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Benzodiazepines are a widely used medication for the treatment of generalized anxiety, primarily due to their fast action and tolerability, although they have serious side effects which make them undesirable for use long-term.
Anxiety is an emotion and is therefore experienced in varying degrees of intensity by different people. At one end of the spectrum it is normal and helps us to function; at another it can be extremely maladaptive and result in considerable distress for the sufferer. It is duration, intensity, and frequency that separate normal, functional anxiety from abnormal, pathological anxiety. Anxiety or stress in response to events that we need to react to is normal. However, this natural response can become a problem if it impairs your ability to live your life fully.

For example, anxiety may be problematic for you if:

  • The anxiety feelings or sensation are very powerful or last a long time
  • Fears or worries you are having seem disproportionate to the situation
  • You change your behavior to avoid scenarios that might cause anxiety
  • Worries that you experience are very distressing or difficult to manage
  • Anxiety symptoms happen frequently or include overwhelming anxiety such as panic attacks
  • Enjoyment of everyday life is affected.

For those suffering from anxiety, medication can prove extremely helpful. In the case of panic attacks, for example, medications can enhance motivation and help speed up progress in recovery. For those experiencing obsessive-compulsive disorder (OCD), medications can change the frequency and intensity of worries and the associated distress. For those with simple phobias, pharmacotherapy can assist with some of the physical sensations associated with entering the fearful situation and reduce anticipatory anxiety. Likewise, with social anxiety, tensions allied with entering the feared situation (such as a racing heart or excessive perspiration) can be reduced, alongside reducing inhibitions which can have an impact upon shyness.

What are benzodiazepines?

Benzodiazepines are one of several types of medication which may be used to help with anxiety. They have a sedating effect on the body which means that they depress or slow down the workings of the central nervous system and its functions. They are often used for both anxiety, insomnia, as a muscle relaxant or anticonvulsant, and in alcohol/substance use withdrawal treatment. Benzodiazepines are a widely used medication for the treatment of generalized anxiety, primarily due to their fast action and tolerability and they work in anxiety by promoting relaxation, alleviating muscular tension and other physical anxiety symptoms.

How do they work?

Oral benzodiazepines will be absorbed in the gut, after which they are processed in the liver. They have a widespread effect on the brain: they affect emotional reactions, memory, cognition, consciousness, muscle tone and physical co-ordination. They work by enhancing the action of the neurotransmitter, Gamma Amino Butyric Acid (GABA), which is the major inhibitory neurotransmitter whose function is to slow things down. Benzodiazepines increase GABA's efficiency and so have a calming effect.

GABA reduces brain activity in the following brain areas:

  • Emotions
  • Rational thought
  • Memory
  • Essential physiological functions, such as breathing

Although benzodiazepines are considered beneficial and effective in short-term anxiety management, they are not considered to be effective in achieving long-term improvement and so when used for anxiety, they are often used as an adjunct to antidepressants until the antidepressant takes effect. There are some situations when their use may be inappropriate.

For example, following bereavement, tranquilizers may have a numbing effect on the emotions and so interrupt the grieving process; however if grief and anxiety are causing insomnia, then they may help you to relax and support the recovery process. In addition they are considered inadvisable in cases of former substance misuse and in the children and elderly as well as during pregnancy and breastfeeding. Certain medications and herbal remedies are also contraindicated as is the consumption of grapefruit products which can have a dangerous enzyme interaction.

Benzodiazepines are very effective in the short term but they may stop working if you take them continuously for a longer period because your brain adapts to their presence. The development of tolerance, dependence and withdrawal are some of most significant problems associated with the long-term use of benzodiazepines.

Owing to their serious side effects and potential for addiction (as well as carrying serious health risks) they are generally avoided in modern prescribing. However where they are prescribed, the following may be used:

  • Alprazolam - OCD, social anxiety, panic, phobias and generalized anxiety
  • Alonazepam - social anxiety, panic, phobias and generalized anxiety
  • Diazepam – panic, phobias and generalized anxiety
  • Lorazepam - panic, phobias and generalized anxiety
  • Oxazepam – phobias and generalized anxiety
  • Chlordiazepoxide – phobias and generalized anxiety

There has been concern for some time now about the high volume of benzodiazepine prescribing by doctors. It has been suggested that some of it may be inappropriate and be contributing to dependency issues or may even be causing underlying depression to be overlooked. As a result, benzodiazepines have generally fallen out of favor — it is argued that the dependency risk, tolerance issues and side effects render them infinitely inferior to the modern SSRI antidepressants.

However, these medications take a while to work and can also in the short term increase anxiety symptoms and it is argued by some that the evidence base for these newer medications is sketchy and industry rather than patient-driven. Many practitioners must conclude that long-term therapy with benzodiazepines is relatively safe, even when compared with Specific Serotonin Reuptake Inhibitors (SSRIs) as they are still widely prescribed. Furthermore, surveys show that benzodiazepines are still being used to treat chronic anxiety, not least as they are often preferred to antidepressants because of their fast action and fewer initial side effects.

Health risks

Using benzodiazepines for long periods of time can, unfortunately, come with a whole host of side side effects. Cognitive impairment, decreased motor coordination, concentration trouble, social phobia, and even depression are among them.

Benzodiazepines are associated with negative effects such as:

  • Daytime sedation
  • Problems with attention
  • Coordination, balance and speech issues
  • Memory impairment
  • Impaired psychomotor performance.
  • Use in older people is associated with increased risk of motor vehicle accidents and hip fractures, presumably from the increased risk of falls.

Cognitive impairment from long-term use of benzodiazepines is an issue gaining increasing attention. Benzodiazepines particularly thought to affect visuo-spatial abilities, processing speed, and verbal learning abilities. So this means they affect the way an individual sees and understands where objects are in relation to other things, the way in which straightforward tasks can be replicated after learning them; skills concerned with speech and language.

Memory, especially anterograde amnesia, is also believed to be adversely affected by long-term benzodiazepine use. This is, however, complicated by the fact that long-term mental health problems, including anxiety disorders, are themselves associated with cognitive deficits, especially in terms of concentration and attention. A recent literature review concluded that after long-term benzodiazepine treatment withdrawal, while patients recovered in many of these areas, they were still impaired when compared with those who had not been prescribed these drugs.

Benzos have additionally been linked to  with an increased risk in developing Alzheimer's disease. A recent study found that the risk of dementia was increased by more than 80 percent in those taking benzodiazepines for more than six months, compared to those who had not.

Withdrawal

Because GABA neurons acclimatize to the drug's presence, and so are underactive when it is stopped, benzodiazepines can cause reactions when no longer taken. This can lead to dependence where people avoid not taking them to avoid those effects. With drugs that take longer to take effect, the withdrawal reaction takes longer to develop so with shorter-acting drugs like benzodiazepines, it may take only a week of daily use and which can kick in just 24 hours after withdrawal.

Physical dependence on benzodiazepines is almost universal after a couple of months of daily use and withdrawal symptoms include insomnia, agitation, anxiety, seizures, blurred vision, sweating, tremors, hallucinations, and nausea and vomiting and unfortunately sometimes these symptoms are difficult to distinguish from returning insomnia or anxiety. Therefore medications in this group should always be tapered off over a long period of time, depending on the period of use.

Despite the gloomy picture and many preferred alternatives, benzodiazepines seem to continue to have a place in anxiety treatment. They are still the most effective treatment for acute anxiety and one of the best ways to treat muscle spasms or interrupt a seizure. In 2004, they accounted for 75 million prescriptions in the United States. Nearly 50 years after their introduction, the benzodiazepine era has not ended and only time will tell whether antidepressants will fully replace them in the treatment of chronic anxiety.

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