Doctors may look at common, everyday prescriptions, from antidepressants to diabetes drugs, to help manage symptoms of Alzheimer’s. Here’s what we know so far.
While headlines trumpet breakthroughs in brand new types of Alzheimer’s drugs, it’s easy to miss a more subtle change in prescription medicine: Neurologists are dusting off medications that were never designed for Alzheimer’s disease — antidepressants, diabetes pills, even an erectile-dysfunction drug — and writing new prescriptions for people living with, or hoping to avoid, dementia.
According to neurologist Dr. Brent Forester, we’re in a new era of drug repurposing. Forester began prescribing the antipsychotic brexpiprazole years ago for schizophrenia and depression. Now, after a Phase 3 trial and an FDA label expansion, he offers the very same drug (brand-named Rexulti) to families grappling with the agitation that sends nearly half of Alzheimer’s patients to emergency rooms.
“Rexulti is the brand name for brexpiprazole. That is indeed the only FDA-approved treatment for agitation for Alzheimer’s. There may be others next year,” Forester told Being Patient, adding that side-effect counseling remains essential.
Psychiatry has helped spotlight other existing drugs with potential for Alzheimer’s symptoms management.
For example, in 2022, University of Colorado scientists mined insurance databases and discovered that people with Alzheimer’s who happened to be taking the antidepressant imipramine or the antipsychotic olanzapine (though antipsychotics have also been found to be dangerous for people living with dementia) scored higher on cognitive tests than peers on similar drugs. “The people who received these drugs developed better cognition and actually improved in their clinical diagnosis,” study senior author Dr. Huntington Potter said, noting that both medications appear to block ApoE4’s toxic interaction with amyloid.
Clinicians already prescribe them to ease depression, insomnia or delusions; the new data hint that they may also nudge disease biology toward a better outcome.
Metabolism drugs are joining the conversation, too. The anti-diabetes medication metformin is at the center of a FINGER-MET trial combining lifestyle coaching with a daily pill.
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Lead investigator Dr. Miia Kivipelto told Being Patient, “We have a lot of evidence, both preclinical and clinical, that metformin affects many of the key pathologies linked to Alzheimer’s disease.”
Although metformin has not yet been found to be safe and effective for people with Alzheimer’s in the official clinical trial and FDA approval process, it has been shown to benefit people with pre-diabetes, including people living with Alzheimer’s.
Sometimes the link emerges from big data. A 2024 Neurology study of 270,000 men found that those prescribed Viagra (sildenafil) had an 18 percent lower incidence of Alzheimer’s over five years, with heavier users faring even better.
Researchers caution that correlation isn’t causation, yet the finding has already prompted mechanistic trials. “Notably, we found that sildenafil use reduced the likelihood of Alzheimer’s in individuals with coronary artery disease, hypertension, and type 2 diabetes, all of which are comorbidities significantly associated with risk of the disease, as well as in those without,” lead author Dr. Feixiong Cheng said. While no neurologist is handing out blue pills solely for brain health, the signal strengthens the case that improving vascular function can echo in cognition.
And on the metabolic horizon are the GLP-1 weight-loss juggernauts Ozempic and Wegovy.
Endocrinologist Dr. Heather Ferris sees the potential: In the end, you don’t care how much plaque you have in your brain, right? You care whether you can remember your grandkid’s name. That’s where I see these drugs fitting in,” Ferris said. “There’s actually not a super great correlation between how much plaque you have and how much memory loss you have. Obesity and diabetes are those things that make lower levels of plaque, maybe, more symptomatic. So, if we can reduce those symptoms, then that’s our end goal.”
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Large Alzheimer’s prevention trials are under way, and some physicians already factor potential cognitive upside into prescribing decisions for patients battling obesity or diabetes.
What this means in the doctor’s office
Repurposed drugs rarely claim headlines, but they can land in pill organizers faster than brand-new compounds because their safety records are decades old and their price tags are generic-level low.
At the same time, there are risks and caveats: The data behind imipramine or Viagra are associative, not causal; Rexulti improves behavior, not memory; metformin can upset the stomach. And again, antipsychotics in people with dementia are linked to higher rates of hospitalization.
As precision medicine researchers map which biological pathways drive each person’s dementia, the roster of “accidental” Alzheimer’s drugs will likely keep growing.
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On the horizon: The next wave of repurposed drugs
The repurposing pipeline is still widening. Among contenders are cannabinoid-based therapies. In the first major UK dementia trial of medical cannabis, King’s College London researcher Chris Albertyn told Being Patient the science isn’t fully there yet.
“Currently there is a scarcity of pharmacological treatments out there and some of them are damaging or dangerous, especially in the long-term. We’re looking for a safer and more effective alternative,” Albertyn said.
His team is testing Sativex, an oral spray that combines THC and CBD, to see if it can safely dial down agitation and aggression. Early-stage lab work meanwhile suggests that non-intoxicating cannabinoids like CBN may help shield neurons from Alzheimer’s-related damage, though large human trials are still in the planning stages.
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Meanwhile, longevity researchers are lobbying for formal Alzheimer’s trials of rapamycin and the age-old diabetes pill metformin. As geroscientist Dr. Matt Kaeberlein put it, “There should have been a clinical trial for rapamycin and Alzheimer’s disease years ago. But the fact is, the clinical trials are really hard and expensive.”
Small groups of patients already take these generics off-label, hoping to tame the biology of aging that underlies dementia. Regulators, however, want stronger safety data before green-lighting large studies.
Finally, lifestyle–drug “hybrids” like intranasal insulin sprays and ketone esters are inching toward the clinic, aiming to shore up the brain’s faltering energy supply — a pathway often compared to “type-3 diabetes.”
For now, none of these experimental avenues is ready for routine prescription. But as cannabis chemistries, GLP-1 agonists, and anti-aging molecules head into ever-larger trials, clinicians and families could soon have an even broader menu of off-the-shelf drugs to fold into Alzheimer’s care.