Chronic pain poses a significant public health crisis, affecting about 50 million Americans, with 20 million unable to work due to its debilitating severity. To alleviate their suffering, millions are prescribed antidepressant medications.
However, a recent comprehensive review of studies reveals that many prescriptions for antidepressants used to manage chronic pain lack adequate and reliable evidence to support their effectiveness. Moreover, the potential risks associated with their usage remain poorly understood.
Antidepressant drugs are typically prescribed for treating depression, but they’re also used for pain relief, especially for chronic pain conditions. Although the exact mechanism by which antidepressants alleviate pain is not fully understood, various theories have been proposed.
“While many mechanisms of action are theorized, including specific activity and action anywhere between the peripheral and central nervous system, these drugs may be effective by restoring some degree of normal nervous system function to baseline,” Dr. Kevin Zacharoff, a chronic pain and opioid-use expert, told The Epoch Times.
“It is possible that these drugs are effective by restoring some degree of normal nervous system function to baseline.”
One potential explanation is the elevation of certain neurotransmitter levels in the spinal cord, potentially reducing pain signal transmission.
Antidepressants may also enhance the activity of neurotransmitters like serotonin and norepinephrine, which play a role in regulating pain perception. By increasing the levels of these neurotransmitters, antidepressant medications could modify pain signaling pathways in the nervous system.
Zacharoff emphasized that antidepressants are typically prescribed as an adjunct pain treatment. “This means medications which can be used to enhance the effects of pain medications, treat concurrent symptoms, and provide analgesia for other types of pain,” he said. “In this context, which would generally mean in addition to more traditional medications, such as opioid analgesics, nonsteroidal anti-inflammatory drugs, or acetaminophen,” he added.
Zacharoff also said that patients with chronic pain might experience varying degrees of coexisting anxiety, depression, or other mental health symptoms that could potentially benefit from the inclusion of an antidepressant in their pain management plan.
Dr. Timothy B. Sullivan, chair of the Department of Psychiatry and Behavioral Sciences at Northwell Health at Staten Island University Hospital, suggests that in certain cases, an antidepressant may be prescribed for pain instead of conventional opioids or NSAIDs. “Due to their potential for inadvertent misuse, as well as intentional misuse, opioids should be used sparingly, especially in the setting of chronic pain,” he said. “The problems associated with long-term addiction to opioids has been clearly highlighted in the literature and in the media.”
He added that although NSAID medications are effective and not associated with addiction, they can have side effects, such as gastric irritation and an increased risk of bleeding, which may limit their use.
Only 1 Drug Showed Effectiveness
A two-year review of prior studies conducted by the non-profit group Cochrane analyzed 176 trials involving nearly 30,000 participants undergoing treatment for three primary types of chronic pain: fibromyalgia, nerve pain, and musculoskeletal pain. The review encompassed a wide range of 25 different antidepressant medications.
The study reviewed the most commonly prescribed antidepressant drugs, including:
- Citalopram, a selective serotonin reuptake inhibitor (SSRI), and amitriptyline, a tricyclic antidepressant. Both medications treat neuropathic pain, which is chronic pain caused by nerve damage.
- Fluoxetine, which is used to treat nociceptive pain. It originates from tissue damage caused by physical or chemical causes such as surgery or chemical burns.
- Paroxetine, which is commonly prescribed as an adjunct medication for bipolar disorder, but is also used for the treatment of chronic headaches, as well as the management of symptoms like tingling, pain, or numbness in the hands and feet.
- Sertraline, which is usually prescribed to alleviate symptoms of obsessive-compulsive disorder and has also been shown effective in one of the studies reviewed for the treatment of noncardiac chest pain and chronic pelvic pain.
- Duloxetine, which is prescribed to manage major depressive disorder and generalized anxiety disorder. The medication also treats fibromyalgia, diabetic peripheral neuropathy, and chronic musculoskeletal pain.
Sullivan noted that the dosage of antidepressants used in the treatment is generally lower than those used for depression, indicating that the pain-relieving properties of these drugs may be independent of their antidepressant effects.
However, despite this expectation, the review found little evidence to support this notion.
“Our review found no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for their safety for chronic pain at any point,” lead author of the study, Tamar Pincus, a professor in health psychology at the University of Southampton, said in a statement.
Nonetheless, one antidepressant showed promise in providing short-term pain relief.
“We did find that duloxetine provided short-term pain relief for patients we studied, [but] we remain concerned about its possible long-term harm due to the gaps in current evidence,” Pincus said.
Duloxetine has been associated with potentially severe side effects, including a specific type of glaucoma, blurred vision, trouble with thinking, and fainting.
The review also found that duloxetine was consistently the highest-rated medication, demonstrating equal effectiveness in treating fibromyalgia, musculoskeletal pain, and neuropathic pain. Furthermore, researchers concluded that standard doses of duloxetine appear to be as effective in reducing pain as higher doses.
“The only reliable evidence is for duloxetine,” Dr. Hollie Birkinshaw, study co-author and postdoctoral research associate at the University of Southampton, said in the statement. “Adopting a person-centered approach is critical to treatment, and when patients and clinicians decide together to try antidepressants, they should start from the drug for which there is good evidence,” she added.
Did Researchers Find a Lack of Effectiveness or Lack of Evidence?
According to Sullivan, the evidence regarding the effectiveness of other antidepressants, whether in the short or long term, was not strong enough to draw definitive conclusions.
Zacharoff explained that the Cochrane review of studies aimed to assess the scientific evidence supporting the benefits of antidepressant therapy in managing chronic pain in adults. “This review did not yield a significant amount of evidence for them in the majority of cases,” he said.
But, Zacharoff pointed out, this lack of evidence does not necessarily mean that antidepressants have no beneficial effect as adjuvant therapeutic agents for chronic pain. They might still be helpful for “people who have chronic pain along with anxiety and/or depression, which might be a significant number of people,” he noted.
Adults with fibromyalgia, which is long-lasting pain throughout the body, are more than three times more likely to have major depression than those without the condition, according to the U.S. Centers for Disease Control and Prevention (CDC).
What this means for patients, according to Zacharoff, is that a patient-centered and individualized pain treatment plan should take into account the potential benefits of adding an antidepressant medication, considering the specific context of each patient, including coexisting medical conditions and other risk factors.