Benzodiazepines: Dosage, Side Effects, And Withdrawal.

Benzodiazepines-drug-effect

In America, more than 30 million people use benzodiazepines. Doctors often prescribe them to fight insomnia, because of their anxiolytic and hypnotic effects.

What are the clinical effects of these drugs? What are their side effects and the undesirable effects they cause? Let’s take a look at benzodiazepines in our special report.

What Are Benzodiazepines? 

Benzodiazepines are a class of drugs with psychotropic effects. They are generally prescribed to reduce anxiety and insomnia, thanks to their anxiolytic and hypnotic action. They also have anti-epileptic effects and reduce muscle contractions.

General Information On Benzodiazepines. 

The molecular structure of benzodiazepines is the result of the combination of a benzene molecule with two nitrogen (dinitrogen) molecules.

Studies have shown that drugs belonging to the benzodiazepine class exert effects on the receptors of a specific neurotransmitter: GABA or gamma-aminobutyric acid.

This element exerts inhibitory effects on the excitability of the brain, more precisely the central nervous system. This action leads to several distinct therapeutic effects:

  • Sedative/Hypnotic: Promotes sleep.
  • Antiepileptic/Anticonvulsant: Acts against convulsions.
  • Anxiolytic: Reduces anxiety.
  • Amnesic: Causes episodic amnesia.
  • Muscle Relaxant: Relaxes muscles.

Logically, these drugs are therefore indicated and prescribed to treat anxiety disorders, epilepsy, insomnia, nocturnal anxiety, spasms, dystonia, or muscle contractures. Some treatments are used in the context of alcohol withdrawal.

There are more than 50 drugs administered and prescribed belonging to the benzodiazepine class. In France, only 22 of them are available.

According to the INN (International Nonproprietary Name), the name of the chemical substances contained in the drugs and belonging to the class “benzodiazepine” take the suffix -zepam. They are only available in pharmacies, following the issue of a secure prescription.

A distinction is made between anxiolytic benzodiazepines (Alprazolam or Xanax, Bromazepam or Lexomil, Oxazepam or Seresta), which are prescribed for difficulties in falling asleep, severe anxiety or neurotic disorders, and hypnotic benzodiazepines, also known as sleeping pills, such as Lormetazepam (Noctamide) or Loprazolam (Havlane). The latter facilitate sleep.

Action Time Of Benzodiazepines.

The half-life of a drug determines the time it takes for the concentration of the drug to decrease in the blood (50% decrease). The onset of action of benzodiazepines varies with each treatment.

Some have a rapid onset of action (less than 1.5 hours). The half-life of benzodiazepines ranges from 2.5 to 148 hours. Benzodiazepines with a short half-life (less than 20 hours) are fast-acting. Benzodiazepines with a half-life of more than 20 hours have a longer duration of action.

It is the doctor who determines the most appropriate treatment and dose for each individual case.

A Specific Prescription.

In France, approximately 7.5% of the population uses this class of medication. Their effectiveness against insomnia has been demonstrated by various studies. They are prescribed in preference to barbiturates because they have fewer side effects than the latter (no drowsiness during the day following the intake, for example, for drugs with a short half-life).

The physician determines the dosage of the treatment according to the individual and the problems encountered (in this case, difficulty falling asleep, partial or total insomnia). Several criteria are taken into account in order to determine the appropriate dose for each individual (weight, age, height, etc.).

Taking benzodiazepines depends on the route of administration prescribed by the doctor. 

In fact, the treatments can be taken:

  • Orally, in the form of pills, drops, or tablets.
  • By injection. It is possible to administer them by
  • Intravenously through infusions or intramuscularly.
  • Vy rectal route (suppositories).

It should also be taken into account that benzodiazepines cause addiction, as well as physical and psychological dependence. This is why their administration is regulated and must be carried out under medical supervision.

Actually, it is recommended to prescribe these drugs for a period that should not exceed 12 weeks for anxiolytic treatments.

When benzodiazepines are prescribed as sleeping pills (hypnotic benzodiazepines), the duration of treatment is shortened to 4 weeks, in order to limit the intake. The physician is obliged to write his prescription on a secure prescription (28-day prescription), named and written in full, to be renewed every month.

The practitioner is also required to inform the patient of the side effects, as well as of the risks incurred following the use of this class of medication.

Discontinuation of the treatment must be considered as soon as it is prescribed, as it must be done in stages, by gradually decreasing the doses. This is to avoid the appearance of a withdrawal syndrome, a phenomenon that we will develop in another paragraph.

Benzodiazepines And Alertness.

Benzodiazepines cause changes in consciousness. These treatments are also associated with:

  • Respiratory Distress.
  • Nervousness.
  • Lowered muscle tone leads to the risk of falling.
  • The appearance of an addiction to the treatment in the case of prolonged use and high doses.
  • Sometimes, the appearance of psychiatric disorders (psychotic episodes, delirium, hallucinations).

The use of benzodiazepines is thought to increase the risk of developing Alzheimer’s disease (an increase of about 50% after more than 3 months of treatment).

Reassuringly, side effects are rare and disappear quickly after taking the drug.

Benzodiazepines are contraindicated in cases of:

  • Respiratory Insufficiency.
  • Hepatic Insufficiency.
  • Allergy to any of the drug’s components.
  • Sleep Apnea.
  • Myasthenia.

To avoid incidents, it is best to follow a few safety guidelines.

Precautions For Use.

The administration of these therapies is closely monitored in people over 65 years of age, pregnant or breastfeeding women, people suffering from kidney or liver disease, young people under 18 years of age, people suffering from addictions, or machine operators.

For people aged 65 and over or suffering from several pathologies, the Agence Nationale de sécurité du médicament et des produits de santé (ANSM) and the Haute Autorité de Santé (HAS) urge physicians to prescribe short-acting benzodiazepines (short half-life) and to limit the doses and the treatment over time, in order to promote the elimination of the chemical compounds from the body.

It is important to detect cases of overdose, as too high a dose can lead to coma and death if left untreated. Hospitalization may be necessary, especially in cases of voluntary intoxication, such as attempted suicide.  Biological monitoring (blood tests) can reveal a blood level that is too high. Fortunately, there is an antidote that cancels the effects of benzodiazepines. It is called Flumazenil.

Addiction And Withdrawal Syndrome.

The French population generally consumes anxiolytics and benzodiazepines for longer than the recommended therapeutic period (from 6 months to 2 years, or even more).

This factor increases the risk of developing dependence, addiction, and the appearance of withdrawal syndrome.

Addiction.

Addiction is a phenomenon that leads to an increase in the intake of benzodiazepines by individuals. The progressive decrease of the therapeutic effect of the treatments leads to self-medication which pushes individuals to increase the doses by themselves. This is done in order to obtain the same expected effects, before the prescription.

At the same time, a process of dependence on medication can be set up. This phenomenon is linked to tolerance, which will lead to the appearance of physical and psychological dependence on the treatment. The risk of dependence is increased in the case of a history of addiction (alcoholism, drugs) and the combination of several benzodiazepines, long-term treatment, and high dosage.

This drug dependence makes it necessary to stop benzodiazepine treatments or at least to reduce the doses. This cessation should not be abrupt and should be implemented gradually. Prescription of anxiolytics or sleeping pills not belonging to the same drug class is also a possible alternative, in order to fight against this undesirable effect.

Withdrawal And Withdrawal Syndrome.

Withdrawal from benzodiazepines must be considered on a therapeutic and psychological level. First, the doctor prescribes a reduction in dosage over several days, until the drug is completely stopped.

Psychological follow-up may be provided during this process to facilitate withdrawal.

Withdrawal syndrome occurs when treatment is stopped abruptly, suddenly, and without support. Identifying this syndrome is not easy, as some symptoms are associated with the side effects of the medication. Here are the signs of withdrawal syndrome to look for when stopping treatment:

  • Tremors.
  • Headaches.
  • Muscle Pain and Weakness.
  • Anxiety.
  • Agitation.
  • Insomnia.
  • Convulsions.
  • Irritability.
  • Pain.
  • Sweating.
  • Nausea/Vomiting.

In more severe cases, delirium, hallucinations, or other psychiatric disorders (psychosis, paranoia) are observed. In extreme cases, delirium may occur.

The withdrawal stages can be carried out without incident. However, stopping the treatment may require readjustments during the process:

  • If symptoms appear when the dosage is decreased, the initial dosage should be resumed and the procedure repeated, decreasing the dosage even more slowly.
  • If severe symptoms develop, management should be reassessed.
  • If mild symptoms occur when discontinuation is effective, psychological follow-up should be initiated. Do not resume treatment.
  • If serious symptoms (hallucinations, delirium) appear during the process, the patient must be hospitalized as a matter of urgency.

Once the benzodiazepines have been stopped, monitoring does not stop. In fact, to be on the safe side, the patient is monitored for several months.

An initial medical consultation is conducted during the first week following the end of treatment. The doctor assesses the presence of withdrawal-related symptoms and informs the patient about the possibility of resumption of the symptoms that preceded the prescription (resumption of sleep disorders/insomnia or more or less severe anxiety manifestations).

Insomnia: Some Alternatives. 

In order to compensate for the inconveniences associated with benzodiazepines, doctors tend to prescribe sleeping pills with the same effects, but without as many undesirable effects: Zopiclone (Imovane) and Zolpidem (Stilnox). Classified as related to benzodiazepines, these two hypnotic drugs promote sleep.

There are other alternatives to the prescription of anxiolytics and hypnotics to treat insomnia. Certain plants such as valerian, chamomile, or passionflower have soothing properties and can help you find sleep.

Used in homeopathy, phytotherapy, or aromatherapy, they are available in the form of infusions, herbal teas, or essential oils.

You can ask your doctor or pharmacist for advice and information in order to determine which form is best suited to your needs. It is preferable to turn to medical treatments as a last resort.

Benzodiazepines Available In France.

Chemical Compound/ International Non-Proprietary Name or INNDrug NameTherapeutic Effects
Oxazepam SerestaAnxiolytic
Bromazepam LexomilAnxiolytic
AlprazolamXanaxAnxiolytic
LorazepamTemestaAnxiolytic
PrazepamLysanxiaAnxiolytic
Diazepam ValiumAnxiolytic
ClonazepamRitrovilAnticonvulsant/Anxiolytic
Clorazepate TranxeneAnxiolytic/Hypnotic
Clobazam UrbanylAnticonvulsant/Anxiolytic
TemazepamNormisonHypnotic
NitrazepamMogadonHypnotic
Loprazolam HavlaneHypnotic
Lormazepam NoctamideHypnotic
Flunitrazepam RohypnolHypnotic
Triazolam HalcionHypnotic
Estazolam NuctalonHypnotic
ClotiazepamVeratranAnxiolytic
NordazepamNordazAnxiolytic
Ethyl loflazepateVictanAnxiolytic
Benzodiazepine RelatedZopiclone ImovaneHypnotic
ZolpidemStilnoxHypnotic

Worth Noting: 

Tetrazepam or Myolastan was a muscle relaxant (muscle relaxant) that was heavily prescribed until 2013. It was withdrawn from the market because it caused serious side effects, including skin disorders (Stevens-Johnson syndrome). It was prescribed in rheumatology, as part of the treatment of pain related to muscle contractures.

Rohypnol is subject to pharmacovigilance, due to its misuse (see side effects of benzodiazepines). This benzodiazepine can only be administered following the issue of a secure prescription. The duration of treatment is limited to 14 days. The pharmacist can only provide treatment in weekly (7-day) increments to patients.

Since January 2012, Rivotril is only dispensed following the issuance of an initial prescription by a hospital physician. Only neurologists and pediatricians are authorized to issue them.

Some Common Misconceptions About Benzodiazepines. 

Let’s take stock of the general ideas surrounding benzodiazepines!

Benzodiazepines Are Prescribed To Treat Depression. 

These treatments are not effective against depression itself. In fact, they have anxiolytic effects; that is, they help limit anxiety and anxiety disorders. They can be prescribed in conjunction with antidepressants to limit the associated anxiety or sleep disorders encountered during depressive states.

Alcohol Should Not Be Consumed While Taking Benzodiazepines. 

Drinking alcohol increases the side effects of these drugs, including alertness and altered consciousness. It is therefore preferable not to drink alcohol while taking the medication.

Can You Become Addicted When Taking Benzodiazepines?

These drugs are habit-forming and addictive. This is why gradual discontinuation is recommended, in order to promote a smooth cessation (risk of withdrawal syndrome). In order to avoid dependency, regulations recommend the prescription of certain treatments for 3 to 4 weeks. In the context of sleep disorders, the use of a benzodiazepine is carried out as a second intention, after having tried alternative methods.

When Taking Benzodiazepines, One Must Be Careful, As They Cause Many Side Effects. 

Drowsiness, confusion, agitation, memory loss… We have discussed the side effects of benzodiazepines in this issue. When benzodiazepines are used as sleeping pills, they are generally effective and help to find sleep. However, it is best to avoid taking them before certain activities that require alertness, such as driving, as this can lead to accidents.

Benzodiazepines Are Contraindicated With Some Treatments.

Like other drugs, benzodiazepines cause drug interactions. They should not be taken at the same time as certain allergy medications, pain medications containing morphine derivatives (because they promote respiratory distress, one of the side effects of benzodiazepines). Do not hesitate to ask your doctor for advice and to inform him/her of any treatment you are taking, in order to avoid incidents.

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