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Benzodiazepine

Alprazolam | Xanax

Clinical Overview

Alprazolam is a short-to-intermediate acting benzodiazepine indicated for anxiety disorders and panic disorder. It is one of the most widely prescribed benzodiazepines due to its rapid onset of action and effectiveness for acute anxiety and panic symptoms, though it carries significant risks of dependence and withdrawal.

Primary Clinical Applications

Alprazolam is indicated for generalized anxiety disorder and panic disorder with or without agoraphobia. It is particularly effective for acute anxiety episodes and panic attacks due to its rapid onset of action. The medication is also commonly used off-label for anxiety associated with depression and situational anxiety.

Mechanism and Clinical Benefits

Alprazolam enhances GABA activity at benzodiazepine receptors, providing rapid anxiolytic and panic-blocking effects. Its relatively short half-life (6-14 hours) allows for flexible dosing but also increases the risk of rebound anxiety and withdrawal symptoms between doses.

Clinical Considerations

While highly effective for anxiety and panic, alprazolam has a high potential for tolerance, dependence, and withdrawal syndrome. The short half-life can lead to breakthrough anxiety and may require multiple daily doses. Extended-release formulations provide longer duration of action and may reduce rebound symptoms. Gradual tapering is essential when discontinuing due to potentially dangerous withdrawal effects.

Prescribing Information

Dosing & Administration

Anxiety Disorders – Adults:

  • Initial: 0.25-0.5 mg three times daily
  • Titration: Increase every 3-4 days by no more than 1 mg daily
  • Range: 0.5-4 mg daily in divided doses
  • Maximum: 4 mg daily

Panic Disorder – Adults:

  • Initial: 0.5 mg three times daily
  • Titration: Increase every 3-4 days by 1 mg daily increments
  • Range: 1-10 mg daily in divided doses
  • Average effective dose: 5-6 mg daily
  • Maximum: 10 mg daily

Extended Release (XR) – Panic Disorder:

  • Initial: 0.5-1 mg once daily in morning
  • Range: 3-6 mg once daily
  • Maximum: 10 mg once daily

Elderly or Debilitated:

  • Initial: 0.25 mg 2-3 times daily
  • Titrate slowly based on response

Administration:

  • Regular tablets: Divide into 2-4 doses daily
  • XR tablets: Once daily in morning, swallow whole
  • ODT (Niravam): Dissolves on tongue without water

Indications

  • Management of anxiety disorders
  • Treatment of panic disorder with or without agoraphobia
  • Short-term relief of anxiety symptoms

Contraindications

  • Hypersensitivity to benzodiazepines
  • Acute narrow-angle glaucoma
  • Concurrent use with ketoconazole or itraconazole
  • Pregnancy (particularly first trimester)

Warnings & Precautions

  • Boxed Warning: Risk of abuse, misuse, dependence; respiratory depression with opioids
  • Physical dependence: Can develop within days to weeks
  • Withdrawal syndrome: Can be severe and life-threatening
  • Rebound anxiety: Common between doses due to short half-life
  • Cognitive impairment: May affect memory and concentration
  • Falls risk: Particularly in elderly patients

Drug Interactions

  • Opioids: Increased risk of respiratory depression and death
  • CNS depressants: Enhanced sedation and respiratory depression
  • CYP3A4 inhibitors: Significantly increase alprazolam levels
  • Alcohol: Dangerous potentiation of effects
  • Grapefruit juice: Increases alprazolam levels

Adverse Reactions

Common (>10%):

  • Sedation, dizziness, depression, headache
  • Constipation, dry mouth, fatigue

Cognitive:

  • Memory impairment, confusion, ataxia

Serious:

  • Respiratory depression, severe withdrawal syndrome
  • Paradoxical reactions (disinhibition, aggression)

Special Populations

  • Elderly: Increased sensitivity, higher fall risk, start with lower doses
  • Hepatic Impairment: Reduce dose, monitor closely
  • Pregnancy: Category D – avoid in pregnancy, especially first trimester
  • High dependence risk: Use shortest duration possible, taper gradually when discontinuing
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.