Appendix 15h: Pharmacological interventions for the treatment of non-cognitive symptoms of dementia Comparisons Included in this Clinical Question Acetylcholinesterase inhibitors (any) vs. placebo for AD
Antipsychotics (any) vs. placebo for AD or VaD
FELDMAN2001 HOLMES2004 NUNEZ2003 ROCKWOOD2001 TARIOT2000 TARIOT2001A WINBLAD2001B
BALLARD2005 BRODATY2003A CN 138-005 DEBERDT2005 DEDEYN1999 DEDEYN2004 DEDEYN2005 F1D-MC-HGAO KATZ1999 MEEHAN2002 MINTZER2006 STREET2000
Aripiprazole vs. placebo for AD
Donepezil vs. galantamine for AD
CN 138-005 DEDEYN2005
WILCOCK2003
Donepezil vs. placebo for AD
Donepezil vs. rivastigmine for AD
FELDMAN2001 HOLMES2004 NUNEZ2003 TARIOT2001A WINBLAD2001B
BULLOCK2005
Donepezil/ galantamine vs. placebo for VaD
Haloperidol vs. placebo for AD & VaD
IM lorazepam vs. placebo
IM olanzapine vs. placebo
Memantine vs. placebo for AD
DEDEYN1999
MEEHAN2002
MEEHAN2002
MD-01 PESKIND2006 REISBERG2003 TARIOT2004C
Olanzapine vs. placebo for AD & VaD
Quetiapine vs. placebo for AD & VaD
Risperidone vs. placebo for AD
Rivastigmine vs. placebo for DLB
DEBERDT2005 DEDEYN2004 F1D-MC-HGAO STREET2000
BALLARD2005 TARIOT2006
BRODATY2003A DEBERDT2005 DEDEYN1999 KATZ1999 MINTZER2006
MCKEITH2000A
BLACK2003 ERKINJUNTTI2002 WILKINSON2003
Galantamine vs. placebo for AD ROCKWOOD2001 TARIOT2000
Characteristics of Included Studies Methods
Participants
Outcomes
Interventions
Notes
BALLARD2005 Study Type: RCT (individual)
n= 93
Study Description: Computer generated block design randomisation. Randomising clinician faxed form to statistician, who communicated allocation to pharmacy ensuring conc
Age: Mean 84
Type of Analysis: ITT
Sex: 19 males 74 females :
Data Used Cohen-Mansfield Agitation Inventory Score
Group
1
N= 31
Placebo with - Matching placebo
Study Quality: 1++
Blindness: Double blind Duration (days): Mean 182
Diagnosis: 100% Alzheimer’s disease
Group
: Setting: Participants living in care facilities in Newcastle, UK. Info on Screening Process: 282 screened, 189 excluded - lack of consent, ineligible, death
2
N= 31
Quetiapine with - Aimed to attain doses of 25-50mg quetiapine twice a day by week 12 and doses of 50mg quetiapine twice a day between week 12 and 26. Group 3 N= 31
: Exclusions: 6 at baseline.
Data Used CIBIC-plus MMSE
Group
1
N= 146
Placebo with Group
2
N= 144
Donepezil with . Mean dose 10mg/day
screen failures, 291 randomised to treatment. Baseline: NPI: Donepezil; 19.55 (SE 1.48), PLB; 19.3 (SE 1.45) Concomitant medication: 11% of donepezil and 8% PLB took psychotropic medication at baseline at during trial.
HOLMES2004 Study Type: RCT (individual)
n= 96
Study Description: Randomisation performed by an independent pharmacist who also provided numbered containers of identical tablets for each patient
Age: Mean 79
Blindness: Double blind
Sex: 37 males 59 females
Notes: 12 weeks open label, 6 weeks randomised.
Group
1
N= 55
Placebo with Group
2
See NICE TA on acetylcholinesterase inhibitors.
N= 41
Donepezil with . Mean dose 10mg/d
: Diagnosis: 100% Alzheimer’s disease by NINCDS-ADRDA
Duration (days): Mean 168 Setting: UK
Data Used NPI
: : Exclusions: No diagnosis of mild to moderate probable AD; MMSE 27; NPI= 48 hours.
Age: Mean 83
Blindness: Double blind Duration (days): Mean 70
Sex: 76 males 208 females : Diagnosis: 100% Alzheimer’s disease by NINCDS-ADRDA
Data Used Adverse events MMSE CGI Severity of Psychosis scale Brief Psychiatric Rating Scale (BPRS) NPI/NH
: Setting: Nursing home
Group
1
N= 91
Quetiapine with . Mean dose 96.9 - max 600 mg per day Group 2 N= 94 Haloperidol with . Mean dose 1.9 - max 12 mg per day Group 3 N= 99 Placebo with
: Exclusions: < 65 years old; < 2 weeks in nursing home; no psychosis; MMSE < 5 at screening & baseline; other clinically significant medical conditions, history of druginduced agranulocytosis, acute orthostasis, clinically significant abnormal electrocardiogram, or concurrent other Axis I DSM-IV diagnosis. Baseline: NPI-NH2 = 9.35 (Que, N=86), 10.78 (Hal, N=86), 9.72 (pla, N=94)
WILCOCK2003 Study Type: RCT (individual)
n= 188
Study Description: Randomisation code generated by Janssen-Cilag UK Research Foundation.
Age: Mean 73 Range 53-88
Blindness: Double blind Duration (days): Mean 365
Sex: 85 males 103 females : Diagnosis: 100% Alzheimer’s disease by NINCDS-ADRDA :
Setting: 18 outpatient clinics in the UK Info on Screening Process: 274 screened, 86 excluded, 188 randomised.
: Exclusions: No diagnosis of probable AD; MMSE 18 Baseline: MMSE: Gal 15.1, Donep 14.8
WILKINSON2003
Data Used ADL ADAS-Cog NPI
Group
1
N= 88
Donepezil with . Mean dose 10mg/d Group
2
N= 94
Galantamine with . Mean dose 24mg/d
Study Quality: 1+
Study Type: RCT (individual)
n= 616
Study Description: Computer generated randomisation protocol used.
Age: Mean 75 Range 38-95
Blindness: Double blind
: Diagnosis: 100% Vascular Dementia by NINCDS-AIREN
Sex: 369 males 247 females
Duration (days): Mean 168 Setting: Conducted at 51 sites in the US, Europe, Canada and Australia. Info on Screening Process: 887 screened 271 excluded Illness or AE, MMSE 26, imaging, laboratory, medications, withdrew consent, AD
Data Used CIBIC-plus ADAS-Cog CIBIS
: : Exclusions: Diagnosis of possible or probable VaD
