Nancy A. Melville

September 24, 2012

September 24, 2012 (Phoenix, Arizona) — Tricyclic antidepressants (TCAs) show greater efficacy than serotonin norepinephrine reuptake inhibitors (SNRIs) in the treatment of chronic pain related to neuropathic pain and fibromyalgia, a new retrospective study suggests.

"Overall, both drug classes were found to be similar in the treatment of depression, however SNRIs were inferior to TCAs in the reduction of average pain score," said coauthor Rajesh Kalra, MD, medical director of Chronic Pain Management with Kaiser Permanente, Union City, California.

"Obviously more studies are needed for better guidance in terms of alternative pain medications for fibromyalgia and neuropathic pain, but knowing that our patients are very complicated in terms of side effects, we should consider issues such as comorbidities before we prescribe these medications for chronic pain," he told Medscape Medical News.

"In our clinic, this study has helped us identify which medications help which patients and what to look out for."

Their results were presented here at the annual meeting of the American Academy of Pain Management.

Head-to-Head Comparison

TCAs are indicated in the treatment of the 2 chronic pain conditions, and although SNRIs are often also used (because they are associated with fewer side effects and a more selective mechanism of action), no head-to-head studies have compared the 2 medications in the treatment of neuropathic pain and fibromyalgia.

For the noninferiority trial, researchers evaluated 127 patients with pain enrolled in the Northern California Kaiser Permanente Chronic Pain Programs from January 2009 to December 2011.

The patients, aged 18 years or older, had received an SNRI or TCA for neuropathic pain or fibromyalgia and had documentation of an average pain score or Patient Health Questionnaire (PHQ-9) score before and after treatment.

The primary endpoints for the trial were a reduction in average pain score based on an 11-point Likert scale ranging from 0 to 10, with 10 being the worst pain, and a reduction in depression score based on the PHQ-9.

The results showed SNRIs to be inferior to TCAs in the primary endpoint of reduction in average pain score (P = .009). Noninferiority, however, was not demonstrated between the 2 drug classes in the reduction of depression. The difference of reduction in depression severity (in the form of PHQ-9) was -0.99 (95% confidence interval, -3.56 to 1.59; P = .56).

Anticholinergic side effects were associated with TCAs; dry mouth occurred significantly more often than with SNRIs (13% vs 2%; P = .02). Other TCA side effects included drowsiness and dizziness. Rates of constipation were similar to those in patients receiving SNRIs.

SNRI-associated side effects, including mood disturbances and insomnia, were clinically significant, with a corresponding statistical validation with TCAs (5% vs 0% and 14% vs 3%, respectively; P < .05).

The most frequently used SNRIs and average daily doses in the study included venlafaxine (87%, 116 mg), duloxetine (11%, 38 mg), and milnacipran (2%, 50 mg). The TCAs used were nortriptyline (90%, 42 mg), amitriptyline (6%, 50 mg), and desipramine (4%, 43 mg).

Complex Distinctions

According to Lawrence D. Robbins, MD, from the Robbins Headache Clinic in Northbrook, Illinois, another important issue to consider in choosing TCAs or SNRIs is the differences among drugs within the classes.

"TCAs are superior for pain, however not all TCAs are alike," he said. "Some in fact resemble SNRIs — amitriptyline for one," he explained.

In taking into account the depression that commonly accompanies chronic pain, the distinctions between the drugs become even more complex.

"For associated depression (with chronic pain), TCAs are underutilized, and several studies indicate that, at least after age 50, TCAs may be superior for depression to SSRIs [selective serotonin reuptake inhibitors]," Dr. Robbins said. "However, TCAs have higher discontinuation rates due to their side effects."

"In this study, interestingly, moods also were not better with SNRIs compared to TCAs, and SNRIs increased insomnia, so it points out that the old drugs still are very useful, and underused."

The authors have disclosed no relevant financial relationships.

23rd Annual Clinical Meeting of the American Academy of Pain Management. Abstract 4. Presented September 21, 2012.