Usage
- Etizolam is prescribed for the short-term treatment of generalized anxiety disorder, panic disorder, and insomnia. It can also be used to manage short-term depression or ease withdrawal symptoms. It may be used to improve anxiety, tension, and muscle tension associated with conditions like cervical spondylosis, low back pain, and tension headaches.
- Pharmacological Classification: Etizolam is a thienodiazepine, a class of psychoactive drugs similar to benzodiazepines. It acts as an anxiolytic, hypnotic, sedative, and muscle relaxant.
- Mechanism of Action: Etizolam enhances the effect of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. This leads to increased chloride ion influx into neurons, causing hyperpolarization and reducing neuronal excitability. This action results in decreased anxiety, muscle relaxation, and sleep induction.
Alternate Names
Etizolam is marketed under various brand names, including Etilaam, Etizest, Depas, Etipax, Etilize, Sedekopan, and Pasaden. Other names include Arophalm, Capsafe, Dezolam, Eticalm, Etidrale, Etisedan, Etizolan, Guperies, Medipeace, Mozun, Nonnerv, Palgin, and Sylazepam.
How It Works
- Pharmacodynamics: Etizolam binds to benzodiazepine receptors in the central nervous system, particularly in the limbic system and hypothalamus, potentiating the inhibitory effects of GABA. This leads to a reduction in neuronal activity, resulting in anxiolysis, sedation, muscle relaxation, and hypnosis.
- Pharmacokinetics: Etizolam is well-absorbed orally, reaching peak plasma concentrations within 1-2 hours. It is metabolized primarily in the liver by cytochrome P450 enzymes (CYP3A4 and CYP2C19), with the primary metabolite being alpha-hydroxyetizolam. It is then excreted mainly through the kidneys. The elimination half-life is approximately 3.5-6 hours. This can vary depending on dosage, co-administered drugs, and the individual’s metabolic rate.
- Mode of Action: Etizolam acts allosterically on GABAA receptors, increasing the frequency of chloride channel opening when GABA binds to the receptor. This influx of chloride ions hyperpolarizes the neuron, making it less likely to fire and thus inhibiting neuronal activity.
- Elimination Pathways: Etizolam is primarily metabolized in the liver by CYP3A4 and CYP2C19 enzymes. Following metabolism, it is conjugated and then primarily excreted in urine. A small percentage might be excreted through feces.
Dosage
Standard Dosage
Adults:
- Anxiety: The initial dose is typically 0.5 mg twice or thrice daily. This may be increased to a maximum of 3 mg daily, divided into multiple doses, as needed and tolerated.
- Insomnia: 1-2 mg before bedtime.
Children:
The safety and effectiveness of etizolam in children have not been established. Therefore it is generally not recommended for pediatric use.
Special Cases:
- Elderly Patients – Start with a lower dose (e.g., 0.25 mg twice daily) and increase gradually as tolerated.
- Patients with Renal Impairment – Reduce the dose and monitor for side effects.
- Patients with Hepatic Dysfunction – Reduce the dose and closely monitor liver function.
- Patients with Comorbid Conditions – Dosage adjustment may be necessary depending on the specific comorbidity.
Clinical Use Cases
Etizolam is not typically used for the listed clinical scenarios. Benzodiazepines such as midazolam or lorazepam are usually preferred in these contexts.
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments
Dosage adjustments should be individualized and made with caution in patients with hepatic or renal impairment, the elderly, and those with concomitant medical conditions.
Side Effects
Common Side Effects
Drowsiness, dizziness, headache, fatigue, ataxia (loss of coordination), muscle weakness, dry mouth, nausea, and constipation.
Rare but Serious Side Effects
Confusion, depression, amnesia, respiratory depression, paradoxical reactions (increased anxiety, aggression), dependence, and withdrawal symptoms upon discontinuation. Allergic reactions can also occur, including skin rash, itching, or swelling.
Long-Term Effects
Cognitive impairment, memory problems, dependence, tolerance. Blepharospasm is a possible long-term side effect, especially in women.
Adverse Drug Reactions (ADR)
Severe allergic reactions (anaphylaxis), Stevens-Johnson syndrome, and toxic epidermal necrolysis (rare but life-threatening skin reactions). Overdose can lead to respiratory depression, coma, and potentially rhabdomyolysis and hypothermia.
Contraindications
- Hypersensitivity to etizolam or benzodiazepines.
- Severe respiratory insufficiency, sleep apnea, or COPD.
- Myasthenia gravis.
- Acute narrow-angle glaucoma.
- Severe hepatic impairment.
- Coma.
- Pregnancy and breastfeeding.
Drug Interactions
Etizolam interacts with several medications, including:
- CNS depressants: Alcohol, opioids, barbiturates, antihistamines, antidepressants (e.g., fluoxetine, trazodone), and antipsychotics can potentiate sedation and respiratory depression.
- CYP450 inhibitors/inducers: Itraconazole, fluvoxamine, and other CYP3A4 inhibitors may increase etizolam levels; carbamazepine and other CYP3A4 inducers can decrease etizolam levels.
- Other medications: Cimetidine, disulfiram, diazoxide, clonidine, and muscle relaxants may interact with etizolam.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Etizolam is contraindicated in pregnancy due to the risk of fetal harm.
- Breastfeeding: Etizolam is excreted in breast milk and can potentially cause drowsiness and other side effects in infants. Avoid breastfeeding while using this medicine.
Drug Profile Summary
- Mechanism of Action: Enhances GABAergic neurotransmission, resulting in anxiolysis, sedation, and muscle relaxation.
- Side Effects: Drowsiness, dizziness, ataxia, muscle weakness, confusion, depression, dependence.
- Contraindications: Hypersensitivity, severe respiratory insufficiency, myasthenia gravis, acute narrow-angle glaucoma, severe hepatic impairment, pregnancy, breastfeeding.
- Drug Interactions: CNS depressants, CYP3A4 inhibitors/inducers, certain other medications (see above).
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: up to 3 mg/day; elderly: start with lower doses.
- Monitoring Parameters: Respiratory rate, blood pressure, mental status, liver function tests.
Popular Combinations
Etizolam is sometimes combined with propranolol to manage anxiety, especially when physical symptoms such as tremors and palpitations are prominent. However, the safety and efficacy of this combination have not been extensively studied, and caution should be exercised.
Precautions
- Obtain a thorough patient history, including allergies, comorbid conditions, and concomitant medications.
- Conduct baseline liver and renal function tests.
- Monitor for respiratory depression and other side effects.
- Advise patients against driving or operating machinery until the effects of the medication are known.
- Taper the dose gradually upon discontinuation to avoid withdrawal symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Etizolam?
A: The recommended starting dose for adults is typically 0.5 mg two to three times daily for anxiety and 1-2 mg before bedtime for insomnia. The maximum daily dose is 3 mg. Elderly patients should start with a lower dose.
Q2: How long does it take for Etizolam to work?
A: The effects of etizolam can be felt within 30-60 minutes after oral administration.
Q3: Can Etizolam be used during pregnancy?
A: No, Etizolam is contraindicated during pregnancy due to potential risks to the fetus.
Q4: What are the common side effects of Etizolam?
A: Common side effects include drowsiness, dizziness, ataxia, muscle weakness, dry mouth, and nausea.
Q5: Can I drink alcohol while taking Etizolam?
A: No, alcohol should be avoided while taking etizolam, as it can potentiate the sedative effects and increase the risk of respiratory depression.
Q6: Is Etizolam addictive?
A: Yes, Etizolam has the potential for dependence and addiction, especially with prolonged use. It should be used only for short-term treatment and tapered off gradually under medical supervision.
Q7: What should I do if I miss a dose of Etizolam?
A: If you miss a dose, take it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and continue with your regular dosing schedule. Do not double the dose.
Q8: Are there any specific dietary restrictions while taking Etizolam?
A: Grapefruit juice should be avoided as it can inhibit the metabolism of etizolam, potentially increasing drug levels and the risk of side effects.
Q9: What are the signs of Etizolam overdose?
A: Signs of overdose include excessive drowsiness, confusion, difficulty breathing, slow heart rate, loss of coordination, and coma. Seek immediate medical attention if an overdose is suspected.
