A potentially groundbreaking meta-analysis of 176 studies was published earlier this year in the Cochrane Database of Systematic Reviews that assessed individual antidepressant medications and whether they proved effective in treating chronic pain in adult patients. In this blog, I will explore the results and how they might soon impact chronic pain treatment methodologies in complex pharmacy management (CPM).
The far-reaching effects of chronic pain
Chronic pain is any long-standing pain — on-and-off or continuous — that persists beyond the usual recovery period of three months. The type of pain can be due to a primary condition or occur in the context of a disease. According to the American Academy of Pain Medicine, more than 1.5 billion people around the world suffer from chronic pain, and it is the most common cause of long-term disability in the U.S., affecting about 100 million Americans.
Chronic pain often has detrimental impacts on a person’s overall well-being, ability to work and physical capabilities. Consequently, it is one of the global leading causes for sickness-related absence and people being unable to work or return to work. Chronic pain is also one of the costliest health problems in the U.S., as it often results in medical expenses, lost income and productivity and compensation payments.
Effective chronic pain management can result in significant improvements in quality of life — including decreased anxiety and depression — and is essential for improvement of pain, mood, sleep and physical function.
Could antidepressants improve chronic pain?
Although antidepressant medications were originally developed to treat medical illnesses like depression, it can also be used “off-label” in clinical practice to treat other conditions, including chronic pain. Research suggests that antidepressants may be effective for pain because the same chemicals that affect mood might also affect pain, according to the meta-analysis.
However, not all medications are created equal — different class types of antidepressants work in different ways. Previous research has shown that certain antidepressants may be effective in reducing chronic pain with some benefit; however, this was the first review that examined first-line antidepressants across most common chronic pain conditions.
The Cochrane analysis leveraged relevant studies that compared any antidepressant with any other treatment for chronic pain, then compared all treatments against each other — allowing researchers to rank the effectiveness of different antidepressants from best to worst. The study excluded patients with depression and anxiety, as those mental health conditions already often accompany chronic pain.
Among the 176 studies reviewed across medical databases, the most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The three most common antidepressant drug classes investigated for their effects on chronic pain were selective norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs). Each class targets a different pathway and helps manage various mental health diseases.
Primary outcomes of the analysis included substantial (50% or higher from baseline) pain relief, and improvements in terms of pain intensity, mood and adverse effects, while secondary outcomes of the analysis included moderate improvements (between 30% and 50% higher than baseline) in terms of pain relief, physical function, sleep and quality of life.
One anti-depressant medication consistently ranked highest and proved superior to all others across efficacy outcomes: duloxetine (otherwise known by its brand name, Cymbalta). The analysis explained that duloxetine (Cymbalta), “probably has a moderate effect on reducing pain and improving physical function.” For every 1000 people taking standard-dose (60 mg) duloxetine, 425 will experience 50% — or substantial — pain relief, the study found. Additionally, the standard dose was equally as effective as a high dose (>60 mg) for most outcomes.
One alternate medication, milnacipran, often ranked as the next most efficacious antidepressant in chronic pain treatment, although the certainty of evidence was lower than that of duloxetine. Across all secondary efficacy outcomes (including moderate pain relief, physical function, sleep and quality of life), duloxetine and milnacipran again ranked highest with moderate-certainty evidence.
The study’s primary conclusion states that despite investigating 25 different antidepressants, the only medication researchers are certain about for treating chronic pain is duloxetine. Some evidence for milnacipran is promising, although further high-quality research is needed to be confident about any conclusions. Evidence for all other antidepressants was low certainty.
While the findings from this meta-analysis can be pertinent for future chronic pain treatment, many questions remain. As the average study included in the meta-analysis lasted 10 weeks, there is no usable data beyond that period. This information would be crucial to understanding long-term effects as most chronic pain lasts beyond 10 weeks. To that end, there is no reliable evidence concerning the safety of taking antidepressants for chronic pain, for example, and there is not enough data to be certain about subsequent unwanted effects of taking it and the length of treatment.
What this review could mean for CPM
Cochrane reviews can be particularly helpful in re-examining generic medications that have little new research surrounding its efficacy since the medication attained FDA-approved labeling years or decades earlier. That allows us to look at, for example, TCA’s — among the earliest antidepressant class developed, introduced in the early 1950’s — in comparison to duloxetine (Cymbalta), an SNRI medication that the FDA approved in 2004. In comparing the two, we can analyze: What have we seen in each drug’s history? What works, what doesn’t? Which patient profile might benefit from SNRIs, instead of TCAs, and vice versa?
In assessing any patient’s treatment, several factors must be weighed to find the right balance. No two patients are exactly alike — making it critical to adopt a people-focused approach. At Sedgwick, we focus on individualizing care while ensuring prescribing patterns are in line with evidence-based guidelines and that employees are receiving optimal support to facilitate their recovery.
We view patients’ cases retrospectively, and holistically. CPM nurses and pharmacists make recommendations to the injured worker’s prescribing physician with this goal in mind. Each recommendation is bolstered by sharp clinical reasoning and lies within the framework of current guidelines — all while aligning with the context of the patient’s medical history.
New research is critical, as evidence-based discoveries can inform future updates to the national guidelines used daily to recommend treatments to patients. Due to the guidelines’ ever-changing nature, CPM clinicians consistently reassess best practices to ensure the best possible treatment is in place.
Sedgwick’s complex pharmacy team is in the process of reviewing best practices and routing rules, while watching closely for updated national/state guidelines considering this analysis. The potential impact this might have is yet to be determined — until then, we will continue adapting our best practices to better support injured workers.
Learn more — read about Sedgwick’s pharmacy solutions for U.S. workers’ compensation claims.