Earn CME/CE in your profession:

Continuing Education Activity

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 misused for recreational purposes because of its disinhibition, euphoria, and anxiolytic effects. FDA-labeled indications include anxiety disorders and panic disorders with or without agoraphobia. This activity outlines the indications, contraindications, activity, adverse events, and toxicity of alprazolam in the clinical setting as relates to the essential points needed by members of an interprofessional team managing the care of patients.


  • Identify the mechanism of action of benzodiazepines, including alprazolam.
  • Review the adverse effects of alprazolam and signs of benzodiazepine toxicity.
  • Explain the proper indications for alprazolam therapy.
  • Outline the importance of collaboration and coordination among the interprofessional team and how it can enhance patient care when dosing alprazolam to improve patient outcomes for patients.


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 subject to misuse 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 to the GABA-A receptor. This receptor is made up of five subunits, e.g., alpha, beta, gamma, delta, epsilon, rho, etc. A common GABA-A receptor found in the CNS is made up of two alpha-1 subunits, two beta-2 subunits and one gamma-2 subunit. The benzodiazepine binding site is between the alpha-1 and gamma-2 subunit. Studies in mice suggest that the alpha-1 subunit mediates sedation, amnesia, and ataxic effects of benzodiazepines, and alpha-2 and alpha-3 subunits mediate anxiolytic and muscle-relaxing effects of benzodiazepines. Also, research suggests that BNZ-1 receptors affect sedation and anti-anxiety, while the BNZ-2 affects muscle relaxation, anticonvulsant activity, memory, and motor coordination. Benzodiazepine binding site appear to exhibit coupling with GABA-A receptors, and this enhances the effects of gamma-aminobutyric acid (GABA) by increasing GABA affinity at the GABA-A receptor. The major inhibitory neurotransmitter GABA, when bound to the GABA-A receptor, mediates the calming or inhibitory effects of alprazolam on the human nervous system.[2][3]



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, 1 mg, 2 mg, and 3 mg. Alprazolam is also available as an oral solution in strengths of 0.5 mg/5 mL and as 1 mg/10 mL. Administration of alprazolam may be without regard to food. Take with food if the patient experiences 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. Alprazolam is a controlled substance with the C-IV designation.[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 1 mg per day.
  • Maximum dose: 4 mg/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: 10 mg/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, avoid abrupt discontinuation of treatment. In all patients, the 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 withdrawal 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 of 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 in the drug dosage form. 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 that inhibit or induce CYP3A4. Drugs that are potent inhibitors of CYP3A may lead to an increase in plasma concentrations, which may result in increased adverse events. Medications known to impact alprazolam include azole antifungals (ketoconazole), cimetidine, certain anti-depressants (fluoxetine, fluvoxamine, and nefazodone), macrolide antibiotics (clarithromycin), rifamycins (rifampin), 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 also require observation 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 misuse potential comes from its pharmacokinetic properties of a 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

Nurses can be an invaluable asset in observing and verifying that the patient is adherent, not misusing the medication, and offering counsel. The pharmacist can verify dosing and check for drug interactions, as well as informing the prescriber of signs of possible misuse (e.g., doctor shopping, early refills, etc.)  When healthcare professionals function as an interprofessional team, alprazolam therapy stands to have increased odds of being effective while avoiding adverse events and misuse, leading to better patient outcomes. [Level V]

Article Details

Article Author

Tobin George

Article Editor:

Jayson Tripp


7/19/2021 12:58:49 PM

PubMed Link:




Hedegaard H,Bastian BA,Trinidad JP,Spencer M,Warner M, Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2011-2016. National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System. 2018 Dec;     [PubMed PMID: 30707673]


Masiulis S,Desai R,UchaƄski T,Serna Martin I,Laverty D,Karia D,Malinauskas T,Zivanov J,Pardon E,Kotecha A,Steyaert J,Miller KW,Aricescu AR, GABA{sub}A{/sub} receptor signalling mechanisms revealed by structural pharmacology. Nature. 2019 Jan;     [PubMed PMID: 30602790]


Ibáñez J,González de la Aleja J,Gallego JA,Romero JP,Saíz-Díaz RA,Benito-León J,Rocon E, Effects of alprazolam on cortical activity and tremors in patients with essential tremor. PloS one. 2014;     [PubMed PMID: 24667763]


Preuss CV,Kalava A,King KC, Prescription of Controlled Substances: Benefits and Risks 2018 Jan;     [PubMed PMID: 30726003]


Quagliato LA,Freire RC,Nardi AE, Risks and benefits of medications for panic disorder: a comparison of SSRIs and benzodiazepines. Expert opinion on drug safety. 2018 Mar;     [PubMed PMID: 29357714]


Guina J,Merrill B, Benzodiazepines I: Upping the Care on Downers: The Evidence of Risks, Benefits and Alternatives. Journal of clinical medicine. 2018 Jan 30;     [PubMed PMID: 29385731]


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. The Journal of clinical endocrinology and metabolism. 1999 Aug;     [PubMed PMID: 10443648]


Yamamoto T,Dargan PI,Dines A,Yates C,Heyerdahl F,Hovda KE,Giraudon I,Sedefov R,Wood DM, Concurrent Use of Benzodiazepine by Heroin Users-What Are the Prevalence and the Risks Associated with This Pattern of Use? Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2019 Jan;     [PubMed PMID: 30066312]


Huang Z,Xu Z,Wang H,Zhao ZQ,Rao Y, Influence of ethanol on the metabolism of alprazolam. Expert opinion on drug metabolism     [PubMed PMID: 29848078]


Navy HJ,Weffald L,Delate T,Patel RJ,Dugan JP, Clinical Pharmacist Intervention to Engage Older Adults in Reducing Use of Alprazolam. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists. 2018 Dec 1;     [PubMed PMID: 30545435]