Do Benzos Cause Alzheimer’s Disease?

Do benzodiazepines cause Alzheimer’s disease?

Do benzodiazepines cause Alzheimer’s disease? Nobody knows, and anyone who answers with a flat yes or a flat no is ahead of the evidence. The more useful question, for a person who has taken a benzodiazepine for years, is what to do about the prescription now, and that question has an answer.

Benzodiazepines, or benzos, are sedative medications such as diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan), and clonazepam (Klonopin). They strengthen the effect of gamma-aminobutyric acid (GABA), the brain’s main calming chemical messenger, and the z-drugs prescribed for sleep, such as zolpidem (Ambien), act on the same receptor. Alzheimer’s disease is the most common cause of dementia.

The people asking are usually patients in their seventies who were given a sleeping pill decades ago, or their adult children, who have noticed a parent repeating stories. The question reaches Dr. Mark Leeds, an osteopathic physician and deprescribing specialist in Fort Lauderdale, from both.

Long-term benzodiazepines do impair memory and attention, and older adults feel it most.

Whatever the answer on dementia, the effect of the drug on thinking is not in doubt: the Ashton Manual, in its first chapter under “Memory impairment”, states that ordinary doses impair the taking in of new information, partly through poor concentration and attention, and that complete tolerance to these effects does not seem to develop. In plain words, the drug blocks new memories, and the years do not fix it. The Manual adds that memory and thinking recover slowly after withdrawal, though sometimes incompletely, which is one more reason not to wait.

Attention, concentration, and executive function, meaning the mental work of planning, deciding, and following a task through, suffer in the same way. These are risks and side effects of the drug itself, present for as long as it is taken.

Older adults get the worst of it. Professor C. Heather Ashton wrote that older people metabolise these drugs less efficiently, so the effects last longer and the drug accumulates, and that the results include confusion, night wandering, amnesia, loss of balance, and hangover effects. A dose that was tolerable at forty can be too much at seventy-five without ever having been raised.

A benzodiazepine can mask early dementia, or mimic it.

The Manual’s list of effects in older people ends with a word that should stop every family in its tracks: “pseudodementia”, which it notes is sometimes wrongly attributed to Alzheimer’s disease. A sedated, forgetful, unsteady older person looks like a person with dementia. Sometimes the whole picture is the pill.

Yet, the reverse also happens. The same sedation that blurs memory can hide the early changes of a real dementia, and the anxiety and insomnia that got the prescription written can themselves be early symptoms of a brain disease, treated with a drug that quiets the symptom and hides the cause.

So, nobody can say what an older brain is doing while it sits under a long-standing sedative. The honest way to find out what is drug and what is disease is to bring the drug down slowly and then look again.

The evidence on dementia is honestly unsettled.

Much of what has been written on this subject claims a strong connection, and that claim is ahead of the evidence. An association between long-term use and later dementia has been described, and later work did not confirm it.

The problem is that anxiety and poor sleep can appear years before a dementia is diagnosed. A person with those symptoms is given a benzodiazepine, is later diagnosed, and is counted as a case where the drug came first, though the early disease may have caused the prescription. No one has shown that these drugs produce the changes in brain tissue that define Alzheimer’s disease.

Dr. Leeds tells patients the question is open, and he tells them what is settled. The drug impairs thinking while it is taken, and the United States Food and Drug Administration (FDA) updated the boxed warning on every benzodiazepine label in September 2020 to cover abuse, misuse, addiction, physical dependence, and withdrawal reactions. Getting off the drug safely answers the question that can be answered.

The old advice to switch to a short-acting benzodiazepine is backwards.

Some articles suggest that a short-acting benzodiazepine carries less risk than a long-acting one. Dr. Leeds does not recommend that switch, and the Ashton Manual moves in the opposite direction. In its second chapter, under “Switching to a long-acting benzodiazepine”, the Manual explains that with drugs such as alprazolam and lorazepam a smooth fall in blood level is not possible, and that many people feel a mini-withdrawal between doses.

That gap is interdose withdrawal: the drug wears off, the anxiety returns sharper than before, and the next pill relieves it, several times a day. The Manual’s answer is a crossover taper to diazepam, whose slow elimination lets the body adjust to a gradually falling concentration, and Dr. Leeds uses that crossover where it fits the patient, as his Ashton Manual page describes.

In fact, the Manual allows one exception to slow reduction. Professor Ashton wrote that triazolam (Halcion), because it is eliminated within hours, can be stopped abruptly without substitution. Dr. Leeds prefers a gradual taper even there, consistent with the FDA’s label advice for the whole class.

Never stop a long-term benzodiazepine abruptly, at any age.

The worried reader’s first impulse is to throw the bottle away. That is the one thing not to do. The 2020 FDA boxed warning states that stopping these drugs abruptly or reducing the dose too quickly can cause withdrawal reactions, including seizures, which can be life-threatening, and it directs prescribers to use a gradual taper. For a seizure, or any medical emergency, call emergency services at once.

The Manual says the same in its second chapter, under “Dosage tapering”: abrupt or over-rapid withdrawal can bring on convulsions, psychotic reactions, and acute anxiety states, and may raise the risk of protracted withdrawal. In an older adult, a sudden stop can also bring acute confusion and a fall, on top of what the Manual lists. A search for “benzo detox” turns up facilities promising a few days, and what the drug requires is a gradual, medically supervised taper over months.

None of this makes the patient a person with an addiction. Someone who took a pill exactly as prescribed for twenty years and cannot stop without becoming ill has physical dependence, a predictable medical condition caused by the medication, which the FDA’s warning notes can begin as early as days to weeks after starting. Physical dependence is not addiction. The treatment is a taper planned by a physician, not addiction treatment.

A slow, supervised taper is shaped like a landing, not a drop.

A taper is the descent of an airplane. The plane comes down steadily for most of the trip, then the descent flattens just before the wheels touch, because the last part of the landing is the riskiest. A cold-turkey stop is the plane pointed straight at the ground.

The Ashton Manual, in the same “Dosage tapering” section, suggests reducing by up to a tenth of the current dose at each step, and it says plainly that the patient is usually the best judge of pace and must be in control. The Maudsley Deprescribing Guidelines explain why the steps must shrink as the dose falls: the drug’s effect on the receptor is not proportional to the dose, so the last small amounts carry a large share of the effect, which is why a hyperbolic taper ends more slowly than it begins.

Dr. Leeds plans each medically supervised benzodiazepine taper with the patient, and the patient sets the pace. Of course, reductions are held when symptoms flare, small doses can be made with compounded liquid formulations, and safe tapering and discontinuation runs over months, sometimes longer, with older adults often needing the slower end. Consent in his practice means the risks first, the alternatives including staying put, an exit plan from the first visit, and the right to decline at any point.

What a family member can do for an older relative on long-term benzodiazepines.

Do not hide the pills, ration them, or stage an ultimatum. A missed dose in an older person can bring on confusion, a fall, or worse, and a parent who feels policed stops talking. The relative is the patient, and the taper is theirs to direct.

Gather the facts instead: which drug, what dose, how many years, who prescribes it, and whether the dose has crept up. Notice the timing of the fog, because thinking that is worst an hour after the pill suggests too much drug, while restlessness that is worst before the next dose suggests interdose withdrawal. Ask the prescriber for a taper plan rather than a memory diagnosis made under sedation.

Expect low mood at times during a taper, and take it seriously. If it deepens into thoughts of suicide, call or text 988, the 988 Suicide and Crisis Lifeline, or call emergency services.

Unfortunately, older patients are often told they are too settled to come off. Fortunately, the Manual says otherwise: older people can withdraw as successfully as younger people. Professor Ashton wrote that a slow taper is easily tolerated even by people in their eighties who have taken the drugs for twenty years or more, and that those who come off report better sleep and better health.

Dr. Leeds’ practice in Fort Lauderdale offers one service: medically supervised benzodiazepine and z-drug tapering for patients in Florida, by concierge arrangement, and Dr. Leeds himself follows every taper. He also helps patients taper other psychiatric medications. A patient or family member who wants to know how much of the fog is the drug can Contact Dr. Leeds.

This article is educational. It is not medical advice, and reading it does not create a doctor-patient relationship. Decisions about starting, continuing, or tapering any medication should be made with your own physician.