Benzodiazepine Medications: Uses, Effects, Side effects & Withdrawal Symptoms

What are Benzodiazepine medications?

Benzodiazepine medications belong to the class of sedative-hypnotics and induce calming effects when used in the treatment of anxiety. They also produce sedation and hypnosis.

In Benzodiazepine medications, CNS depression is more common than sedation and sleep induction. These cause respiratory depression when used in high doses as they affect the medulla, leading to coma and death.

Their effect is usually dose-dependent. The higher the dose, the higher the impact.

Benzodiazepine medications act immediately; all drugs in this class have slight variation in their effect and pharmacokinetic properties. The common effects produced by Benzodiazepine Medications are:

• Sedation
• Anxiolytic effect
• Muscle relaxant
• Hypnotic effect
• Anti-convulsant effect

These are absorbed rapidly in the brain and produce their effect & are ideal for anxiety attacks and symptoms when immediate treatment is needed.

Agents included in Benzodiazepine medications with their brands are;

Drug	Brand
Alprazolam	Xanax
Chlordiazepoxide	Librium
Clonazepam	Tranxene
Clorazepate	Klonopin
Diazepam	Valium
Estazolam	ProSom
Flurazepam	Dalmane
Lorazepam	Ativan
Midazolam	Versed
Oxazepam	Serax
Quazepam	Doral
Temazepam	Restoril
Triazolam	Halcion

Effects of Benzodiazepines:

As we know that benzodiazepine medications work by showing their effect on GABA_A receptors and enhancing their inhibitory activity.

Different effects produced by Benzodiazepines are;

Sedation:

Benzodiazepine medications reduce anxiety and produce different levels of sedation depending upon their given dose. The patient usually observes anterograde amnesia, which is unable to remember events during sedation time under the influence of medicines.

Sleep and Hypnosis:

One of the primary Benzodiazepine medications other than as anxiolytic is inducing sleep.

The hypnotic or sleep effects of benzodiazepines depend upon the following factors;

• Dosage used
• Frequency of administration
• Type of drug used

Generally, the hypnotic effects produced are;

• Decreased time to fall asleep
• Duration of NREM sleep (non-rapid-eye movement) is increased
• The time of REM sleep (Rapid eye movement) decreases.

Anticonvulsant effects:

Although benzodiazepines are not the first line of treatment and drug of choice for treating seizures. Lorazepam, Diazepam, Clonazepam, and Nitrazepam produce anticonvulsant effects when used to treat seizures.

Anesthesia:

Benzodiazepines like diazepam, lorazepam and midazolam are used in high doses intravenously with other agents to induce anesthesia. Benzodiazepines, when used as an anaesthetic is that they cause respiratory depression. Respiratory depression can be reversed with the use of Flumazenil.

How does Benzodiazepines Work to reduce anxiety?

Benzodiazepines work by increasing the inhibitory activity of GABA_A receptors in our brain.

GABA (Gamma Amino Butyric Acid) is an inhibitory neurotransmitter. Its receptors are present in our brain, which produces the inhibitory effect in our central nervous system.

When our central nervous system is unusually more active, it produces anxiety, nervousness, restlessness, reduced arousal, etc.

Benzodiazepines work by increasing the inhibitory effects of GABA, which in turn calm down our nervous system and reduce anxiety, nervousness, restlessness etc.

How to Choose?

Benzodiazepine medications are primarily used for anxiety disorders and help treat many. Still, they are not generally in use for Panic Disorders due to reports of worsening panic attacks after their use.

The choice of selecting benzodiazepines for the treatment of anxiety depends on the following factors:

Duration Of Action:

Lorazepam and Alprazolam are potent anxiolytics, but their duration of action is small compared to Diazepam.

Benzodiazepine medications have a short duration of action. Multiple tablet dosing is needed, leading to anxiety peaks in-between the doses.

Both of them, being in small tablet strength available commercially and with higher potency than Diazepam, are often used in excessive dosage, leading to their adverse effects, increased dependency, and difficult withdrawal.

Diazepam is the most commonly used anxiolytic and is suitable for most patients. It has a rapid onset of action and slow elimination from the body.

Due to this property, inter dose anxiety peaks are less observed than with the treatment of Lorazepam and Alprazolam, making it very ideal for controlling anxiety.

Clonazepam is a long-acting anxiolytic of all Benzodiazepines and is more potent than Diazepam. It is not commonly used as its withdrawal is difficult, so it is mainly reserved for epilepsy and severe anxiety disorders.

Dosage:

Dosage of Benzodiazepine Medications as anxiolytic:

Sr No.	Drug Name	Dosage (mg/day)	Half-Life (Hours)
1	Alprazolam	0.5-1.5 mg	13
2	Chlordiazepoxide	30 mg	12
3	Clonazepam	2-4 mg	35
4	Diazepam	5-30 mg	32
5	Lorazepam	1-4 mg	12
6	Oxazepam	30 mg	8
7	Temazepam	10-20 mg	8

Diazepam is considered the base agent and the equivalency of other drug dosages compared to 10mg of diazepam activity.

Dosage of Benzodiazepine Medications as Hypnotics:

For inducing sleep and hypnosis, the following Benzodiazepines medications are used and are given at bedtime:

Sr No.	Drug	Dosage
1	Estazolam	0.5–2 mg
2	Lorazepam	2–4 mg
3	Quazepam	7.5–15 mg
4	Temazepam	7.5–30 mg
5	Triazolam	0.125–0.5 mg

Adverse Effects / Side Effects of Benzodiazepines:

The adverse effects of Benzodiazepines are pretty common due to their central nervous system depression. These adverse effects  commonly include;

Side Effects of Benzodiazepine Medications

Confusion

Amnesia

Light-headedness

Drowsiness

Unusual increase in aggression

Increased risk of Falls

Increased risk of Road Accidents due to impaired concentration and drowsiness

But these above symptoms subside with the continuous therapy of 2-4 weeks.

• Long term use of Benzodiazepines also causes memory impairment. Also, they impair learning and thought processes.
• Chronic use of benzodiazepines also causes depression and increased suicide attempts.
• These are usually non-toxic, but when used with alcohol, they cause severe respiratory depression, which may even cause death.
• One adverse effect is that some patient cannot express their emotions. They cannot tell a feeling of pleasure or sorrow due to excessive use.

Withdrawal of Benzodiazepines:

Withdrawal effects are a significant problem in using benzodiazepine therapy to treat anxiety. These symptoms occur from standard dosages and after short-term use, e.g., after missed doses or once the medication has been stopped.

Withdrawal symptoms are controlled when the appropriate method is used under medical care. The dose is tailored and tittered down, and frequency is also changed etc.

Common withdrawal symptoms of Benzodiazepines include:

Nausea

Vomiting

Headache

Restlessness

Irritability

Increased Anxiety.

Insomnia

Vivid dreams or nightmares.

Dizziness and headache.

Muscle Pain and twitches

Jiggly Legs

Withdrawal from high doses exhibits severe side effects,

• Depersonalization,
• Derealization
• Hallucinations
• Distortion of body image
• Tingling, numbness, altered sensation
• Skin prickling (formication)
• Sensory hypersensitivity
• Muscle cramps, jerks
• Tinnitus
• Psychosis
• Confusion, Delirium
• Convulsions

Drug interactions :

All benzodiazepines are contraindicated with other

• CNS depressants
• TCA (Tricyclic Antidepressants)
• Alcohol
• Opioids
• Antihistamines
• Sedative Antipsychotics

The use of benzodiazepines with these produces an additive effect which increases sedation, and severe respiratory depression, which may lead to accidents and death.

Can you use Benzodiazepines in Pregnancy?

Benzodiazepines accumulate in fetal tissues and cause abnormalities like oral clefts, low birth weight, neonatal depression etc.

These are excreted in breast milk, hence not recommended in feeding mothers. It causes depression, low weight, sedation, and lethargy in newborn babies.