Clonazepam (Klonopin)
BZD • Last reviewed 2025-09-23
General information
Clonazepam is a long-acting benzodiazepine indicated for seizure disorders and panic disorder; in psychiatric care it is used off-label for catatonia, acute agitation, and anxiety adjunctive to antipsychotics (clonazepam_label_2023, baldwin2014).
Tablets and orally disintegrating tablets (0.5, 1, 2 mg) enable rapid sublingual administration. Typical psychiatric dosing begins at 0.25–0.5 mg twice daily with titration based on response; higher doses (up to 4 mg/day) may be required for catatonia but should be tapered once symptoms stabilise (clonazepam_label_2023, ungvari2018).
Clonazepam potentiates GABA-A receptor-mediated chloride influx, producing anxiolytic, anticonvulsant, and muscle-relaxant effects. Compared with lorazepam it has a longer half-life and more sustained coverage but slower onset (clonazepam_label_2023).
Hepatic metabolism via CYP3A generates inactive metabolites; elimination half-life averages 30–40 hours, allowing twice-daily dosing but increasing accumulation risk in hepatic impairment or older adults (clonazepam_label_2023, baldwin2014).
Dosing & administration
Panic disorder: start 0.25 mg twice daily; increase every 3 days to 1 mg twice daily; maximum 4 mg/day.
Catatonia/agitation (off-label): 0.5–1 mg orally or sublingually every 8–12 hours; titrate to effect and reassess daily (ungvari2018).
Seizure disorders: start 0.5 mg three times daily, increasing by 0.5–1 mg every 3 days; maximum 20 mg/day.
Reduce doses in hepatic impairment, respiratory disease, or when combined with other CNS depressants.
Dose adjustments
- Elderly or debilitated
- Start 0.25 mg once daily; monitor cognition and balance.
- Hepatic impairment
- Use lower doses and monitor closely; avoid in severe hepatic insufficiency.
- Concomitant opioids
- Avoid if possible; if necessary, use lowest doses and counsel regarding respiratory depression.
- Discontinuation
- Taper 5–10% every 1–2 weeks; slower taper for long-term therapy.
Mechanism of action
Clonazepam binds to benzodiazepine sites on GABA-A receptors, increasing GABA affinity and enhancing inhibitory neurotransmission in cortex, limbic structures, and spinal cord (clonazepam_label_2023).
Its high intrinsic potency (0.5 mg ≈ 10 mg diazepam) and prolonged half-life offer sustained symptom control but elevate dependence risk if used chronically (baldwin2014).
- Positive allosteric modulator of GABA-A receptors (requires endogenous GABA).
- Minimal activity at serotonin, dopamine, or adrenergic receptors.
- Higher potency than lorazepam or diazepam on a milligram basis.
Metabolism & pharmacokinetics
Oral clonazepam is ~90% bioavailable with peak concentrations in 1–4 hours; high lipophilicity facilitates CNS penetration (clonazepam_label_2023).
Metabolised primarily by CYP3A with renal excretion of inactive metabolites; elimination half-life averages 30–40 hours but may reach 60 hours in older adults (clonazepam_label_2023, baldwin2014).
Drug interactions
CNS depressants (opioids, alcohol, antipsychotics) produce additive sedation and respiratory depression.
CYP3A inhibitors (azole antifungals, macrolides) raise clonazepam levels; reduce dose accordingly.
Enzyme inducers (carbamazepine, phenytoin) may lower clonazepam concentrations and efficacy.
| Mechanism | Agents / factors | Management |
|---|---|---|
| Additive CNS depression | Opioids, alcohol, antihistamines | Avoid or minimise; provide overdose education. |
| CYP3A inhibition | Ketoconazole, clarithromycin, ritonavir | Reduce clonazepam dose and monitor for excessive sedation. |
| Enzyme induction | Carbamazepine, phenytoin | Monitor clinical response; adjust dose if necessary. |
Monitoring & safety checks
Sedation, cognition, coordination
Each visit • Long half-life increases fall and cognitive impairment risk.
Respiratory status
Baseline and during dose escalations • Monitor for hypoventilation especially with other depressants.
Signs of misuse or dependence
Every encounter • Schedule IV agent with abuse liability.
Set expectations for time-limited use and arrange a taper once target symptoms improve.
For catatonia, reassess daily and consider lorazepam challenge or ECT if inadequate response (ungvari2018).
Discontinuation guidance
Taper by 5–10% every 1–2 weeks; long-term users may require slower tapers over several months to avoid withdrawal seizures or rebound anxiety.
Cross-taper to a longer-acting benzodiazepine is reserved for patients unable to tolerate direct taper due to interdose withdrawal.
Special populations
Pregnancy: third-trimester exposure may result in neonatal sedation or withdrawal; use only if benefits outweigh risks and monitor neonates (clonazepam_label_2023).
Older adults: heightened sensitivity to cognitive impairment and falls—use lowest effective dose and reassess frequently (baldwin2014).
Hepatic impairment: reduced metabolism increases accumulation; dose adjustments and LFT monitoring are recommended.
Adverse effects
Common: somnolence, dizziness, ataxia, memory impairment.
Less common: depression, paradoxical agitation, respiratory depression in susceptible individuals.
Serious: dependence, withdrawal seizures, overdose—particularly when combined with opioids.
References
- Klonopin (clonazepam) prescribing information — DailyMed (2023)
- Evidence-based pharmacological treatment of anxiety disorders — Depression and Anxiety (2014) DOI: 10.1002/da.22260
- Benzodiazepines for catatonia: systematic review and meta-analysis — Schizophrenia Research (2018) DOI: 10.1016/j.schres.2017.12.012
- ASAM guideline on benzodiazepines — Journal of Addiction Medicine (2020) DOI: 10.1097/ADM.0000000000000743
- Management of catatonia in schizophrenia — Therapeutic Advances in Psychopharmacology (2021) DOI: 10.1177/20451253211045473
Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.