Benzodiazepine Long-Term Use and Its Cognitive Effects on Memory

In the 1960’s the drug industry in the United States changed dramatically with the introduction of a new category of drugs called benzodiazepines. Since the dawn of time anxiety has been an issue with people, but before the introduction of benzodiazepines there were much different treatments for anxiety problems.

In ancient Greece a cure for men would be to engage in sexual intercourse, which would release the excess stored “female semen” which could cause men to act high-strung and peculiar. In the Renaissance period there were the witches who, as most know, were burned at the stake or tortured to end their witchy ways. And in the Civil War day’s men who were experiencing what we now know to be PTSD, were treated with opium.

In most of these cases the ‘treatments’ of anxiety ended up causing more problems that it was worth e. g. death, nerve damage. So the introduction of benzodiazepines was in a way, a lifesaver, but at a cost. Benzodiazepines just as almost every other drug on the market have a list of risks associated with their use. With their widespread use throughout the United States that brings about the question of how the long-term use of benzodiazepines affect memory.

As benzodiazepines have been around in clinical usage since 1960 there has been an insurmountable amount of research done on the various cognitive effects on memory (Buffett-Jerrott & Stewart, 2002). Today there are over 50 types of benzodiazepines prescribed in clinical practices with Xanax being the most widely prescribed. Benzodiazepines have many different uses that include use as a sedative, muscle-relaxant, a treatment for insomnia and an anxiety reducer (Holbrook, Crowther, Lotter, Cheng, & King, 2000).

But as with any drug there is risk for dependency, as 2 BENZODIAZEPINE LONG-TERM USE long term use will build tolerance and have adverse effects when withdrawal occurs (Greenblatt, Shader, &Abernaethy, 1983).

Benzodiazepines like many other drugs have a risk of dependency, but with this type of drug there is both pharmacological and skeletal dependence (O’Brien, 2005). With this THERE IS ALSO THE ADDICTION THAT COMES WITH THE THRILL-SEEKING PARTIERS WHO MAY NOT NEED TO take the drug but are addicted and seek out the drug. The pharmacological dependence is different from this in that the user may gain tolerance and have to have higher doses, not from abuse, but from daily dosage prescribed from a doctor.

Some argue that because of the IMPACTS OF LONG-TERM ABUSE OR USE OF BENZODIAZEPINES THE DRUG SHOULD ONLY BE USED IN SHORT-TERM SITUATIONS AS THE DRUG DOES MORE BAD THAN GOOD FOR THE PATIENT OR USER (O’BRIEN, 2005). Benzodiazepines while having an affect on many cognitive areas have a profound affect on memory.

But to say that they have an affect on memory would be too simple as there are several different types of memory, short-term, long-term, and sensory memory. Short-term (primary) memory is the memory most used by our minds with the need for rehearsal to be able to be added to long-term memory. STM can usually hold nine items as it is constantly being added to from the world around us.

Long-term memory is the library of our minds, containing all of the items that we find important or have committed to memory for various reasons. Sensory memory contains the sensory images after they have appeared, they can be in either visual or auditory systems (Ghoneim, & Mewaldt, 1990). 3 BENZODIAZEPINE LONG-TERM USE In a test of short-term memory there was no significant impairment of stimulus encoding into STM.

In the sense of long-term memory effects while on benzodiazepines Roth and Roehrs did a study that found, that while it seemed that benzodiazepines effected long-term memory, as there was a disruption in consolidation of information into LTM.

They further saw that this disruption was because of the rapid speed of sleep onset, which is also an effect of benzodiazepines. To summarize it was the side effect of the drug that caused the memory issues, not the drug itself (Roth, Roehrs, Wittig, & Zorick, 1984). Other studies have shown that it is the time that the drug is taken that affects the retention into long-term memory.

One such study showed that when the benzodiazepines were administered before the task inhibited memory, rather than when the benzodiazepines were administered after the task (Buffett-Jerrott, & Stewart, 2002).

As of today there has been no research done on the effects of benzodiazepines on sensory memory. As one can imagine the dosage would effect the ability for memory retention. A study conducted by Ghoneim and Mewaldt was preformed on 120 volunteers to see the effects of dosage of diazepam (Valium) on memory (Ghoneim, & Mewaldt, 1990).

They were administered doses of either 0. 1, 0. 2, 0. 3mg/kg, or placed in a placebo group. They were then required to complete four different tasks, immediate free recall, delayed free recall, serial number learning, and semantic categories. In immediate and delayed free recall, the subject remembered less with the increasing dosage. In serial number learning the recall was about the same across all of the groups; and generally improved as the number of trials increased.

In semantic categories the 4 BENZODIAZEPINE LONG-TERM USE results were as to be expected in that identification became slower as the dosage of the drug went higher. This research shows that as the dosage goes up for benzodiazepines, memory function generally goes down. Which also brings back the statement of the long-term use of benzodiazepines, as with long-term use there is potential for higher doses, which in the end can end up impairing the memory of the user.

Mode of delivery can also affect memory when using benzodiazepines, as was seen in a study done in administration of benzodiazepines both orally and intravenously. It was found that intravenously the effects were seen much sooner as the brain was immediately delivered the drug.

Whereas the participants who took the drug orally were shown to have the effects of the benzodiazepine, just at a slower rate (Kothary, 1981). The researchers in this study also found there to be differences in memory retention based on the delivery of the drug.

Most benzodiazepines in today’s market are delivered orally, which makes it harder to test more differences in the different administrations of the drug. Benzodiazepines affect a very specific area of the grain called the GABA (gamma-amino butyric acid) receptors.

This is a specific neurotransmitter which, when activated, can slow or stop the neural activity. Benzodiazepines when present cause an influx of GABA which the causes the nerve impulses of the body to slow down. This is one of the reasons why benzodiazepines are used as a muscle relaxant.

With this there was also a study done that found that they different types of GABA receptors correspond to the different types of memory (Savic,Obradovic, Ugresic, & Bokonjic, 2005). 5 BENZODIAZEPINE LONG-TERM USE Recovery after benzodiazepines has been a well document procedure with both abrupt discontinuation and a gradual taper discontinuation studied.

In abrupt disconsolation of benzodiazepines there was a 27% relapse rate in patients who were using long half-life benzodiazepines; and a 57% relapse rate in patients using short half-life benzodiazepines. Users on the short half-life benzodiazepines showed more severe withdrawal symptoms. It was also shown that patients who stayed off the drug for more than five weeks had less anxiety than they had before they began taking the pills (Rickels, Schweizer, Case, & Greenblatt,1990).

In the gradual tapering discontinuation of the pills 90% of patients experienced withdrawal factors, but they were listed as mild to moderate only. And compared to the abrupt stop of the benzodiazepines only 32% of the long half-life patients and 42% of the short half-life patients were not able to stop using the drug (Schweizer, Rickels, Case, & Greenblatt, 1990).

This research showed that while there are side effects of long-term use of taking benzodiazepines there are ways to end the usage of the drug, with a relatively low relapse rate if done correctly.

In conclusion it has been shown in many different studies that benzodiazepine use has some effect on long-term and short-term memory alike. While there is some severe side effects of lone-term use on the brain and the GABA receptors do show a slowing the neural impulses with continued use of the drug, the drug is helpful to a large percentage of Americans and people all over the world.

And while the uses of benzodiazepines are considerably better than the former treatments of anxiety in the past, there is still room for concern on the continual use of the drug in long-term manners, specifically in memory retention.

In closing, the use of benzodiazepines can be helpful, but it is at a cost to the subject, and that is for the subject to decide if the benefits outweigh the risks. 6 BENZODIAZEPINE LONG-TERM USE References Buffett-Jerrott, S. E. , & Stewart, S. H. (2002). Cognitive and sedative effects of benzodiazepine use. Current pharmaceutical design, 8(1), 45-58. doi:10. 2174/1381612023396654 Ghoneim, M. M. , & Mewaldt, S. P. (1990).

Benzodiazepines and human memory: a review. Anesthesiology, 72(5), 926-938. Greenblatt, D. J. , Shader, R. I. , Abernaethy, D. R. New England Journal of Medicine, 1983, 309, 410-416. Holbrook, A. M., Crowther, R. , Lotter, A. , Cheng, C. , & King, D. (2000). Meta-analysis of benzodiazepine use in the treatment of insomnia. Canadian Medical Association Journal, 162(2), 225-233. Kothary, (1981). Time course of antirecall effect of diazepam and lorazepam following oral administration. Anesthesiology (Philadelphia), 55(6), 641. O’Brien, C. P. (2005).

Benzodiazepine use, abuse, and dependence. J Clin Psychiatry, 66(Suppl 2), 28-33. Rickels K, Schweizer E, Case W, Greenblatt DJ. , (1990). Long-term Therapeutic Use of Benzodiazepines: I. Effects of Abrupt Discontinuation. Arch Gen Psychiatry. ;47(10):899- 907. doi:10.

1001/archpsyc. 1990. 01810220015002. Roth, T. , Roehrs, T. , Wittig, R. , & Zorick, F. (1984). Benzodiazepines and memory. British journal of clinical pharmacology, 18(S1), 45S-49S. Savic, M. M. , Obradovic, D. I. , Ugresic, N. D. , & Bokonjic, D. R. (2005). Memory effects of benzodiazepines: memory stages and types versus binding-site subtypes.

Neural plasticity, 12(4), 289-298. doi:10. 1155/NP. 2005. 289 7 BENZODIAZEPINE LONG-TERM USE Schweizer, E. , Rickels, K. , Case, W. G. , & Greenblatt, D. J. (1990). Long-term therapeutic use of benzodiazepines: II. Effects of gradual taper. Archives of General Psychiatry, 47(10), 908-915.

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