Club. 1998 Jan-Feb;128:3. doi:10.7326/ACPJC-1998-128-1-003

Source Citation

Jung AC, Staiger T, Sullivan M. The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain. J Gen Intern Med. 1997 Jun;12:384-9.



To determine the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the management of chronic pain.

Data sources

Studies were identified by searching MEDLINE (1966 to 1997) using the keywords pain, neuropathy, migraine, fibromyalgia, serotonin uptake inhibitors, sertraline, paroxetine, fluoxetine, fluvoxamine, femoxetine, zimelidine, and citalopram. Additional studies were identified by searching bibliographies of review articles and by contacting manufacturers of SSRIs.

Study selection

Studies were selected if they were randomized, double-blind, controlled trials done on humans and published in English.

Data extraction

Data were extracted on study design; type of pain, including headache, chronic pain, neuropathy, and fibromyalgia; patient numbers; and clinical response.

Main results

19 studies met the selection criteria. 10 studies with 550 patients evaluated the effectiveness of SSRIs in patients with chronic headache. In 3 separate studies, improvement in chronic tension-type headache was found with paroxetine (P < 0.05), fluoxetine (P = 0.029), and fluvoxamine (P < 0.05). However, in 1 placebo-controlled study, no improvement was found with citalopram (P = 0.68). Studies on migraine headache had conflicting results. 1 study found that fluoxetine improved headache scores compared with placebo (P < 0.05), whereas another found that it had no benefit. 2 placebo-controlled studies of femoxetine showed no improvement compared with placebo; however, in 1 study of femoxetine and propranolol, both drugs showed equal improvement from baseline (P < 0.001). A trial comparing fluvoxamine and low-dose amitriptyline found both drugs to show similar improvement, but patients who received fluvoxamine had fewer side effects. 3 studies that evaluated 83 patients with diabetic neuropathy also had conflicting results. 1 study found no difference between fluoxetine and placebo for pain reduction (P = 0.34). However, in 2 other studies, patients who received paroxetine or citalopram had improved pain reduction compared with those who received placebo (P < 0.01 and P = 0.02, respectively). 3 studies of 83 patients with fibromyalgia were done; 2 studies found no differences between SSRIs (fluoxetine and citalopram) and placebo for fibromyalgia, whereas 1 study found improvement with fluoxetine, especially when used with amitriptyline. 3 studies of 119 patients with mixed chronic pain showed more pain relief and improvement in intensity in patients who received zimelidine, fluoxetine, or amitriptyline compared with placebo (P < 0.05). Fluoxetine showed greater pain relief than amitriptyline (P < 0.001).


Selective serotonin reuptake inhibitors are effective for mixed chronic pain, but it is unclear whether they are beneficial for tension headaches, migraine, diabetic neuropathy, and fibromyalgia.

Source of funding: No external funding.

For article reprint: Dr. A.C. Jung, Department of Medicine Residency Office, Box 356421, University of Washington, Seattle, WA 98195, USA.


This important review by Jung and colleagues about the efficacy of SSRIs in patients with chronic pain may be limited by publication bias and the varied group of conditions it covers. However, for clinicians who use SSRIs to treat patients with chronic pain, the review validates their use in some defined groups. Further, accumulating evidence suggests that SSRIs are better tolerated than tricyclic antidepressants (1) and may be preferred by patients and prescribers alike.

Treatment of chronic pain usually involves a multidisciplinary approach, and antidepressants are rarely prescribed in isolation. The interaction of different treatments may produce more clinically relevant results (2). The debate concerning the use of SSRIs is complicated and influenced by many factors, not the least of which is financial barriers (1).

Charlotte Feinmann, MD
Eastman Dental InstituteLondon, England, UK


1. Thase ME. Do we really need all these new antidepressants? Weighing the options. J Practical Psychiatry Behav Health. 1997;3:3-17.

2. Harrison S, Glover S, Feinmann C, Pearce C, Harris M. A comparison of antidepressant medication alone and in conjunction with cognitive behaviour therapy for chronic idiopathic facial pain. In: Jensen TS, Turner JA, Wiesenfield Z, eds. Progress in Pain Research and Management. Proceedings of the 8th World Congress on Pain, v 3. Seattle: IASP Press; 1997:663-72.