Scheduled Acetaminophen to Minimize Neuropsychiatric Symptoms in Wernicke-Korsakoff Syndrome

After the first full day in the CLC, the nursing staff observed anger and agitation that seemed to start midafternoon and continued until around dinnertime. The veteran displayed verbal outbursts, refusal to cooperate with the staff, and multiple attempts to leave the CLC. With the guidance of a geriatric psychiatrist, risperidone 1 mg once daily as needed was initiated, and staff continued with verbal redirection, both with limited efficacy. After 3 days, due to safety concerns for the veteran, other CLC patients, and CLC staff, risperidone dosing was increased to 1 mg twice daily, which had limited efficacy. Lorazepam 1 mg once daily also was added. A careful medication review was performed to minimize any potential AEs or interactions that might have contributed to the veteran’s behavior, but no pharmacologic interventions were found to fully abate their behavioral issues.

After 5 weeks of ongoing intermittent behavioral issues, the medical team again met to discuss new treatment options.A case reported by Husebo and colleagues used scheduled acetaminophen to help relieve neuropsychiatric symptoms of dementia in a patient who exhibited similar behavioral issues and did not respond well to antipsychotics or benzodiazepines.⁸ Although our veteran did not express or exhibit obvious pain, the medical team chose to trial this intervention, and the veteran was started on acetaminophen 650 mg orally 3 times daily. A comprehensive metabolic panel, including GGT and thyroid-stimulating hormone, was performed before starting acetaminophen; no abnormalities were noted. The clinical examination did not reveal physical abnormalities other than ataxia.

After 5 days of therapy with the scheduled acetaminophen, the veteran’s clinical behavior dramatically improved. The veteran exhibited infrequent agitated behavior and became cooperative with staff. Three days later, the scheduled lorazepam was discontinued, and eventually they were tapered off risperidone. One month after starting scheduled acetaminophen, the veteran had improved to a point where the staff determined a safe discharge plan could be initiated. The veteran’s nystagmus resolved and behavioral issues improved, although cognitive impairment persisted.

Due to COVID-19, a teleconference was scheduled with the veteran’s spouse to discuss a discharge plan. The spouse was pleased that the veteran had progressed adequately both functionally and behaviorally to make a safe discharge home possible. The spouse arranged to take family leave from their job to help support the veteran after discharge. The veteran was able to return home with a safe discharge plan 1 week later. The acetaminophen was continued with twice-daily dosing and was continued because there were no new behavioral issues. This was done to enhance postfacility adherence and minimize the risk of drug-drug interactions. Attempts to follow up with the veteran postdischarge were unfortunately unsuccessful as the family lived out of the local area.

Discussion

Alcohol misuse is a common finding in many US veterans, as well as in the general population.^1,3 As a result, it is not uncommon to see patients with physical and psychological symptoms related to this abuse. Many of these patients will become verbally and physically abusive, thus having appropriate pharmacologic and nonpharmacologic interventions is important.

In this case study, the veteran was diagnosed with WKS and exhibited physical, cognitive, and emotional symptoms consistent with this disease. Although the physical symptoms improved with thiamine and abstinence from alcohol, their cognitive impairment, verbal outbursts, and aggressive demeanor persisted.

After using antipsychotic and anxiolytic medications with minimal clinical improvement, a trial of acetaminophen 650 mg 3 times daily was instituted. The patient’s behavior improved; demeanor became calmer, and they were easily redirected by the nursing staff. Psychological support was again employed, which enhanced and supported the veteran’s calmer demeanor. Although there is limited medical literature on the use of acetaminophen in clinical situations not related to pain, there has been research documenting its effect on social interaction.^9,10

Acetaminophen is an analgesic medication that acts through central neural mechanisms. It has been hypothesized that social and physical pain rely on shared neurochemical underpinnings, and some of the regions of the brain involved in affective experience of physical pain also have been found to be involved in the experience of social pain.¹¹ Acetaminophen may impact an individual’s social well-being as social pain processes.¹¹ It has been shown to blunt reactivity to both physical pain as well as negative stimuli.¹¹

Conclusions

A 2019 survey on alcohol and drug use found 5.6% of adults aged ≥ 18 have an alcohol use disorder.¹² In severe cases, this can result in WKS. Although replacement of thiamine is critical for physical improvement, psychological deficits may persist. Small studies have advanced the concept of using scheduled acetaminophen even when the patient is not verbalizing or displaying pain.¹³ Although more research needs to be done on this topic, this palliative approach may be worth considering, especially if the risks of antipsychotics and anxiolytics outweigh the benefits.