'Prehab,' SSRIs May Reduce Postsurgical Opioid Use

Nancy Melville

April 12, 2019

MILWAUKEE — Revised April 16 with additional comments — Following a strict preoperative rehabilitation protocol ("prehab") and use of antidepressants are both linked to reduced opioid use after surgery, two new studies suggest.

The first study, which included 175 veterans, showed that 92% of those who went through prehab before undergoing spinal surgery were opioid-free 1 year later vs 28% of those who did not go through prehab.

The multidisciplinary protocol included transitioning from opioid to non-opioid medications and enrollment in smoking cessation, exercise, and behavioral programs, as needed.

The study also showed greater improvement in scores of pain, chronic pain acceptance, and pain catastrophizing for the prehab group.

The second study assessed more than 11,000 veterans who underwent total knee arthroplasty (TKA) procedures. Results showed that perioperative use of selective serotonin reuptake inhibitors (SSRIs), but not use of norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs), was associated with a significant reduction in opioid use up to 30 days post-surgery.

"I was somewhat surprised to see SSRIs associated with reduced opioid use 30 days after TKA," lead author Jordan B. Starr, MD, Departments of Anesthesiology and Pain Medicine, University of Washington, Seattle, told Medscape Medical News.

"I was expecting more benefit from SNRIs/TCAs instead," Starr said.

Both the prehab study and antidepressants study were presented here at the American Pain Society (APS) Annual Meeting 2019.

Opioids for Life?

The prehab protocol was created amid efforts to reduce postoperative opioid overuse, a leading contributor to the opioid addiction crisis.

Lead investigator Sina Pourtaheri, MD, assistant professor in the Orthopedic Surgery Department at the University of California, San Diego, said that when he started in his other current position as director of spine surgery at the VA San Diego Healthcare System, he noticed a high rate of opioid addiction and chronic pain syndrome in patients with spinal disorders.

"I also noticed when these patients had spine surgery they rarely improved in terms of symptom relief, and the majority stayed on opioids for life," Pourtaheri told Medscape Medical News.

"This was not acceptable to me. Our patients deserved better," he said.

To explore the effects of the prehab protocol on reducing those problems, Pourtaheri and colleagues evaluated 175 veterans (90% men) with chronic pain and opioid addiction.

Among the study population, about half were treated prior to the implementation of the multidisciplinary protocol (mean age, 59.6 years), while the others were treated once the protocol was in place (mean age, 57.3 years).

All had undergone spine surgery between 2013 and 2017. Types of spinal surgery were similar between the two groups.

Under the prehab protocol for spine surgery, patients were required to transition from opioids to non-opioid medication, patients who were smokers had to enroll in a smoking cessation program, and those who were obese had to enroll in the MOVE! exercise program.

In addition, all participants were referred to behavioral medicine to address issues of alcohol dependence, if appropriate, and any underlying psychiatric concerns of anxiety, depression, or posttraumatic stress disorder (PTSD).

Patients who did not meet the preoperative goals either had their surgery delayed or canceled.

"Healthier Relationship With Pain"

Results showed that 92% of patients who met the goals of the prehab criteria were opioid-free 6 months or more following surgery, compared to just 28% of those receiving surgery prior to the protocol (P < .0001).

Meanwhile, improvement in scores on the visual analog scale for neck, back, arm, or leg pain from presurgery to 1-year postsurgery were twofold greater for patients in the prehab group, as were radiculopathy levels, compared to those without prehab (both, P < .001).

Significant improvements at 1-year postsurgery were also found for those in the prehab group vs non-prehab group in the 9-item Patient Health Questionnaire (8.0 pre-protocol vs 4.4 post-protocol, respectively; P < .001), the Chronic Pain Acceptance Questionnaire (58.8 vs 89.1, P < .001), and Pain Catastrophizing Scale (25.0 vs 12.6, P < .001).

"A multidisciplinary 'prehab' program for patients with opioid addiction and chronic pain syndrome going for spine surgery is efficacious at reducing opioid addiction and pain, improving quality of life and depression, and forging a healthier relationship with pain," the investigators write.

They note that the prehab program was developed by a multidisciplinary team of spine surgeons who were joined by practitioners in psychiatry, psychology, pain management, pharmacy, primary care, physical therapy, and nutrition.

The findings underscore that "treating patients with a holistic approach and not just fixing the spinal disorder is paramount for spinal care," Pourtaheri said. "Sometimes as spine surgeons we focus on how to fix the structural problem of the spine and not the patient as a whole."

He compared pain related to spine surgery to the experiences of pain with amputation, such as that patients who have had a leg amputation can often still feel the amputated limb.

Likewise, "if patients have had pain due to a structural problem to their spine for years and have been on pain medications for years, in order to make the pain go away you can't just address the structural problem," Pourtaheri said.

"The pain will not go away, just like the sensation of an amputated limb doesn’t just disappear from the mind," he added.

Vicious Cycle

The prehab program's criteria are based on evidence that factors such as opioid, nicotine, and alcohol use can negatively influence spine surgery success, as can obesity and psychiatric comorbidities.

"Despite this knowledge, risk-factors for poor outcomes are seldom addressed prior to surgery," the researchers write.

Pourtaheri noted that with the stakes as high as they are with the opioid crisis, physicians should not be hesitant to use prehab programs, which may not be as difficult as expected.

"Transitioning patients off opioids with non-opioid medications is a lot easier than it seems," he said. "There are several non-opioid medications that treat pain related to spinal disorders."

Perpetuating a cycle of opioid use is well known to accomplish little in actually treating the pain, Pourtaheri noted, adding that chronic opioid usage causes hyperalgesia (increased sensitivity to pain).

"Chronically blocking pain receptors with opioids actually increases the number of pain receptors, which causes the patient to experience more pain," he said.

"It's a vicious cycle to be on pain medications chronically and have chronic pain syndrome," Pourtaheri said. "As physicians, we need to put an end to it."

Treatment of psychiatric concerns such as anxiety and depression, which are known to be linked to chronic pain, is an important component of the prehab program. Although this study did not include data on antidepressant use, the issue was the focus of another study presented at the meeting.

Protective Effect?

"Depression is one risk factor for chronic post-surgical pain, but it is unknown if antidepressants modulate the risk for chronic post-surgical pain or prolonged postoperative opioid use in patients undergoing procedures at high-risk for chronic post-surgical pain," the authors of the TKA/antidepressants study write.

In their research, investigators used national VA data and identified 11,564 patients (90.6% men; 77% white; mean age, 65 years) who underwent TKA procedures between April 2012 and April 2016.

Of these patients, 1237 were using a perioperative SSRI and 482 were using either an SNRI or TCA. Perioperative use was defined as having had a prescription filled within 90 days before or after surgery, as well as during hospitalization.

Results showed that the use of SSRIs was associated with significant reductions in opioid use through 30 days after surgery (odds ratio [OR], 0.83; P = .008).

However, similar reductions were not observed with SNRI/TCA use (OR, 0.98; P = .868) after adjusting for factors such as age, body mass index, general or regional anesthesia use, non-opioid adjunct pain medication use, and comorbidities recorded in the VA Surgical Quality Improvement Program.

At 90 days, SSRI-related reductions in opioid use were no longer significant (OR, 0.87; P = .230), while SNRI/TCA use was associated with greater opioid use (OR, 1.34; P = .050). The use of opioids after 1 year, still not significant with SSRIs, was even greater with SNRI/TCA use (OR, 1.70; P = .014).

"To my knowledge, other studies have not shown similar results, but I am not aware of other studies that really asked the same questions we did," Starr said.

Starr noted an important finding: the improvements with SSRIs in reducing opioid use at 30 days were seen even in patients without depression, which could reflect the use of antidepressants for other indications in the VA population.

"The VA population is somewhat atypical because more patients take SSRIs for other indications, like anxiety or PTSD," he explained. "Ideally, a trial of SSRIs for postsurgical pain will include patients without depression as well."

He noted that if a causal relationship is established in the future between SSRIs and reduced opioid use, "it may be that reductions in anxiety and depression positively affect patients' perceptions of pain and/or attitudes towards recovery after surgery."

Ultimately, the findings underscore the potential benefits of SSRI treatment perioperatively.

"The significance of these findings is that they indicate SSRIs may be worth adding to postoperative pain regimens to reduce pain and opioid use, especially in high-risk patients or procedures," Starr said.

"However, this is only a retrospective study. So prospective research is needed to elucidate if there is a role for antidepressants as non-opioid analgesics in specific surgical populations," he added.

Analgesic Mechanism?

Commenting on the TKA/antidepressants study for Medscape Medical News, David Craig, PharmD, clinical pharmacologist, Moffitt Cancer Center, Tampa, Florida, said the findings offer important insights into how the various antidepressants interact with opioids.

"I find this study interesting as it could support the idea that the SSRIs were acting in some analgesic type of mechanism," said Craig, who was not involved with the research.

"The higher opioid requirements could also suggest that the TCAs and SNRIs were acting in an opposite fashion," he added. "It is known that the TCAs and some SNRIs could negatively interact with some opioids, so this could explain this finding of higher opioid doses needed."

However, he noted that because this was a pilot study, the findings should be interpreted cautiously.

"Clearly there is a relationship between pain and depression, but in this study there wasn't a consistent trend regarding opioid use and the presence or absence of an antidepressant," Craig said.

Another caveat is that the study does not specify which antidepressants the patients were receiving, "and not all opioids interact with antidepressants in the same way," he added.

"This information would have been vitally important to include, in my opinion," Craig said.

"Of course, there are also always limitations regarding genetic influence on study results when pharmacological agents, including opioids and antidepressants, are utilized," Craig said. Inevitably, "the question that often comes up is what role the patient's genetics play in the findings of the study."

The study authors have disclosed no relevant financial relationships. Craig reports having been a consultant to Nektar Therapeutics and SpecGx.

American Pain Society (APS) 2019: Abstract 363, Abstract 388.
Presented April 5, 2019.

For more Medscape Neurology news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.