Kate Johnson

September 07, 2012

September 7, 2012 (Milan, Italy) — Patients on chronic opioid therapy for low back pain show cognitive deficits that appear to be reversible after treatment stops, according to new research.

When opioid therapy is replaced with nonpharmacologic, multidisciplinary pain management, cognitive function eventually improves to the level of healthy controls, reported investigator Haili Wang, MD, from University Hospital of Heidelberg, in Germany.

The findings are important, given the growing number of patients worldwide who are being treated with long-term opioids, Dr. Wang told Medscape Medical News.

"We should be careful when we prescribe opioids for longer than 3 months to patients who have chronic pain," she said. "After 3 months, we should evaluate whether the pain has improved or not. We had patients coming to us on the highest dose of opioids for a long time, but they didn't have improvement in their pain, and they had side effects such as constipation [and] dizziness, and they felt like they were…not so awake."

Results were presented here at the International Association for the Study of Pain 14th World Congress on Pain.

Impaired Cognitive Function

After observing these side effects in many of their low back pain patients taking chronic opioid therapy, Dr. Wang's team decided to compare opioid-treated patients (n = 37) with a group of unmedicated patients experiencing low back pain (n = 33), and with healthy controls (n = 25).

They used 3 subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB): the Choice Reaction Time (CRT) test to measure attention; Pattern Recognition Memory (PRM), a visual memory test; and the Spatial Span (SSP), a test of executive function, working memory, and planning.

In addition, they used the Trail Making Test (TMT), a measure of visual scanning, graphomotor speed, and mental flexibility, and the Mehrfachwahl-Wortschatz Test (MWT), a German language multiple choice vocabulary test.

At baseline, medicated patients were taking a mean daily morphine equivalent dose of 100.2 mg/day. On the visual analog scale, medicated patients had slightly higher pain scores than unmedicated patients (7.2 vs 6.6), and slightly higher depression and anxiety scores (11.7 and 10.39 out of 20 vs 9.24 and 10.06).

Baseline scores on the TMT and SSP cognitive tests were significantly worse for medicated patients than for unmedicated patients, and similarly, unmedicated patients performed worse than healthy controls.

Impaired cognitive function correlated with depression and anxiety, independent of opioid use, said Dr. Wang.

All pain patients were initiated into a nonpharmacologic multidisciplinary pain management program, and cognitive testing was performed again.

"We advise patients to stop their medication altogether because chronic low back pain is very complicated and multifactorial," explained Dr. Wang. "Our multidisciplinary pain therapy is based on biomedical, psychological, and social aspects."

At 3 weeks post initiation of the nonpharmacologic multidisciplinary pain management program, both patient groups showed cognitive improvement, with the previously medicated group improving the most, she said. By 6 months, both patient groups showed cognitive function comparable with that of healthy controls.

Good News

Asked to comment, Brigitte L. Kieffer, PhD, told Medscape Medical News that the findings of reversibility are "good news."

"I think this is a very interesting finding," said Dr. Kieffer, who is from the Institut de Génétique et de Biologie Moléculaire et Cellulaire, in Illkirch, France. "There have been very few human studies on opiate therapy and cognition and…[such] cognitive deficits have not even been well studied in animals."

"Opioid receptors are strongly expressed, for example, in the prefrontal cortex, which is important for decision making and self-control, so opioid therapy may alter these and other high-order brain functions as well," she added.

The researchers have disclosed no relevant financial relationships.

International Association for the Study of Pain 14th World Congress on Pain: Abstract PF 034. Presented August 31, 2012.