Researchers in a recent study, published in the BMJ, 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 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.
The current study provided evidence for effectiveness of serotonin and norepinephrine reuptake inhibitors (SNRIs). All four scenarios in which scientists concluded with “moderate certainty” that antidepressants worked for chronic pain involved 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.
“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 co-director 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.
Previous research suggests that antidepressants are routinely prescribed for chronic pain and are used more often for this purpose than their mental-health benefits. In the United States, a study of prescription records found that SSRIs were the most commonly prescribed antidepressants for chronic pain which, according to the new BMJ study, may not be effective in many cases.
The preference for antidepressants can be explained partly due to the limited effectiveness, dangerous side effects, or the potential for addiction of other prescription medicines for pain. Opioids can be effective but carry a risk of addiction. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen increase the risk of kidney problems, 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.
“Antidepressants are fairly safe certainly safer than opioids and without the renal and cardiac risks of NSAIDs,” says Dr Christopher Goodman, MD, a clinical assistant professor of medicine at the University of South Carolina in Columbia. “They can be good options for people who have overlapping features of chronic pain and depression.”
The study had certain limitations. Due to inconsistencies in the methods used to assess pain, and the variety of treatments tested, it is difficult to determine the effectiveness of the treatments, particularly when the benefits are small but meaningful. Additionally, the analysis didn’t examine how often people taking antidepressants for chronic pain also had an underlying psychological condition that might benefit from these drugs.
Medications aren’t the only option for managing chronic pain. “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.