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To Benzo, or Not to Benzo: An Interview With Carl Salzman

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Carl Salzman removes the stigma from the much maligned benzo, reminding us of when they are essential to treatment and when they cause harm. Dr. Salzman is the past chairman of the American Psychiatric Association’s Benzodiazepine Task Force.

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Published On: 07/18/2022

Duration:  21 minutes, 18 seconds

Referenced Article: Benzodiazepines: A Reevaluation of Their Benefits and Dangers,” The Carlat Child Psychiatry Report, June 2022 Chris Aiken, MD, Kellie Newsome, PMHNP, and Carl Salzman, MD have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Transcript: 

Today, Dr. Carl Salzman lifts the stigma from benzodiazepines to remind us of when they are essential and when they are harmful. 

Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

To benzo, or not to benzo, that is the question we posed to Carl Salzman in the July issue of the Carlat Report. And the answer…

DR. SALZMAN: I think benzodiazepines are still widely used, both appropriately and inappropriately. The SSRIs were supposed to replace the benzos for long-term treatment of anxiety, but while the use of these antidepressants has increased in anxiety disorders, the use of benzos has barely fallen.

I’m speculating, but one reason is that benzos are more potent anxiolytics. In generalized anxiety disorder, their effect size is in the medium range (0.5) compared to SSRIs, which have a small effect size of 0.3. The second reason is the benzos work faster. Finally, they are helpful for sleep. They may not always be the best drugs for sleep, but they are reliable

KELLIE NEWSOME: Dr. Salzman is a Professor of Psychiatry at Harvard Medical School and past chairman of the American Psychiatric Association’s Benzodiazepine Task Force. He was interviewed by Dr. Marcia Zuckerman, who is a clinical assistant professor in psychiatry at Tufts School of Medicine. Dr. Zuckerman serves on our editorial board and trained under Dr. Salzman as a resident at Mass Mental Health Center Residency.

DR. SALZMAN: Yes. I call it “benzo hysteria.” It’s very hard to get a doctor to prescribe a benzodiazepine, though on their own they are almost never fatal in overdose. Some benzo use is inappropriate: the wrong patient, the wrong dose, the wrong duration, or the wrong interaction with other drugs like alcohol, opioids, or other sedative-hypnotics. But if you take away those situations and just look at the legitimate medical use of benzos, these are good drugs and they are effective. We know the pharmacology. We know how they work in the brain. They are sedative-hypnotics and can cause dependence, but that depends on the dose and duration. 

Once you’re above 3 mg/day of clonazepam, you begin to think, “Why does this person need more? Am I missing something?” Or when their dose keeps increasing and you’re getting calls saying, “I’m still anxious and can’t sleep.” We don’t like to use benzodiazepines long term, but there are many people who suffer from serious chronic anxiety that is not well managed by antidepressants but is well managed by modest doses of a benzo. Benzos are also useful for short-term control of agitation, and they are very good for panic disorder and phobias. Two are FDA approved in panic disorder—alprazolam and clonazepam—and we have the best data supporting their use in panic disorder.

KELLIE NEWSOME: As Dr. Salzman was saying there, panic disorder is where benzodiazepines have the most robust evidence supporting their use in psychiatry. Panic disorder is one of the top 10 causes of disability in working age adults, and if your patient is not getting better with CBT or SSRIs, a benzo is a reasonable next step. 

CHRIS AIKEN: We’re talking about a disorder that is functionally impairing, and I would use a benzo in panic if it improved the patient’s functioning. I’ll tell patients “only take this if it helps you move forward and do the things you need to – the things that anxiety is getting in the way of. Don’t take a benzo if you are staying in bed all day.”

KELLIE NEWSOME: Two benzodiazepines are FDA approved in panic disorder – clonazepam (Klonopin) and alprazolam (Xanax), and Dr. Salzman explains why fast-acting benzodiazepines like these are better for panic than others, and this gets into a common misconception about benzos. It’s not about the half-life, it’s about the lipid solubility – how fast it gets into the brain.

DR. SALZMAN:

KELLIE NEWSOME: OK are you getting that – short half life benzos don’t act faster, they just leave the body faster. What matters is how fast it gets into the brain. And on the other side, long half-life benzos don’t necessarily last longer. They may leave the brain early, before their half life is up, which is why you’ll sometimes see that patients only get temporary benefits from benzos with long half-lives like alprazolam (Xanax) and diazepam (Valium). 

CHRIS AIKEN: Dr. Salzman highlighted oxazepam as the quintessential slow-acting benzo, and he’s right – this one takes 1-2 hours to start working, as opposed to about ½ an hour for most other benzos. But that’s not a reason to avoid it entirely. Oxazepam also has the lowest abuse liability, and the lowest risk of accidental overdose when combined with opioids. Besides its slow onset – which means it is less rewarding – there is also evidence from animal studies that oxazepam raises neurosteroids that further block the rewarding properties of drugs of abuse – including opioids as well as stimulants. In one study, alprazolam (Xanax) made rats more likely to self-administer methamphetamine, while oxazepam (Serax) made them less likely to self-administer it.

KELLIE NEWSOME: But for insomnia and panic attacks, you don’t want a benzo that’s slow to act. Dr. Salzman illustrates that with an unlikely story of a cross-continental flight. Sidenote: I was a flight attendant for Ansett Australia before becoming a nurse. I saw a lot, but I’ve never heard a story like this one.

DR. SALZMAN:

CHRIS AIKEN: Dr. Salzman sure assuages one of my biggest phobias there.

KELLIE NEWSOME: What’s that?

CHRIS AIKEN: That the flight attendant will sound that fateful call – “Is there a doctor on the plane” – and I’ll be the only one – and what good is a psychiatrist when a passenger is having a heart attack or something?

KELLIE NEWSOME: Oh Dr. Aiken get over yourself. Try being a flight attendant. Or a nurse. We deal with that stuff all the time. Let me give you some facts. About 1 in 10,000 passengers have a medical emergency on board the flight, and about three quarters of them are fully managed by the cabin crew. We have defibrillators and a good stock of emergency medications on board the flight – often including lorazepam and intramuscular diazepam. 

The top in-flight medical crises are chest pain, collapse, asthma, head injury – usually when heavy items fall from overhead storage bins, abdominal problems, low blood sugar from diabetes, allergic reactions, OBGYN – babies are born on planes, and, yes psychiatric problems are on the list. So don’t be ashamed to raise your hand when duty calls. Psychiatric problems are among the most common ones we see in the plane, and your skills may be needed. Just be sure to check how much alcohol the passenger has consumed before given that benzo. We see a lot of panic attacks, as well as disruptive behavior – whether from mania, psychosis, or illicit drug use. 

CHRIS AIKEN: As in life, context is everything in medicine. It may seem a little loose to give a benzo to someone who is not your patient on a flight, but the standards of risk and benefit are much different when you’re 30,000 feet in the air. Our licenses are granted by society, and it’s our calling to take care of people in society. Boundaries are important, but in emergencies that calling extends beyond the office walls.

KELLIE NEWSOME: And that context changes on the ground. Dr. Salzman does not recommend benzodiazepines for patients who misuse opioids, or patients who are demanding, threatening, or running out early – including those patients who call your practice saying they just moved from another state and are about to run out and want a refill before their next appointment. If he does honor that extreme request, he only gives a week’s supply.

DR. SALZMAN:

KELLIE NEWSOME: You’ll learn more from Carl Salzman in our online interview. Do benzos cause dementia? How do you use them safely in the elderly, or in patients with a history of alcohol use disorder? Which benzo is best for which situation? How do you taper off a benzo, and which medications help soothe benzodiazepine withdrawal?

And we close with 3 offers for you…

Want CME for this podcast? Click NOTES at the top of the podcast screen and follow the link. 

Want daily updates on practice-changing research? Follow Dr. Aiken on LinkedIn or Twitter – @ChrisAikenMD. Let’s see, last week he posted on a natural fatty acid for mania; the generic debut of Vilazodone/Viibryd, an herbal therapy for OCD, and an abbreviated version of DBT for borderline personality disorder.  

References: 

 


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