Alprazolam (Xanor, Xanax)

What Is Alprazolam and What Is It Used For?

Quick Answer: Alprazolam is a benzodiazepine (anxiolytic medication) used in adults for the short-term treatment of severe anxiety symptoms that are disabling or cause significant distress. It works by enhancing the calming effects of the neurotransmitter GABA in the brain, producing rapid relief from acute anxiety within 15–30 minutes of oral administration.

Alprazolam belongs to the triazolobenzodiazepine subclass of benzodiazepines, distinguished by the presence of a triazole ring fused to its chemical structure. First synthesized in the 1960s and approved for medical use in the United States in 1981, alprazolam has become one of the most widely prescribed psychotropic medications globally. It is included in the World Health Organization (WHO) Model List of Essential Medicines as an anxiolytic, reflecting its established therapeutic role in the management of anxiety disorders.

The primary approved indication for alprazolam is the short-term relief of severe anxiety symptoms that are disabling or cause the patient extreme distress. In clinical practice, this encompasses generalized anxiety disorder (GAD) with prominent somatic and psychological symptoms, as well as anxiety states that are unresponsive to non-pharmacological interventions. The American Psychiatric Association (APA) Practice Guidelines and the National Institute for Health and Care Excellence (NICE) emphasize that benzodiazepines including alprazolam should be reserved for cases where anxiety is severe, and should only be used for the shortest duration necessary.

In some countries, alprazolam is also approved for the treatment of panic disorder with or without agoraphobia. The FDA-approved labelling in the United States includes panic disorder as a specific indication, supported by randomized controlled trials demonstrating efficacy in reducing the frequency and severity of panic attacks. However, this indication is not universally approved in all regulatory jurisdictions, and the European Medicines Agency (EMA) summary of product characteristics typically limits the indication to anxiety disorders.

Mechanism of Action

Alprazolam exerts its pharmacological effects by binding to the benzodiazepine site located on gamma-aminobutyric acid type A (GABA-A) receptors in the central nervous system. GABA is the principal inhibitory neurotransmitter in the brain, and GABA-A receptors are ligand-gated chloride ion channels. When alprazolam binds to the allosteric benzodiazepine site, it increases the affinity of the receptor for GABA, enhancing the frequency of chloride ion channel opening. This results in increased chloride influx into the neuron, producing membrane hyperpolarization and reduced neuronal excitability.

The net effect of this enhanced GABAergic neurotransmission is a spectrum of central nervous system depressant actions: anxiolytic (anxiety-reducing), sedative (calming), hypnotic (sleep-inducing), muscle relaxant, and anticonvulsant effects. Among benzodiazepines, alprazolam is classified as a high-potency agent, meaning that relatively low doses (milligram for milligram) produce significant pharmacological effects compared to lower-potency benzodiazepines such as diazepam or chlordiazepoxide.

Pharmacokinetics

Alprazolam is rapidly and completely absorbed after oral administration, with an oral bioavailability of approximately 80–90%. For standard (immediate-release) tablets, peak plasma concentrations are typically reached within 1 to 2 hours. Extended-release formulations achieve peak levels more slowly, generally in 5 to 11 hours, providing more sustained plasma levels with less fluctuation throughout the day.

The drug is metabolized primarily in the liver by the cytochrome P450 enzyme CYP3A4, producing two main metabolites: alpha-hydroxyalprazolam (which retains some pharmacological activity, approximately 50% of the potency of the parent compound) and a benzophenone derivative (which is clinically inactive). The elimination half-life of alprazolam ranges from 6 to 27 hours, with a mean of approximately 11 hours. This relatively short half-life, compared to longer-acting benzodiazepines like diazepam (half-life 20–100 hours), contributes to both the rapid onset of action and the potential for interdose withdrawal symptoms, which is a clinically significant consideration in managing patients on this medication.

What Should You Know Before Taking Alprazolam?

Quick Answer: Alprazolam must not be used in patients with myasthenia gravis, severe respiratory problems, sleep apnoea, or severe liver disease. It carries substantial risks of dependence, memory impairment, and mood changes including depression and suicidal thoughts. Special caution is required in elderly patients, those with a history of substance abuse, and during pregnancy or breastfeeding.

Contraindications

Before starting alprazolam, your doctor must be made aware of your complete medical history, as there are several absolute contraindications — conditions in which the medication must never be used:

• Allergy to alprazolam or any benzodiazepine: If you have previously experienced an allergic reaction to alprazolam or any other benzodiazepine (such as diazepam, lorazepam, or clonazepam), or to any of the inactive ingredients in the tablets, you must not take this medication.
• Myasthenia gravis: This autoimmune neuromuscular disorder causes muscle weakness, and benzodiazepines can worsen the condition by further impairing neuromuscular transmission, potentially leading to respiratory failure.
• Severe respiratory insufficiency: Patients with severe chronic obstructive pulmonary disease (COPD), chronic bronchitis, or emphysema should not use alprazolam, as it depresses the respiratory drive and can precipitate respiratory failure.
• Sleep apnoea syndrome: The central nervous system depressant effects of alprazolam can worsen obstructive sleep apnoea by further relaxing upper airway muscles and reducing respiratory drive during sleep, increasing the risk of potentially fatal apnoeic episodes.
• Severe hepatic impairment: Because alprazolam is extensively metabolized in the liver, severe liver disease results in dramatically reduced clearance, leading to accumulation and excessive sedation.
• Acute intoxication: Alprazolam must not be administered to patients who are acutely intoxicated with alcohol, opioids, or other central nervous system depressants, as the combined effects can be fatal.

Warnings and Precautions

Several conditions and situations require particular caution when using alprazolam. Discuss the following with your doctor before starting treatment:

• Kidney impairment: Although alprazolam is primarily hepatically metabolized, reduced kidney function can slow the elimination of metabolites, potentially requiring dose adjustments.
• Mild to moderate liver impairment: Even in less severe liver disease, reduced metabolism of alprazolam may necessitate lower doses and careful monitoring.
• Depression and suicidal ideation: Alprazolam can unmask or worsen depression, and benzodiazepines are associated with increased risk of suicidal thoughts and behaviour in patients with depressive disorders. If you are depressed or have a history of suicidal thoughts, your doctor should monitor you closely. Seek immediate medical attention if you develop thoughts of self-harm.
• History of substance misuse: Individuals with a history of alcohol or drug dependence are at significantly higher risk of developing alprazolam dependence and misuse. Your doctor may need to provide additional support when discontinuing treatment.
• Elderly patients: Older adults are more sensitive to benzodiazepines due to age-related changes in drug metabolism and increased sensitivity of the central nervous system. They face a particularly high risk of excessive sedation, confusion, impaired balance, and falls, which can lead to hip fractures and other serious injuries. The Beers Criteria and other geriatric prescribing guidelines strongly caution against benzodiazepine use in the elderly.
• Memory impairment: Alprazolam can cause anterograde amnesia (difficulty forming new memories), particularly at higher doses. This typically occurs several hours after taking the medication and can be more pronounced when sleep duration is insufficient.
• Paradoxical reactions: In rare cases, benzodiazepines can produce effects opposite to those intended, including increased anxiety, agitation, irritability, aggression, rage, hallucinations, and psychosis. These paradoxical reactions are more common in children, adolescents, elderly patients, and individuals with pre-existing psychiatric conditions. If such reactions occur, treatment should be discontinued.
• Tolerance: With continued use, the effectiveness of alprazolam may diminish as the body develops tolerance to its effects, meaning that higher doses may be needed to achieve the same therapeutic effect. This is another reason why treatment should be as short as possible.

Pregnancy and Breastfeeding

Pregnancy: Alprazolam should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the risk to the foetus. Observational studies in humans have suggested an association between first-trimester benzodiazepine exposure and an increased risk of congenital malformations, particularly cleft palate, though the absolute risk remains low. Use of alprazolam during the third trimester or around delivery can cause neonatal withdrawal syndrome (symptoms including irritability, tremor, feeding difficulties, and respiratory problems in the newborn) and “floppy infant syndrome” (characterized by hypotonia, hypothermia, and respiratory depression). If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, inform your doctor immediately.

Breastfeeding: Alprazolam passes into breast milk and can cause sedation, feeding difficulties, and other adverse effects in nursing infants. Breastfeeding is not recommended while taking alprazolam. If treatment is essential, your doctor will discuss whether you should discontinue breastfeeding or seek an alternative medication.

Children and Adolescents

Alprazolam is not recommended for use in children and adolescents under 18 years of age. Safety and efficacy have not been established in this population. The developing brain may be more susceptible to the adverse effects of benzodiazepines, and the risk of paradoxical reactions (agitation, aggression) is higher in younger patients.

Driving and Operating Machinery

Alprazolam causes drowsiness, impaired concentration, muscle weakness, and delayed reaction times. These effects can significantly impair your ability to drive safely or operate machinery, particularly if combined with inadequate sleep or alcohol. You should not drive or operate machinery while taking alprazolam. These impairments may persist into the day following evening dosing, even if you feel alert. Your individual response to the medication should be fully assessed before engaging in any activities requiring mental alertness.

How Does Alprazolam Interact with Other Drugs?

Quick Answer: Alprazolam has clinically significant interactions with many medications, particularly opioids, antifungals, macrolide antibiotics, HIV protease inhibitors, and other CNS depressants. The most dangerous interaction is with opioids and alcohol, which can cause fatal respiratory depression. Always inform your doctor of all medications you are taking.

Because alprazolam is primarily metabolized by the liver enzyme CYP3A4, any drug that inhibits or induces this enzyme can significantly alter alprazolam blood levels. Additionally, combining alprazolam with other central nervous system depressants produces additive or synergistic effects that can be dangerous or fatal. The following table summarizes the most clinically important drug interactions:

Major Interactions (Potentially Life-Threatening)

Moderate Interactions

Food and Alcohol Interactions

Alprazolam tablets can be taken with or without food. Swallow the tablet whole with a small amount of water. Grapefruit juice should be avoided, as it inhibits CYP3A4 in the gut wall and can increase alprazolam absorption and blood levels, leading to excessive sedation.

Alcohol must be strictly avoided during treatment with alprazolam. Alcohol and alprazolam both depress the central nervous system, and their combined effect is greater than the sum of their individual effects. This synergistic interaction can cause profound sedation, loss of consciousness, severe respiratory depression, and death, even with moderate alcohol consumption.

What Is the Correct Dosage of Alprazolam?

Quick Answer: The typical starting dose for anxiety is 0.25–0.5 mg three times daily, with a usual maintenance dose of 0.5–3 mg per day. Elderly patients should start with 0.25 mg two to three times daily. Treatment should not exceed 2–4 weeks. Your doctor will determine the appropriate dose for your individual situation.

Always take alprazolam exactly as prescribed by your doctor. The dosage is individualised based on the severity of your symptoms, your response to treatment, your age, and any other medical conditions. Treatment should ideally be initiated, monitored, and discontinued by the same physician. Treatment usually begins with a low dose that is gradually increased if necessary, according to your doctor’s instructions.

Adults

If you experience significant side effects after your first dose, your doctor may reduce the dose. Never change your prescribed dose without medical advice. The extended-release tablets (such as Xanor Depot) are designed to release the medication slowly over time, providing more consistent blood levels and potentially fewer interdose fluctuations in symptoms.

Elderly Patients

Children and Adolescents

Missed Dose

If you forget to take a dose of alprazolam, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your normal dosing schedule. Do not take a double dose to make up for a forgotten dose, as this increases the risk of excessive sedation and other adverse effects.

Overdose

Symptoms of alprazolam overdose may include:

• Severe drowsiness and difficulty staying awake
• Confusion and disorientation
• Slurred speech
• Impaired coordination and difficulty walking (ataxia)
• Slowed or shallow breathing (respiratory depression)
• Low blood pressure (hypotension)
• Muscle weakness and diminished reflexes
• Loss of consciousness or coma
• In severe cases, particularly with co-ingestion of other CNS depressants: respiratory arrest and death

The specific antidote for benzodiazepine overdose is flumazenil, which can reverse the effects of alprazolam. However, flumazenil must only be administered by medical professionals in a hospital setting, as it can precipitate seizures in benzodiazepine-dependent individuals.

Stopping Treatment

When it is time to discontinue alprazolam, your doctor will create an individualised tapering schedule, gradually reducing your dose over several weeks or months. The rate of dose reduction depends on multiple factors, including how long you have been taking the medication, your current dose, and your individual sensitivity to withdrawal effects.

Abrupt discontinuation of alprazolam can produce severe withdrawal symptoms, particularly after prolonged use or high-dose therapy. Withdrawal symptoms may include:

• Severe rebound anxiety (often more intense than the original symptoms)
• Insomnia and sleep disturbances
• Headaches and muscle pain
• Irritability, restlessness, and agitation
• Confusion and difficulty concentrating
• Tremor and sweating
• Nausea and loss of appetite
• In severe cases: depersonalisation, derealisation, sensory hypersensitivity (to light, sound, and touch), numbness and tingling, hallucinations, mood swings, and epileptic seizures

These symptoms may appear days after the last dose and can persist for weeks. Your doctor will provide detailed instructions on how to gradually reduce your dose to minimise these withdrawal effects.

What Are the Side Effects of Alprazolam?

Quick Answer: The most common side effects of alprazolam include drowsiness, dizziness, fatigue, memory problems, slurred speech, and constipation. More serious but less common side effects include paradoxical reactions (agitation, aggression), depression, jaundice, and severe allergic reactions. Seek immediate medical help if you experience difficulty breathing, facial swelling, or signs of a severe allergic reaction.

Like all medicines, alprazolam can cause side effects, although not everyone experiences them. The likelihood and severity of side effects are generally related to the dose, duration of treatment, and individual patient factors such as age and concurrent medications. Side effects are typically most pronounced during the first few days of treatment and may diminish as your body adjusts to the medication.

Dependence and Withdrawal

One of the most clinically significant adverse effects of alprazolam is the development of physical and psychological dependence. The risk of dependence is dose-dependent and increases substantially with treatment duration beyond 2–4 weeks. Patients with a history of alcohol or substance misuse are at particularly high risk. When dependence has developed, abrupt discontinuation or rapid dose reduction will produce withdrawal symptoms, which may be severe and potentially life-threatening (see Stopping Treatment section above).

An important clinical phenomenon is rebound anxiety — a transient return of the original anxiety symptoms with greater intensity than before treatment began. Rebound anxiety typically occurs within days of dose reduction or discontinuation and can be distinguished from true relapse by its transient nature and temporal relationship to dose changes. Gradual tapering under medical supervision significantly reduces the risk and severity of both withdrawal symptoms and rebound anxiety.

Tolerance

With repeated use, patients may develop tolerance to the sedative and anxiolytic effects of alprazolam, meaning that the same dose produces progressively less effect over time. Tolerance to the sedative effects tends to develop relatively quickly (within days to weeks), while tolerance to the anxiolytic effects develops more gradually. This phenomenon contributes to dose escalation and is another reason why alprazolam treatment should be limited to the shortest effective duration.

How Should You Store Alprazolam?

Quick Answer: Store alprazolam at room temperature below 30°C (86°F) in the original packaging, protected from moisture. Keep out of sight and reach of children. As a controlled substance, store securely to prevent unauthorized access. Do not use after the expiry date.

Proper storage of alprazolam is important both for maintaining the medication’s effectiveness and for safety, as it is a controlled substance that can be subject to misuse. Follow these storage guidelines:

• Temperature: Store at or below 30°C (86°F). Do not freeze.
• Packaging: Keep the tablets in the original blister packaging to protect them from moisture.
• Children: Keep this medication out of the sight and reach of children. Accidental ingestion by a child requires immediate emergency medical attention.
• Security: Because alprazolam is a controlled substance that may be sought by individuals who misuse prescription medications, store it in a secure location where it cannot be accessed by others.
• Expiry date: Do not use alprazolam after the expiry date printed on the blister pack and outer carton (EXP). The expiry date refers to the last day of that month.
• Disposal: Do not dispose of unused or expired alprazolam by flushing it down the toilet or putting it in household waste. Return unused medication to a pharmacy for safe disposal, which helps protect the environment and prevents misuse.

What Does Alprazolam Contain?

Quick Answer: Each tablet contains either 0.25 mg or 0.5 mg of the active ingredient alprazolam. Inactive ingredients include lactose monohydrate, maize starch, crospovidone, povidone, magnesium stearate, and polysorbate 80. Colouring agents vary by strength.

The active pharmaceutical ingredient in all alprazolam tablets is alprazolam itself. The amount of active ingredient per tablet corresponds to the labelled strength. The inactive ingredients (excipients) serve various pharmaceutical functions including binding, filling, and facilitating disintegration of the tablet in the gastrointestinal tract.

Tablet Identification

The score line on the tablets is not intended for dividing the tablet into equal doses; it is designed solely to help with swallowing. Available pack sizes include 10, 20, 30, 50, 60, and 100 tablets in blister packs, as well as unit-dose perforated blisters. Not all pack sizes may be marketed in every country.