Xanax
Alprazolam
Generic Name
Alprazolam
Mechanism
- Enhances GABAA receptor activity by binding to a high‑affinity benzodiazepine site.
- Increases chloride conductance → neuronal hyperpolarisation and reduced excitability.
- Exhibits the classic anxiolytic, hypnotic, anticonvulsant, and muscle‑relaxant effects of benzodiazepines.
Pharmacokinetics
- Absorption: Rapid (Cmax 1–2 h), high oral bioavailability (~80 %).
- Distribution: Widely distributed; protein binding ~85 %; crosses blood‑brain barrier efficiently.
- Metabolism: Hepatic (CYP3A4/2C19); major metabolites are inactive.
- Elimination: Renal excretion (~70 % unchanged); short half‑life 11–15 h (tolerant individuals), 12–30 h in chronic use.
- Drug interactions:
- Potentiated by CYP3A4 inhibitors (ketoconazole, ritonavir).
- Reduced by inducers (rifampin, carbamazepine).
- Avoid concomitant opioids, sedatives → additive CNS depression.
Indications
- Acute generalized anxiety disorder (GAD) (short‑term rescue).
- Panic disorder – rapid symptom control.
- Tremor‑freezing due to benzodiazepine withdrawal.
- Adjunctive therapy in short bursts for other psychiatric conditions (e.g., major depressive disorder, OCD).
Contraindications
- Absolute contraindications:
- Severe respiratory insufficiency, sleep‑apnea with hypoventilation.
- Acute narrow‑angle glaucoma.
- Bipolar disorder – risk of mania.
- Hepatic impairment (CYP3A4/2C19 dysfunction).
- Warnings:
- Addiction potential; develop tolerance, physical dependence, and withdrawal syndrome.
- Cognitive/psychomotor impairment → caution driving, operating machinery.
- Pregnancy category C – potential fetal harm (withdrawal).
- Elderly/renal failure → prolonged effects.
Dosing
| Condition | Initial Dose | Titration | Max Daily | Duration |
| Panic Disorder | 0.25 mg PO BID | Increase 0.25 mg/2 days until effect | 4 mg/day | 2–4 weeks (up to 6 weeks) |
| GAD (short‑term) | 0.25 mg PO TID | Increase 0.25 mg per TID until symptom control | 3 mg/day | ≤ 4 weeks |
| TNF‑stress | 0.5 mg PO QHS | Stable | 2 mg/day | ≤ 2 weeks |
• Taper over 2–4 weeks to prevent withdrawal.
• Missed dose → take immediately; do not double dose.
Adverse Effects
- Common (≤ 10 %): drowsiness, dizziness, fatigue, dry mouth, mild ataxia.
- Serious (> 10 % or rare):
- Dependence, tolerance, withdrawal (e.g., seizures, rebound anxiety).
- Psychomotor impairment → accidents, vehicular fatalities.
- Respiratory depression (rare, with co‑sedatives).
- Hepatotoxicity (rare, idiosyncratic).
Monitoring
- Baseline:
- Cognitive/motor assessment, liver function tests, serum creatinine.
- Ongoing:
- Symptom score (Hamilton Anxiety Rating Scale).
- Dosage escalation logs.
- Signs of intoxication (slurred speech, impaired coordination).
- After prolonged use (> 4 weeks):
- Evaluate for tolerance, dependence, and withdrawal planning.
Clinical Pearls
- “Rapid‑Onset Rescue”: Start with the lowest dose (0.25 mg) and titrate every 24–48 h; this limits tolerance while still providing sufficient anxiolysis.
- Withdrawal Protocol:
- Reduce dose by 25–50 % per week; demonstration of clinical safety → transition to a long‑acting benzodiazepine if continuation is needed.
- Pregnancy & Lactation: Avoid due to risk of fetal withdrawal and neonatal CNS depression; consider non‑benzodiazepine anxiolytics.
- Kidney/Old Adult: Use 0.25 mg PO BID; monitor for prolonged sedation because of decreased clearance.
- Polypharmacy Alert: Co‑administration with SSRIs or MAO‑Is can potentiate serotonergic or hypotensive effects; monitor BP and platelet counts.
- Prescription Writing Tip: Indicate clear taper schedule on the prescription to reduce misuse.
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• *References available upon request.*