Alprazolam – action, use, contraindications, dosage, risk of addiction

Proven content

Alprazolam is an organic chemical compound that is used as a psychotropic drug to treat anxiety, panic attacks, agoraphobia, and depression. It is highly effective and highly addictive, therefore it is recommended to use alprazolam under strict medical supervision and for the shortest possible time.

Alprazolam – what is it?

Alprazolam (also known as Xanax, from the first drug to contain it as an active ingredient), is a short-acting sedative of the class of triazolobenzodiazepines (TBZD), or benzodiazepines (BZD) linked to a triazole ring. It is most commonly used for the short-term treatment of anxiety disorders, in particular anxiety disorder or generalized anxiety disorder (generalized anxiety disorder). Other uses include treating chemotherapy-induced nausea, along with other treatments. Generalized anxiety disorder treatment generally improves within a week. Alprazolam is generally taken by mouth.

Due to concerns about misuse, some people do not recommend alprazolam as the initial treatment for panic disorder. Alprazolam is also known as a popular remedy that is used to relieve everyday stress, relax or forget about life problems. Such a procedure is highly inadvisable due to the possibility of addiction, which in turn often leads to a situation in which everyday functioning without the obligatory dose of the drug becomes impossible. It should be added that taking alprazolam is associated with the risk of committing suicide and doubling the risk of death from any cause.

See also: Psychiatrist: suicides give signals, but we don’t notice them

Alprazolam – action

Alprazolam is a positive allosteric modulator of the A-type gamma-aminobutyric acid (GABA) receptor. When it binds to the receptor, the effect of GABA is enhanced, leading to inhibition of neurons in the brain. This produces effects including anxiety reduction, muscle relaxant, antidepressant, and anticonvulsant effects. The activity of alprazolam in the central nervous system is dose-dependent.

Alprazolam is classified as a high-potency triazolobenzodiazepine (a benzodiazepine with a triazole ring attached to its structure). As a benzodiazepine, alprazolam has a number of therapeutic and side effects by binding to the benzodiazepine GABAA receptor site and modulating its function. GABA receptors are the most fertile inhibitory receptors in the brain. The chemical and receptor systems of GABA mediate the depressant or sedative effects of alprazolam on the nervous system.

The binding of alprazolam to the GABAA receptor, the chloride ion channel, enhances the action of GABA, the neurotransmitter. When GABA binds to the GABAA receptor, the channel opens and chlorine enters the cell, making it more resistant to depolarization. Therefore, alprazolam depresses synaptic transmission, reducing anxiety.

The GABAA receptor is made up of 5 out of 19 possible subunits, and the GABAA receptors made up of different combinations of subunits have different properties, different locations in the brain and importantly different activities with respect to benzodiazepines. Alprazolam and other triazolo-benzodiazepines, such as triazolam, that have a triazole ring attached to a diazepine ring appear to have antidepressant properties. This is perhaps because of the similarity with tricyclic antidepressants, as they have two benzene rings attached to a diazepine ring.

Alprazolam causes marked suppression of the hypothalamic-pituitary-adrenal axis. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic and amnestic. However, alprazolam is mainly used as an anxiolytic.

It has been shown that administration of alprazolam, compared to lorazepam, causes a statistically significant increase in extracellular concentrations of dopamine D1 and D2 in the striatum.

See also: Poisoning with sleeping pills

Alprazolam – application

Alprazolam is most commonly used for the short-term treatment of anxiety disorders, panic disorder, and nausea caused by chemotherapy. Alprazolam may also be indicated in the treatment of generalized anxiety disorder, as well as in the treatment of anxiety conditions associated with depression.

Alprazolam and anxiety disorder

Alprazolam is effective in relieving moderate to severe anxiety and panic attacks. However, it is not the first line treatment since the development of selective serotonin reuptake inhibitors. Most of the evidence shows that the benefits of alprazolam in the treatment of panic disorder only last for 4 to 10 weeks. However, people with panic disorder have been treated openly for up to 8 months with no apparent loss of benefit. Alprazolam is recommended by the World Federation of Associations of Biological Psychiatry (WFSBP) for refractory panic disorder with no history of tolerance or dependence.

Alprazolam and panic disorder

Clinical trials have shown that efficacy in anxiety disorders is limited to 4 months. However, studies on the antidepressant properties of alprazolam are weak and have only assessed its short-term effects on depression.

Alprazolam and nausea caused by chemotherapy

Alprazolam can be used in conjunction with other drugs for chemotherapy-induced nausea and vomiting.

Alprazolam – contraindications

Benzodiazepines require special care when used in children and people who are addicted to alcohol or drugs. Particular caution should be exercised in pregnant or elderly people, people with a history of substance use disorders (especially alcohol addiction), and people with comorbid psychiatric disorders.

Alprazolam should be avoided or carefully monitored in people with: myasthenia gravis, acute angle-closure glaucoma, severe hepatic impairment (e.g. cirrhosis), severe sleep apnea, pre-existing respiratory depression, severe lung failure, chronic psychosis, hypersensitivity or allergy to alprazolam or other benzodiazepines and borderline personality disorder (where it may cause suicide attempts and out of control).

Like all CNS depressants, higher than normal doses of alprazolam can significantly reduce alertness and increase sleepiness, especially in people who are not used to the effects of the drug.

Elderly people should be cautious when using alprazolam due to the possibility of increased susceptibility to side effects, especially loss of coordination and drowsiness.

See also: New dangerous psychoactive substances

Alprazolam – dosage

Alprazolam is sold as tablets for oral use. In one tablet, the concentration of the substance may vary from 0,25 mg to 2 mg. The size of the prescribed doses and their frequency should be determined by the doctor. It should be emphasized that using the drug on your own, without medical consultation, significantly increases the risk of side effects!

In the case of generalized anxiety disorder or anxiety disorders coexisting with depression, it is recommended to use a dose of 0,25 to 0,5 mg three times a day (the total daily dose should not exceed 3 mg).

In the case of panic disorder or agoraphobia, the initial doses should be 0,5-1 mg once a day at bedtime, then, as directed by your doctor, are gradually increased (the maximum daily dose is 10 mg).

The use of alprazolam should be as short as possible and using the lowest daily doses possible, and the total duration of treatment should not exceed 8-12 weeks.

In turn, it is not recommended to discontinue the drug overnight due to the possibility of withdrawal symptoms. The doses taken should be reduced gradually, in accordance with the doctor’s guidelines, most often not faster than by 0,5 mg every 3 days.

The acute use of the drug does not pose a risk of addiction.

The tablets should be swallowed whole (crushing them, dissolving them or sucking them in the mouth may reduce the effectiveness of the active substance). Increasing the recommended daily dose does not increase the therapeutic effect, but may cause the appearance of side effects and promote the development of addiction.

Alprazolam – overdose

Alprazolam overdose can be mild to severe, depending on the amount ingested and whether other medications are taken at the same time.

Alprazolam overdose causes excessive central nervous system (CNS) depression and may include one or more of the following symptoms:

1. coma and death when alprazolam is combined with other substances;
2. fainting;
3. hypotension (low blood pressure);
4. hypoventilation (shallow breathing);
5. impaired motor functions;
6. dizziness;
7. balance disorders;
8. disturbed or absent reflexes;
9. muscle weakness;
10. orthostatic hypotension (fainting when getting up too quickly);
11. somnolence.

See also: What is the disconnection from life support equipment in Poland?

Alprazolam – side effects

Sedatives, including alprazolam, are associated with an increased risk of death.

Possible side effects include:

1. anterograde amnesia and difficulty concentrating;
2. ataxia, slurred speech;
3. disinhibition;
4. drowsiness, light-headedness, dizziness, fatigue, instability and impaired coordination;
5. skin rash, respiratory depression, constipation;
6. thoughts of suicide or attempted suicide;
7. muscle weakness.

Relatively rare side effects are:

1. dry mouth;
2. hallucinations;
3. jaundice;
4. epileptic seizures;
5. urinary retention.

It has also been shown that the following paradoxical effects of the drug may occur:

1. aggression;
2. mania, agitation, hyperactivity and anxiety;
3. rage, hostility;
4. vibrations and tremors.

Alprazolam – interaction with other agents

Alprazolam is mainly metabolised by CYP3A4. The combination of CYP3A4 inhibitors such as cimetidine, erythromycin, norfluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene and ritonavir delays the hepatic clearance of alprazolam, which may result in its accumulation and severity of side effects.

It was also found that imipramine and desipramine were increased by an average of 31% and 20%, respectively, with the simultaneous administration of alprazolam tablets. In turn, the contraceptive pill reduces the clearance of alprazolam, which may lead to an increased plasma concentration of alprazolam and its accumulation.

It should also be emphasized that alcohol is one of the most common interactions with alprazolam. Alcohol and alprazolam when taken in combination act synergistically and can cause severe sedation, behavioral changes and intoxication. The more alcohol and alprazolam you take, the worse the interaction. Combining alprazolam with kava pepper may cause the development of a half-coma. On the contrary, plants of the genus Hypericum (including St. John’s wort) can lower the plasma level of alprazolam and reduce its therapeutic effect.

See also: Dangerous interactions

Alprazolam – pregnancy and breastfeeding

Benzodiazepines cross the placenta, enter the fetus and are also excreted in breast milk. Chronic administration of diazepam, another benzodiazepine, to nursing mothers has been reported to cause drowsiness and weight loss in their babies.

It should also be added that the use of alprazolam during pregnancy is associated with birth defects, and the use in the last trimester of pregnancy may cause fetal addiction and withdrawal symptoms in the postpartum period, as well as laxity of the newborn and breathing problems. However, in long-term users of benzodiazepines, abrupt withdrawal due to teratogenesis concerns carries a high risk of causing extreme withdrawal symptoms and a strong rebound effect associated with the underlying mental health disorder. Miscarriages can also result from the sudden discontinuation of psychotropic drugs, including benzodiazepines.

See also: Fetal development stages – the first, second and third trimesters of pregnancy

Alprazolam – addiction and withdrawal symptoms

The abuse potential among people taking alprazolam for medical reasons is controversial, with some expert opinions saying the risk is low and similar to other benzodiazepine medications. Others argue that there is a significant risk of misuse and dependence in both patients and non-medical users, and that the short half-life and rapid onset of action may increase the risk of misuse. Compared to the large number of prescriptions, relatively few people increase the dose on their own initiative or engage in drug research.

Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA receptor (gamma-aminobutyric acid). When it is bound to these sites, which are termed benzodiazepine receptors, it modulates the action of GABAA receptors and thus GABAergic neurons. Long-term use causes adaptive changes in benzodiazepine receptors, making them less sensitive to stimulation and thus reducing the potency of drugs

Withdrawal and rebound symptoms are common and require tapering of the dose in order to minimize the effects of the withdrawal upon discontinuation.

Not all withdrawal effects are evidence of true addiction or withdrawal. A recurrence of symptoms, such as anxiety, may simply indicate that the drug was having the expected anxiolytic effect and that, in the absence of the drug, symptoms have returned to pre-treatment levels. If symptoms are more severe or frequent, a person may experience a rebound effect due to drug removal. Either of these situations can occur without a person actually becoming addicted to drugs.

Alprazolam and other benzodiazepines may also cause the development of physical dependence, tolerance, and benzodiazepine withdrawal symptoms during rapid dose reduction or treatment discontinuation after long-term treatment. Withdrawal reactions are more likely to occur if the drug is administered at a higher dose than recommended, or if the person stops taking the drug altogether without the body slowly adjusting to the lower dosing regimen.

Some common symptoms of alprazolam withdrawal include malaise, weakness, insomnia, tachycardia, and dizziness.

It should be noted that people taking more than 4 mg per day have an increased potential for addiction. Alprazolam can cause withdrawal symptoms when discontinued abruptly or rapidly tapering, which in some cases resulted in seizures, as well as marked delirium similar to that produced by the anticholinergic tropane alkaloids from Datura (scopolamine and atropine). Discontinuation of alprazolam may also cause the anxiety states to come back.

In a 1983 study, only 5% of patients who suddenly stopped taking long-acting benzodiazepines after less than 8 months showed withdrawal symptoms, and in patients who took them longer than 8 months, 43% struggled with these symptoms. For alprazolam – a short-acting benzodiazepine – taken for 8 weeks, 65% of patients experienced a significant relapse of their anxiety states.

Benzodiazepines, diazepam and oxazepam have been found to cause fewer withdrawal reactions than alprazolam, temazepam or lorazepam. Factors determining the risk of mental or physical dependence and the severity of benzodiazepine withdrawal symptoms when reducing the dose of alprazolam include: dosage used, duration of use, frequency of dosing, personality traits of the recipient, previous use of cross-dependent drugs / cross-tolerant drugs (alcohol or other sedative and sedative drugs). hypnotics), current use of addicted / cross-tolerant drugs, use of other short-acting, potent benzodiazepines, and how to withdraw them.