Benzodiazepine tranquilizers, which became widespread almost half a century ago, retain their leading positions in psychiatric practice and are among the most frequently prescribed prescriptions among physicians in the treatment of various nosological forms of diseases with anxiety-depressive, anxiety-phobic, obsessive-compulsive component, sleep disorders, epilepsy, extrapyramidal symptoms.

Alprazolam, a derivative of 1,4-triazolbenzodiazepine, has to varying degrees all the properties of classical tranquilizers: anxiolytic, sedative, hypnotic, muscle relaxant and anticonvulsant. At the same time, he has found to be higher than most other tranquilizers, affinity to benzodiazepine receptors. Due to the peculiarities of the chemical structure, this drug has a number of pharmacokinetic and pharmacodynamic different from other members of the group.

The most important of them include the average duration of action, less pronounced sedation and behavioral toxicity, due to which alprazolam is actively used in outpatient practice.

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Be sure to consult your doctor for contraindications and special instructions for using alprazolam. Tell your doctor about all medicines you are currently taking in order to avoid negative consequences when used with alprazolam

What is alprazolam and how it works

Considering the pharmacokinetics and pharmacodynamics of alprazolam, it is necessary to take into account the following practical features. Peak plasma levels can be reached significantly faster with oral than sublingual administration of the drug. No pronounced the influence of gender or the menstrual cycle on pharmacokinetics, however, the concomitant use of oral contraceptives may be associated with some increase in the severity of psychomotor effects, difficulties in performing test tasks.

Alprazolam is found in breast milk, so lactating women are advised to stop feeding while taking the drug. Use in pregnant women during the first trimester may lead to fetal malformations.

In the elderly, the plasma level of the drug is higher than in the young, and the clearance is reduced, which leads to an increase in the half-life, but, in general, according to different studies, the pharmacokinetics of alprazolam does not change significantly during the course of treatment and increase in daily dosage. About 80% of the drug is excreted by the kidneys unchanged, and the rest is metabolized in the liver with the participation of cytochrome P450 isoenzymes to, in principle, two short-lived metabolites with a slight affinity for benzodiazepine receptors and, therefore, do not contribute to the clinical effect of the drug. This almost completely eliminates the possibility of its cumulation and makes the use of the drug more predictable.

Based on the characteristics of metabolism, as in other similar cases, before prescribing the drug, it is necessary to verify the functional state of the liver, especially in persons with its diseases. The clearance is markedly reduced and the half-life is increased in patients with inflammatory and fibrotic changes in the liver.

Kidney disease may also contribute to decreased clearance leading to accumulation in the body of alprazolam and its metabolites. Drugs with an inhibitory effect on cytochrome P450 isoenzymes are likely to alter the pharmacokinetics of alprazolam - increase the half-life and peak plasma concentration.

The most significant inhibitors that can be encountered in everyday clinical practice include antiviral (atazanavir) and antifungal (ketoconazole, fluconazole) drugs, antibiotics (erythromycin, ciprofloxacin), selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, paroxetine), selective serotonin and norepinephrine reuptake inhibitors (duloxetine), histamine blockers (cimetidine), proton pump inhibitors (omeprazole), anticonvulsants (carbamazepine). Significant inhibition of isoenzymes by sertindole or grapefruit juice components has not been experimentally confirmed.

Due to the relatively short clinical action of alprazolam (3 to 6 hours) it is necessary to take into account the need for multiple administration of the drug during the day. This may affect fluctuations in the concentration of the drug in plasma. Moreover, these fluctuations may be a consequence of the "double peak" phenomenon - two maxima of increasing concentration in plasma with an interval of 1.5-2 hours after taking the drug. This phenomenon is associated with a temporary weakening of intestinal motility due to the muscle relaxant effect of the drug.

Alprazolam compared to other tranquilizers

Numerous literature data indicate that alprazolam has a unique spectrum of psychotropic activity to a large extent distinguishes it from other tranquilizers. The drug is most effective in the treatment of disorders, the clinical picture of which is mainly determined by a variable anxiety component. These include panic disorder, generalized anxiety disorder, a variety of anxiety-depressive states, including reactive ones, anxiety states in somatic diseases, some variants of obsessive-compulsive disorder, withdrawal states, isolated phobias.

At the same time, it is indicated that, in addition to the anxiolytic effect, the drug apparently has an antidepressant effect, which distinguishes it from other representatives of benzodiazepine tranquilizers. Thus, in the 80–90s in European countries, the USA and Australia, a large-scale study of alprazolam in the treatment of panic disorder, characterized by recurring paroxysms of anxiety and concomitant avoidant behavior, showed a significantly greater efficacy of the drug in comparison with placebo after 4 weeks of use, and the average daily dosage, according to different authors, ranged from 4 to 7 mg.

At the same time, there was no linear relationship between the level of the drug in blood plasma and clinical improvement, which emphasizes the need for individual dosage selection to achieve the optimal effect.

In a number of comparative studies of the effectiveness of alprazolam and other benzodiazepine tranquilizers in the treatment of panic disorder have been found to be at least as effective as diazepam, clonazepam, or lorazepam. Moreover, in some studies indicate that alprazolam in such cases even has advantages over diazepam: it reduces the incidence of panic attacks to a greater extent, while reducing the severity of anxiety and depressive symptoms. It is the opportunity affect, in fact, the symptoms of panic attacks, and not just the anxiety of anticipation, according to a number of authors, "radically distinguishes it from other tranquilizers of the benzodiazepine series."

Another aspect to which attention is drawn in the treatment of panic disorder is is the possibility of influencing the so-called secondary depressive symptoms. Generally, in these cases, it is proposed to use alprazolam as monotherapy without additional prescription of antidepressants. When comparing the efficacy of alprazolam and the tricyclic antidepressant imipramine for panic disorder, there was a more rapid (within the first week) improvement in symptoms in the group receiving alprazolam and equal efficacy after 8 weeks use. The average dosage of alprazolam was 5.7 mg per day, and imipramine - 155 mg per day. In addition, in the group of patients treated with imipramine, there were more dropouts due to the development of cholinergic side effects. Long-term treatment (8 months) for panic disorders with alprazolam showed that clinical improvement was achieved without significant dosage changes.

Generalized anxiety disorder, manifested by persistent diffuse anxiety, not limited by any circumstances, accompanied by somatovegetative manifestations and individual fears and forebodings, is effectively treated with alprazolam at an average daily dosage of 0.5 mg to 3 mg when compared with placebo. In the treatment of GAD, alprazolam is not inferior in effectiveness to such benzodiazepine tranquilizers, like diazepam and lorazepam, but alprazolam has fewer side effects.

Moreover, some studies have shown an advantage of alprazolam over diazepam in terms of anti-anxiety action. When compared with imipramine, alprazolam was at least equal in overall efficacy, but superior in relief of somatic symptoms. It should be noted a fairly rapid onset of the effect after the start of the drug, which manifests itself already during the first week of treatment. In a study of the efficacy of alprazolam in combination of GAD and irritable bowel syndrome after 4 weeks of active treatment was revealed a significant reduction in anxiety in 98% and a reduction in gastrointestinal complaints in 89% of participants. These results were maintained for 4 weeks of gradual dose reduction. and 4 weeks after cessation of therapy.

In the treatment of anxiety associated with severe somatic diseases, for example, cancer, positive results were also achieved already in the first week of use. An effect has also been observed in the treatment of moderate to severe alcohol-related anxiety. withdrawal states.

Indications for use

Anxious conditions; neurosis accompanied by a sense of anxiety, danger, restlessness, tension, worsening sleep, irritability, as well as somatic disorders; mixed anxiety-depressive states; neurotic reactive-depressive states, accompanied by a deterioration in mood, loss of interest in the environment, anxiety, sleep disturbances, decreased appetite, somatic disorders; neurotic depression that developed against the background of somatic diseases; panic disorder with or without phobic symptoms.


Hypersensitivity to benzodiazepine derivatives, acute alcohol poisoning, anesthetics, hypnotics and psychotropic drugs, myasthenia gravis, acute angle-closure glaucoma; should not be prescribed to patients under the age of 18, during lactation and in the first trimester of pregnancy.

Side effects

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From the side of the central nervous system: at the beginning of treatment (especially in elderly patients) drowsiness, fatigue, dizziness, decreased ability to concentrate, ataxia, disorientation, gait instability, mental and motor reactions slowdown; rarely - headache, euphoria, depression, tremor, memory loss, impaired coordination of movements, depressed mood, confusion, dystonic extrapyramidal reactions (uncontrolled movements, including the eyes), weakness, myasthenia gravis, dysarthria; in some cases, paradoxical reactions (aggressive outbursts, confusion, psychomotor agitation, fear, suicidal tendencies, muscle spasm, hallucinations, agitation, irritability, anxiety, insomnia).

On the part of the digestive system: dry mouth or salivation, heartburn, nausea, vomiting, loss of appetite, constipation or diarrhea, impaired liver function, increased activity of hepatic transaminases and alkaline phosphatase, jaundice.

On the part of the hematopoietic system: possible leukopenia, neutropenia, agranulocytosis (chills, hyperthermia, sore throat, excessive fatigue or weakness), anemia, thrombocytopenia.

From the urinary system: possible urinary incontinence, urinary retention, impaired renal function, decreased or increased libido, dysmenorrhea.

On the part of the endocrine system: possible changes in body weight, libido disorders, menstrual disorders.

From the side of the cardiovascular system: a decrease in blood pressure, tachycardia is possible.

Allergic reactions: possible skin rash, itching.

Special instructions

To prevent withdrawal symptoms, alprazolam should be discontinued gradually, especially after long-term use in high doses. Special care should be taken when prescribing alprazolam to patients with ataxia, severe chronic respiratory failure (hypercapnia), severe liver and kidney damage, persons with episodes of sleep apnea, severe depression, suicidal attempts, elderly patients (especially with concomitant cardiorespiratory insufficiency), patients with chronic alcoholism, drug or drug addiction.

Drug interactions

With the simultaneous use of psychotropic, anticonvulsant drugs and ethanol, an increase in the inhibitory effect of alprazolam on the central nervous system is observed.

With simultaneous use of histamine H2 receptor blockers, they reduce the clearance of alprazolam and increase the inhibitory effect of alprazolam on the central nervous system; macrolide antibiotics - reduce the clearance of alprazolam.

With simultaneous use of hormonal contraceptives for oral administration, increase T1 / 2 of alprazolam.

With the simultaneous use of alprazolam with dextropropoxyphene, a more pronounced CNS depression is observed than in combination with other benzodiazepines, tk. it is possible to increase the concentration of alprazolam in the blood plasma.

The simultaneous use of digoxin increases the risk of developing intoxication with cardiac glycosides.

Alprazolam increases the concentration of imipramine in plasma.

With the simultaneous use of itraconazole, ketoconazole enhance the effects of alprazolam.

With the simultaneous use of paroxetine, it is possible to enhance the effects of alprazolam, due to the inhibition of its metabolism.

Fluvoxamine increases the plasma concentration of alprazolam and the risk of its side effects.

With the simultaneous use of fluoxetine, an increase in the concentration of alprazolam in the blood plasma is possible due to a decrease in its metabolism and clearance under the influence of fluoxetine, which is accompanied by psychomotor disorders.

It is impossible to exclude the possibility of enhancing the action of alprazolam with simultaneous use with erythromycin.

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