Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)

OBJECTIVES: The primary objective of the Low-Dose Opiate Therapy for Discomfort in Dementia
(L-DOT) project was to determine whether low-dose opiates are effective and well tolerated
for the treatment of pain (as manifest by discomfort) in patients with advanced dementia.

RESEARCH DESIGN: This study was a two-week double-blind, double-dummy, placebo-controlled,
crossover trial of low-dose hydrocodone/acetaminophen (Lortab) for discomfort among veterans
with a dementia, followed by six weeks of open-label therapy for patients who tolerated
treatment during the first two weeks (eight weeks total treatment on study).

METHODOLOGY: After consent, patients over age 55 with dementia residing in a nursing home
care unit (or at home who receive care) at Tuscaloosa VAMC who demonstrate significant
discomfort (as measured by the Pain Assessment in Advanced Dementia - PAINAD) were
randomized to one of two groups, using a double-blind, double-dummy, placebo-controlled,
crossover design. Patients were randomly assigned to treatment with either
hydrocodone/acetaminophen 2.5mg/250mg q8hrs scheduled with placebo q8hrs PRN or placebo
q8hrs scheduled with hydrocodone/acetaminophen 2.5mg/250mg q8hrs PRN. After one week's
treatment, patients were crossed over to the other (opposite) regimen, for a total of two
weeks of blinded treatment. Patients who tolerated treatment with hydrocodone/acetaminophen
were eligible for a six-week, open-label continuation phase. The primary outcome measure was
pain/discomfort. Preliminary sample size calculations indicated that 42 patients (48
patients accounting for dropouts) would be needed to be enrolled over three years to detect
a difference between treatments with power of .80 and two-tailed alpha of .05.

SIGNIFICANCE: There is evidence that pain is both under recognized and undertreated in long
term care settings. This study hoped to make a significant contribution to the evidence base
for a common and problematic situation among veterans with advanced dementia. Advances in
pain and symptom control are central to the improvement of palliative care intervention for
dementia patients. Low-dose opiates are the logical next category of analgesics to consider,
but have been rarely studied for this purpose in this population.

Inclusion Criteria:

- 55 years of age or older;

- Must have a diagnosis of dementia;

- Advanced stage of dementia demonstrated by a score of 6 or greater on the Functional
Assessment Staging (FAST) scale;

- Unable to report pain in a reliable and consistent manner;

- Have a PAINAD score of at least 2 on two consecutive assessments (separated by at
least two days) OR an average PAINAD score of at least 2 on three consecutive
assessments each separated by at least two days;

- The patient must have at least one medical condition associated with pain recorded on
the CPRS problem list.

Exclusion Criteria:

- The existence of an effective analgesia treatment regimen;

- Pain treatment related to angina or pain judged to be related to angina;

- Current pain treatment with opiates that cannot, in the opinion of the attending
physician, be discontinued without placing the patient at risk for increased pain or
opiate withdrawal;

- Current pain treatment with tramadol that cannot, in the opinion of the attending
physician, be discontinued;

- Presence of necessary drug therapy that is incompatible with or has potential for
clinically significant drug interaction with either hydrocodone or acetaminophen;

- A history of allergy, hypersensitivity, or intolerance to either hydrocodone or
acetaminophen;

- Constipation refractory to current treatment measures or a condition that would make
constipation dangerous for the patient in the opinion of the attending physician;

- The presence of liver disease, hepatic encephalopathy, or clinically significant
elevation of liver function tests (LFTs), as determined by the attending physician;

- The presence of renal failure, clinically significant renal insufficiency, or
clinically significant elevations of serum BUN or creatinine levels, as determined by
the attending physician; OR

- Evidence, based on assessment by a geriatrician, that the apparent behavioral
manifestations of discomfort are better explained by another problem (e.g., fever,
infection, dehydration, delirium, psychosis)