Greater risk of death by antipsychotics in dementia patients, research suggests

The effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported, researchers say.

The use of antipsychotic drugs in people with dementia poses a higher mortality risk than previously identified, and the risk increases with dose, study finds

The risk of death caused by use of antipsychotic drugs in people with dementia is greater than previously thought, and increases in line with dose, research suggests. 

Recognition has grown over the past ten years of the adverse events — including pneumonia, cardiac failure and cerebrovascular disorders — associated with the treatment of behavioural and psychological symptoms of dementia (BPSD). The latest study, published by JAMA Psychiatry on 18 March 2015[1]
, sought to identify the absolute increase in risk of death and the number needed to harm (NNH; a metric looking at the number of patients who receive a treatment that would be associated with one death) with these agents by comparing the outcomes of using various antipsychotics with no treatment or alternative psychotropics. 

The retrospective case-control study involved 46,008 patients with dementia treated with haloperidol, olanzapine, quetiapine or risperidone, valproic acid or its derivatives, and antidepressants, compared with receiving either no treatment or only antidepressants. The medication and non-medication groups were matched across several risk factors, and followed up over 180 days. 

Compared with matched non-users, haloperidol had a 3.8% increase in the risk of death, with an NNH of 26; risperidone followed, at 3.7% (NNH 27); olanzapine showed a 2.5% increase (NNH 40); and quetiapine, a 2.0% increase (NNH 50). Compared with antidepressant users, haloperidol was associated with a 12.3% increase in mortality risk (NNH 8); and quetiapine with a 3.2% increase (NNH 31). 

The study also looked at the impact of different doses of olanzapine, quetiapine and risperidone on mortality. An overall increase in risk was identified: 3.5% greater in the high-dose subgroup compared with the low-dose group. Risperidone and olanzapine showed a 1.7% and 1.5% increase in dose-adjusted mortality risk, respectively, when compared with quetiapine. 

Doug Brown, director of research & development at the UK charity, Alzheimer’s Society, says that in light of these risks, antipsychotic drugs should only ever be used as a last resort for people with dementia. “Although they are important for a minority of people with dementia, disturbingly they are still often prescribed inappropriately or unnecessarily,” he says. 

“Training professionals in safe alternatives for managing distressing behaviour can reduce the need for antipsychotic medication,” adds Brown. 

He pointed out that the Alzheimer’s Society has shown through its training programmes that a focus on patient-centred care can nearly halve the use of antipsychotics in care homes. “By empowering staff with the knowledge they need to understand dementia and the person behind the condition, it helps them provide good quality, individually-tailored care.” 

Simon Ridley, head of research at Alzheimer’s Research UK, also advocated an alternative approach: “Identifying and addressing triggers for these [BPSD] behaviours could provide a safer first-line approach which is safer and has longer-term benefits. Triggers may include pain or changes in routine or environment, which could be addressed initially through changes in management or care.” 

Ridley says concerns about the use of antipsychotic drugs in dementia patients have led to a reduction of more than half in the number prescribed over the past eight years. 


[1] Maust DT, Kim HM, Seyfried LS et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia. JAMA Psychiatry 2015. doi:10.1001/jamapsychiatry.2014.3018.

Last updated
The Pharmaceutical Journal, PJ, 4/11 April 2015, Vol 294, No 7856/7;294(7856/7):DOI:10.1211/PJ.2015.20068212

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