February 27, 2025 • Brooke Siem
Negative Xanax Trials, PSSD in the New York Times, SNOMED creates a code for withdrawal: A roundup of notable news in the world psychiatric drugs and withdrawal.
Publication Bias in Original Xanax Trials
A new study on publication bias of the benzodiazepine Xanax has been released. According to researchers from Harvard, Massachusetts General Hospital, McLean Hospital, and former FDA reviewer Eric Turner, four of the five original studies on the effectiveness of alprazolam (Xanax) found it to be no better than a placebo. Furthermore, only one of the five studies reviewed by the FDA showed a positive result. It is curious when you consider that the FDA “expects that the drug maker will submit results from two well-designed clinical trials to be sure that the findings from the first trial are not the result of chance or bias.”
Publication bias is the practice of picking and choosing what gets published and how it gets published. This is extremely common across all hard and soft scientific disciplines, and it’s a big reason why relying on published, peer-reviewed research should not be the be-all, end-all of human existence.
Negative and neutral trials, for example, often don’t make it into literature. Not only do the researchers not want to draw attention to a failed hypothesis, but journals don’t want to waste space on science that doesn’t work. Furthermore, the media rewards breakthroughs, not duds. Thus, an unknown amount of research is left on the cutting room floor.
The problem with this is that when you look at the body of research that does get published, it tells a very different story. British physician Ben Goldacre explains it well. I’ve fast-forwarded to the most relevant part for your convenience:
This is exactly what happened in the Xanax approval process. The FDA received data on five Phase 2 and Phase 3 trials. They considered four of them to be negative but approved the drug due to the strength of Study 2. Furthermore, the results of Study 1 were spun to look positive, despite the FDA statistician determining the study failed because improvement was not noted in all seven primary endpoints (the FDA deems “studies positive only if all primary endpoints achieve statistical significance”).
Studies 3, 4, and 5 failed or were nonsignificant, and none of these studies were published.
Thus, the published literature reflected that Xanax was a successful intervention for panic disorder, which led to a frenzy of prescriptions thanks to media and marketing departments that use published literature for headlines and campaigns.
And here we are, thirty years later, with a raging global opioid crisis, in part thanks to the misuse of benzodiazepines.
The New York Times writes about Post SSRI Sexual Dysfunction, indicating a new wave of psychiatric drugs is coming
You know Big Pharma is prepping to push a new class of drugs when the narrative starts changing around the golden pharmaceutical children of yore.
Drug patents in the United States typically last 20 years, and given that there’s been no meaningful pharmacological advance in the mechanism of antidepressants during that time, most SSRIs and SNRIs have fallen off the patent cliff and are available in generic form. Generics, of course, don’t bring in the dough. So, pharmaceutical companies use a variety of tactics to bury generic competition, including but not limited to:
- blocking generic companies from getting samples of the brand-name drug so they can’t prove to the FDA that the generic is equivalent
- refusing to cooperate with generic companies on drug safety plans
- making slight alterations to a drug’s dosage or delivery mechanism right before the patent expires, and then shifting the market to the new version that is protected by a glittery new patent
Two themes are appearing in the media that make me think we’re heading for a classic shift. First, we’re seeing headlines about new antidepressants, specifically Zurzuvae (zuranolone) and Zulresso (brexanolone), both of which act on GABA receptors (like benzodiazepines) and are being targeted at vulnerable new mothers with postpartum depression.
Zulresso, by the way, costs $34,000.
The New York Times reported on these new drugs on August 4, 2023. On November 9, 2023, the New York Times also reported on Post SSRI Sexual Dysfunction, a devastating and often permanent side-effect of antidepressants that can rob people not their libdo, function, and feeling in their genitals. Chemical castration, effectively.
Both articles include a pithy offer of journalistic objectivity, adding a quote or two from the “opposition” to satisfy the reader with an attempt at balance. But the tone of each article is clear: New shiny drugs, good! Old generic drugs, beware!
Curioser and curioser.
SNOMED creates a code for antidepressant withdrawal
In good news, SNOMED (Systematized Nomenclature of Medicine Clinical Terms) has created code 1285639002 for “Protracted antidepressant withdrawal syndrome (disorder).”
SNOMED is a non-profit organization responsible for determining global standards for health terminology. It is designed to support a wide range of healthcare processes, including clinical documentation, decision support, and data analysis. It encompasses a broad spectrum of clinical concepts, relationships between them, and associated terms. This standardized terminology helps ensure consistency and interoperability in health information systems.
Without a formal code, an ailment essentially doesn’t exist. That means that prior to code 1285639002, precisely 0 cases of protracted withdrawal have been formally recorded because there wasn’t a way to do it.
In the UK, doctors have to activate the code in order to use it. Once that happens, researchers will be able to start tracking case rates. In the US, it’s irrelevant because of our dumbass system. I’m told that we likely won’t have a code until the DSM recognizes it, which would lead to a bit of the emperor has no clothes situation. But SNOMED is a start, and I’ll take it.
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