II. Indications: Outpatient
- Sedation in surgical, Medical and Psychiatric procedures
- Seizure disorder
- Alcohol Withdrawal and withdrawal from other drugs
-
Anxiety Disorder
- Consider limiting to short-term stabilization until SSRI or SNRI (e.g. Venlafaxine) takes effect
- Adjunct to Cognitive Behavioral Therapy and other Anxiety Management
-
Insomnia
- Consider alternative agents and methods (Trazodone, Melatonin, CBT-I, Sleep Hygiene)
- Consider Benzodiazepine Receptor Agonist instead (e.g. Ambien)
- Muscle spasm
III. Contraindications
- Myasthenia Gravis
- Acute narrow-angle Glaucoma
- Substance Abuse (relative contraindication)
IV. Mechanism
- Potentiates activity of gamma-aminobutyric acid (GABA)
- GABA is an inhibitory neurotransmitter in the CNS
- Muscle relaxant
- Anticonvulsant
- Anxiolytic
- Anti-aggressiveness
- Sedation
V. Precautions
- Benzodiazepines have significant risks
- Double the risk of motor vehicle accidents, and falls (and Hip Fractures) in the elderly
- Double the risk of COPD exacerbations
- Benzodiazepine misuse and abuse is common
- Hospital admissions for Benzodiazepine Abuse have increased three-fold since the early 2000s
- Alprazolam is among the most addictive Benzodiazepines (responsible for 10% of drug-misuse related visits to the ED)
- Avoid combining Benzodiazepines if possible
- Risk of falls, memory problems, excessive Sedation
- In some cases, occasional as needed dosing of a short acting Benzodiazepine in a user of a long acting Benzodiazepine may be appropriate
- Frequent as needed dosing should prompt re-evaluation with consideration of increasing the long-acting Benzodiazepine dose
- Non-Benzodiazepine sedatives (e.g. Ambien) can have additive effects with Benzodiazepines
- References
- (2014) Presc Lett 21(8): 45
- Zigman (2012) J Psychopharmacol 26: 1507-11 [PubMed]
VI. Advantages
- Rapid onset of action
- Anxiolytic effect within 1-2 days
- Tolerance develops rapidly to adverse effects
- Tolerance does not develop for Anxiolytic effect
- Few Drug Interactions
- Good safety profile
VII. Preparations
- Long Acting Benzodiazepines
- Chlordiazepoxide (Librium)
- Diazepam (Valium, Valrelease)
- Flurazepam (Dalmane)
- Chlorazepate (Tranxene)
- Clonazepam (Klonopin)
- Quazepam (Doral)
- Halazepam (Paxipam)
- Medium Acting Benzodiazepines
- Short acting Benzodiazepines
VIII. Absorption
IX. Metabolism
- Renal Excretion
- Hepatic Metabolism
- Microsomal oxidation
- Conjugation by glucuronyl transferases
X. Dosing: Strategies
- Initiate treatment with low dose Benzodiazepine
- Prevent symptoms completely by using a regular regimen
- Escalate dose slowly, no more often than every 2 weeks
- Maintain lowest effective dose for several months
- Start with 50% of typical dose in at risk cohorts
- Elderly
- Hepatic dysfunction
- Renal dysfunction
- Tapering dose
- Periodically attempt to lower dose or ideally, titrate off completely
- Indications for prolonged taper periods (2-4 weeks per dose step-down)
- Higher Benzodiazepine doses
- Longer duration of Benzodiazepine use
- Short-acting Benzodiazepines (e.g. Alprazolam, Lorazepam)
- Example taper protocol
- Decrease dose by 25% for 1 week (2-4 weeks if prolonged taper indicated) THEN
- Decrease dose by 25% for 1 week (or 2-4 weeks if prolonged taper indicated) THEN
- Decrease dose by 10% per 1 week (or 2-4 weeks if prolonged taper indicated) until off
- Change to longer half-life drug if symptom breakthrough
XI. Dosing: Equivalent to Valium 60 mg (for withdrawal)
- High Potency Benzodiazepines
- Alprazolam (Xanax) 6 mg
- Clonazepam (Klonopin) 24 mg
- Lorazepam (Ativan) 12 mg
- Low Potency Benzodiazepines
- Chlordiazepoxide (Limbitrol) 150 mg
- Flurazepam (Dalmane) 90 mg
- Halazepam (Paxipam) 240 mg
- Oxazepam (Serax) 60 mg
- Temazepam (Restoril) 60 mg
XII. Safety: Pregnancy and Lactation
- Pregnancy Category: D
- Lactation: Not allowed
XIII. Adverse Effects
-
Drug Dependence
- Risk Benzodiazepine Withdrawal (Seizures may occur, especially if underlying Seizure disorder)
- Sedation
- Nausea
- Blood dyscrasia
- Anterograde amnesia
- Cognitive Impairment
- Respiratory depression
- Hyponatremia or Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
XIV. Monitoring: Consider in patients on longterm therapy
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| Definition (MSH) | A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring. |
| Definition (CHV) | a drug used to relieve nervousness, tension and anxiety |
| Definition (CHV) | a drug used to relieve nervousness, tension and anxiety |
| Definition (NCI) | Drugs from this chemical class are used for their central nervous system depressant properties including sedation, facilitation of sleep, seizure control, general anesthesia, anxiolytic, amnestic, and for detoxification from similar (cross tolerant) drugs |
| Definition (CSP) | bicyclic structure consisting of fused benzene and diazepine rings; many compounds with this structure have psychotropic and neurotropic properties, and are used as sedatives, anticonvulsants, muscle relaxants, and in related applications. |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D001569 |
| SnomedCT | 349890003, 16047007, 372664007 |
| LNC | LP15014-1, MTHU001123 |
| English | Benzodiazepines, BENZODIAZEPINE CPDS, benzodiazepines (medication), benzodiazepines, Benzodiazepines [Chemical/Ingredient], Benzodiazepine, Benzodiazepine (product), Benzodiazepine (substance), benzodiazepine, Benzodiazepine, NOS, Benzodiazepine Compounds |
| Swedish | Bensodiazepiner |
| Czech | benzodiazepiny |
| Finnish | Bentsodiatsepiinit |
| French | Composés de benzodiazépine, Benzodiazépine, Benzodiazépines |
| Italian | Composti benzodiazepinici, Benzodiazepine |
| Russian | BENZODIAZEPINY, БЕНЗОДИАЗЕПИНЫ |
| Japanese | ベンゾジアゼピン, ベンゾジアゼピン誘導体 |
| Croatian | BENZODIJAZEPINI |
| Polish | Benzodiazepiny pochodne, Benzodwuazepiny pochodne |
| Norwegian | Benzodiazepiner, Benzodiazepin |
| Spanish | Benzodiacepinas, benzodiacepina (producto), benzodiacepina (sustancia), benzodiacepina, benzodiazepina (sustancia), benzodiazepina, Benzodiazepinas |
| German | Benzodiazepine |
| Portuguese | Benzodiazepinas |
