Pain Patients at Cognitive Risk From Anticholinergic Burden?

Pauline Anderson

April 15, 2013

Fort Lauderdale, Florida — Young patients with chronic pain who take medications other than opioids to cope with their symptoms may experience cognitive adverse effects from these drugs, a new study has found.

Although researchers expected that patients with chronic pain would have a higher anticholinergic cognitive burden than healthy persons, they were surprised to find that the highest burden was among those aged 30 to 39 years.

"Physicians should be aware of the potential cholinergic effects of medicines they prescribe to patients and whether or not there's a cumulative effect to these medicines," said lead author Cady Block, a PhD candidate at the University of Alabama at Birmingham with an interest in the neuropsychology of pain.

She presented the findings here at the American Academy of Pain Medicine (AAPM) 29th Annual Meeting.

Common Medications

The study included 30 patients with chronic pain who had an average age of 40.51 years; 62.10% were female, and 86.2% were white. The average number of medications was 3.93, and the average pain intensity rating during testing was 4.76. No patients were using opioid analgesic medications.

Patients were compared with 30 control patients (average age, 38.56 years; 56.70% female and 70.0% white). In this group, the average number of medications was 1.20 and the average pain intensity rating was 0.14.

Common medications that have anticholinergic effects include those taken for pain (atropine, codeine), for sleep (alprazolam, amitriptyline), for mood (bupropion, haloperidol), for gastrointestinal discomfort (dimenhydrinate, loperamide), and for cardiac issues (atenolol, dipyridamole).

These drugs block cholinergic transmission at muscarinic receptor sites. These receptors mediate the primary cognitive effects attributed to cholinergic pathways, including attention, learning, and short-term memory.

Researchers used the Anticholinergic Cognitive Burden (ACB) Scale developed at the Indiana University Center for Aging Research. The scale identifies the severity of anticholinergic effects of prescription and over the counter (OTC) medications divided into "possible" (score of 1) and "definite" (score of 2 or 3 depending on the strength of the effect) categories.

The easy-to-use scale, available online, "is a nice way to capture potential cognitive effects of these medicines, which as a variable are hard to account for sometimes in research," commented Block. This is the first time that the scale, which is typically applied in an older population, was used in patients with chronic pain, she said.

Researchers also used several neuropsychological tests to measure psychomotor speed, attention/concentration, memory, and executive function.

After adjustment for demographic characteristics, patients with chronic pain had a significantly higher ACB score (P < .01) than the controls. Those in the 30- to 39-year-old age group had the highest ACB scores. Whereas patients in this younger age group took about the same number of medications as older persons (3.66 vs 4.02), the ones they took were more likely to have anticholinergic properties.

The executive function of patients with chronic pain who have a higher ACB score appeared to be affected. On the Wisconsin Card Scoring Test-64, they made more perseverative errors than healthy controls (P = .05).

It's typically older people who have neuropsychological deficits with the use of anticholinergic medications. As the body ages, the central nervous system becomes more sensitive to these medications.

The study should serve as a reminder that when a patient needs a different medication, physicians might consider an option that doesn't increase the risk for cognitive dysfunction, said Block.

Polypharmacy a Problem

Polypharmacy among patients with chronic pain is a growing problem. These patients take medications not only for their pain but also for depression, anxiety, sleep problems, and adverse drug effects, such as constipation and drowsiness, said Block. As well, these patients might reach for OTC medications that can also have cholinergic effects.

Block sees "a big role" for neuropsychological assessment in pain management, and the ACB scale could be a valuable addition to assessment. For example, she said, it could be used to assess how patients are doing before and after an intervention to find out what happens in the aging population as they are being treated for pain, and to assess pain in the rehabilitation population, she said.

Keith Susko, MD, a specialist in pain relief and physical medicine in Fort Myers, Florida, found the study results "surprising" and novel.

"She's right on target with this problem with the anticholinergic drugs effecting cognition of patients, which has been overlooked. She has overturned some rather surprising findings here where there was actually a worse response in the younger age group of 30-39 years than in the elderly age group due to anticholinergic effects."

There's not enough being done on the neuropsychology of pain, added Dr. Susko.

The study was part of a larger IIS grant funded by Teva Pharmaceuticals.

American Academy of Pain Medicine (AAPM) 29th Annual Meeting. Poster 221. Presented April 12, 2013.