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Alprazolam

Brands and Forms

  • Xanax
    • immediate-release tablet: 0.25mg, 0.5mg, 1mg, 2mg
  • Xanax XR
    • extended-release tablet: 0.5mg, 1mg, 2mg, 3mg
  • Alprazolam Intensol
    • oral solution: 1mg/ml
  • Niravam
    • orally disintegrating immediate-release tablet: 0.25mg, 0.5mg, 1mg, 2mg

Uses of Alprazolam

Alprazolam is used to treat states of anxiety, restlessness, agitation, and insomnia that can occur in a variety of psychiatric conditions, especially Anxiety Disorders. It is indicated as monotherapy (ie. it can be used on its own without other medications) for Generalized Anxiety Disorder and Panic Disorder, though in clinical practice it is more common for Alprazolam to be used in combination with other medications, and mainly in instances where extra help is needed to control symptoms of anxiety, restlessness, agitation, and insomnia.

How Alprazolam Works

Alprazolam is a benzodiazepine. It enhances the effects of GABA in the central nervous system by binding to GABA-A channels and making these channels more receptive to the actions of the brain's naturally occurring GABA.

Alprazolam is a short-acting benzodiazepine that tends to produce a clinical effect lasting about 1-3 hours.

Cautions when Using Alprazolam

Regular Alprazolam use over a period of even a week can lead to tolerance, dependence and abuse. Ideally, this medication should be avoided in individuals with histories of substance abuse, or else used only with very close monitoring by the prescribing physician.

Compared with other benzodiazepines, Alprazolam's short duration of action means that it is more likely to cause withdrawal symptoms following each dose and to lead to abuse or dependence. It is thus recommended to use the extended-release form of this medication (Xanax XR), or to choose a different longer-acting benzodiazepine such as Diazepam or Clonazepam.

Caution should be used when Alprazolam is taken by elderly individuals, as this medication can cause memory and concentration difficulties as well as confusion in these individuals, and also make them more prone to falls.

Stopping Alprazolam abruptly after long-term regular use can lead to serious and potentially life-threatening withdrawal symptoms.

Alprazolam should not be used by individuals with obstructive sleep apnea, especially if positive airway pressure (C-PAP) treatments are not being used, as this could lead to prolonged periods of apnea. Use with caution in individuals with other kinds of respiratory disease.

Alprazolam should not be combined with alcohol due to the risk of excessive CNS depression.

People should not drive or operate heavy machinery while taking Alprazolam.

Alprazolam should not be used by individuals with narrow angle-closure glaucoma.

Alprazolam should not be combined with Ketoconazole or Itraconazole.

Dosing of Alprazolam

When used on an as-needed basis for episodic symptoms of anxiety, restlessness, agitation or insomnia, the recommended starting dose of Alprazolam is 0.25mg. Higher doses should be used only if it is found that 0.25mg is not effective. At any dose, this medication can be expected to produce its effects within 30min and to last for a couple of hours.

When used to control symptoms of anxiety or restlessness throughout the day, the recommended starting dose is 0.75-1mg/day. If the immediate-release form is used, it would need to be given in divided doses 3 or 4 times a day. Even at that rate, it is common that withdrawal symptoms can occur after 2-3 hours of taking a dose as the effects of the medication begin to wane.

For this reason, it is usually preferred to use to extended-release form, Xanax XR, which is longer-acting and can be given once a day in the morning. Depending on the clinical effects, the dose can be increased by as much as 1mg/day every 3 days. Usually 3-6mg/day is required, but in some cases as much as 10mg/day may be needed.

When wanted to stop Alprazolam after it has been used regularly for a prolonged period, the dose should be tapered gradually over a period of a few weeks. In these situations, avoiding withdrawal symptoms can be easier if the medication is first switched to a longer-acting benzodiazepine such as Diazepam, which would then be tapered gradually.

When wanting to switch Alprazolam to a different benzodiazepine, please refer to the Benzodiazepine Equivalency Table for information on dose conversion.

Onset of action

Therapeutic effects are immediate.

Kidney impairment

Lower dose and use with caution.

Liver impairment

Lower dose by half and use with caution.

Side-effects of Alprazolam

Below is a list of most of the reported side-effects of Alprazolam. Most of these side-effects occur in only a minority of individuals, and many also resolve with time while the medication is continued.

Cardiovascular: tachycardia; hypotension; palpitations.

Central Nervous System: drowsiness; fatigue/tiredness; sedation; memory impairment; cognitive impairment; light-headedness; decreased libido; dysarthria; confusional state; abnormal coordination; unsteadiness; disturbed attention; disorientation, paresthesia; dyskinesia; talkativeness; abnormal dreams; lethargy; hypesthesia; hypersomnia; malaise; weakness; headache; dizziness; tremor; insomnia; nightmares.

Dermatologic: rash; increased sweating.

Endocrine/Metabolic: increased or decreased appetite; weight gain or weight loss.

Eyes, Ears, Nose and Throat: nasal congestion; allergic rhinitis; vertigo; blurred vision.

Gastrointestinal: constipation; nausea; vomiting; diarrhea; abdominal distress; dry mouth; increased salivation; dyspepsia; abdominal pain; elevated liver enzymes.

Genitourinary: urination difficulties; abnormal menstruation; sexual dysfunction; urinary incontinence; gynecomastia.

Muskuloskeletal: rigidity; joint and muscle pains; muscle twitching.

Psychiatric: depressed mood; apathy; disinhibitted behavior; dissociative symptoms; irritability (usually from withdrawal); anxiety (usually from withdrawal); restlessness (usually from withdrawal); mania (very rare); psychosis (very rare).

Respiratory: upper respiratory tract infection; shortness of breath; hyperventilation; respiratory depression.

Common side-effects of Alprazolam

Drowsiness, fatigue, memory impairment, slowed thinking, light-headedness, decreased libido, depressed mood, slurred speech, confusion, constipation, nausea, vomiting, diarrhea, abdominal distress, dry mouth, urination difficulties, irregular menstruation, increased or decreased appetite, weight gain or loss.

Rare but serious side-effects of note of Alprazolam

  • Liver damage can occur in very rare cases
  • See cautions above.

Alprazolam withdrawal

Individuals who take Alprazolam regularly over an extended period of time, which could be as little as one week but more commonly several weeks, are at risk of developing a withdrawal syndrome if they stop the medication abruptly.

The severity of the withdrawal symptoms will be proportional to the size of the Alprazolam dose that was being used on a regular basis. With heavy use, most of the following symptoms could occur:

In the first stages of this syndrome, the individual will experience tremors, autonomic hyperactivity (sweating, fever, elevated blood pressure, rapid heart rate), anxiety, agitation, nausea, vomiting, and insomnia.

If left untreated, the next symptoms to appear are confusion and disorientation, hallucinations (mainly visual ones, but also auditory, tactile and olfactory) and delusions.

Seizures and cardiovascular collapse can then ensue, and are the most concerning symptoms.

This syndrome is considered a medical emergency. The main treatment is to restart the Alprazolam at the most recent dose, or to switch it to the equivalent of another longer-acting benzodiazepine such as Diazepam.

To prevent this syndrome, the dose of the medication should be reduced gradually over a period of a few weeks. Because of Alprazolam's short duration of action, it is often easier to first switch it to a longer-acting benzodiazepine such as Diazepam, which would then be tapered gradually.

Alprazolam overdose

Somnolence, confusion, impaired coordination, diminished reflexes, coma, death.

Alprazolam and pregnancy

Category D: benzodiazepines such as Alprazolam have been associated with a risk of less than 1% of causing cleft lip or palette to the fetus when used in pregnancy [ref]. A fetus exposed to benzodiazepines in utero is also at risk for developing a withdrawal syndrome shortly after birth, which would require medical treatment.

Alprazolam should only be used in pregnancy if clearly needed and if benefits outweigh potential risks. However, because the effects of Diazepam in pregnancy have been more closely studied, it would be prudent to use Diazepam if a benzodiazepines is required during pregnancy [ref].

Medical Monitoring for Alprazolam

None for healthy individuals, although periodic liver function tests may be prudent.

Drug Interactions with Alprazolam

  • Alprazolam should not be combined with Ketoconazole or Itraconazole.
  • Alprazolam should not be combined with alcohol due to the risk of excessive CNS depression.
  • Use caution when combining Alprazolam with other medications that can cause sedation or CNS depression.
  • Alprazolam blood concentrations can be increased by Cimetidine, Disulfiram, oral contraceptives, Diltiazem, Fluoxetine, Fluvoxamine, grapefruit juice, Isoniazid, macrolide antibiotics (Erythromycin), Nefazodone, nonnucleoside reverse transcriptase inhibitors (Delavirdine, Efavirenz), protease inhibitors (indinavir), Omerprazole
  • Alprazolam blood concentrations can be decreased by Carbamazepine and Rifampin.
  • Alprazolam can increase blood concentrations of Desipramine, Imipramine, and Digoxin.