Iwas a junior in college. One afternoon my anxiety got so intense I couldn’t peel myself from the ceiling. I had no clue as to what was going on, much less what to do about it. Then it hit me, go to the E.R…
The first benzodiazepine, chlordiazepoxide (Librium), hit the market in 1960. Any idea what #2 was?
The benzodiazepines are a huge player in the treatment of the anxiety disorders. In fact, alprazolam (Xanax) is annually one of the top twenty-five most prescribed drugs in the US.
Just as we did with the antidepressants, it’s time to get started on a benzodiazepine need-to-know series. We’ll handle our business in three parts.
What are benzodiazepines?
Benzodiazepines (benzos) are actually anticonvulsants. And they aren’t all alike. Each benzo possesses hypnotic (sleep-inducing), anxiolytic (anxiety-relieving), sedative, anticonvulsant, muscle relaxant, and/or amnesic (memory-compromising) characteristics.
Benzos are typically used to treat anxiety, panic, agitation, seizures, insomnia, and substance withdrawal. They’re also used for medical sedation.
Two tidbits of interesting history…
- The first benzodiazepine, chlordiazepoxide (Librium), hit the market in 1960. Any idea what #2 was? diazepam (Valium).
- The predecessors of the benzos were the barbiturates – e.g., phenobarbital (Luminal).
The benzos are Schedule IV drugs in the US, Schedule IV in Canada, and Class C in the UK. You get the idea.
Short, intermediate, and long-acting
In very broad terms, let’s categorize the benzos according to action…
- Short-acting: Elimination half-life of 1–12 hours. They have few residual effects if taken before bedtime. Rebound insomnia may occur upon discontinuation, and they might cause daytime withdrawal symptoms such as next day rebound anxiety with prolonged usage. Examples: brotizolam (Lendormin), midazolam (Versed), and triazolam (Halcion).
- Intermediate-acting: Elimination half-life of 12–40 hours. They may have some residual effects in the first half of the day if used as a hypnotic. Rebound insomnia, however, is more common upon discontinuation of intermediate-acting benzos than longer-acting. Examples: alprazolam (Xanax), estazolam (ProSom), flunitrazepam (Rohypnol), clonazepam (Klonopin), lormetazepam (Noctamid), lorazepam (Ativan), nitrazepam (Mogadon), and temazepam (Restoril).
- Long-acting: Elimination half-life of 40–250 hours. They have a risk of accumulation in the elderly and in individuals with severely impaired liver function, but they have a reduced severity of rebound effects and withdrawal. Examples: diazepam (Valium), chlorazepate (Tranxene), chlordiazepoxide (Librium), and flurazepam (Dalmane).
A couple of details…
- A drug’s elimination half-life is the time it takes for its plasma concentration to reach half of its original level. This is accomplished by our metabolic and elimination systems.
- Benzos are not approved by the US FDA for long-term use. You’ll find out why in a short.
How do benzodiazepines work?
Gamma-amino butyric acid (GABA) is by far our most abundant inhibitory (slows things down) neurotransmitter.
Located all over the brain, GABA has the ability to unlock and actually bring to life anxiety-inhibiting receptors on nerve cells. It also has sleep-inducing characteristics.
Sounds like the perfect target amid a nasty case of anxiety. Well, it is – and benzos enhance the action of GABA. And that’s why they can make you feel so good.
Do benzodiazepines have adverse effects?
Benzos can pose some serious problems in the immediate and down the road. The reason they aren’t approved for long-term use by the FDA is because of the risk of tolerance, dependence, and withdrawal symptoms upon cessation.
Other potential problems stemming from long-term use are psychomotor and cognitive (including memory) impairments. Depression and anxiety may also present.
Potential risks that come with short-term benzo use include cognitive impairments, aggression, and other behavioral disinhibition.
And then there are paradoxical effects, which are presentations of the exact opposite of the intended effects. These include increased seizures in people who have epilepsy, irritability, impulsivity, and suicidal ideation and behavior.
Paradoxical effects occur in much greater frequency in individuals who abuse benzos, those with borderline personality disorder, children, and individuals using high-dosage regimens.
The most common side effects of the benzos are drowsiness, dizziness, decreased alertness and concentration, lack of coordination (particularly in the elderly), impairment of driving skills, decreased libido, erectile dysfunction, depression, and disinhibition. With intravenous benzo use, hypotension and suppressed breathing may occur.
Side effects not as likely to present are nausea, appetite change, blurred vision, confusion, euphoria, depersonalization, and nightmares. Cases of liver toxicity have been noted, but are very rare.
If you endure symptoms of depression or have recently abused substances, benzos aren’t for you. The same applies to pregnancy.
Be sure to discuss use, potential use, and cessation with your physician.
Come back for more
I think we got off to a great start. Can you see why benzodiazepines are dicey business? Well, we’re on a roll, so go ahead and dig in to part two, as we talk about benzodiazepine dependence.
The Chipur benzodiazepines articles…
Are you looking for more mood and anxiety disorder reading material? Have at the Chipur titles.