Use of Compounded Dextromethorphan–Quinidine Suspension for Pseudobulbar Affect in Hospice Patients

Introduction

Pseudobulbar affect (PBA) consists of unprovoked and uncontrollable episodes of laughing and/or crying, which are not congruent to the patient's emotional state. It is often seen as a sequela of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, traumatic brain injury (TBI), dementia, Parkinson's disease (PD), and other neurological diseases or brain injuries. ¹ In end-of-life situations, the symptoms can be especially distressing to family and friends during an already heightened emotional time. Loved ones often feel guilty or confused as they associate the emotional displays as caused by their interaction with the patient.

A combination product consisting of dextromethorphan 20 mg and quinidine sulfate 10 mg (DMQ) under the trade name Nuedexta^® was FDA approved for use in PBA in 2010 and has been shown to be effective across various causes of PBA. ² Unfortunately, many hospice patients are unable to swallow any solids or semisolids as they decline toward death. We present here two cases in which we used a compounded DMQ suspension successfully to treat PBA symptoms in the weeks before the patients' death.

Case Description

Patient #1 was a 97-year-old female residing in a skilled nursing facility (SNF) with a terminal diagnosis of Alzheimer's disease (AD) with dementia and comorbidities, including chronic anemia, kidney disease, hypertension, and a history of osteomyelitis. During her final months, the patient presented with unpredictable bouts of crying and weeping, which ultimately led to a diagnosis of PBA. ³

In 2015, she began a decline of a few months, which led to her subsequent hospice admission. Upon her admission, the patient was alert, oriented, and having random bouts of weeping as per the previous caregivers. Over the next few days, the patient's uncontrollable crying and weeping had continued, along with increased agitation and anxiety. There had also been attempts by the patient to move around her room, which had led to multiple falls.

She was started on lorazepam 0.25 mg by mouth every 12 hours as needed. However, her symptoms continued. According to the SNF behavior monitoring record, she had 14 recorded episodes of weeping and 4 recorded attempts to self-ambulate over the next 10 days of her stay. On the 11th day, with symptoms still present, a diagnosis of PBA was made. Upon diagnosis and family agreement, lorazepam was discontinued and DMQ capsules were initiated according to manufacturer recommendations with no signs of adverse effects or complaints. Over the next 29 days, with all doses of DMQ being administered, five episodes of weeping were reported as well as three attempts to self-ambulate with no signs of adverse effects, noting that three of the five weeping episodes were recorded within the first 24 hours of DMQ initiation.

Twenty-nine days into her DMQ regimen, the patient's oral intake became compromised. With the inability to tolerate oral solid medications, a compounded DMQ suspension (19.7 mg DM/11.1 mg Q per 10 mL) was substituted at a dose of 10 mL orally twice daily to be consistent with the previous DMQ capsule administration.

After switching from DMQ capsule to the DMQ suspension, there were no recorded weeping episodes, attempts to self-ambulate, or adverse reactions over a period of 25 days until her death according to the SNF behavior monitoring record. Adherence remained high as the patient tolerated most doses, only refusing the two doses the day before her death and one morning dose the day of her death.

Patient #2 was a 70-year-old woman diagnosed with having secondary malignant neoplasm of the brain following an admission to the emergency department with fever, weakness, slurred speech, and headaches. Upon receiving this diagnosis, she declined surgery, chemotherapy, and radiation therapies and was admitted to hospice home care. During her stay, she developed PBA and was also treated with DMQ suspension with good effect.

Upon admission, she was alert and oriented and able to make her needs known despite mild confusion. The patient needed total care for all daily activities and had a decreased appetite with occasional dysphagia; only tolerating small bites and sips of liquids. The patient refused aggressive treatments and only wished to receive comfort and support. Approximately 1 month into her hospice home care admission, she became very weepy and anxious despite adequate pain control. She also began to refuse or cheek her oral solid medications. With medication adherence as a concern, her lorazepam was switched to a concentrated liquid formulation and morphine sulfate extended release oral tablet was converted to liquid morphine given around the clock and delivered sublingually.

The patient's weeping and anxious episodes continued for three more days, and when asked why, she stated “I don't know why I am crying.” After a full review of her clinical history and current clinical status, PBA was suspected. With patient and family/caregiver agreement, DMQ was initiated for her suspected PBA. However, due to her intolerance to oral medications, the patient was started on the DMQ suspension. The caregivers were instructed to give 10 mL orally once daily for 1 week and then increase to 10 mL orally twice daily; similar to the dose escalation of Nuedexta manufacturer recommendations. ⁴

Within one day of starting the quinidine sulfate/dextromethorphan suspension, her weeping episodes were decreased to an acceptable level as per nursing staff and family with no signs of adverse drug reactions. Weekly checks from nursing, massage therapist, and spiritual care reported minimal weeping until her passing 19 days after the initiation of DMQ suspension.

Comment

Hospice patients are disproportionately affected by PBA. Data from the National Hospice and Palliative Care Organization in 2013 show that dementia accounts for 15.25% of primary admission diagnoses, while stroke/coma, non-ALS motor neuron disease, and ALS account for 5.2%, 1.8%, and 0.4%, respectively. ⁷ As these are primary diagnoses, these data do not account for the prevalence of conditions associated with PBA that are comorbid to the primary diagnosis. In addition, cancer accounts for 36.5% of hospice patients, but since many patients decline further investigation, it is unclear how many could have PBA due to brain metastasis.

Prevalence of PBA has been reported in several resources with wide ranges depending upon the method used to detect PBA. Schiffer and Pope reported the following ranges of prevalence: AD 10%–74%, ALS 2%–49%, MS 7%–95%, stroke 11%–52%, and TBI 5%. ¹ The PBA Registry Series (PRISM) enrolled patients with six common neurological conditions associated with PBA to establish prevalence. PRISM was designed to prospectively estimate the prevalence of PBA in six different conditions: AD, ALS, MS, PD, stroke, or TBI. The Center for Neurologic Study-Lability Scale ⁸ was used to evaluate the 5290 participants in this multiclinic study, which found an overall prevalence in these six conditions to be 36.7%. The findings for each condition are as follows: AD 29.3%, ALS 44.8%, MS 45.8%, PD 26.0%, stroke 37.8%, and TBI 52.4%. ⁹

The Centers for Medicare and Medicaid Services reported that non-Alzheimer's dementia, AD, CVA/stroke, and PD were among the top 20 hospice admitting diagnoses in 2008, accounting for 113,204, 60,488, 56,986, and 24,289 patients, respectively. ¹⁰ Using the findings from PRISM, this would extrapolate to nearly 79,000 hospice patients annually who suffer from PBA or 5.9% of all hospice patients. This estimate is low as it only accounts for those with the four formerly notated diagnoses as the primary reason for admission and does not account for other PBA-associated diagnoses or for PBA-associated diagnoses as comorbid conditions.

Hospice patients lose the ability to swallow with increasing incidence as they decline toward death with estimates in the overall hospice population of up to 79%. ¹¹ In those conditions associated with PBA, Table 1 summarizes the estimated prevalence of dysphagia. Management strategies for dysphagia in hospice patients include avoiding thin liquids and avoiding hard or chewy substances and thickening fluids. ¹² Medications are often crushed or capsules are opened; however, there are significant concerns with these practices, which cast doubt on the effectiveness and safety of these techniques.^13–15 The time-consuming process of extemporaneously creating a dosage form at the bedside can lead to loss of active ingredient through adhesion to administration tools (e.g., tablet crusher, soufflé cups, plastic spoons). The pharmacokinetic properties of crushed tablets or opened capsules may be altered leading to supra- or subtherapeutic blood levels. ¹³ In senior care facilities, contamination of administration instruments, spillage, and hygiene problems have occurred. ¹⁵ Facility personnel may be exposed to active ingredients or excipients that are potentially carcinogenic, teratogenic, fetotoxic, or allergenic. ¹³

The described DMQ product was ordered to be given orally and swallowed. In hospice patients, the sublingual route is often used with highly concentrated liquids. The DMQ suspension could be administered by the sublingual route, but it would be a time-consuming process as only about 1 mL could be given at a time and the patient would have to swallow it as the suspension would not be absorbed through the sublingual or buccal mucosa. This may preclude the use of DMQ suspension through the sublingual route. Administration through a G-tube would be an appropriate administration route so long as sufficient liquid also would be administered to flush the tube of any adhering DMQ suspension. The sublingual and G-tube administration route observations are based upon the clinical experience of the authors as we have no data to support these claims as both of the cases described took the DMQ suspension orally. The compounded DMQ product that was used in both patients was well tolerated with nearly 100% adherence while also proving to be clinically effective.

In summary, many hospice patients may encounter PBA symptoms with the added difficulty of dysphagia. The DMQ suspension described here provides an alternative for those patients and allows them to maintain dignity through the end-of-life process.