- Sometimes doctors prescribe antidepressants for conditions other than depression — this is called off-label prescribing.
- Occasionally, when someone is suffering from ongoing pain, doctors will prescribe antidepressants to try to treat pain symptoms.
- A new study analyzed prior reviews in an effort to determine whether using antidepressants to treat pain should be standard practice.
- The study results showed that more often than not, using antidepressants to treat pain was not effective.
A group of researchers from Australia and other countries collaborated to analyze reviews on prescribing antidepressants to treat chronic pain issues.
The researchers utilized 26 different reviews in their analysis — these reviews covered using medications such as sertraline and amitriptyline for conditions such as fibromyalgia and rheumatoid arthritis.
While the researchers noted some medications were helpful for people with certain chronic conditions, they said doctors need to weigh the pros and cons with their patients. The results of the study are published in The BMJ.
Chronic pain overview
When someone undergoes an injury or illness and experiences pain, this typically clears up after the body goes through its healing process. However, other people have diseases or conditions that cause them to experience persistent pain — this is called chronic pain.
Some diseases and conditions that can cause chronic pain include fibromyalgia, rheumatoid arthritis, migraine, irritable bowel syndrome, and osteoarthritis.
According to the Centers for Disease Control and Prevention (CDC), a 2019 study showed that approximately 20% of adults in the United States experience chronic pain. Additionally, 7.4% of adults experience disruption in work due to their pain.
The CDC notes that chronic pain is “associated with decreased quality of life, opioid dependence, and poor mental health.”
There are a number of ways in which health providers attempt to treat chronic pain, ranging from physical therapy to medications. These include:
- physical therapy
- massage therapy
- transcutaneous electrical nerve stimulation (TENS)
- nonsteroidal anti-inflammatory drugs (NSAIDs)
- muscle relaxers
- prescription pain medication, including opioids and antidepressants.
The National Institutes of Health (NIH) mention that “physicians should always consider a multidisciplinary approach to providing treatment options as chronic pain does not respond to medical monotherapy alone.”
Why antidepressants for pain?
Pain treatments are not always effective. Additionally, some methods — such as the use of opioid medication — can contribute to additional problems such as addiction.
While it may seem odd to prescribe antidepressants for pain, Dr. Kelly Johnson-Arbor, not involved in the meta-analysis, explained why this happens in an interview with Medical News Today.
“Antidepressants are believed to increase the amounts of chemicals in the brain and spinal cord that are involved in pain pathways,” said Dr. Johnson-Arbor. “These chemicals, including norepinephrine and serotonin, play a role in the transmission of pain signals from the brain to the rest of the body.”
Dr. Johnson-Arbor is a toxicology expert and treats patients at MedStar Georgetown University Hospital in Washington, DC.
“By increasing the amounts of these chemicals in the central nervous system, antidepressants may block pain signals and improve pain,” continued Dr. Johnson-Arbor. “For this reason, antidepressants are often used to treat some types of pain, including nerve-related pain.”
The researchers searched multiple databases to find reviews for the study. Some of the requirements for study inclusion were for the reviews to have undergone peer review and for the efficacy of any antidepressant to be compared to a placebo.
From their research, the scientists found 26 reviews to include in their study. The reviews covered 156 trials that had a combined 25,000 participants.
The study authors found eight classes of antidepressants that were used to treat 22 different pain conditions.
The antidepressant classes included serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants. Some of the antidepressants included duloxetine (an SNRI), escitalopram (an SSRI), and imipramine (a tricyclic antidepressant).
Some pain conditions included fibromyalgia, back pain, rheumatoid arthritis, bladder pain syndrome, and chronic migraine.
The researchers compared antidepressants to the condition they were used to treat and described each one as “efficacious, not efficacious, or inconclusive.”
SNRIs most effective for treating pain
The results of this study are not very promising for the overall use of off-label prescription of antidepressants for pain.
“We found evidence of efficacy of antidepressants in 11 (26%) of the 42 comparisons included in this overview of systematic reviews,” write the authors.
Out of the reviews the study authors analyzed, they found that SNRI medications were best for some pain conditions.
“Moderate certainty of evidence suggested that SNRIs were efficacious for chronic back pain, postoperative pain, fibromyalgia, and neuropathic pain,” write the authors.
The SNRIs duloxetine (Cymbalta) and venlafaxine (Effexor) had a higher efficacy for pain treatment.
Tricyclic antidepressants showed little efficacy, despite being commonly prescribed for pain. The researchers noted that tricyclic antidepressants make up almost 75% of antidepressants prescribed for pain, yet their review shows this class is only effective for three out of 14 pain conditions.
While SSRIs were helpful with comorbid depression with pain, they were not otherwise beneficial for pain conditions.
Where SNRIs were helpful with fibromyalgia, there was no evidence of the benefit of SSRIs compared to placebo for this condition. Additionally, SSRIs were not helpful with back pain, functional dyspepsia, or non-cardiac chest pain.
“Recommending a list of antidepressants without careful consideration of the evidence for each of those antidepressants for different pain conditions may mislead clinicians and patients into thinking that all antidepressants have the same effectiveness for pain conditions,” says study author Dr. Giovanni Ferreira. “We showed that is not the case.”
Dr. Ferreira works for The Institute for Musculoskeletal Health and Sydney Musculoskeletal Health at the University of Sydney.
One concern with this study was the lack of industry-independent reviews the authors were able to consider. Dr. Sudhir Gadh, a board-certified psychiatrist based in New York City, noted this in an interview with MNT.
“The limited amount of industry-independent studies is a major limitation,” commented Dr. Gadh. “Another is the studies themselves and how their content is based on self-report rather than more objective metrics of pain relief — range of motion, strength, sleep, possible cytokine measurements.”
Despite this weakness, Dr. Gadh believes this line of research has merit:
“It’s very important for us to look at how antidepressant use can enhance pain resolution. We consider pain to be more peripheral than central, but it’s both with varying fractions. By being mindful of how untreated central pain processing affects recovery, we can be proactive.”
Dr. Johnson-Arbor also highlighted the industry limitation in her interview with MNT.
“A significant limitation of the study was that nearly half of the articles reviewed for this study were sponsored or otherwise connected to industry, meaning that those articles may have been affected by bias that could have altered the study results,” Dr. Johnson-Arbor explained.
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