'Mitigating the Risk For Tardive Dyskinesia in Elderly Patients on Antipsychotics'

 While any patients taking an anti-dopaminergic agent may develop tardive dyskinesia (TD) -- a movement disorder hallmarked by abnormal and involuntary tics of the face, trunk, and limbs -- older adults are particularly vulnerable.

Being older than 55 is listed as a risk factor for developing TD in practice guidelines from the American Psychiatric Association (APA) on treating schizophrenia.

"Older adults treated with anti-dopaminergic medications are at greatest risk for development of tardive dyskinesia," noted Omar Ghosn, MD, of the University of California San Diego in La Jolla, and colleagues in a 2021 review.

"It is important to recognize risk factors and accurately diagnose TD early," they wrote. "New FDA-approved treatments and investigational agents are now available to manage the condition, however further research to optimally prevent and manage TD in the older adult population remains necessary."

Older People, Higher Prevalence

Development of TD can occur after treatment with dopamine receptor-blocking agents, like antipsychotics used to treat schizophrenia, due to dysregulation of dopamine transmission. Certain factors can increase TD risk, including longer duration of antipsychotic treatment, higher doses, and the use of first-generation versus second-generation agents.

But older patients have a heightened risk for TD even with shorter exposure to newer second-generation antipsychotics, according to a Neuropsychiatric Disease and Treatment review by Leslie Citrome, MD, MPH, of New York Medical College in Valhalla, and colleagues.

TD occurs at a rate of around 4% to 8% per year among adults treated with first-generation antipsychotics, which is about three times higher than rates among second-generation antipsychotic users, according to APA guidelines. In contrast, a study of 261 neuroleptic-naïve patients ages 55 and older reported cumulative TD incidences of 25%, 34%, and 53% after the first, second, and third year of first-generation antipsychotic use, respectively.

While lower antipsychotic doses can help mitigate TD risk in younger patients, this strategy isn't quite as effective in older adults. One study of 330 older adults with dementia (mean age 82.5 years) reported that 2.6% developed TD symptoms after being treated with risperidone -- a second-general antipsychotic -- at average doses of less than 1 mg/day for 1 year. On the other hand, another study of a mixed-age adult population treated at an average risperidone dose of 3.9 mg/day for 6 months reported no new cases of TD.

"The mechanism underlying age-related increased susceptibility is unclear but may be due to higher cumulative exposure to antipsychotics as well as an age-related decrease in dopaminergic neurons in the substantia nigra," Citrome's group noted.

Off-Label Use

Off-label antipsychotic use, especially in nursing homes, is another piece of the puzzle.

"Older adults residing in skilled nursing facilities are prescribed antipsychotic medications more often than community-dwelling older adults," Ghosn's group pointed out.

According to a 2010 study of elderly nursing home residents, 23.5% received at least one second-generation antipsychotic agent and 86.3% received their antipsychotic off-label. Most (56.9%) still received an antipsychotic for an evidence-based use, with higher use among older individuals and those with dementia.

"Antipsychotic medications, which are often the culprits for TD, are widely prescribed for older adults for a variety of reasons including psychotic spectrum and mood disorders as well as the behavioral and psychological symptoms of dementia (BPSD)," explained Ghosn and co-authors. "Although antipsychotic medications are not the first-line for treating BPSD, given the lack of FDA-approved medications for this indication and progressive severity of the illness, they are utilized off-label in 12.3% to 37.5% of patients for management of BPSD symptoms such as agitation, aggression, and psychosis."

Prevention and Management

"Given the prevalent prescription of dopamine receptor blockers for older adults, and the vulnerability of this population to develop this adverse effect, it is important for clinicians to accurately assess, monitor, and manage TD," Ghosn's group urged.

They advised following the adage "start low, go slow" to reduce the risk of TD with anti-dopaminergic drugs in older adults. "The clinician should aim to achieve the lowest effective dose, routinely re-evaluate whether antipsychotic medication is necessary for patients who do not have a primary psychotic disorder diagnosis, and regularly monitor for signs of TD," they said.

But for older patients who require antipsychotic treatment, quetiapine and clozapine are considered "less risky for causing TD [and] extrapyramidal symptoms," they noted. A review of 13 studies suggested that clozapine may help to reduce dyskinetic symptoms over time.

If moderate-to-severe TD symptoms persist, treatment with newer VMAT-2 inhibitors, including deutetrabenazine (Austedo, Austedo XR) and valbenazine (Ingrezza, Ingrezza Sprinkle), is recommended. A post-hoc analysis suggested that adults 55 and older may be more likely to achieve a maximal response from once-daily valbenazine than younger patients.

https://www.medpagetoday.com/spotlight/tardive-dyskinesia/117751