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WARNING - These Sleep and Anxiety Drugs May Cause Dementia

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Benzodiazepines were once the darling of the medical world and they are still prescribed in high frequency. However, a spate of recent evidence from multiple clinical trials and epidemiological studies is highlighting that the dangers of this class of drugs far outweigh the benefits. This article catalogs the many side effects of benzodiazepines and provides a body of scientific work that proves they can cause dementia in old age. Are you still taking prescription benzodiazepines for your sleep and anxiety problems? Find out why you should stop now.

Advances in public health are ensuring that more people live long enough into old age. With this aging population, there is a rise in the prevalence of certain chronic diseases associated with old age. One of these diseases is dementia especially Alzheimer’s disease.

While diseases involving cognitive decline such as Alzheimer’s disease are often regarded as inevitable in old age, there are indications that old age does not necessarily cause these diseases.

Increasingly, studies suggest that dietary and lifestyle habits, as well as prescription medications, may account for the rising diagnoses of old age diseases.

A 2012 landmark study published in the British Medical Journal got a lot of press for demonstrating that the risk of dementia among the elderly is increased by the use of a class of drugs known as benzodiazepines.

However, this is not the first study to associate benzodiazepines with cognitive decline nor is it the first study to highlight that the serious, long-term adverse effects of benzodiazepines may far outweigh any possible benefits to be derived from them.

But what are benzodiazepines? What ailments are they prescribed for and what are their dangerous side effects?

What are Benzodiazepines?

Benzodiazepines are psychoactive drugs structurally synthesized from two fused rings of benzene and diazepine.

The first benzodiazepine on the market was diazepam or Valium. It was released in 1963. Since then newer generations of this class of drugs have come to market. Popular benzodiazepines include Xanax, Lexotan, Ambien, Restoril, Klonopin, and Halcion.

These drugs are prescribed for several conditions. The therapeutic uses of benzodiazepines are derived from their anxiolytic, hypnotic, sedative, anticonvulsant, and muscle relaxant properties.

Therefore, benzodiazepines are used in the treatment of insomnia, anxiety, muscle spasms, seizures, and alcohol withdrawal.

Benzodiazepines primarily act on the GABA (gamma-aminobutyric acid) pathways in the body.

GABA is an atypical amino acid. While it is not used to synthesize proteins, it acts as a neurotransmitter in the central nervous system. In fact, it is the chief inhibitory neurotransmitter in the brain and its effects counteract the actions of stimulants and excitatory neurotransmitters such as epinephrine.

Outside the nervous system, GABA also inhibits nerve conduction and, therefore, has a relaxing effect on muscles.

Therefore, when benzodiazepines bind to GABA-A receptors, they enhance the actions of GABA. Through this interaction, benzodiazepines can induce sleep, relieve anxiety, and relax skeletal muscles.

Benzodiazepines: A Catalog of Side Effects

The most common side effects of benzodiazepines include drowsiness, dizziness, impaired mental alertness, lack of muscular coordination, and decreased libido. These side effects are at their worst in the elderly.

Less common side effects include euphoria, mental confusion, loss of personality, blurred vision, nausea, loss of appetite, and nightmares. In rare cases, benzodiazepines can cause liver damage.

When given by intravenous route, benzodiazepines have been known to cause hypotension and slow down breathing.

Cognitive Side Effects

Benzodiazepines rapidly affect cognition. This is not surprising considering that these drugs are meant to act in the central nervous system. Therefore, even a single dose and short-term therapy can impair different aspects of mental performance.

Benzodiazepines can affect the ability to form and recall memories. In some cases, it has been shown to even cause amnesia.

There is also strong evidence that long-term use of benzodiazepines progressively worsens cognitive impairment. The types of cognitive decline associated with benzodiazepines include impaired mental concentration, verbal learning, eye-limb coordination, and even intelligence.

Paradoxical Side Effects

Paradoxical side effects are adverse drug reactions that cause the very symptoms that are supposed to treat. Therefore, instead of relaxing the muscles, benzodiazepines can sometimes tighten the muscles and cause seizures.

Other paradoxical side effects of benzodiazepines include irritability, violence, suicidal tendencies, and other personality changes.

While paradoxical side effects are estimated to only affect 1% of benzodiazepine users, certain patient groups are more likely to be affected than others. For example, these side effects are a lot more common among children and teenagers taking benzodiazepines as well as among those given high doses of these drugs.

Withdrawal Syndrome

Benzodiazepine withdrawal syndrome is a broad aspect of the damage these drugs can do. The body can easily develop tolerance to benzodiazepines. Also, the addiction potentials of these drugs are high.

This means that patients placed on benzodiazepines will need increasingly higher doses of the drugs to produce the same therapeutic effects. Furthermore, they will still crave benzodiazepines even when they no longer need the drugs.

However, abruptly stopping benzodiazepine therapy carries a whole set of problems.

By suddenly discontinuing benzodiazepines (or even reducing their doses too quickly), users can either develop rebound symptoms or withdrawal symptoms.

Those who experience rebound symptoms experience the same set of symptoms for which they were given benzodiazepines. However, the severity of the rebounding symptoms is worse.

Withdrawal symptoms are a new set of symptoms but they are nonetheless severe.

Symptoms of Benzodiazepine Withdrawal
  • Insomnia
  • Muscle spasms and seizures
  • Gastrointestinal discomfort
  • Fear and agitation
  • Irritability
  • Profuse sweating
  • Depression
  • Loss of personality and sense of reality
  • Delirium and psychosis
  • Suicidal tendencies

The Elderly

Researchers agree that benzodiazepines provide the least benefits for old people and the greatest danger.

Often, the side effects of these drugs are at their worst in the elderly. Also, benzodiazepine use is closely tied to cognitive decline in old age. Therefore, early use of benzodiazepines can increase the risk of dementia later in life.

In fact, benzodiazepine-induced dementia is reported to account for the majority of memory impairments in elderly patients.

Most of the side effects of benzodiazepines in the elderly are linked to the activities of the drugs in the central nervous system.  Therefore, these drugs can cause mental confusion, dizziness, syncope, vertigo, sleepwalking, agitation, paranoia, hallucinations (visual and auditory), aggression, panic, delirium, depersonalization, and insomnia.

Researchers have demonstrated that when taken off benzodiazepines, most of these symptoms quickly resolve in the elderly, and often the underlying condition being treated does not get worse.

The longest debate about the adverse effects of benzodiazepines in the elderly involves the effects of the drugs on the risk of dementia. However, recent studies have repeatedly and conclusively proven that benzodiazepines in the elderly is not only a bad idea but linked to the increased diagnoses of dementia in this age group.

Benzodiazepine and Cognitive Decline in the Elderly

Possible Links

A 2002 paper published in the Journal of Clinical Epidemiology detailed a nested case-control study conducted to investigate the possible association between benzodiazepine use and the risk of dementia in an elderly population.

For this study, the researchers recruited a total of 3,777 elderly persons who were at least 65 years old between 1989 and 1997. Benzodiazepine use among this study population was correlated with the incidence of diagnosed dementia.

The results of the study revealed that

  • patients who had ever used benzodiazepines had an increased risk of dementia
  • patients who used to take benzodiazepines had significantly increased risk of dementia
  • dementia was not observed in patients who are currently (and newly) taking benzodiazepines

These results show that benzodiazepines can indeed raise the risk of dementia even though their negative effects on cognition take a while to set in.

A 2005 review of past studies published in the journal, Psychological Medicine, searched through the medical research database, MEDLINE, to find well-designed studies investigating the link between dementia and benzodiazepine use.

The reviewers found 7 qualifying studies. Two of these found no association between benzodiazepine and dementia; another 2 found that benzodiazepines lower the risk of cognitive decline, and 3 studies found an increased risk of cognitive decline among benzodiazepine users.

The reviewers called for more epidemiological studies to fully address the possible effect of benzodiazepines on cognition.

They believed that with the high rate at which benzodiazepines are prescribed, even a slight increase in the risk of cognitive decline will make the dangers of benzodiazepines easily outweigh any possible benefits of taking the drugs.

Definitive Proof

Even before the 2005 review was published, the sort of large epidemiological studies requested by the reviewers had already been conducted.

One of these studies was published in 2002 in the Journal of Clinical Psychopharmacology. In this paper, the authors used data from the Epidemiology of Vascular Aging Study conducted in the city of Nantes. Their data pool involved 1,389 people aged between 60 and 70 years.

The researchers divided benzodiazepine users into 4 groups: non-users; and episodic (used only once), recurrent (used at least twice), and chronic (long-term) users.

The results of the epidemiological study showed that chronic users had significantly higher risks of cognitive decline than non-users of benzodiazepines. Also, the results showed that chronic users scored the least on mental alertness tests.

In comparison, episodic and recurrent users scored better than chronic users but their risks of cognitive decline were still higher than for non-users.

The researchers, therefore, concluded that long-term use of benzodiazepines was a risk factor of increased cognitive decline in the elderly. This study also shows that while short-term use of benzodiazepines is safer than long-term use, it can still raise the risks of cognitive decline.

The 2012 British Medical Journal article that has gotten so much press lately also used data from French epidemiological studies.

In this case, the researchers pooled 1,063 elderly persons who had no dementia before the study and who only started taking benzodiazepines no earlier than the third year of the 15-year period under investigation.

The results of this study showed that the new use of benzodiazepines in old people was associated with an increased risk of dementia.

Furthermore, the researchers demonstrated that, compared to people who never took benzodiazepines, even single uses of the drugs were associated with a 50% increase in the risk of dementia.

The authors of this study considered their methodology design robust enough and their results conclusive enough to warn against the indiscriminate prescription of benzodiazepines.

In their opinion, benzodiazepines should be used far less not only because of the increased risk of dementia demonstrated by their study but also because of the many serious adverse effects associated with this class of medications.

Alzheimer’s disease and Benzodiazepine Receptors

In Living Patients

A 1995 study used brain imaging techniques to investigate the affinity of benzodiazepine for GABA-A receptors as well as the slow metabolism of glucose in the brains of people with Alzheimer’s disease.

The results of the study published in the Archives of Neurology found that the transport rate of the benzodiazepine, flumazenil, was slower in the brains of Alzheimer’s patients compared to healthy patients. However, the affinity of the benzodiazepine for the GABA receptor was still preserved.

These results indicate the kind of response elicited by benzodiazepines in Alzheimer’s patients. The study shows that the binding of benzodiazepines to GABA receptors in the brain is likely to be the cause of reduced glucose metabolism in Alzheimer’s disease.

Therefore, the damage caused by benzodiazepines in Alzheimer’s disease is partly explained by the drugs’ ability to prevent the brain from optimally utilizing glucose to generate energy for its own sustenance.

Post-mortem Investigations

A 1988 study published in the Annals of Neurology took a retrospective look at the kind of changes made to the brain by benzodiazepine use.

For this study, the researchers conducted autopsies on 7 normal controls and 7 Alzheimer’s patients.

They found that benzodiazepine binding sites were significantly reduced in the frontal and temporal cortices of the hippocampus in brains of the Alzheimer’s patients.

This study suggests that benzodiazepines increasingly provide fewer benefits for people suffering from dementia even as they make changes in the brain that impairs cognitive functions.





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