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One in seven people with dementia who lived outside nursing homes had overlapping prescriptions for three or more drugs that acted on the central nervous system (CNS), Medicare Part D claims data showed.

Of nearly 1.2 million Medicare beneficiaries with dementia, 13.9% were prescribed CNS-active polypharmacy, defined as more than 30 days of overlap for at least three drugs that were antidepressants, antipsychotics, anti-epileptics, benzodiazepines, non-benzodiazepine receptor agonist hypnotics, or opioids, reported Donovan Maust, MD, MS, of University of Michigan in Ann Arbor, and co-authors in .

Gabapentin (Neurontin) -- a drug approved for seizures, nerve pain, and restless legs syndrome that's frequently used for -- was the most common medication and was associated with 33% of polypharmacy-days.

CNS-active polypharmacy prescribing is "considered potentially inappropriate by the because it increases the risk of fall-related injury and impacts cognition," Maust said. "The specific combinations of an opioid with a benzodiazepine, an antipsychotic, or an anti-epileptic are of particular concern because these increase the risk of respiratory suppression and death," he told MedPage Today.

"In addition to the harms, it's not really that clear that these combinations are actually helpful," Maust pointed out. "Gabapentin is sort of the poster child for limited evidence of benefit. While it is included and classified as an anti-epileptic medication, I suspect the majority of use is off-label for chronic pain."

This is the first review of CNS-active polypharmacy in community-dwelling older adults with dementia, Maust noted. "In general, this type of prescribing has been examined much more closely in nursing home settings," he said.

The study looked at Medicare beneficiaries who had Part D coverage in 2018, including 1,159,968 older adults with dementia with a median age of 83. About two-thirds (65.2%) were women; 39.7% had Alzheimer's disease, and 14.6% had vascular dementia.

Of 161,412 patients who met the criteria for CNS-active polypharmacy, the median number of polypharmacy-days was 193. About 29% were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.

The majority of dementia patients (85.6%) who received CNS-active polypharmacy had non-cancer pain, most frequently arthritis and back pain. Nearly half (48.1%) had depression, 44.3% had anxiety, and 15.0% had insomnia.

Almost all (92%) polypharmacy-days included an antidepressant. About half (47.1%) included an antipsychotic, 40.7% included a benzodiazepine, and 32.3% included an opioid. The most common medication class combination was an antidepressant, an anti-epileptic, and an antipsychotic, which represented 12.9% of polypharmacy-days.

After gabapentin, the next most-prescribed medications that contributed to polypharmacy were trazodone at 26.0% and quetiapine (Seroquel) at 24.4%. "I suspect quetiapine, while considered an antipsychotic, is being used frequently for sleep or for anxiety," Maust noted.

The remaining medications in the top 10 spots were the antidepressant drugs mirtazapine (Remeron) at 19.9%, sertraline (Zoloft) at 18.7%, escitalopram (Lexapro) at 14.7%, and duloxetine (Cymbalta) at 14.5%, followed by three benzodiazepines: lorazepam (Ativan) at 12.9%, clonazepam (Klonopin) at 12.0%, and alprazolam (Xanax) at 12.0%. The most common opioids were hydrocodone (11.5%) and tramadol (9.2%).

Findings are limited to Medicare Part D beneficiaries in 2018. In 2019, the FDA issued a warning that serious breathing difficulties may occur in patients taking gabapentin or a similar drug, pregabalin (Lyrica), with opioids or other drugs that depress the central nervous system.

The study has other limitations, Maust and co-authors said. Claims may have overestimated polypharmacy exposure if prescriptions were filled but not taken, or if they were used only on an as-needed basis. Without knowing indications or dosages, it's not possible to assess whether prescribed drug combinations were appropriate.

The researchers are now looking at which provider prescribed each drug to patients with CNS-active polypharmacy to identify patterns and opportunities to educate or put systems in place after hospitalizations or other events.

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