An expanding pipeline of novel psychiatric medications with persistently thin evidence and significant safety concerns for older adults is fostering caution in prescribing among geriatricians, according to experts who reviewed emerging antipsychotics and insomnia treatments at the American Geriatrics Society 2026 Annual Scientific Meeting.

While newer mental health agents may offer mechanistic advantages or improved tolerability, prescribing decisions in older patients remain constrained by frailty, polypharmacy, and limited geriatric-specific data, said Nicole Brandt, PharmD, professor and Parke-Davis Chair in geriatric pharmacotherapy at the University of Maryland School of Pharmacy in Baltimore. 

“We need to have more science focusing on our older adults to advance and inform the use of” these new drugs, Brandt said.

Strong Warnings

Brandt outlined several newer antipsychotic agents with novel mechanisms, including lumateperone (Caplyta) and combination products such as xanomeline/trospium (Cobenfy). These agents may reduce certain adverse effects associated with older agents, such as extrapyramidal symptoms or weight gain.

Still, she cautioned that most recently approved drugs were studied primarily in younger populations with schizophrenia, leaving clinicians with limited guidance for older adults.

“You wouldn’t want to be necessarily starting our older adults on these because it has not been as well studied in” this population, Brandt said.

Some newer antipsychotics, such as risperidone (Risperdal) and aripiprazole (Abilify), carry boxed warnings for increased mortality in older adults with dementia-related psychosis.

Brandt also pointed to practical barriers such as cost and formulary placement, when adopting these newer medications.

That caution was echoed by Dan Haimowitz, MD, geriatrician in Levittown, Pennsylvania, who urged clinicians to avoid antipsychotics whenever possible in older patients.

“We don’t want to use them unless there’s nothing else that we can use” for older patients, he said.

Haimowitz highlighted well-documented risks, including increased risk for cardiovascular events, infection, and stroke that are associated with these drugs. The mortality rate with antipsychotics is “double, mostly from cardiovascular events and infections,” he said.

He also warned against inappropriately diagnosing older adults with schizophrenia to justify prescribing an antipsychotic.

New-onset schizophrenia is “exceedingly rare” for adults older than 75, he said.

Instead, Haimowitz advocated for nonpharmacologic approaches and careful reassessment of ongoing medication use.

“If you have anybody on any medicine for a couple years and it’s not working, you’ve got to do one of two things: increase the dose or change the medication,” he said.

Promising, but Not Plug-and-Play

Cynthia Fields, MD, geriatric psychiatrist at Johns Hopkins School of Medicine in Baltimore, highlighted newer antidepressants entering clinical practice, including dextromethorphan-bupropion (Auvelity) and vortioxetine (Trintellix).

Dextromethorphan-bupropion stands out for its novel glutamatergic mechanism and speed of action, she said.

“It’s been shown to have a rapid antidepressant effect, separating out from placebo in a week,” Fields said.

However, evidence that this drug works in older adults is limited, and the fixed-dose combination presents practical challenges.

“It’s not advisable to start two new medications at once otherwise it’s hard to assess tolerance,” she said, adding that she often starts with bupropion alone before considering the fixed-dose combination dextromethorphan-bupropion. Vortioxetine, meanwhile, may offer cognitive as well as mood benefits.

“What’s really exciting is that it looks like [vortioxetine] improves cognitive functioning in multiple domains,” Fields said, adding that the cognitive data are limited and not based on large trials of older adults.

Insomnia Drugs

One area where newer medications may offer clearer benefit is insomnia, which is common in older adults.

Dual-orexin receptor antagonists, including lemborexant and daridorexant, promote sleep by targeting wakefulness pathways rather than broadly depressing the central nervous system.

“These changes help shift the rate towards an inhibited sleep-friendly state, leading to improvement in insomnia,” Brandt said.

Studies in adults aged 65 or older suggest these agents may be safer than traditional sedative-hypnotics, although adverse effects such as fatigue and gait disturbances remain concerns in an older patient.

Brandt, Fields, and Haimowitz reported having no relevant conflicts of interest.

Lara Salahi is a health journalist based in Boston.