Do antipsychotics decrease agitation and psychosis in dementia?
Germany: A Cochrane review suggested that there is some evidence that typical antipsychotics might reduce psychosis and agitation in dementia patients. The review stated that atypical antipsychotics reduce agitation in dementia slightly, but their effect on psychosis in dementia is negligible.
In daily practice, the apparent effectiveness of the drugs may be explained by a favorable natural course of the symptoms, as seen in the placebo groups. Both the classes of drug increased somnolence risk and other adverse events. In patients with severe and dangerous symptoms, if antipsychotics are considered for sedation, this should be discussed openly with the patient and legal representative.
Typical and atypical antipsychotics are used widely for the treatment of pschosis and agitation in dementia. However, it is not clear whether or not they . are beneficial. Some trials have yielded negative results and effectiveness may be outweighed by harms.
Against the above background, Viktoria Mühlbauer, Neu-Ulm University of Applied Sciences, Neu-Ulm, Germany, and colleagues aimed to assess the efficacy and safety of antipsychotics for agitation and psychosis treatment in people with Alzheimer's disease and vascular dementia.
For this purpose, the researchers searched the online databases on 7 January 2021. the title and abstract were independently screened by two review authors of the hits, and two review authors assessed the full text of studies that got through this screening.
Randomised, placebo-controlled, parallel-arm trials comparing the effects of antipsychotics and placebo for the treatment of agitation or psychosis in people with dementia due to Alzheimer's disease or vascular dementia, or both, irrespective of age, severity of cognitive impairment, and setting were included.
The primary outcomes were (1) reduction in agitation or psychosis in patients with agitation or psychosis, respectively at baseline, and (2) the number of participants with adverse events: somnolence, extrapyramidal symptoms, any adverse event, any serious adverse event (SAE), and death.
The search led to 8233 separate hits. 24 trials that met the eligibility criteria were included after assessing the full-text of 35 studies. A total of 6090 participants (12 to 652 per study) were included in the studies.
The findings of the study were as follows:
- For typical antipsychotics (e.g. haloperidol, thiothixene), we are uncertain whether these drugs improve agitation compared with placebo (standardised mean difference (SMD) -0.36, 4 studies, n = 361); very low-certainty evidence, but typical antipsychotics may improve psychosis slightly (SMD -0.29, 2studies, n= 240; low-certainty evidence) compared with placebo. These drugs probably increase the risk of somnolence (risk ratio (RR) 2.62, 3 studies, n = 466; moderate-certainty evidence) and increase extrapyramidal symptoms (RR 2.26, 3 studies, n = 467; high-certainty) evidence.
- There was no evidence regarding the risk of any adverse event.
- The risks of SAEs (RR 1.32, 1 study, n = 193) and death (RR 1.46, 6 studies, n = 578) may be increased slightly, but these estimates were very imprecise, and the certainty was low.
- The effect estimates for haloperidol from five trials were in line with those of the drug class.
- Atypical antipsychotics (e.g. risperidone, olanzapine, aripiprazole, quetiapine) probably reduce agitation slightly (SMD -0.21, 7 studies, n = 1971; moderate-certainty evidence), but probably have a negligible effect on psychosis (SMD -0.11, 12 studies, n = 3364; moderate-certainty evidence). These drugs increase the risk of somnolence (RR 1.93, 13 studies, n - 3878; high-certainty evidence) and are probably also associated with slightly increased risk of extrapyramidal symptoms (RR 1.39, 15 studies, n = 4180; moderate-certainty evidence), serious adverse events (RR 1.32,15 studies, n= 4316; moderate-certainty evidence) and death (RR 1.36, 17 studies, n= 5032; moderate-certainty evidence), although the latter estimate was imprecise.
- The drugs probably have a negligible effect on the risk of any adverse event (RR 1.05, 11 studies, n = 2785; moderate-certainty evidence).
- The findings from seven trials for risperidone were in line with those for the drug class.
To conclude, "if antipsychotics are considered for sedation in patients with severe and dangerous symptoms, this should be discussed openly with the patient and legal representative."
Reference:
Mühlbauer V, Möhler R, Dichter MN, Zuidema SU, Köpke S, Luijendijk HJ. Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia. Cochrane Database Syst Rev. 2021 Dec 17;12(12):CD013304. doi: 10.1002/14651858.CD013304.pub2. PMID: 34918337; PMCID: PMC8678509.
