Schneider 2006 CATIE‐AD.

Study characteristics
Methods	Study design: randomised controlled trial Study grouping: parallel group Study duration: 2 to 36 weeks, but endpoint for outcomes is 12 weeks Rescue medication: allowed
Participants	Number randomised: 421 (100 olanzapine 94 quetiapine 85 risperidone 142 placebo) Mean age: 77.9 years Sex (female): 56% Type of dementia: Alzheimer's disease Severity of dementia: moderate Indication: generic NPS, but 82% had delusions and 86% agitation. Setting: outpatients living at home or assisted‐ living facility with regular contact to caregiver Country: USA
Interventions	Intervention characteristics Olanzapine dose: flexible, tablets of 2.5 mg and 5.0 mg. Mean last dose 5.5mg/day. Quetiapine dose: flexible, tablets of 25 mg and 50 mg. Mean last dose 56.5mg/day. Risperidone dose: flexible, tablets of 0.5 mg and 1.0 mg. Mean last dose 1.0mg/day. Placebo The treating physician could adjust the dosage, as indicated clinically, over the 36 weeks of the trial. The mean initially prescribed doses were 3.2 mg of olanzapine per day, 34.1 mg of quetiapine per day, and 0.7 mg of risperidone per day. The last prescribed mean dose in phase 1 was 5.5 mg of olanzapine per day, 56.5 mg of quetiapine per day, and 1.0 mg of risperidone per day.
Outcomes	Agitation: Neuropsychiatric Inventory (NPI) agitation Number of responders for agitation Extrapyramidal symptoms Somnolence Death Any adverse event Any serious adverse event Discontinuation (any reason) Discontinuation due to adverse events Cognitive function: Mini‐Mental State Examination (MMSE) Health‐related quality of life: Alzheimer’s Disease Related Quality of Life (ADRQL) Functioning in activities of daily living: Alzheimer’s Disease Cooperative Study–Activities of Daily Living Inventory (ADCS‐ADL) Carer burden or carer quality of life: The Caregiver Activity Survey (CAS)
Identification
Notes	Sponsorship source: Supported by a grant (NO1 MH9001) from the NIMH. AstraZeneca Pharmaceuticals, Forest Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly provided medications for the studies.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information provided.
Allocation concealment (selection bias)	Low risk	"Randomization was performed with the use of permuted blocks of nine per site without stratification and was implemented with the use of an interactive voice‐response telephone system."The use of blocks diminishes concealment, but the blocks are large and an interactive voice‐response telephone system is used.
Comparability of groups (selection bias)	Unclear risk	Many small baseline differences varyingly in favour of a drug or placebo. Analyses were adjusted for differences in age, sex, MMSE score, and total BPRS score.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	The trials was "double‐blind" and "Medications were dispensed at each visit in the form of identically appearing small and large capsules [...]". Persons blinded has not been specified.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The trial was "double‐blind" and "Medications were dispensed at each visit in the form of identically appearing small and large capsules [...]". Persons blinded has not been specified.
Incomplete outcome data (attrition bias) All outcomes	High risk	The overall rate of discontinuation of treatment at 12 weeks was 63% (primary outcome).Other outcomes are analysed with modified ITT (patients without an assessment after baseline are excluded).
Selective reporting (reporting bias)	Unclear risk	Study protocol available but no outcomes prespecified.
Other bias	Low risk	Washout from previous treatment and run‐in periods were not used because of the patients’ acute clinical symptoms; instead, the study design allowed for rapid assignment and initiation of treatment to be consistent with clinical practice.