Benzodiazepines (BZDs) Fact Sheet:
Mechanism of Action: Potentiate activity of GABA at GABAa receptors. This leads to anxiolytic and sedating effects.
*Pause* Does this make sense? GABA is an inhibitory neurotransmitter. BZDs increase the activity of GABA, which means more inhibitory effects. This leads to a sedating effect.
Onset of action: They usually start working within minutes of administration
- Quickest: Lorazepam
- Slowest: Chlordiazepoxide
ALL BZDs are controlled medications. This is because the body can develop physical dependence and tolerance to all of them over time. Because of this potential dependence, BZDs must be tapered off before discontinuing the medication. Abrupt stoppage can cause significant withdrawal, leading to increase seizure risk, insomnia, and anxiety.
Even opioid withdrawal is as dangerous because of that seizure risk!
Adverse Effects:
- Sedation and Psychomotor Impairment | GABA potentiation
- Anterograde amnesia and worsening delirium | GABA potentiation
- CNS (respiratory) Depression – this is the most common adverse effect of BZD
- Avoid opioids and alcohol!!!!
- Withdrawal | Physical dependence
A note on withdrawal. This is experienced in one-quarter to one-half of patients discontinuing BZDs. While all BZDs can induce physical tolerance, the onset and duration depend on the half-life of BZD.
Common ADR: anxiety, insomnia, restlessness, muscle tension, and irritability
Serious ADR: diaphoresis, nausea, blurred vision, nightmares, depression, hyperreflexia, ataxia
Life-threatening: hallucinations, confusion, paranoid delusions, seizures
BZDs lower seizure threshold with high doses and long duration of use
List of Benzodiazepines:
- Rapid onset with short duration:
- Lorazepam (Ativan)
- Rapid onset with intermediate duration:
- Alprazolam (Xanax)
- Rapid onset with long duration:
- Clonazepam (Klonopin)
- Diazepam (Valium)
- Intermediate onset with short duration:
- Oxazepam (Serax)
- Delayed onset with long duration
- Chlordiazepoxide (Librium)
Conversion factor (I know it’s not the prettiest picture 🙂 )
This is a conversion chart. It’s also known as CALDO and Cross -Tolerance.
First, calculate 24-hour dose of current BZD: 1mg clonazepam TID = 3mg daily dose.
Second, plug the number in using.
CALDO(current BZD)/CALDO(target BZD)
If we’re converting clonazepam to diazepam, it will look like 0.25/5 = 0.05
Third, divide the 24-hour dose of the current BZD.
Continuing with the example, we divide 3mg by 0.05. This gets us to 3/0.05 = 60mg daily diazepam dose. If the patient is taking diazepam QID, then the SIG would look like diazepam 15mg QID. If, while switching, the prescriber wants to decrease the total daily dose by 15%. You time the target medication daily dose by 85% or 0.85. This gives us a 51mg daily diazepam dose.
The Role of BZDs in Treatment
Regardless of what you’re treating, please remember that benzodiazepines should ONLY be used as adjunctive therapy. They are very effective at what they do, which is to mask symptoms, but they do not fix the problem.
Knowing this, I do not want to minimize the role of BZDs because even though they’re just masking the symptoms, this can be very crucial for certain patients.
BZDs are indicated for generalized anxiety disorder, panic disorder, insomnia, seizure disorder, muscle relaxation, and anesthesia.
When choosing which BZDs to use, think about what kind of onset you’re looking for. If you’re using choosing a BZD for a panic attack, you want a quick onset, so choosing chlordiazepoxide, which has a delayed onset, is not beneficial.