Alprazolam (Xanax) and Clonazepam (Klonopin) are both benzodiazepines that help to calm anxiety, and treat other disorders. Alprazolam (Xanax) is used to treat anxiety disorders, panic disorders, and anxiety associated with depression. Clonazepam (Klonopin) may be prescribed for epilepsy, as well as for panic disorder, seizures, anxiety disorders, parasomnia, OCD and clinical depression.
Comparison chart
 | Alprazolam | Clonazepam |
|---|---|---|
| Trade names | Xanax, Xanax XR, Alprazolam Intensol, Niravam | Klonopin, Rivotril, Clonotril |
| Prescribed for | Anxiety disorders, panic disorders, anxiety associated with depression, agoraphobia | Panic disorders, seizures, epilepsy, anxiety disorders, parasomnia, OCD, clinical depression, restless leg syndrome, akathisia |
| Mechanism of action | GABA-A receptor positive allosteric modulator; preferentially binds α1 subunit; enhances chloride influx | GABA-A receptor positive allosteric modulator; broader receptor binding including α1, α2, α3 subunits |
| Starting dose (adults) | 0.25-0.5mg three times daily for anxiety; 0.5mg three times daily for panic disorder | 0.25mg twice daily for panic disorder; 0.5mg three times daily for seizures |
| Maximum dose | 4mg daily for anxiety; 10mg daily for panic (rarely exceeded) | 20mg daily for seizures; 4mg daily for panic disorder |
| Elderly dosing | Start with 0.125-0.25mg 2-3 times daily; maximum 2mg daily; high fall risk | Start with 0.25mg once or twice daily; preferred over short-acting benzos in elderly |
| Pediatric use | Safety and efficacy not established under age 18; rarely used off-label for severe anxiety | FDA approved for seizures in children; used off-label for anxiety in adolescents |
| Onset of action | 15-30 minutes orally; 5-10 minutes sublingually | 1-4 hours orally; 15-60 minutes IV |
| Duration of action | 4-6 hours (immediate release); 8-12 hours (extended release) | 6-12 hours (up to 24 hours in some patients) |
| Half-life | Immediate release: 11.2 hours; Extended release: 10.7–15.8 hours | 18-50 hours (average 30-40 hours); longer in elderly |
| Bioavailability | 80–90%; not significantly affected by food | 90%; not significantly affected by food |
| Protein binding | ~80% (primarily to albumin) | ~85% (primarily to albumin) |
| Metabolism | Hepatic via CYP3A4 (primary), CYP3A5; active metabolites: α-hydroxyalprazolam | Hepatic via CYP3A4; metabolites: 7-aminoclonazepam (inactive) |
| Excretion | Renal (80%); fecal (20%) | Renal (50-70%); fecal (10-30%) |
| Available forms | Tablets: 0.25mg, 0.5mg, 1mg, 2mg; XR tablets: 0.5mg, 1mg, 2mg, 3mg; Oral solution: 1mg/mL; ODT: 0.25mg, 0.5mg, 1mg, 2mg | Tablets: 0.5mg, 1mg, 2mg; ODT: 0.125mg, 0.25mg, 0.5mg, 1mg, 2mg; Injectable: 1mg/mL |
| Legal status | Schedule IV (US, CA, UK, AU); High abuse potential; DEA tracking required | Schedule IV (US, CA, UK, AU); Moderate-high abuse potential; DEA tracking required |
| Common side effects (>10%) | Drowsiness (77%), dizziness (29%), fatigue (49%), memory impairment (33%), ataxia (28%), dysarthria (24%), constipation (26%) | Drowsiness (50%), dizziness (12%), fatigue (28%), ataxia (6%), memory problems (18%), hypersalivation (7%), upper respiratory infection (10%) |
| Serious side effects | Respiratory depression (especially with alcohol/opioids), severe withdrawal seizures, paradoxical disinhibition, suicidal ideation, severe memory impairment | Respiratory depression, withdrawal seizures, blood dyscrasias (rare), hepatic dysfunction, severe depression, suicidal ideation |
| Memory effects | Significant anterograde amnesia risk; higher risk than clonazepam due to receptor selectivity | Moderate anterograde amnesia risk; less than alprazolam but still clinically significant |
| Contraindications | Narrow-angle glaucoma, pregnancy, concurrent strong CYP3A4 inhibitors, severe respiratory disease, sleep apnea | Severe liver disease, narrow-angle glaucoma, severe respiratory insufficiency, myasthenia gravis, sleep apnea |
| Drug interactions | CYP3A4 inhibitors (ketoconazole +190%, fluoxetine +46%), grapefruit juice, cimetidine; avoid with opioids, alcohol, other CNS depressants | CYP3A4 inhibitors (less effect than alprazolam), carbamazepine (decreases levels), phenytoin; avoid with CNS depressants |
| Effectiveness for panic disorder | Highly effective for panic attacks; faster relief; 80-90% response rate in clinical trials | Equally effective for panic disorder prevention; 70-85% response rate; better for anticipatory anxiety |
| Effectiveness for anxiety disorders | Excellent for acute anxiety episodes; less ideal for GAD due to short duration and rebound anxiety | Good for generalized anxiety disorder; better for chronic management; less rebound anxiety |
| Effectiveness for seizures | Not indicated; may worsen seizure disorders during withdrawal | First-line for certain seizure types; effective for Lennox-Gastaut syndrome, myoclonic seizures |
| Cost (approximate) | Generic: $4-15/month; Brand: $200-400/month; XR: $100-300/month | Generic: $4-20/month; Brand: $100-250/month; ODT: $50-150/month |
| Generic availability | Widely available; multiple manufacturers; 90%+ prescriptions are generic | Widely available; multiple manufacturers; 85%+ prescriptions are generic |
| Physical dependence timeline | Can develop within 2-4 weeks of regular use; rapid due to short half-life and receptor selectivity | Typically 4-6 weeks of regular use; slower onset due to long half-life |
| Abuse potential | High - creates rapid reward cycle; often preferred by recreational users; significant street value | Moderate-High - longer duration makes it less preferred for abuse; some street value |
| Street value/abuse patterns | $2-5 per 2mg tablet; commonly diverted prescription drug; popular for poly-drug abuse | $1-3 per 2mg tablet; less street demand than alprazolam; used in poly-drug combinations |
| Withdrawal syndrome | Severe, rapid onset within 12-24 hours; includes rebound anxiety, panic, seizures, delirium; requires medical supervision | Less severe but prolonged; onset 2-7 days; includes anxiety, seizures, perceptual disturbances; easier to taper |
| Tapering schedule | 0.25mg every 3 days or 10-25% weekly reduction; may take 4-8 weeks; often requires inpatient detox | 10-25% every 1-2 weeks; may take 3-6 months due to long half-life; usually outpatient manageable |
| Drug testing detection | Urine: 1-6 days (up to 30 days heavy use); Blood: 12-24 hours; Hair: up to 90 days; Saliva: 2-3 days | Urine: 3-30 days; Blood: 24-48 hours; Hair: up to 90 days; Saliva: 1-10 days |
| Pregnancy safety | Category D - Evidence of risk; crosses placenta; associated with cleft palate, floppy infant syndrome | Category D (US), Category C (AU) - Evidence of risk; crosses placenta; teratogenic potential |
| Breastfeeding safety | Excreted in breast milk; causes sedation and poor feeding in infants; avoid breastfeeding | Excreted in breast milk; may accumulate due to long half-life; avoid breastfeeding |
| Use in elderly | High fall risk; cognitive impairment; Beers Criteria recommends avoiding; start lowest dose if essential | Preferred over short-acting benzos if needed; still significant fall risk; monitor closely |
| Hepatic impairment | Reduce dose by 50% in severe hepatic impairment; contraindicated in severe liver disease | Reduce dose significantly in hepatic impairment; contraindicated in severe liver disease |
| Renal impairment | No dose adjustment needed for mild-moderate renal impairment; monitor in severe impairment | No dose adjustment needed for renal impairment; metabolites are inactive |
| Overdose symptoms | Respiratory depression (especially with opioids/alcohol); confusion; severe sedation; coma; rarely fatal alone | Respiratory depression; prolonged sedation; confusion; coma; less likely to be fatal as monotherapy |
| Overdose treatment | Supportive care; flumazenil (caution - may precipitate seizures); avoid gastric lavage; monitor respiratory status | Supportive care; flumazenil (use cautiously); longer monitoring period due to long half-life |
| Food/dietary interactions | Can be taken with or without food; avoid grapefruit juice; alcohol amplifies effects dangerously | Can be taken with or without food; avoid alcohol; less interaction with grapefruit than alprazolam |
| Driving/machinery warnings | Significant impairment; avoid driving for 8+ hours after dose; amplified with alcohol/other drugs | Prolonged impairment due to long half-life; may affect driving next day; avoid for 12+ hours |
| Suicide risk warnings | FDA black box warning for increased suicidal thoughts; monitor closely especially first few weeks | FDA black box warning for increased suicidal thoughts; particular concern with depression comorbidity |
| Monitoring requirements | Baseline: mental status, fall risk, substance use history; Ongoing: cognition, dependence signs, liver function | Baseline: liver function, mental status; Ongoing: CBC with long-term use, cognitive assessment, dependence monitoring |
| Chemical formula | C17H13ClN4 | C15H10ClN3O3 |
| CAS registry number | 28981-97-7 | 1622-61-3 |
Classification
Both alprazolam and clonazepam are classified as Schedule IV controlled substances in the United States, indicating they have accepted medical use but carry a risk of dependence and abuse. This classification requires special prescribing procedures and DEA tracking.
Forms Available
Klonopin is available in 0.5mg, 1mg and 2mg tablets, and in 0.125mg, 0.25mg, 0.5mg, 1mg and 2mg disintegrating tablets. Injectable forms are also available for medical use.
Xanax is available in 0.25mg, 0.5mg, 1mg and 2mg tablets. The 2mg tablets are multi-scored and can be divided. Extended-release formulations (Xanax XR) are available in 0.5mg, 1mg, 2mg, and 3mg strengths. Oral solutions and orally disintegrating tablets are also available.
Mechanism of Action
Both Klonopin and Xanax increases the effect of gamma-aminobutyric acid (GABA) in the brain to calm the nervous system. They work as positive allosteric modulators of GABA-A receptors, enhancing chloride influx into neurons. Alprazolam shows preferential binding to α1 subunit receptors, contributing to its faster onset, while clonazepam has broader receptor binding across α1, α2, and α3 subunits. They can cause drowsiness or sedation.
Pharmacokinetics
Onset and Duration: Alprazolam has a rapid onset of action (15-30 minutes) but shorter duration (4-6 hours for immediate release), while clonazepam has a slower onset (1-4 hours) but longer duration (6-12 hours).
Half-life: Alprazolam has a half-life of 11.2 hours (immediate release) to 10.7-15.8 hours (extended release). Clonazepam has a significantly longer half-life of 18-50 hours, averaging 30-40 hours.
Metabolism: Both drugs are metabolized primarily by the liver via the CYP3A4 enzyme system, making them susceptible to drug interactions with CYP3A4 inhibitors and inducers.
How Klonopin Works
This video shows how Klonopin or Clonazepam works and can help people with epilepsy:
How Xanax Works
How Xanax or Alprazolam works:
Uses
Klonopin may be prescribed for epilepsy, as well as for panic disorder, seizures, anxiety disorders, parasomnia, OCD and clinical depression. It is particularly effective for certain seizure types including myoclonic seizures and Lennox-Gastaut syndrome.
Xanax is used to treat anxiety disorders, panic disorders, and anxiety associated with depression. It is particularly effective for acute panic attacks due to its rapid onset of action.
Effectiveness
Klonopin and Xanax will have different effectiveness for different individuals. A study by Massachusetts General Hospital in 1991 found that Klonopin and Xanax were equally effective at treating panic disorders [1].
To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.
Clinical Differences: While equally effective for panic disorder, alprazolam is often preferred for acute panic attacks due to its rapid onset, while clonazepam may be better for preventing panic attacks and managing generalized anxiety due to its longer duration of action.
Scientific studies
The following scientific studies provide useful information relevant to the effects of xanax and klonopin:
- A 1997 study found that alprazolam (xanax) increases physiological activation (heart rate, respiratory rate) under acute stress conditions and hinders therapeutic effects of exposure in flying phobia. In other words, Xanax did not always help people who have a fear of flying.
- A study published in 2011 examined the effects of klonopin (clonazepam) and xanax (alprazolam) and concluded that the immune system and blood vessels can be adversely affected to a greater extent by short-term chronic administration of Xanax than by klonopin, and these toxic effects are aggravated by stress.
- Co-administration with Prozac (Fluoxetine): A 1992 research study found that when Xanax is co-administered with Prozac, the half-life of Xanax is prolonged and its clearance is impaired. Prozac has no such effect on klonopin.
- A 1988 study found that it is possible to substitute clonazepam for alprazolam when patients become dependent on alprazolam.
- A study in 2000 examined old medical records from 1989 and 1990 to determine whether Xanax or klonopin cause an increase in uninhibited "problem" behavior such as self-injury or assault. The study concluded that the risk of such behaviors was no different than when a placebo was administered.
Dosage
Clonazepam: Starting doses are typically 0.25mg twice daily for panic disorder and 0.5mg three times daily for seizures. Maximum doses can reach 20mg daily for seizures and 4mg daily for panic disorder. Doses should not be increased rapidly, and treatment duration should be regularly evaluated. Doses higher than 0.5-1mg per day are associated with significant sedation.
Alprazolam: For adults with anxiety disorder, initial Xanax doses are of 0.25mg to 0.5mg, three times daily. This dose may be increased up to 4mg daily in divided doses for anxiety, with higher doses (up to 10mg daily) sometimes used for panic disorder under careful medical supervision. Dosage must be decreased gradually.
Elderly Patients: Both medications require dose reductions in elderly patients due to increased sensitivity and fall risk. Starting doses should be half the typical adult dose.
Side Effects
Common Klonopin side effects include drowsiness, dizziness, memory problems, feeling tired, muscle weakness, loss of balance, slurred speech, drooling or dry mouth, runny or stuffy nose, loss of appetite, nausea, blurred vision, headache, sleep problems, skin rash or weight changes. More serious side effects can include confusion, hallucinations, involuntary eye movements, pounding heartbeats, painful urination, pale skin, easy bruising, and seizures.
Common Xanax side effects include drowsiness, dizziness, blurred vision, headache, memory problems, trouble concentrating, sleep problems, swelling in hands and feet, muscle weakness, lack of balance and coordination, slurred speech, upset stomach, nausea, vomiting, increased sweating, dry mouth, stuffy nose, appetite or weight changes, and loss of interest in sex. More serious side effects include depressed mood, confusion, chest pain, tremor, seizure and jaundice.
Memory Effects: Both medications can cause anterograde amnesia (inability to form new memories), with alprazolam generally causing more significant memory impairment than clonazepam due to its receptor selectivity.
Contraindications and Restrictions
Klonopin should not be used by people who have severe liver disease, narrow-angle glaucoma, severe respiratory insufficiency, myasthenia gravis, or who are allergic to other benzodiazepines. It should not be mixed with alcohol.
Xanax also should not be used by people allergic to benzodiazepines or by women who are pregnant. Those with narrow-angle glaucoma, severe respiratory disease, sleep apnea, and those who are taking strong CYP3A4 inhibitors (such as ketoconazole or itraconazole) should also not take Xanax. It should not be mixed with alcohol.
Drug Interactions
Alprazolam is significantly affected by CYP3A4 inhibitors such as ketoconazole (increases levels by 190%), fluoxetine, and grapefruit juice. Co-administration with opioids or alcohol can cause dangerous respiratory depression.
Clonazepam is less affected by CYP3A4 interactions than alprazolam, but levels can be decreased by enzyme inducers like carbamazepine and phenytoin. Alcohol and other CNS depressants should be avoided.
Withdrawal
Klonopin can be addictive, and so dosage should be reduced gradually. Withdrawal symptoms include anxiety, irritability, insomnia, tremors, seizures and potentially exacerbated panic disorder. Due to its long half-life, withdrawal symptoms may be less severe but more prolonged, with tapering typically taking months.
Xanax also has a danger of withdrawal, and so dosage should be reduced gradually (usually 0.25mg every 3 days or 10-25% weekly reduction). Withdrawal from alprazolam can be more severe and rapid due to its shorter half-life, with symptoms appearing within 12-24 hours and often requiring medical supervision.
Dependence and Abuse
Unlike SSRIs such as Zoloft, Lexapro, and Prozac, both Klonopin and Xanax are benzodiazepines with significant abuse potential. As Schedule IV controlled substances, they have higher abuse potential than many other psychiatric medications but lower than Schedule III substances.
Klonopin and Xanax abuse occurs when the drug is used over an extended period of time or in ways other than prescribed. Signs of abuse include using the drug every day, always having it on hand, needing to take the medication to get the day started, willingness to do something illegal to acquire it, taking it without medical reason, and needing to take a larger dose to get the same results as before.
Physical dependence can develop within 2-4 weeks with alprazolam and 4-6 weeks with clonazepam. Alprazolam tends to have higher street value and abuse potential due to its rapid onset and short duration, which creates a more immediate reward cycle.
Klonopin is the second most frequently used benzodiazepine that leads to emergency department visits, including drug abuse, overdose and adverse reactions to legitimate use of the medication.
Pregnancy and Breastfeeding
Both medications are classified as Pregnancy Category D, indicating evidence of risk to the fetus. They cross the placenta and have been associated with cleft palate, floppy infant syndrome, and withdrawal symptoms in newborns. Both medications are also excreted in breast milk and can cause sedation and feeding problems in nursing infants.
Special Populations
Elderly: Both medications are included in the Beers Criteria as potentially inappropriate for elderly patients due to increased risk of falls, cognitive impairment, and prolonged sedation. If absolutely necessary, clonazepam is generally preferred over alprazolam due to its longer half-life and less potential for rebound anxiety.
Liver Disease: Both medications require dose reduction in hepatic impairment and are contraindicated in severe liver disease.
FDA Warning
Both medications carry FDA black box warnings regarding increased risk of suicidal thoughts and behaviors, particularly during initial treatment and dose changes.
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