Alprazolam


Alprazolam, sold under the brand name Xanax among others, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly prescribed in the management of anxiety disorders, especially panic disorder and generalized anxiety disorder. Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken orally.
Common side effects include sleepiness, depression, suppressed emotions, mild to severe decreases in motor skills, hiccups, dulling or declining of cognition, decreased alertness, dry mouth, decreased heart rate, impairment of judgment, and decreased memory formation, depending on dosage. Some of the sedation and drowsiness may improve within a few days.
Benzodiazepine withdrawal symptoms may occur if use is suddenly decreased.
Alprazolam was developed by Jackson Hester Jr. at the Upjohn Company and patented in 1971 and approved for medical use in the United States in 1981. Alprazolam is a Schedule IV controlled substance and is a common drug of abuse. It is available as a generic medication. In 2023, it was the 37th most commonly prescribed medication in the United States, with more than 15million prescriptions.

Medical uses

Alprazolam is used in the management of anxiety disorders and nausea due to chemotherapy. Alprazolam is indicated for the treatment of generalized anxiety disorder and panic disorder with or without agoraphobia in adults.

Panic disorder

Alprazolam is effective in the relief of moderate to severe anxiety and panic attacks. In Australia, alprazolam is not recommended for the treatment of panic disorder because of concerns regarding tolerance, dependence, and abuse. Most evidence shows that the benefits of alprazolam in treating panic disorder last only four to ten weeks. However, people with panic disorder have been treated on an open basis for up to eight months without apparent loss of benefit.
Alprazolam is recommended by the World Federation of Societies of Biological Psychiatry for treatment-resistant cases of panic disorder where there is no history of tolerance or dependence.
A 2023 meta-analysis of published and unpublished FDA-submitted regulatory trials of alprazolam extended-release for panic disorder found that only one of five clinical trials showed a positive efficacy outcome, while the rest were negative and did not demonstrate effectiveness. In the published literature, three trials were published conveying a positive outcome, but of these, only one was positive and the other two were considered to have been inappropriately spun as positive. The effect size of alprazolam for the treatment of panic disorder based on the five clinical trials was 0.33 and based on the published trials was 0.47, equating to an increase of 0.14 or 42%. The authors concluded that publication bias substantially inflated the effectiveness of alprazolam for panic disorder.

Anxiety disorders

associated with depression is responsive to alprazolam. Clinical studies have shown that the effectiveness is limited to four months for anxiety disorders. However, the research into antidepressant properties of alprazolam is poor and has only assessed its short-term effects against depression. In one study, some long term, high-dosage users of alprazolam developed reversible depression.
In the US, alprazolam is indicated for the treatment of generalized anxiety disorder and panic disorder with or without agoraphobia.
In the UK, alprazolam is indicated for short-term symptomatic treatment of anxiety in adults.

Chemotherapy-induced nausea and vomiting

Alprazolam may be used in combination with other medications for chemotherapy-induced nausea and vomiting.

Contraindications

Benzodiazepines require special precaution if used in children and in alcohol- or other drug-dependent individuals. Particular care should be taken in pregnant or elderly people, people with substance use disorder history, particularly alcohol dependence, and people with comorbid psychiatric disorders.
Alprazolam should be avoided or carefully monitored by medical professionals in individuals with myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies such as cirrhosis, severe sleep apnea, pre-existing respiratory depression, marked neuromuscular respiratory, acute pulmonary insufficiency, chronic psychosis, hypersensitivity, allergy to alprazolam or other benzodiazepines, and borderline personality disorder, where it may induce suicidality and dyscontrol.
Like all central nervous system depressants, alprazolam in larger-than-normal doses can cause significant deterioration in alertness and increase drowsiness, especially in those unaccustomed to the drug's effects.

Side effects

drugs, including alprazolam, have been associated with an increased risk of death.
Possible side effects include:
In September 2020, the US Food and Drug Administration required that boxed warnings for all benzodiazepine medications be updated to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.

Paradoxical reactions

Although unusual, the following paradoxical reactions have been shown to occur:
Benzodiazepines cross the placenta, enter the fetus, and are also excreted in breast milk.
The use of alprazolam during pregnancy is associated with congenital abnormalities, and use in the last trimester may cause fetal drug dependence and withdrawal symptoms in the post-natal period as well as neonatal flaccidity and respiratory problems. However, in long-term users of benzodiazepines, abrupt discontinuation due to concerns of teratogenesis has a high risk of causing extreme withdrawal symptoms and a severe rebound effect of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications, including benzodiazepines.

Overdose

The maximum recommended daily dose is 10 milligrams per day.
Overdoses of alprazolam can be mild to severe depending on the quantity ingested and if other drugs are taken in combination.
Alprazolam overdoses cause excess central nervous system depression.

Dependence and withdrawal

The potential for misuse among those taking it for medical reasons is controversial, with some expert reviews stating that the risk is low and similar to that of other benzodiazepine drugs. Others state that there is a substantial 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 individuals increase their dose on their own initiative or engage in drug-seeking behavior.
Alprazolam, like other benzodiazepines, binds specifically on an allosteric site on the GABAA receptor. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and thus making the drugs less potent.
Withdrawal and rebound symptoms commonly occur and necessitate a gradual reduction in dosage to minimize withdrawal effects when discontinuing.
Not all withdrawal effects are evidence of true dependence or withdrawal. Recurrence of symptoms such as anxiety may simply indicate that the drug was having its expected anti-anxiety effect and that, in the absence of the drug, the symptom has returned to pretreatment levels. If the symptoms are more severe or frequent, the person may be experiencing a rebound effect due to the removal of the drug. Either of these can occur without the person actually being drug dependent.
Alprazolam and other benzodiazepines may also cause the development of physical dependence, tolerance, and benzodiazepine withdrawal symptoms during rapid dose reduction or cessation of therapy after long-term treatment. There is a higher chance of withdrawal reactions if the drug is administered in a higher dosage than recommended, or if a person stops taking the medication altogether without slowly allowing the body to adjust to a lower-dosage regimen.
In 1992, Romach and colleagues reported that dose escalation is not a characteristic of long-term alprazolam users and that the majority of long-term alprazolam users change their initial pattern of regular use to one of symptom control only when required.
Some common symptoms of alprazolam discontinuation include malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness.
Those taking more than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms upon abrupt withdrawal or rapid tapering, which in some cases have been known to cause seizures, as well as marked delirium similar to that produced by the anticholinergic tropane alkaloids of Datura. The discontinuation of this medication may also cause rebound anxiety.
In a 1983 study, only 5% of patients who abruptly ceased taking long-acting benzodiazepines after less than eight months demonstrated withdrawal symptoms, but 43% who had been taking them for more than eight months did. With alprazolam, a short-acting benzodiazepine, taken for eight weeks, 65% of patients experienced significant rebound anxiety. To some degree, these older benzodiazepines are self-tapering.
The benzodiazepines diazepam and oxazepam have been found to produce fewer withdrawal reactions than alprazolam, temazepam, or lorazepam. Factors that determine the risk of psychological dependence or physical dependence and the severity of the benzodiazepine withdrawal symptoms during dose reduction of alprazolam include: dosage used, length of use, frequency of dosing, personality characteristics of the individual, previous use of cross-dependent/cross-tolerant drugs, current use of cross-dependent/-tolerant drugs, use of other short-acting, high-potency benzodiazepines, and method of discontinuation.