Table 2.

Clinical studies investigating the efficacy of analgesic treatment on pain intensity or typical behavior of pain in people with advance dementia

Pain medication	Authors, year, nationality, gradea	Population	Method	Outcomes	Findings
Paracetamol/acetaminophen	Chibnall et al. [35], 2005, USA, B	25 NH patients with moderate-to-severe dementia (degenerative 13, AD 4, multi-infarct dementia 4)	Randomized, double-blind, placebo-controlled, crossover trial; 4 weeks placebo, 4 weeks treatment	DCM CMAI; no pain tool	Patients were more active and spent more time in social surroundings and interacting with others (p < 0.05, η 2 from 0.15 to 0.25); no effect on agitation, emotional well-being or as-needed psychotropic medication
	Buffum et al. [34], 2004, USA, B	39 NH patients with dementia (AD/VaD) and pain rel. degenerative joint disease; mean MMSE 4.3 and GDS 5.7	Double-blind, placebo-controlled, crossover 4-week trial investigating scheduled (650 mg × 4/day) vs. as-needed acetaminophen administration	DS-DAT	No differences were found between scheduled or as-needed acetaminophen application; 2600 mg/day acetaminophen is inadequate for NH patients with degenerative joint disease
1 % solution of lidocaine, a local anesthetic	Benedetti et al. [40], 2006, I, B	28 people with AD; mean 74 years; baseline MMSE 22–25, after 1 year 13–20	Placebo-related analgesic study with open (expected)/hidden (unexpected) paradigm lidocaine gel	NRS–self rating	People with dementia/reduced FAB show reduced placebo effect of analgesic treatment [post hoc Tukey test, q(42) = 13.524, p < 0.001]. Analgesics should be increased to compensate for the loss of placebo effect
Morphine	Manfredi et al. [36], 2003, USA, B	47 people with dementia (unknown type) from one NH (1999–2001); mean 86 years; MMSE <20; CMAI ≥40	All patients received placebo for 4 weeks followed by treatment with oxycodone 20 mg/day or morphine 20 mg/day	CMAI; no pain tool	25 patients completed the study; no differences in agitation between placebo and opioid phases, though patients ≥85 years old (N = 13) were less agitated (CMAI score −6.4; 95 % confidence interval −10.96 to −1.8). No group differences in sedation; high drop-out rate
	Klapwijk et al. [39], 2014, NL, C	24 dying patients with most severe dementia (type unknown); two NHs; median age 91 years	Observational study of the last days of life; small sample size; pain instruments not validated for EoL care	PAINAD DS-DAT EOLD-CAD MMSE	Mean 4.3 observations per patient; all participants received morphine (dosage not available). Low symptom burden but direct effect of morphine was not estimated
Vitamin D	Björkman et al. [33], 2008, Finland, B	202 NH patients with pain and dementia (type unknown); mean 85 ± 7 years; CPS 4.9 ± 1.4, range 1–6	Randomized, double-blind placebo-controlled 6-month trial with vitamin D supplement in three groups: 0, 400 or 1200 IU cholecalciferol	RAI PAINAD DS-DAT CPS	38–84 % of the patients were in pain; vitamin D deficiency was not associated to pain or pain behavior; prevalence of painlessness or pain scores not changed after vitamin D treatment

AD Alzheimer’s disease, CMAI Cohen-Mansfield Agitation Inventory [86], CPS Cognitive Performance Scale, DCM Dementia Care Mapping, DS-DAT Discomfort Scale–Dementia of Alzheimer Type [87], EoL end-of-life, EOLD-CAD End-of-Life in Dementia–Comfort Assessment in Dying [88], FAB Frontal Assessment Battery [89], GDS Global Deterioration Scale [90], I Italy, MMSE Mini-Mental State Examination [95], NH nursing home, NL Netherlands, NRS Numerical Rating Scale, PAINAD Pain Assessment in Advanced Dementia [91], RAI Resident Assessment Instrument, rel related to, VaD vascular dementia

^aQuality grade according to the Oxford grading of evidence