Welcome to my blog, a place to explore and learn about the experience of running a psychiatric practice. I post about things that I find useful to know or think about. So, enjoy, and let me know what you think.

Tuesday, March 1, 2016

Benzodiazepines are Confusing

For about a year now, I've been trying to figure out what to make of data coming in about the association between Benzodiazepine (BZD) use and dementia.

To start from the very beginning, I recognize that BZDs are potentially addictive, can cause gait and memory impairment, and precipitate withdrawal seizures with continued use, and don't mix well with other drugs like EtOH and Opioids, for instance. They're not ideal drugs.

But for a certain subpopulation, they're helpful. Anxious people who are on other meds that don't quite hold them, and who don't escalate their doses, for instance. Patients who are scared of flying, and who need a Xanax to get them there, and another to get them back. And sure, everyone knows BZDs have, at best, a short duration of helping with insomnia, and still, some patients do well with them long-term.

I'm definitely more liberal with BZDs than I was taught to be as a resident, where they were viewed as the evil purview of manipulative drug seekers. I consider that perspective a bit extreme. On the other hand, I try to encourage other methods for coping with anxiety, and taper patients off them, when I can.

Lately, though, I've been worrying about the connection between BZDs and dementia. In a 2012, French study by Billioti de Gage, et al, 1063 men and women, (mean age 78.2) who were dementia free were followed for up to 15 years. Those who used BZDs prior to the onset of the study were excluded, so only  those who used BZDs three or more years into the study were included. They found that new use of BZDs was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60, 95% confidence interval 1.08 to 2.38). They also found that:

"Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users. The results were similar in past users (odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but reached significance only for past users."

This was the part I found particularly perplexing. I didn't understand this separate, complementary study, or what to make of "ever use" vs. "never use".  For instance, what are the implications for someone who gets a versed fentanyl drip for a colonoscopy? Does that constitute "ever use"?

Other studies  cited by this one demonstrate increased risk of dementia in chronic use, former use, and ever use (please see study for citations). The "ever use" particularly bothered me, because why should I encourage patients to stop taking BZDs if their risk is already well-established.

Another study, (same author, 2014) looked at people already diagnosed with Alzheimers, and considered a dose response relationship to BZDs. They found an association with "ever use", but not with cumulative dose. Also, the strength of association was greater for long half-lifed BZDs than for short half-lived. There were a whole bunch of confusing points and confounders.

Finally, there's this study:
Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study, by Gray, et al, published in the BMJ last month. It's a prospective, population-based study done in Seattle, "To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline."

They had 3434 participants age > 65, dementia-free at study entry. They screened for dementia every 2 years over the course of 10, with the CASI (Cognitive Abilities Screening Instrument), and got data about BZD use via computerized pharmacy records.

They concluded:

The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.

There's so much inconsistency here that I don't know what to think. At least all three of the articles are open access.

I'm off to the Far East for several weeks, see you when I get back.