Why Is Age a Key Risk Factor for Tardive Dyskinesia?

Tardive dyskinesia (TD) is up to five to six times more prevalent in elderly adults compared with younger individuals, in part because of the off-label use of antipsychotics (APs) for dementia-related behavioral and psychological conditions, according to findings published in Neuropsychiatric Disease and Treatment.

Age represents a key factor for developing TD, according to according to Leslie Citrome, MD, MPH, and colleagues. Dr. Citrome and colleagues examined, with a specific focus on the elderly, risk for TD, the burden of TD, and the management of the condition.

Prevalence & Risk Factors

The mean prevalence of TD among people treated with APs was 20% to 25%, according to meta-analyses of articles published from 1959-2015. Another large, retrospective, observational study that examined EHRs reported an estimated annual TD prevalence of 7.6-9.7 per 1,000 people; nearly 80% of study participants were being treated with second-generation APs, according to Dr. Citrome and colleagues.

“A direct comparison of annualized incidence between first- and second-generation APs indicates a reduced but not eliminated risk of TD with use of second-generation APs (range of 0.8% to 3% with use of second-generation APs vs 5.4% to 7.7% with use of first-generation APs),” the researchers wrote.

In addition to age and exposure to dopamine receptor-blocking agents (DRBAs)—which includes first-generation and second-generation APs and medications such as metoclopramide—other risk factors for the development of TD include female sex, mood disorders, dementia, and previous drug-induced parkinsonism. “Smoking and substance abuse may also be associated with a higher risk of developing TD,” Dr. Citrome and colleagues wrote.

The Role of Age in Developing Tardive Dyskinesia

In their review of age in relation to the development of TD, the investigators noted that APs can be used off-label for dementia-related psychosis and aggression. As a result, “TD can be encountered in this population, particularly within facilities that care for older people,” they wrote, adding that as many as 33% of patients in nursing homes or assisted living facilities are treated with APs, primarily in the form of off-label use.

“A survey of 350,000 nursing home residents in 8 states, representing 40% of residents nationally, found that in 2006, 27.6% of residents had taken APs in the last 7 days, and only 20.7% of these were for treatment of the primary indications of schizophrenia or bipolar disorder,” wrote Dr. Citrome and team. “The National Nursing Home Survey of 300,000 residents found that 23% of respondents had received at least 1 second-generation AP, and 86.3% of these prescriptions were for off-label indications. Dementia is one of the most common indications for off-label AP use in these facilities, despite the bolded ‘black box’ warning against AP use in patients with dementia-related psychosis. Behavioral issues related to dementia may in part drive AP use in this population.”

In addition, the effect of TD on a person’s physical, mental, and economic health may increase with age, according to Dr. Citrome and colleagues. “The social and emotional effects of symptoms are highly debilitating for people with TD of all ages, but feelings of isolation and depression may be especially profound for older people,” they wrote “Older individuals are also uniquely vulnerable to the physical consequences of TD, such as impaired gait and balance, which can lead to falls.”

Treating Tardive Dyskinesia & Minimizing Risk

The irreversible nature of TD necessitates the use of preventative strategies, the researchers noted. Strategies include restricting the use of medications known to induce TD and, secondarily, identifying the symptoms of TD early. Clinicians can also examine the pharmacology of different APs to choose therapies that are least likely to induce TD, according to Dr. Citrome and colleagues.

Timely diagnosis is also “the first step” in outlining the best treatment approach for TD. Treating TD initially involves changing the use of current APs if it is clinically feasible to do so, though the study team noted that this approach is not often successful.

“Avoiding TD by eliminating exposure to DRBAs may be the best option for older persons,” Dr. Citrome and colleagues wrote. “Several novel agents are being studied for their antipsychotic properties. Alternative mechanisms, including serotonin inverse agonism/antagonism in the absence of dopamine receptor blockade, agonism of TAAR1 receptors, and modulation of muscarinic cholinergic receptors, may provide different therapeutic approaches for patients who require a medication with an AP effect [to] avoid contributing to the risk of developing TD.”