Benzodiazepines are among the most prescribed drugs in the US, and just like opioids, are vastly overprescribed by doctors and midlevel practitioners.  Benzodiazepine dependency/addiction is the third most common addiction in the elderly behind tobacco and alcohol. Much of the prescribing for those with senile dementia or who are simply querulous are prescribed benzodiazepines to placate caretakers, their children, and the nursing staff in nursing homes, but in the absence of a legitimate accepted diagnosis, and despite the increased risk of interactions with other drugs, respiratory depression, severe memory loss, inability to focus on tasks and feeling "fuzzy in the head", and frequent falls. In fact, benzodiazepine prescribing increases with age despite the fact that the age group with the highest anxiety (the most common use for benzodiazepines) is in the age 30-44 year old group (MMWR Surveill Summ. 2015 Oct 16;64(9):1-14).  However, there is much benzodiazepine prescribing begins long before the patients become elderly.  These drugs are prescribed from the age of the early 20's onward for sleep disturbances and anxiety without any formal testing, and frequently continued for decades, sometimes well after the situational anxiety resolved.  30% of patients become dependent on benzodiazepines being prescribed by physicians, and cannot quit using them (Curr Psychiatry Rep. 2016 Jan;18(1):8). A 2010 study that found benzodiazepine usage rates in the general population ranged from about 2% to almost 18%. In the study, about one-third of people who received an initial prescription stayed on the drug long term – despite the recommendation in treatment guidelines that suggests limited short-term use. The physicians continue to prescribe despite the studies demonstrating long term sleep effects are actually worse with benzodiazepines (some patients feel like zombies during the day due to the lack of REM sleep that is decreased by benzodiazepines), that there is little evidence anxiety is improved when long term prescribing is used, and ignoring the fact that the benzodiazepines taken chronically actually cause anxiety.  The patients are frequently never taken off the benzodiazepines, and in some cases due to the increasing anxiety and sleep disturbances caused by the long term benzodiazepine prescribing, another benzodiazepine may be added to the first or the doses escalated, and frequently a sleeping aid that acts of the benzodiazepine receptors or close to them is also added. This dangerous combination of drugs is not uncommon.  In fact, doctors frequently prescribe benzodiazepines (especially high dose benzodiazepines) to the patients who are at higher risk for adverse events from the medications including those with sleep apnea, substance abuse, chronic alcohol abuse, and severe COPD (J Gen Intern Med. 2016 Sep;31(9):1027-34). Benzodiazepines interfere with cognitive behavior therapy and other forms of psychological counseling because they cause impairment of memory and processing of information. High dose benzodiazepines cause respiratory depression when buprenorphine is used (Basic Clin Pharmacol Toxicol. 2008 Sep;103(3):228-39) and most of the uncommon deaths involving buprenorphine also involve benzodiazepines 82% of the time and alcohol 58% of the time (Eur J Clin Pharmacol. 2012 Mar;68(3):301-9).  

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Properties of Benzodiazepines

Acute Side Effects-Relaxation, anxiety reduction, memory impairment (amnesia), sedation, muscle relaxation

Overdose Effects-Weakness, severe confusion, impaired physical skills and driving ability, respiratory depression, incoordination, slurring of the speech pattern, comatose.  These effects are worsened and may occur at much lower dosages if combined with opioids, alcohol, and some other sedatives.

Chronic Abuse Side Effects- Anxiety, sleep disturbance, headaches, loss of appetite, and weakness.  These side effects are the same symptoms that benzodiazepines were used to treat in the first place, suggesting benzodiazepines should only be prescribed for short term use only.  In particular, the patient who tries to stop their use of benzodiazepines or their physician tries to stop the use suddenly or gradually will precipitate the withdrawal syndrome for benzodiazepines. 

Benzodiazepine Dependence (NICE)  

A cluster of physiological, behavioural, and cognitive phenomena as manifested by three (or more) of the following, occurring within a 12-month period:

• A strong desire or sense of compulsion to take benzodiazepines.

• Difficulties in controlling benzodiazepine consumption in terms of its onset, termination, or levels of use.

• A physiological withdrawal when benzodiazepines use has ceased or has been reduced.

• Evidence of tolerance, such that increased doses of benzodiazepines are required in order to achieve effects originally produced by lower doses.

• Progressive neglect of alternative pleasures or interests because of benzodiazepine use, increased amount of time necessary to obtain or take the substance or to recover from its effects.

• Persisting with benzodiazepine use despite clear evidence of overtly harmful consequences.

Benzodiazepine Withdrawal Syndrome-Occurs from too rapid a withdrawal or sudden withdrawal: Severe irritability, emotional outbursts, inability to concentrate, cannot perform simple tasks, severe memory problems, body aches, pain, muscle stiffness and soreness, severe sleep disturbance (cannot get to sleep or stay asleep), massive anxiety, panic attacks, suicidal ideations, seizures, death in severe cases.​ 

Short-acting benzodiazepines include oxazepam, alprazolam and temazepam. Withdrawal typically begins 1-2 days after the last dose, and continues for 2-4 weeks or longer.

Long-acting benzodiazepines include diazepam and nitrazepam. Withdrawal typically begins 2-7 days after the last dose, and continues for 2-8 weeks or longer

 

Benzodiazepines- interactions with opioids are one of the most frequent causes of death.

 

Benzodiazepine Abuse and Addiction

Abuse and dependency may occur at a young age if the drug is prescribed for more than a month. Benzodiazepines are frequently traded among friends and family without a thought as to the felony behavior. Overdose is a common reason for emergency room visits from excessive dosing or using the medications in combination with other drugs, especially opioids or alcohol.  But the number one reason for benzodiazepine abuse is due to excessive supply by physicians for questionable diagnosis and for much longer than is supported by the scientific literature.      

 

Benzodiazepines Used in the US

Xanax (alprazolam) is the most commonly used benzodiazepine in the US.  Very rapid uptake into the blood stream causing a high level of the drug and rapid relaxation.  It is a commonly requested drug by patients, and on the street are called "bars" or Zanies. The half life is 6-25 hours and the 5mg diazepam equivalent is 0.25mg.

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Klonopin (clonazepam) is frequently used by psychiatrists to get people off of Xanax, via substitution therapy.  The half life is 22-54 hours and the 5mg diazepam equivalent is 0.5mg.

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Valium (diazepam) has been available for over 5 decades, has a slow action of onset, and a long half life of 20-80 hours. 

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Librium (chlordiazepoxide) was the original benzodiazepine from the 1950s.  It was called a minor tranquilizer and is still used to treat delirium tremlens. 

 

Restoril (temazepam) was designed as a treatment for insomnia.  It is inappropriately prescribed in combination with other benzodiazepines such as clonazepam or alprazolam. The half life is 5-15 hours.  The 5mg diazepam equivalent 10mg

 

Serax (oxazepam) is a very short acting benzodiazepine with a half life of 4-15 hours, and with a 5mg diazepam equivalent is 15mg

 

Halcion (triazolam) has a very long half life and causes significant amnesia and cognitive impairment.  The half life is 1-3 hours then is metabolized into other active benzodiazepines.  The 5mg equivalent to diazepam is 10mg

 

Ativan (lorazepam) has a relatively long clinical life and is frequently prescribed for mild anxiety in the elderly. The halflife is 12-16 hours but in the elderly may have a much more apparent long effect due to tight adherence to the benzodiazepine receptors

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Guidelines for Prescribing

NICE Guidelines (Europe)

• Prescribe the lowest possible doses of benzodiazepines and only prescribe for 2-4 weeks. It is important to remember that patients can get withdrawal symptoms between doses if they are given short-acting benzodiazepines.

• Use the lowest dose which will control the symptoms, for the shortest possible time.

• Use only for severe or disabling anxiety or insomnia.

• Use of benzodiazepines for short-term mild anxiety is inappropriate. National Institute for Health and Care Excellence (NICE) guidelines state a benzodiazepine should not be used for treatment of generalised anxiety disorder.[7][8] 

• Where used as a hypnotic, advise intermittent use if possible.

• Taper off gradually when stopping benzodiazepines.

• Where possible, use alternatives to benzodiazepines, such as non-pharmacological strategies, and medication with less risk of dependence. See the separate articlesInsomnia and Generalised Anxiety Disorder for options.

• Advise patients of the risk of dependence and impaired reaction times. Advise that this may affect ability to drive or operate machinery. Also advise that effects of alcohol may be exacerbated.

• Elderly patients are particularly prone to adverse effects of benzodiazepines and, therefore, there is a need to be even more cautious when prescribing.

• Be aware that benzodiazepines cross the placenta, and may lead to neonatal side-effects.

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