(P308) Tricyclic Antidepressants and Diabetes-related Peripheral Neuropathy: Deprescribing Considerations for Brain Health

Key Takeaways of Your Research: Several current guidelines for treatment of painful diabetic peripheral neuropathy include tricyclic antidepressants, sometimes specifically amitriptyline, as treatment options without discussing the risk for long-term cognitive decline. Furthermore, none of the current guidelines encourage drug-free intervals to facilitate deprescribing medications used to treat diabetic peripheral neuropathy. A growing body of evidence associates use of anticholinergic medications with mild cognitive impairment and incident dementia. The association is consistent across multiple studies, including exposure over a decade prior to diagnosis of dementia. Consistently among the culprits are tricyclic antidepressants, particularly amitriptyline. Providers should ensure proper education and facilitate a discussion with persons with diabetes about the benefits and risks of adverse effects associated with long-term use of tricyclic antidepressants. Furthermore, providers and diabetes care and education specialists should advocate for drug-free intervals and facilitate deprescribing anticholinergic medications with significant cognitive risk used to treat painful diabetic peripheral neuropathy to promote brain health.

Background/Purpose: Anticholinergic medications are consistently associated with cognitive decline and incident dementia in epidemiologic studies. Tricyclic antidepressants (TCAs) are a treatment option for painful diabetic peripheral neuropathy (DPN) but are commonly associated with adverse events including CNS depression, cardiovascular risks, and significant anticholinergic burden. DPN treatment guidelines have an opportunity to incorporate appropriate content considering the long-term risks associated with TCA use. Research Hypothesis and/or Research Questions and Specific

Aims: Aim 1: Review current DPN guidelines for content related to cognitive burden associated with long-term TCA use. Aim 2: Highlight existing evidence supporting the risk of long-term anticholinergic use. Aim 3: Propose guidance on drug-free intervals and counseling points for providers who manage treatment for individuals with painful DPN. Methods/Methodology: A literature review was conducted, identifying treatment guidelines with recommendations for painful DPN. Each guideline was assessed for its recommendation to use TCAs, side effects discussed regarding TCAs, and any recommendation for drug-free intervals to facilitate deprescribing. Background literature was also reviewed associating TCAs with mild cognitive impairment and incident dementia to propose guidance on drug-free intervals to facilitate deprescribing.

Results: Multiple guidelines recommend TCAs for the treatment of DPN without a comprehensive discussion of their risks. Only two out of nine (22%) guidelines discuss cognitive effects of TCAs; limited to cognitive impairment in the context of increased fall risk in older adults. Upon literature review, a significant body of evidence supported the association between anticholinergic use and cognitive impairment or dementia. The severity of a medication’s effect on cognition can be evaluated by the Anticholinergic Cognitive Burden List. No guidelines recommend drug-free intervals or deprescribing for any medication used to treat DPN. Additional prospective research is necessary to address whether stopping anticholinergics reduces dementia risk. Conclusions (Impact on Diabetes Care and Education): Diabetes care and education specialists must discuss the long-term cognitive effects of TCA use in individuals experiencing DPN. Currently, no evidence-based guidelines for deprescribing exist, which presents an opportunity to study the advantages and disadvantages of deprescribing. Drug-free intervals might facilitate deprescribing of TCAs. An interval of two to four weeks may be appropriate to help diminish the incidence of cognitive decline and incident dementia. Source of Funding for this Research: None