Summary of findings 1. Summary of findings ‐ Typical antipsychotics compared to placebo in people with Alzheimer's disease and vascular dementia.
| Outcomes |
Absolute mean change from baseline or absolute risk in each group |
Comparison of mean changes or risks between groups (treatment effect) |
Certainty of the evidence (GRADE) |
Comments | ||
| Placebo group |
Antipsychotics group (95%CI) |
Relative effect, RR (95% CI) |
Absolute effect, MD or RD (95% CI) |
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|
Agitation ‐ presented in units on CMAI (higher is worse)a ‐ 361 persons in 4 RCTs of 3 to 16 weeks |
15.0 decrease | 20.2 decrease (17.2 to 23.3)b |
NA | 5.2 greater decrease (2.2 to 8.2) |
⊕⊝⊝⊝ Very lowc,d,e |
Baseline mean on CMAI was 58.8; SMD 0.36 less (0.57 to 0.15) |
|
Response for agitation ‐ as defined by authors of RCTs ‐ 367 persons in 4 RCTs of 3 to 16 weeks |
52 per 100 | 61 per 100 (52 to 71) |
1.18 (1.01 to 1.38) |
9 more per 100 (0 to 19) |
⊕⊕⊕⊝ Moderatec |
Example of response: improvement on CGIS |
|
Psychosis ‐ presented in units of NPI‐NH P (higher is worse)f ‐ 240 persons in 2 RCTs of 6 to 10 weeks |
4.7 decrease | 6.3 decrease (4.9 to 7.7)g |
NA | 1.6 greater decrease (0.2 to 3.0) |
⊕⊕⊝⊝ Lowe,h |
Baseline mean on NPH‐NH P was 11.2; SMD 0.29 less (0.55 to 0.03) |
|
Response for psychosis ‐ as defined by authors of RCTs ‐ 259 persons in 2 RCTs of 6 to 10 weeks |
27 per 100 | 35 per 100 (24 to 52) |
1.31 (0.90 to 1.92) |
8 more per 100 (3 less to 35 more) |
⊕⊕⊝⊝ Lowe,h |
Example of response: improvement on CGIS |
|
Extrapyramidal symptoms ‐ assessed with different instruments ‐ 467 persons in 3 RCTs of 3 to 16 weeks |
15 per 100 | 33 per 100 (23 to 48) |
2.26 (1.58 to 3.23) |
18 more per 100 (8 to 33 more) |
⊕⊕⊕⊕ High |
‐ |
|
Somnolence ‐ assessed with different instruments ‐ 466 persons in 3 RCTs of 3 to 16 weeks |
7 per 100 | 19 per 100 (11 to 33) |
2.62 (1.51 to 4.56) |
12 more per 100 (4 to 26 more) |
⊕⊕⊕⊝ Moderated |
‐ |
|
Death ‐ 578 persons in 6 RCTs of 3 to 16 weeks _________________________________________ |
25 per 1000 ______________ |
36 per 1000 (13 to 98) ____________________ |
1.46 (0.54 to 4.00) ________________ |
11 more per 1000 (12 less to 73 more) __________________ |
⊕⊕⊝⊝ Lowi _____________ |
‐ _____________________________ |
CGIS: Clinical Global Impression scale; CI: confidence interval; CMAI: Cohen‐Mansfield Agitation Inventory; MD: mean difference; NA: not applicable (to changes from baseline); NPH‐NH P: NPH‐NH psychosis subscale; RR: risk ratio; RD: risk difference; RCT: randomised controlled trial; SMD: standardised mean difference
GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
a The CMAI is a well‐known and much used scale for agitation (possible range 29‐203)
b The weighted average SD of change from baseline on the CMAI was 14.4 in the intervention groups
c Downgraded one level for risk of bias: all studies were rated at high risk of bias in at least one of the following domains: selection bias (comparability of study groups), attrition bias (incomplete outcome data), and other bias (use of a run‐in period)
d Downgraded one level for inconsistency: pronounced statistical heterogeneity (I2 > 50%)
e Downgraded one level for imprecision: confidence interval indicates both an important effect and an effect with no clinical relevance
f NPH‐NH P was the most frequently used scale (possible range 0‐24)
g The weighted average SD of change from baseline on the NPI‐NH psychosis subscale was 5.4 in the intervention groups
h Downgraded one level for risk of bias: all studies were rated at high risk of other bias (use of a run‐in period)
i Downgraded two levels for imprecision: confidence interval encompasses an important harmful effect as well as a protective effect