Doctors sometimes prescribe antidepressants to treat chronic pain when other, more common pain relievers aren’t working. But new research suggests not all types of antidepressants have the desired pain-reducing effect.
For the study, published February 1 in the BMJ, researchers examined 26 systematic reviews, aggregating data from 156 clinical trials involving more than 25,000 participants who were prescribed either an antidepressant or a placebo to ease chronic pain. The investigators used a pain scale from 0 to 100 to estimate how well eight different antidepressants might work for a wide variety of chronic conditions such as back pain, migraine, rheumatoid arthritis, and fibromyalgia.
Scientists found not one instance where they could say with “high certainty” that a particular kind of antidepressant helped relieve chronic pain for a particular condition. There were only four instances where scientists could conclude with “moderate certainty” that a particular type of antidepressant might relieve a given type of chronic pain, says the lead study author, Giovanni Ferreira, PhD, a researcher at the Institute for Musculoskeletal Health at the University of Sydney in Australia.
“Most studies that have investigated the effectiveness of antidepressants for chronic pain are small and have very low quality,” Dr. Ferreira says. “We need better science in this field.”
SNRI Antidepressants Have the Best Evidence for Chronic Pain Treatment
In the new study, all four scenarios in which scientists concluded with “moderate certainty” that antidepressants worked for chronic pain involved drugs in a family of medicines known as serotonin and norepinephrine reuptake inhibitors (SNRIs). These drugs ease depression by increasing levels of two chemicals in the brain: serotonin and norepinephrine. Serotonin helps regulate mood, and norepinephrine helps improve attention and energy.
In the BMJ analysis, SNRIs were found to reduce chronic symptoms of back pain, fibromyalgia, neuropathic pain, and postoperative pain.
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Researchers found only “low certainty” evidence to support the use of SNRIs for pain caused by breast cancer treatment, chronic pain associated with depression, and pain caused by arthritis in the knee joints.
They also found “low certainty” evidence for two other types of antidepressants. Tricyclic antidepressants (TCAs) may relieve pain from irritable bowel syndrome, neuropathic pain, and chronic tension headaches. Selective serotonin reuptake inhibitors (SSRIs) may ease chronic pain associated with depression.
“In general, those antidepressants that address norepinephrine levels in the brain and spinal cord are more helpful than the classic antidepressants that only address serotonin,” says Chad Brummett, MD, the codirector of the Opioid Prescribing Engagement Network and a professor of anesthesiology at the University of Michigan in Ann Arbor, who wasn’t involved in the new study.
“Hence, the finding that serotonin and norepinephrine reuptake inhibitors (SNRIs) are more effective than the selective serotonin reuptake inhibitors (SSRIs) makes sense and is consistent with how most pain physicians practice,” Brummett says.
Treating Chronic Pain Can Be Challenging
Previous research suggests that antidepressants are routinely prescribed for chronic pain, and that patients are more likely to take these drugs for this purpose than for their mental-health benefits. One study of prescription records in the United States, the United Kingdom, and Taiwan, for example, found that chronic pain was the most common reason doctors cited for prescribing antidepressants, accounting for up to 68 percent of cases. In the United States, the study found, SSRIs were the most commonly prescribed antidepressants for chronic pain — which, the new BMJ study suggests, may not be effective in many cases.
This is happening in part because other prescription medicines for pain are imperfect, with limited effectiveness, dangerous side effects, or the potential for addiction. Opioids can be effective but carry a risk of addiction. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen can sometimes ease pain but increase the risk of kidney problems and heart attacks and strokes with long-term use. Another well-known over-the-counter pain medicine, acetaminophen, can ease some types of pain but carries a risk of liver damage with long-term use.
“In general, research on the role of antidepressants in chronic pain shows narrow benefits, but that is also true of nearly every medication for chronic pain,” says Christopher Goodman, MD, a clinical assistant professor of medicine at the University of South Carolina in Columbia, who wasn’t involved in the new study.
“Antidepressants are fairly safe — certainly safer than opioids and without the renal and cardiac risks of NSAIDs,” Dr. Goodman says. “They can be good options for people who have overlapping features of chronic pain and depression.”
One limitation of the study is that all of the smaller trials included in the analysis used different methods for assessing pain and a variety of treatment options for different forms of chronic pain, which may have made it difficult to detect small but meaningful treatment benefits. The analysis also didn’t examine how often people taking antidepressants for chronic pain also had an underlying psychological condition that might benefit from these drugs.
Some People Opt for Nondrug Pain Therapies
Medications aren’t the only option for managing chronic pain, Brummett notes.
“For some patients, no medications are needed at all — many prefer physical therapy, a home exercise program, or behavioral treatments, which are all very effective,” Brummett says. “For others, medications can be helpful.”
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