Dementia Linked To Benzodiazepines, Sleeping Pills, Anticholinergics

In recent years, increasing evidence has suggested that certain types of commonly prescribed medications may cause increased risk of developing dementia. This ranges from drugs used to treat anxiety (e.g. Xanax) to over-the-counter drugs (e.g. Benadryl). A majority of these medications tend to depress activity in the CNS and help minimize arousal and/or anxiety.

Dementia is responsible for nearly 500,000 deaths annually, and is characterized by neurodegeneration of the brain. Onset of dementia is responsible for significant difficulties with memory, speech, cognitive function, and attention. Although dementia often has a genetic component, the fact that certain medications are associated with increased risk is something that cannot be ignored.

Drug Classifications Linked To Dementia

Below is a list of drug classifications that are linked to the development of dementia. It is important to realize that although a “link” does not imply causality, it also doesn’t dismiss it. If you are taking any of these medications, it is highly recommended to consider pursuing alternative options, especially if you need long-term relief.

1. Benzodiazepines

Benzodiazepines are a group of psychiatric drugs developed via fusion of a benzine and diazepine ring. They have been around since the 1950s and are commonly utilized for the short-term management of severe anxiety. In some cases they may be prescribed to help with seizures, insomnia, drug withdrawal, and the mitigation of stress prior to a surgical procedure.

They function by amplifying the effect of the neurotransmitter GABA (gamma-aminobutyric acid) in the brain. This leads a person to feel sedated and/or sleepy while taking them. Although they are extremely potent for dealing with anxiety, usage over the long-term can be problematic in that it leads to deficits in memory and cognitive function – possibly neurodegeneration.

• Ativan (Lorazepam)
• Klonopin (Clonazepam)
• Valium (Diazepam)
• Xanax (Alprazolam)

If you are currently taking a benzodiazepine, you may want to consider some alternative options. You may want to read the article(s): “Xanax Alternatives” as well as “How To Deal with Anxiety” which lists treatments in a hierarchical order based on safety and efficacy. Realize that although many natural treatments like meditation and exercise require consistent effort, they can yield the same (if not better) benefits over the long-term.

2. Sleeping pills (Z-drugs)

“Z-drugs” or sleeping medications are classified as nonbenzodiazepines in that they function similar to benzodiazepine drugs to elicit their effects. Most would agree that they carry a similar risk-profile and are likely to pose the same long-term risk of developing dementia. Although they may differ from benzos in regards to molecular composition, they modulate GABA receptors in the brain, binding to the benzodiazepine site.

• Ambien (Zolpidem)
• Lunesta (Eszopiclone)
• Sonata (Zaleplon)

If you are currently taking sleeping pills, you may want to consider looking into natural ways of dealing with broken sleep and/or insomnia. While natural options may not provide immediate relief from sleeping difficulties, they can help improve sleep quality over the long-term. Consider consulting a sleep specialist and testing non-pharmaceutical methods such as: investing in a more comfortable mattress, eliminating electronics before bed, guided meditation, and/or an activity to lower arousal before sleep.

3. Anticholinergics

These are drugs that tend to inhibit the neurotransmission of acetylcholine within the nervous system. There are three major categories of anticholinergic drugs including: antimuscarinic agents, neuromuscular blockers, and , ganglionic blockers (which are rarely used). Many other medications such as certain antidepressants, antihistamines, and antipsychotics can contain anticholinergic properties significant enough to potentially cause neurodegeneration.

• Advil PM (Diphenhydramine)
• Benadryl (Diphenhydramine)
• Chlorphenamine
• Dramamine (Meclizine)
• Oxybutynin
• Silenor (Doxepin)
• Zyprexa (Olanzapine)

Antidepressants: Some drugs used to treat depression like Doxepin (a tricyclic antidepressant) may contain anticholinergic properties.  It is the anticholinergic mechanism that is suspected to play a role in possibly contributing to cognitive decline and dementia.  If you want to be on the safe side, do a little bit of research and make sure that the medication you’re taking isn’t associated with anticholinergic effects.

Antihistamines: An antihistamine is a drug used to help combat symptoms of allergies. They may help in reducing symptoms of a variety of conditions including: hay fever, indoor allergies, food allergies, nasal congestion, etc. Some people even use them on an off-label basis to help reduce anxiety, cope with insomnia, and deal with itchiness.  Several with anticholinergic properties are thought to be linked to dementia onset.

Antipsychotics: While antipsychotics may be the most favorable treatment for severe forms of mental illness like schizophrenia, they do not come without long-term effects. Many studies have reported that over the long-term, users actually lose brain volume and functioning as a result of the drug. Most of the potential for dementia development comes from antipsychotics with significant anticholinergic side effects (e.g. Zyprexa).  Antipsychotics should only be used by individuals with severely debilitating psychiatric conditions that fail to respond to other treatments.

Fortunately there remain a considerable number of alternatives to medications with anticholinergic properties.  If you are taking a drug that has an anticholinergic effect, it’s likely that you’ll be able to find a replacement that has a less pronounced anticholinergic mechanism.

How These Drugs May Cause Dementia

There aren’t many theories as to how these drugs may cause dementia with long-term usage. The commonality shared among them is that long-term usage is thought to provoke memory impairment, cognitive deficits, and neurodegeneration (in the form of dementia). Since the implications of using these drugs is (potentially) significant, it is important to analyze the mechanisms of action and hypothesize why they may be contributing to dementia.

• Acetylcholine: Many of these drugs reduce the function of acetylcholine in the brain. In order to perform cognitively demanding tasks, it is recommended to have sufficient levels of acetylcholine. When this neurotransmitter and its functioning become reduced, the brain isn’t working as well as it should. If sustained over a long-term period, this functional impairment may become permanent. The opposite of anticholinergic drugs called “acetylcholinerase inhibitors” are considered neuroprotective agents and are frequently used as nootropics.
• Cognitive impairment: These drugs tend to impair cognition and slow response time. It is difficult to think clearly or engage in advanced, logical thinking while taking depressants. Since the brain is unable to receive adequate stimulation to perform advanced cognitive functions, certain regions may effectively “retire” and/or stop working as well as prior to taking the drug.
• CNS depressant: All of these drug classifications tend to depress the central nervous system, leading to feeling sedated and/or drowsy. It is the depressant effect that takes away our worries, anxieties, and leads to us feeling relaxed and calm. However, a drug-induced depression of the CNS may lead to less brain activation. The decrease in CNS activation may be responsible for the neurodegeneration over time.
• Dopamine: The function of dopamine tends to get reduced when taking these depressants. This neurotransmitter is responsible for facilitating motivation, pleasure, cognition, and memory. The lack of dopamine in the brain (as a result of using these drugs) may lead to impaired functions and possible permanent deficits as a person continues to age.
• GABA: Drugs that stimulate GABA neurotransmission via activity on receptors blunt signals of various neurotransmitters.  Since the signals between neurons becomes blunted, brain activity, arousal, and overall stimulation becomes inhibited.  It is the inhibiting of the neural excitement and activation over a prolonged period that may lead to permanent functional deficits.
• Inadequate stimulation: When the brain is sedated for extended periods of time, certain parts may become functionally impaired for life. The lack of stimulation in the prefrontal cortex and/or other areas may contribute to a worsening in cognitive function and/or memory tasks. The expression “if you don’t use it, you lose it” may apply to brains exposed to these drugs for a long-term.
• Memory impairment: Many of these drugs tend to detrimentally affect memory function while taking them. It is thought that the impairment in memory following long-term usage may be permanent. The degree to which memory becomes impaired may be a result of numerous individualized factors.
• Neurodegeneration: The drugs may directly be causing neurodegeneration within certain parts of the brain. This means that using them consistently over a long-period of time will lead to more sustained damage and a greater degree of mental impairment. Each drug classification may be causing this neurodegeneration via different mechanisms.
• Receptor depletion: It is believed that receptors for certain neurotransmitters get depleted with long-term usage. Someone taking an anticholinergic medication may end up with significantly lower counts of cholinergic neurons and/or receptors – leading to a variety of functional abnormalities. It is thought that certain drugs like antipsychotics may also affect dopaminergic functioning over the long-term.

Factors that influence risk of dementia

There are many factors that influence dementia risk as a result of taking these depressant medications. These factors include things like: dosage, frequency of usage, duration, as well as the specific drug(s) used.

1. Duration

In general, the duration over which a person has taken a benzodiazepine, anticholinergic, antihistamine, or antipsychotic appears to matter. Those that have taken these drugs for long-terms (i.e. years) are increasingly likely to develop dementia than those who were on them for a short period of time. In order to decrease your risk for neurodegeneration, it is recommended to use these drugs only when necessary.

Those who take benzodiazepines for less than 3 months have approximately the same risk of developing dementia as someone who never uses one. Taking benzos for 3 to 6 months raises Alzheimer’s risk by roughly 32% – which is relatively significant. If you have been on a benzodiazepine for over 6 months, your risk further increases by 84%.

2. Frequency of usage

The more frequently you use the drug, the more likely you are to suffer neurodegeneration. Currently it is unknown as to whether taking the drug, followed by a sober period of a few days has any effect on reducing likelihood of developing dementia. It should be speculated that intermittent or “as needed” usage is less likely to produce impairment over the long term than consistent, daily usage. Using these drugs on a daily basis further increases risk of long-term cognitive deficits.

3. Dosage

The higher the dosage you take, the greater the extent to which the drug will affect your brain. Those taking lower dosages may be at less risk of developing dementia. Taking high doses over a long-term can lead to neurodegeneration and may leave more of an irreversible mark on brain function than lower doses. Therefore if you must take these drugs, it is always recommended to take the “minimal effective dose.” Unfortunately though, it is relatively easy to build up tolerance (especially to benzodiazepines), making it difficult to avoid an increase in dose.

4. The specific drug(s)

The specific drug(s) that you take (or took) play a role in determining your dementia risk. Those who are on “long-acting” benzodiazepines (e.g. Valium) are at greater risk for impairment than those taking a “short-acting” drug (e.g. Xanax). The longer the drug produces a sedating, anxiolytic effect, the greater likelihood that you will experience impairment over the long-term.

While most people are only taking one of these medications at a time, poly-drug usage is still prevalent. Using multiple CNS depressants simultaneously can be fatal, yet people still do. Over the long-term, utilizing multiple medications associated with dementia may further increase risk of neurodegeneration.

5. Individual factors

It is important to consider other factors that may increase risk of developing dementia as a result of taking these drugs. It is possible that the drugs may interact with a person’s physiology and genetic expression to cause dementia. It also means that some people may have genetics that make them more resilient and less prone to developing a condition like Alzheimer’s as a result of taking Xanax.

The lifestyle you live, amount of stress you endure, whether you get adequate sleep, other drugs you take, your diet, and heredity may also contribute to developing dementia. Consider the possibility that all of these symbiotic factors may collectively (or indirectly) contribute to development of dementia.

Weighing the Pros and Cons

If you are taking drugs within any of the classifications listed above, you should think critically about the benefits vs. the cons. Obviously the major “con” that this article addresses is the possible development of dementia. Sure it may be great to medicate your anxiety or sleep problems with a potent drug, but short-term gain may equal long-term brain atrophy.

Benefits: There are many benefits that can be obtained from taking drugs within the classifications listed above. Most of the drugs provide immediate relief, are highly effective, and help people that aren’t responsive to other medications.

• Efficacy – Most of these drugs are prescribed because they are highly effective in the management of symptoms. Those that take benzodiazepines tend to have some of the most severe cases of anxiety and need something that’ll work well; these drugs deliver.
• Immediate relief – Using antidepressants and/or other drugs as alternatives doesn’t always work. Many antidepressants can take a long time to work (e.g. 4 to 6 weeks) and drugs like benzos tend to help immediately. Therefore a person doesn’t have to worry about experimenting with various drugs because they know taking a sleeping pill for insomnia will do the trick.
• Unresponsive to other meds – A variety of people simply don’t respond to other medications and need some of these treatments available. These individuals may be willing to risk long-term effects such as dementia simply because they may be unable to function without these medications.

Drawbacks: There are many drawbacks to consider when taking some of these drugs (e.g. benzodiazepines). The potential drawbacks include: tolerance development, addiction, and long-term impairments.

• Dependence – People can develop rapid tolerance on these drugs and inevitably become dependent on them for functioning. Pretty soon, the person will be taking the highest recommended dosage and become tolerant to that amount. When that occurs, a person may consider withdrawal, but realize that they are “trapped” on the medication.
• Addiction – It is common for some individuals to become addicted to the depressant effects that these drugs tend to provide. This may result in abuse, which leads to increased tolerance and other long-term problems. For individuals with addictive personalities, benzodiazepines especially should be avoided.
• Withdrawal – The withdrawal process can be a nightmare for people coming off of these drugs. Benzodiazepine withdrawal is characterized by a returning and amplification of original symptoms. This means that the anxiety you experienced prior to taking these drugs will be compounded
• Long term effects – The [potential] long-term effects cannot and shouldn’t be ignored. Even if you don’t develop dementia, you may suffer permanent memory impairment and/or other cognitive deficits. Most potential long-term effects are severe enough that they may make a person currently taking one of these drugs to reconsider.

Be aware of the dementia risk, use these drugs responsibly…

I had been using Xanax for over a year in high school and was fortunately taking it “as needed” most of the time. However, I also took the “XR” (extended-release) version which lasted all day when I was at school. At the time, there was no risk associated with the drug other than potential abuse/dependence. Fortunately now we are aware that using benzodiazepines carry more risk than solely addiction.

Before jumping to an extreme and stating that using these drugs causes dementia, it is important to consider the fact that correlation doesn’t equal causation. The drugs listed above may not be causing the dementia, rather results from studies may have been skewed as a result of people with dementia onset using these drugs to medicate their symptoms. Experiencing anxiety and sleep problems may make an individual more likely to use benzos. This sets up for a “chicken egg” scenario in which it is difficult to determine which came first – the neurodegeneration or the benzodiazepine usage.

The bottom line is that numerous people are taking these medications without being aware of the link. Most psychiatrists (including my own) are up-to-date with the latest research and will inform patients if their medications are associated with any (potential) long-term detriment in brain functioning. While further research is necessary to investigate a potential causal relationship between certain drugs and dementia, it’s still best to err on the side of caution if you plan on using them.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/23045258
• Source: http://www.bmj.com/content/349/bmj.g5205
• Source: http://archinte.jamanetwork.com/article.aspx?articleid=2091745
• Source: http://www.ncbi.nlm.nih.gov/pubmed/21300943

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