Powerful antipsychotic medications have commonly been prescribed to people with Alzheimer’s disease and other serious cognitive dementias found amongst the elderly population, especially if they are in a nursing home or hospital environment. Why?
Almost all older dementia patients will experience, along with the cognitive and functional decline typical of the illness, some neuropsychiatric symptoms. These symptoms can include agitation, aggression, and psychosis, and are often devastating for the older patient and his or her family and caregiver.
Managing these symptoms is often a prime concern for health-care providers and families. Neuroleptics (sometimes called antipsychotics) are the class of drugs often used to manage or control neuropsychiatric problems, but there have been questions about their safety and appropriateness. Safety concerns involve risk of stroke, parkinsonism, sedation, edema, and chest infections but also include a worsening of cognitive decline with prolonged use of neuroleptics.
A recent study examined the long-term effectiveness of using such medications and was published in the online journal, PLoS Medicine. The researchers studied 128 patients who were randomized to either a placebo control group or treatment with a neuroleptic medication — both the older style typical antipsychotics, and the new atypical antipsychotics that are supposed to have better side effect profiles and provide greater tolerability in people who take them.
At both 6 and 12 months, the researchers found that there were no differences between the two groups (continued treatment and placebo) in terms of cognitive decline. The placebo group may have had less cognitive decline, but this was not statistically significant. They also found no overall differences between the two groups in the change in the number of neuropsychiatric symptoms over these time periods.
Patients with severe neuropsychiatric problems at the outset of the trial did better on continued neuroleptic therapy, but this advantage was not statistically significant.
These findings are largely consistent with other recent findings into the use of antipsychotic medications in people with Alzheimer’s disease or dementia:
The authors of the recent CATIE study, a large, pragmatic, 36-wk placebo-controlled trial of atypical neuroleptics in Alzheimer’s disease, concluded that the modest benefits were not sufficient to justify therapy in the presence of the increased risk of serious adverse events. Clinicians should certainly try to replace atypical neuroleptics with safer management approaches.
Taking into consideration CATIE, the results of 6- to 12-wk placebo-controlled trials, and our own data, we would suggest that there is, however, a limited place for atypical neuroleptics in the maintenance treatment of severe neuropsychiatric manifestations (particularly aggression) in AD when there is tangible risk or severe distress, and the symptoms have been refractory to other treatment approaches.
There were some issues with the current study, namely the fact that their sample sizes were less than half than they had designed the study for. This means that the study was far less powerful or able to detect smaller, more subtle differences than a larger study may have found. It also suggests that it is not as robust or as generalizable had the study obtained its target of 110 patients per treatment group. And this disclaimer from the authors:
[…] and the number of deaths and withdrawals precluded meaningful analysis of data beyond the 6 mo follow-up.
A reliable six month followup is better than none. But it does beg the question — would further analysis or a larger sample size confer some insight into the causes of the deaths and withdrawals from the medications? For instance, antipsychotics are often used to help reduce agitation and reduce physical injury in these settings. Did the placebo group have a higher incidence of deaths? And did the neuroleptic group have a higher incidence of withdrawal? Unfortunately, the researchers didn’t provide details on the circumstances leading to half of each group dropping out from their treatment group (due to death or withdrawal).
Research on elderly patients in nursing homes is difficult, and a certain amount of attrition can be expected even in the best-designed studies. Death and withdrawal from a treatment (whether it’s a drug or the placebo) is also to be expected. But it would be interesting to see if there was any relationship between these factors and a specific prescribed medication or placebo.
The upshot is that in one of the first studies of its kind, antipsychotic medications didn’t seem to be all that effective in helping treat the symptoms they were prescribed to treat, except in the most extreme and severe cases. Think about that next time you talk to the doctor overseeing the care of your elderly, dementia-impaired parent or loved one.
Hat tip to Furious Seasons for their write-up on this study too. See also their report on a recent British MP claim that antipsychotics are killing thousands every year.
Ballard C, Lana MM, Theodoulou M, Douglas S, McShane R, et al. (2008). PLoS Medicine – A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial). PLoS Medicine, 5(4), e76 doi:10.1371/journal.pmed.0050076.