Alprazolam

Alprazolam is a triazolo benzodiazepine — a central nervous system depressant that enhances the effect of gamma-aminobutyric acid (GABA) at the GABA-A receptor, producing anxiolytic, sedative, muscle relaxant, and anticonvulsant effects. It is one of the most commonly prescribed benzodiazepines in the United States and among the most potent in its class on a per-milligram basis. Alprazolam has a relatively short half-life of approximately 11 hours (range 6–27 hours), which contributes to both its rapid onset of action and its potential for interdose anxiety and withdrawal symptoms with regular use.¹

It is a Schedule IV controlled substance under the Controlled Substances Act, reflecting recognized medical use combined with potential for abuse, physical dependence, and psychological dependence.

Alprazolam is FDA-approved for:¹

• Generalized anxiety disorder (GAD)
• Panic disorder — with or without agoraphobia

For anxiety: typically 0.25–0.5 mg three times daily, with gradual upward titration as needed. Maximum dose is generally 4 mg/day for anxiety.

For panic disorder: doses may be higher, with some patients requiring 1–10 mg/day in divided doses. The extended-release (XR) formulation allows once-daily dosing.¹

Oral tablets (immediate-release and extended-release). Orally disintegrating tablets also available.

Store at controlled room temperature, away from heat, moisture, and light. Keep out of reach of children. As a Schedule IV substance, keep in a secure location.¹

Boxed warning: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use for patients for whom alternatives are inadequate.¹

Key considerations:

• Dependence and withdrawal: Physical dependence develops with regular use. Abrupt discontinuation can cause life-threatening withdrawal seizures. Always taper slowly under medical supervision when discontinuing.
• CNS depression: Additive sedation with alcohol, opioids, other benzodiazepines, sleep aids, antihistamines, and muscle relaxants. Avoid driving or operating machinery.
• CYP3A4 interactions: Alprazolam is metabolized by CYP3A4. Inhibitors (ketoconazole, itraconazole, nefazodone, fluvoxamine, cimetidine) increase alprazolam levels significantly. Inducers decrease effectiveness.
• Cognitive effects: Impairs memory, concentration, and coordination — particularly in older adults, who are at increased fall risk.
• Masking hypoglycemia: Beta blockers and some sedatives can mask hypoglycemia symptoms; relevant in diabetic patients on multiple medications.
• Pregnancy: Benzodiazepines cross the placenta and can cause neonatal withdrawal syndrome. Not recommended during pregnancy.
• Abuse potential: Alprazolam has high abuse and misuse potential, particularly the immediate-release form. Combination with opioids is especially dangerous.