Cochrane for Clinicians

Putting Evidence into Practice

Antidepressants to Treat Nonspecific Low Back Pain

adrienne kassis, MD, UCSF Department of Family and Community Medicine, San Francisco, California

The Cochrane Abstract on the next page is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Dr. Kassis presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www.cochrane.org/reviews/en/ab001703.html.

Clinical Scenario

A 42-year-old woman presents with a long-standing history of low back pain. Her pain has not improved with over-the-counter analgesics or physical therapy, and she is requesting a new pain medication. Treating her with an antidepressant is a consideration, but the benefits are uncertain.

Clinical Question

Are medications such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and atypical antidepressants effective for the treatment of nonspecific low back pain?

Evidence-Based Answer

Although antidepressants have been shown to be superior to placebo in some forms of chronic pain, they do not reduce pain or improve functional status or depression in patients with nonspecific low back pain.

Practice Pointers

Antidepressants are prescribed for a variety of chronic pain syndromes. Nearly one fourth of primary care physicians in the United States prescribe antidepressants for low back pain.1 There is some evidence to support this practice.2-4 The logic behind prescribing antidepressants for various pain syndromes is threefold: first, patients with chronic pain frequently have comorbid depression, and treating depression may increase pain tolerance; second, many antidepressants are thought to have an analgesic effect separate from their mood-elevating benefit; and third, the sedating effects of many of these medications are thought to improve insomnia in patients with low back pain. However, according to this Cochrane review, current evidence does not support the treatment of low back pain with antidepressants.

The authors of this study found 10 randomized controlled trials published between 1976 and 2005 that compared various antidepressant medications with placebo. Studies included a variety of antidepressant medications, including TCAs, SSRIs, and atypical antidepressants. Outcome measures varied and included decreased pain intensity, improved functional status, and improved mood. However, there was inconsistency between the trials with respect to patient selection (pain duration), antidepressant dose, treatment duration, and number of patients with depression. Six of the 10 studies were considered high-quality. The authors estimate that there are sufficient high-quality data to conclude that the evidence does not support the use of antidepressants to reduce pain or depression in patients with low back pain. This review does not apply to patients who have major depression or other pain syndromes (e.g., neuropathic pain, fibromyalgia).

Although this review concluded that antidepressants are not effective for the treatment of low back pain, other recent systematic reviews that used slightly different methods came to divergent conclusions. The Cochrane review included all antidepressants and all patients with low back pain (including acute and chronic), and patients with and without associated radiculopathy, herniated disc, and spondylolisthesis. It excluded back pain from a specific cause, such as infection, metastasis, or rheumatoid arthritis. It is possible that specific antidepressants might be effective for subgroups of patients with low back pain. The American College of Physicians and the American Pain Society recently published a joint practice guideline based on their own systematic review.5 This guideline recommends TCAs, but not SSRIs, for chronic low back pain.6 Additionally, the review addressed adverse effects of antidepressants. Not unexpectedly, this was a significant issue because the antidepressants studied were associated with a higher rate of dry mouth, constipation, drowsiness, and dizziness than placebo.

Address correspondence to Adrienne Kassis, MD, at adrienne.kassis@ucsfmedctr.org. Reprints are not available from the author.

Author disclosure: Nothing to disclose.

REFERENCES

1. Urquhart DM, Hoving JL, Assendelft WW, Roland M, van Tulder MW. Antidepressants for non-specific low back pain. Cochrane Database Syst Rev. 2008;(1):CD001703.

2. Institute for Clinical Systems Improvement. Health care guideline: assessment and management of chronic pain. March 2007. http://www.icsi.org/pain__chronic__assessment_and_management_of_14399/
pain__chronic__assessment_and_management_of__guideline_.html. Accessed May 6, 2008.

3. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007;(4):CD005454.

4. ACOG Committee on Practice Bulletin-Gynecology. ACOG Practice Bulletin No. 51. Chronic pelvic pain. Obstet Gynecol. 2004;103(3): 589-605.

5. Chou R, Huffman LH. Medications for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline [published correction appears in Ann Intern Med. 2008;148(3):247-248]. Ann Intern Med. 2007;147(7):505-514,I45.

6. Chou R, Qaseem A, Snow V, et al.; for the Clinical Efficacy Assessment Subcommittee. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society [published correction appears in Ann Intern Med. 2008;148(3):247-248]. Ann Intern Med. 2007;147(7):478-491,I45.

Cochrane Briefs

Over-the-Counter Medications for Acute Cough Symptoms

Clinical Question

Are over-the-counter (OTC) cough medications safe and effective in reducing acute cough symptoms in children and adults?

Evidence-Based Answer

It is uncertain whether OTC cough medications are effective in reducing cough symptoms in adults; in children, no trials show a statistically significant benefit in the treatment compared with the placebo groups. Overall, the quality of evidence is poor; adult studies show conflicting results from heterogeneous studies. Evidence from trials about adverse effects is limited; however, national databases have reported ingestion-related harms in children.

Practice Pointers

The authors of this Cochrane review found 17 trials in adults and eight trials in children. The 17 adult trials (n = 2,876) compared antitussives, antihistamines, expectorants, or combinations with placebo and measured self-reported and objective cough symptoms.

Two out of three adult studies of dextromethorphan, including one meta-analysis of five studies, found a statistically significant benefit: a 30-mg single dose was more effective than placebo in reducing cough symptoms, as measured by cough counts, frequency, effort, and intensity.

Based on the findings of two adult trials of codeine (n = 163) and three trials of antihistamines (n = 1,900), neither medication is more effective than placebo in reducing cough symptoms. Two adult trials (n = 356) comparing antihistamine-decongestant combinations with placebo showed conflicting results, with only the smaller of the two studies showing a statistically significant reduction in mean cough severity rating (mean severity rating 1.4 versus 2.0 out of 4 on days three to five [P < .05]).

Two adult trials compared guaifenesin with placebo with mixed results: in the larger study (n = 239), a greater percentage of patients in the guaifenesin group than in the placebo group reported reduction of cough frequency and intensity at 72 hours (75 versus 31 percent [P < 0.01]). The second study (n = 65) found no statistically significant reduction in cough frequency and intensity in the treatment group, but did show more participants reporting a reduction in sputum thickness in the treatment group compared with placebo (96 versus 54 percent [P = .001]).

In children, all treatment trials of medications available in the United States showed no statistically significant difference in cough-related benefits in the treatment group compared with placebo. Three studies of dextromethorphan, one trial of pediatric cough syrup combinations (dextromethorphan, guaifenesin, and pseudoephedrine; and dextromethorphan, guaifenesin, and pseudoephedrine), and two trials of antihistamine-decongestant combinations showed that these treatments are no more effective than placebo in reducing daytime or nocturnal cough symptoms in children.

Likewise, combination dextromethorphan and albuterol is no more effective than placebo in parent-reported symptom scores. Two trials (n = 243) comparing antihistamines with placebo showed no statistically significant difference in cough symptoms or in parent and child sleep.

Many studies did not report adverse events. Adverse effects reported for adults taking decongestant-antihistamine medications included dry mouth, headache, insomnia, and dizziness. Antihistamine in adults reported adverse effects, including drowsiness, giddiness, and headache. In children, decongestant-antihistamine combination adverse effects included reported hyper-activity and sleepiness.

The U.S. Food and Drug Administration (FDA), in January 2008, strongly advised against the use of OTC cough and cold medications in children younger than two years because of the risk of life-threatening side effects.1 A 2008 Centers for Disease Control and Prevention report estimated that in a two-year period (January 2004 to December 2005), about 7,000 children (younger than 12 years) were treated in emergency departments for adverse drug events attributable to cough and cold medications.2

The American Academy of Pediatrics (AAP) supports the 2008 FDA recommendation against the use of OTC cough and cold medications in those younger than two years. In their last published statement, the AAP concluded that parents should be educated about the lack of proven antitussive effects and the potential risks of these medications in children.3

The American College of Chest Physicians 2006 practice guideline on the evaluation and treatment of cough recommends treating adults who have acute cough caused by the common cold with a first-generation antihistamine-decongestant combination, such as dexbrompheniramine and sustained-release pseudoephedrine (Drixoral Cold and Allergy 6 mg/120 mg 12-hour tablet). It also endorses the use of naproxen (Naprosyn) in this circumstance.4

janelle guirguis-blake, MD

Source: Smith SM, Schroeder K, Fahey T. Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2008;(1):CD001831.

Author disclosure: Nothing to disclose.

REFERENCES

1. U.S. Food and Drug Administration. Nonprescription Drug Advisory Committee meeting. Cold, cough, allergy, bronchodilator, antiasthmatic drug products for over-the-counter human use. October 2007. http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4323b1-02-FDA.pdf. Accessed May 6, 2008.

2. Schaefer MK, Shehab N, Cohen AL, Budnitz DS. Adverse events from cough and cold medications in children. Pediatrics. 2008;121(4): 783-787.

3. Use of codeine- and dextromethorphan-containing cough remedies in children. American Academy of Pediatrics. Committee on Drugs. Pediatrics. 1997;99(6):918-920.

4. Irwin RS, Baumann MH, Bolser DC, et al.; for the American College of Chest Physicians (ACCP). Diagnosis and management of cough: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 suppl):1S-292S.

This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). See CME Quiz on page 25.

The series coordinator for AFP is Clarissa Kripke, MD, Department of Family and Community Medicine, University of California, San Francisco.

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