Dosage Equivalency (mg)Onset of Action (hrs)Duration of Action (hrs)Half-Life (hrs)
Alprazolam (Xanax)0.50.5-13.0-4.011.0-16.0
Chlordiazepoxide (Librium)10.0-25.01.0-2.0---5-200 (with active metabolite)
Clonazepam (Klonopin)0.25-0.514.0-8.020-80
Diazepam (Valium)50.54.0-6.0>100
Lorazepam (Ativan)10.5-14.0-6.010.0-20.0
Temazepam (Restoril)15-300.5-14.0-6.09.0-18.0

What are Benzodiazepines?


Benzodiazepines are a class of medications used to treat anxiety disorders, seizures, mania, muscle tension, sleep disorders, and alcohol withdrawal. Benzodiazepines are commonly prescribed short-term (e.g., 2 weeks) when initiating antidepressants such as selective serotonin reuptake inhibitors (SSRIs) to ameliorate the activating side effects that can occur when initiating antidepressants. Benzodiazepines temporarily decrease activity in the brain by promoting the effects of the major inhibitory neurotransmitter GABA. Each benzodiazepine medication is different as some are more effective at promoting sleep whereas others are more effective at relieving anxiety. Each medication has a unique pharmacokinetic profile that also determines the onset of action, the duration of clinical action, and abuse potential. The first benzodiazepines were Chlordiazepoxide (1959) and Diazepam (1963). Alprazolam, brand name Xanax,  was the first benzodiazepine approved for panic disorder in 1981.


All benzodiazepines have structural similarity in that they all have a 1,4-benzodiazepine ring system.


How do Benzodiazepines Work?

All Benzodiazepines are positive allosteric modulators (i.e., they bind outside of the active site but still influence receptor dynamics) of the GABA-A Receptor. They increase the binding affinity of GABA for its receptor and increase the frequency of opening of the chloride channel embedded within the GABA-A receptor. This leads to increased chloride influx and hyperpolarization of the dendritic portion of neurons bearing GABA-A receptors). Benzodiazepines that preferentially bind to the α1 subunit of the GABA-A receptor are thought to have more sedative/hypnotic (i.e., sleep-promoting) effects while those that preferentially bind to the α2 and α3 subunits of the GABA-A receptor are thought to have more anti-anxiety effects


Important facts to know about benzodiazepines:


  • A benzodiazepine’s rate of distribution and lipid solubility determine its duration of action. Diazepam has a rapid onset of action due to its rapid absorption and distribution (very lipid-soluble). Diazepam has a shorter duration of clinical action than lorazepam after one dose.
  • When benzodiazepines are administered to individuals suffering from acute stress disorder, the probability of conversion to Post Traumatic Stress Disorder is roughly doubled (i.e., benzodiazepines may interfere with post trauma adaptation). 
  • Exposure therapies for anxiety disorders and PTSD may be less effective with concurrent use of benzodiazepines
  • The following benzodiazepines have little, if any, phase 1 metabolism in the liver and primarily undergo glucuronidation (and therefore they are preferred for individuals with hepatic impairment): Oxazepam, Temazepam, and Lorazepam
  • Benzodiazepines alone are unlikely to cause respiratory arrest in healthy individuals due to the fact that benzodiazepines, unlike barbiturates, require GABA to be bound to the receptor to function (this means there is a plateau in the clinical effect). HOWEVER, in patients with cardiopulmonary disease (COPD, Asthma, Sleep Apnea) respiratory compromise can occur with benzodiazepines so caution is advised. 
  • Prescribing an opioid and a benzodiazepine increases risk of death significantly.
  • Despite claims of neurological damage associated with benzodiazepines, it is unclear how accurate this is. Nonetheless, it is a rare possibility. 


Benzodiazepines have been associated with the following: 


Tolerance, physical dependence, withdrawal

Abuse potential


Diminished attention

Failure of memory consolidation

Increased risk of falls in the elderly

Increased risk of delirium in the elderly

Benzodiazepine Withdrawal 


Dependence and/or withdrawal symptoms can occur after 4-6 weeks of continuous use of a benzodiazepine (sometimes less). About one-third of long term users experience problems with dosage reduction. While benzodiazepines are very effective anxiolytics, they are meant for short term use (example: when initiating antidepressants or for panic attacks only). Typically, they should be prescribe only for a few weeks. In some cases, long-term use is necessary to control symptoms. Withdrawal symptoms usually last no longer than a few weeks but some may experience withdrawal symptoms for much longer (we call this “protracted withdrawal”).


Problems on withdrawal from benzodiazepines:




Gastrointestinal disturbance


Flu like symptoms

Visual disturbances



Rebound anxiety/insomnia



Decreased memory and concentration




How to Taper Benzodiazepines:

Unfortunately, there is not an abundance of literature supporting any one taper schedule over another


General idea: Calculate total daily dose of shorter acting benzodiazepine (Xanax/Alprazolam) the patient is taking and then convert to a longer acting benzodiazepine (Valium/Diazepam, Klonopin/Clonazepam, Librium/Chlordiazepoxide) and then slowly taper over the course of months.


  • Prescribe no more than 1-2 week supply of medication at any one time
  • Make it clear that treatment is not long term
  • Encourage CBT, Relaxation techniques, and other psychosocial supports
  • Offer symptomatic relief with medications with low abuse potential (see medications for side effects below)
  • Always address social stressors and comorbid psychiatric illnesses


Example Taper for an individual who takes Alprazolam (Xanax) 4mg TOTAL daily


  1. Alprazolam (Xanax) 4mg total daily is roughly 4mg of Clonazepam (Klonopin) total daily. 
  2. Start patient on 2mg twice daily of Clonazepam (Klonopin)
  3. Reduce the dose by 0.25mg – 0.5mg per day every 2-3 weeks until off. As soon as intolerable withdrawal symptoms appear, either increase the dose back to previous dose and go slower and/or use other medications to help with symptoms
  4. It is important to note that the longer a patient has been taking a benzodiazepine, the longer the taper process (generally speaking but not absolute). 


Medications used to help with withdrawal symptoms:


Mirtazapine (Remeron)

Propranolol (Inderal)

Carbamazepine (Tegretol)

Valproic Acid (Depakote)

Duloxetine (Cymbalta)

Amitriptyline (Elavil)

Gabapentin (Neurontin)



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