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Alprazolam, known by various trade names, is the most commonly prescribed psychotropic medication in the United States. Alprazolam is frequently prescribed to manage panic and anxiety disorders. Alprazolam has also been used for recreational purposes because of its disinhibition, euphoria, and anxiolytic effects. Most of the near-fatal cases with alprazolam are due to polydrug use.[1]

 FDA- labeled indications

  • Anxiety disorders- Generalized anxiety disorder
  • Panic disorders- With or without agoraphobia

 Non-FDA-labeled indications

  • Insomnia
  • Premenstrual syndrome
  • Depression

Mechanism of Action

Alprazolam belongs to a class of psychoactive medications called benzodiazepines. Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ-1 and BNZ-2. The BNZ-1 receptors affect sedation and anti-anxiety, while the BNZ-2 affects muscle relaxation, anticonvulsant activity, memory, and motor coordination. Benzodiazepine receptors appear to exhibit coupling with GABA-A receptors, and this enhances the effects of GABA by increasing GABA affinity at the GABA receptor. The neurotransmitter GABA, when bound to the GABA receptor, mediates the calming or inhibitory effects of alprazolam on the nervous system.[2][3]


Absorption: Alprazolam is rapidly absorbed after oral administration with a peak plasma concentration at 1 to 2 hours. The bioavailability of oral alprazolam averages 80 to 100%. 


Alprazolam is 80% bound to serum protein, mainly albumin.


Alprazolam is metabolized in the liver by cytochrome P450 3A4 (CYP3A4) to 4-hydroxyalprazolam and alpha-hydroxyalprazolam metabolites


Alprazolam and its metabolites are filtered out by the kidneys and excreted in the urine. The mean plasma half-life of alprazolam is about 11.2 hours in healthy adults.


Alprazolam is available as a regular release and orally disintegrating tablets in strengths of 0.25 mg, 0.5 mg, 1 mg, and 2 mg tablets, while extended-release tablets are available in strengths of 0.5 mg, 1mg, 2mg, and 3 mg. Alprazolam is also available as an oral solution in strengths of 0.5 mg/5 mL and as 1 mg/10mL. Alprazolam may be taken without regard to food. Take with food if you experience an upset stomach. The orally disintegrating tablets must remain in their original packaging and must not put tablets in a pillbox. The extended-release tablets are not to chewed, crushed or split, but instead swallowed whole.[4][5]

Treatment of Anxiety Disorders

 Oral dosage forms (tablets, orally disintegrating tablets, and solution):

Adult Dosage

  • 0.25 to 0.5 mg 3 times a day
  • Dosage increases should occur at intervals of 3 to 4 days with increments of no more than 1mg per day.
  • Maximum dose: 4mg/day

 Geriatric Dosage

  • 0.25 mg 2 or 3 times a day.

Treatment of Panic Disorders

Oral Dosage form (extended-release tablets):

Adult Dosage

  • 0.5 to 1 mg once a day
  • Maintenance dose: 3 to 6 mg orally per day
  • Maximum dose: 10 mg/day

Geriatric Dosage

  • 0.5 mg orally once a day

Oral Dosage forms (tablets, orally disintegrating tablets, solution):

Adult Dosage

  • 0.5 mg 3 times a day
  • Maximum dose: 10mg/day

Geriatric Dosage

  • 0.25 mg 2 or 3 times a day

Hepatic Impairment Dose Adjustments

Oral dosage forms (tablets/orally disintegrating tablets):

  • 0.25 mg orally 2 or 3 times daily

Oral dosage forms (extended-release tablets):

  • 0.5 mg orally once a day

Debilitating Disease Dose Adjustments

Oral Dosage forms (tablets/orally disintegrating tablets):

  • 0.25 mg orally 2 or 3 times daily

Oral Dosage forms (extended-release tablets):

  • 0.5 mg orally once a day

Dose Reduction

As a result of the danger of withdrawal, abrupt discontinuation of treatment is to be avoided. In all patients, dosage should undergo gradual reduction when discontinuing therapy or when decreasing the daily dosage. The suggested method is that the daily dosage reduction is not by not more than 0.5 mg every three days and some patients may require an even slower dosage reduction. In patients with long term chronic alprazolam use, one should switch to a longer-acting benzodiazepine such as clonazepam or diazepam and titrate down gradually; this results in fewer side effects. 

Adverse Effects

Common adverse effects for patients taking alprazolam are[6]:

  • Drowsiness
  • Tiredness
  • Dizziness
  • Sleep problems (insomnia)
  • Memory problems
  • Poor balance or coordination
  • Slurred speech
  • Trouble concentrating
  • Irritability
  • Diarrhea
  • Constipation
  • Increased sweating
  • Headache
  • Nausea
  • Vomiting
  • Upset stomach
  • Blurred vision
  • Appetite or weight changes
  • Swelling in your hands or feet
  • Muscle weakness
  • Dry mouth
  • Stuffy nose
  • Loss of interest in sex


Contraindications to alprazolam include patients with known alprazolam or benzodiazepine hypersensitivity or known allergies to any of its components. Alprazolam should be avoided if possible by anyone with pulmonary disease. Using alprazolam with CNS depressants, especially opioids, increases the risk of respiratory depression, low blood pressure, and death.[7]

Drug Interactions:

Alprazolam is affected by drugs with that inhibit or induce CYP3A4. Drugs that are potent inhibitors of CYP3A may lead to increase plasma concentrations which may result in increased adverse events. Drugs known to impact alprazolam include azole antifungals, cimetidine, certain anti-depressants (fluoxetine, fluvoxamine, and nefazodone), macrolide antibiotics, rifamycins, St. John’s wort, seizure medications (carbamazepine, phenytoin), antihistamines and muscle relaxants.


The patient's respiratory and cardiovascular status should undergo monitoring when treated with alprazolam. Patients should also have monitoring for orthostasis, excessive sedation, and a periodic basic metabolic panel. Liver function tests and complete blood counts should be monitored during chronic therapy. Patients at risk for substance misuse disorder should require surveillance as alprazolam can become addictive in patients.


In alprazolam overdose cases; respiration, blood pressure and pulse rate require monitoring. Intravenous fluids are necessary and an adequate airway maintained. Flumazenil, a benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines.[8][9]

Enhancing Healthcare Team Outcomes

Alprazolam abuse potential comes from its pharmacokinetic properties of short half-life, rapid absorption, and low lipophilicity. Compared to other benzodiazepines, alprazolam effects may be felt within 30 minutes and can last for about 6 hours. Alprazolam taken in large doses produces strong depressive effects which may cause memory loss. Due to alprazolam's many adverse effects, the nurse practitioner, a pharmacist, and the primary care provider must educate the patient on how to use the drug[10]:

  • Discuss the specific use of alprazolam with the patient as it relates to treatment
  • Discuss possible adverse effects and immediately report signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), severe fatigue, shortness of breath, severe dizziness, passing out, change in balance, confusion, memory impairment, difficulty speaking, menstrual changes, or difficult urination
  • Discuss to the patient how taking alprazolam may cause drowsiness and sedation, so they should not drive, operate dangerous machinery, or perform any other activity or task that requires optimal attention
  • Discuss the use of alcohol and/or illegal drugs with alprazolam increases the chances of life-threatening side effects


To access free multiple choice questions on this topic, click here.


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Arvat E, Maccagno B, Ramunni J, Di Vito L, Giordano R, Gianotti L, Broglio F, Camanni F, Ghigo E. The inhibitory effect of alprazolam, a benzodiazepine, overrides the stimulatory effect of metyrapone-induced lack of negative cortisol feedback on corticotroph secretion in humans. J. Clin. Endocrinol. Metab. 1999 Aug;84(8):2611-5. [PubMed: 10443648]
Yamamoto T, Dargan PI, Dines A, Yates C, Heyerdahl F, Hovda KE, Giraudon I, Sedefov R, Wood DM., Euro-DEN Research Group. Concurrent Use of Benzodiazepine by Heroin Users-What Are the Prevalence and the Risks Associated with This Pattern of Use? J Med Toxicol. 2019 Jan;15(1):4-11. [PMC free article: PMC6314928] [PubMed: 30066312]
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Bookshelf ID: NBK538165PMID: 30844192


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