The title, basically, which is why this issue is a day late.

Last week, I tore my ACL after taking a bad landing during practice for a gymnastics meet I was supposed to compete in this week. Everyone who hears about it wants to tilt their head and make some comment about getting older, which pisses me off because this injury was the result of gravity and physics, not age. The only time I’ve been feeling my age is when I look around at the world and simultaneously think, my god, I’ve been around long enough to see the bullshit double back on itself and come back again and also I’ve still got a lot more of this left to go.

In theory, anyway.

I can’t say I’ve been thriving over the past eight months, and this injury and its long road to recovery isn’t exactly righting me on the road to flourishing. I’m not looking to beleaguer you for pity or words of encouragement. They’ll roll right off me and I don’t want to hear it. I only bring it up to convey the state of mind I’m in, which is probably why I’m purposely picking a public fight with Harvard psychiatrist Roy Perlis, who with all his Ivy League wisdom, truly thinks it’s a good idea to make antidepressants available over the counter.

On April 8, Stat News posted an opinion piece by Perlis titled, “The time has come for over-the-counter antidepressants,” wherein Perlis argues that antidepressants should be available without a prescription, just like ibuprofen or laxatives. (Don’t bother rewarding Stat with views by clicking the link. I’m going to break it down below.)

As sure as I am about the overall harm caused by casual, mass psychiatric drugging of the human psyche, I still leave the door open for counterarguments. I consider it part of my duty to stick to my guns only if they’re loaded, which means forcing myself to get out of the echo chamber and hear opposing opinions. So I read the piece, expecting a Harvard professor to at least make a well-substantiated argument, even if I didn’t agree with it.

Instead, it’s 900 words of one of the dumbest, most poorly cited pieces of “journalism” I have ever read in the mental health space. And that’s saying a lot, given the drivel that comes from pop-wellness websites.

Let’s take a look, paragraph by paragraph. Perlis begins:

Anyone can now walk into a pharmacy in the United States and buy oral contraceptives over the counter without a prescription, thanks to the FDA’s approval of norgestrel (Opill). This change reflects the drug’s safety and the public health imperative to ensure wider access to birth control. But another safe class of medicine that addresses a massive public health need remains unavailable except by prescription: the antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

Let’s start with the immediate oddity. Why in the world is Perlis comparing an SSRI to hormonal birth control? What do these things have in common other than being a political football? If he’d instead compared an SSRI to over-the-counter supplements that act on the serotonin system, like St. Johns Wort or tryptophan, then maybe we have the basis for a relevant argument. Instead, he chooses birth control (in all likelihood to signal that he is not one of the Bad Men who took women’s rights away) and throws the word “safe” in front of both of them, as if there is any 100% safe medication. All interventions carry risk, and half the point of a doctor is to assess whether the risk of treatment outweighs the risk of the illness. Perlis sort of addresses this later in the article, but even by using the word “safe” in such a casual way, he is grossly generalizing while also patronizing readers.

These medications, which have been used in the U.S. for three decades, have repeatedly been shown to be safe and effective for treating major depression and anxiety disorders.

There’s that word again, right above the fold. Note how there is zero reference to support this. We are supposed to take his word because of the letters after his name. When someone else on Twitter pushed back against the safety claim with a study questioning antidepressant safety, Perlis chastised the user for “spreading misinformation” and then linked a meta-analysis he co-wrote along with a dozen others as evidence for antidepressant safety. I looked that paper over and noticed that at least half of the authors had declared conflict of interest statements. I responded to the tweet, asking Perlis why he would use a paper with so much declared conflict of interest to support a pro-pharma argument. Perlis blocked me along with the original user who called him out, and his response with the problematic paper is now deleted.

Perlis goes on to list the usual mental health woes including increasing rates of depression, long wait times for mental health services, and oddly, telehealth services whose quality of care is “difficult to measure.” He does not elaborate on how removing any clinical professional from the equation would improve measurement, but that’s par for the course for this dialogue, so I’m going to blow past it and focus on more egregious issues.

In reality, many OTC products treat symptoms or rely on consumers to diagnose themselves — think yeast infections, acid reflux, or respiratory infections. In the case of major depression or generalized anxiety, screening surveys have been developed for primary care that could help people determine their likely diagnosis with at least the degree of confidence of many OTC applications.

Ah yes, the screening survey. In no other area of medicine does a doctor make full diagnoses and prescribe solely based on a patient’s answers to a handful of leading questions. It’s working so well, too! People are thriving after being asked if, in the past two weeks, they’ve felt hopeless. Please circle “a little, sometimes, a lot of the time, or all the time.” And after you do that, we’ll give you a drug for the despair we can’t measure and convince you it’s your brain chemicals, stupid.

What about use or misuse? Depression is associated with increased risk for suicide, and medication overdose is among the most common methods of suicide. But walk through the aisles at your local pharmacy and pick any given medicine off the shelf: the odds are good it is more dangerous in overdose than an SSRI. Fatal overdoses are far more likely to involve drugs other than antidepressants.

Here’s where he really starts to lose me. Perlis uses overdose to defend his reasoning for the safety of SSRIs, claiming that it is more likely to overdose on other OTC drugs rather than SSRIs. This is bizarre because a Harvard psychiatrist should know that most people commit suicide by firearms or hanging and that even amongst poisonings or overdoses, people aren’t using their bottle of Zoloft to do it.

I’m unclear if Perlis was trying to make the argument that antidepressants are less fatally toxic at high levels than other OTC drugs, or if he’s trying to create a red herring that distracts people from the fact that suicidality and suicidal thoughts can be induced by antidepressants. I initially thought it was a poorly constructed argument for the former, but the next paragraph muddles it.

Among people age 25 and older, there is clear evidence that taking antidepressants does not increase the risk for suicide — in fact, the risk of suicidal thoughts or acts is reduced in this group, particularly among those 65 and older. For those younger than 25, the risk for suicidal behaviors or thoughts in clinical trials was modestly greater than that of placebo. So buying SSRIs over the counter could be restricted to people 25 and older, at least at first, just as some states restrict OTC pseudoephedrine (Sudafed) purchases to people age 18 or older.

Perlis is pulling data from a review by the FDA that examined the effects of black box warnings on antidepressants. Thanks to this study and others, it is well known that antidepressants increase suicidality significantly in younger populations. (A recent study used to approve the use of Lexapro for 7 to 12-year-olds documented a 6x increase in suicidality among kids who were put on the drug…and yet it was still approved by the FDA. See Dr. Roger McFillin’s take on that absurdity, here.)

It is incomprehensible to me that a psychiatrist in good standing would not only suggest a drug with a black box warning should be available over the counter, but that we can mitigate that risk by simply ID’ing whoever is buying it, as if the drug couldn’t then just be given to those under 25 as soon as the buyer walks out the door.

If Perlis ever grants me the interview I asked of him on Twitter**, my first question would be this: If some fifteen-year-old hangs themselves two weeks after starting OTC sertraline bought for them by their parents, who is responsible? The kid? The parents? Or the teller ID’ing folks at CVS?

Another objection to over-the-counter SSRIs is that not everyone believes in pills for depression. Some still question the biological basis of this disorder, despite the identification of more than 100 genes that increase depression risk and neuroimaging studies showing differences in the brains of people with depression.

Perlis goes on to draw an odd line between people not “believing” in the biological basis for depression and a study that looks at neuroimaging biomarkers as well as a Scottish study that concluded that people who “carried over 100 [changes to their DNA] were much more likely to develop the disorder in future.”

First off, the neuroimaging study he linked was connected to identifying the individuals who are most likely to benefit from targeted neurostimulation therapies, NOT antidepressants, which makes that reference null. Second, even if we did have the ability to easily test for these 100 or so mystery genes that cause depression (according to one study), does Perlis expect every person who walks into a CVS to have completed a full neuroimaging evaluation or DNA test before purchasing their sertraline with their toilet paper? If not, then how can you argue that this would be a broadly effective strategy?

To be sure, there are alternatives to pills. Certain talk therapies, like cognitive behavioral therapy, can be as effective as antidepressants, and some people prefer talking with a therapist to taking a medicine. But not everyone: weekly visits for eight to 12 sessions or more can entail substantial time and money. Here too, access to psychotherapists is a massive problem, particularly for individuals who seek to use insurance, or have none.

What this is saying is that Perlis is perfectly okay mass drugging lower-income folks under the guise of do-gooder benevolence. Please refer to the rise of Nazis for historical precedence on how that works out.

No treatment works for everyone, but around one in three people with depression get well with an initial antidepressant medication. Allowing over-the-counter access is not a panacea, but could open the door to a safe, effective, and inexpensive treatment for many who need it.

Perlis uses the STAR*D trial to report that one in three people who take antidepressants get well. Putting aside the recent calls to retract the STAR*D trial results due to significant violations of the originally submitted research protocol, Perlis’ own argument still suggests that the majority of people do not improve on antidepressants. Yet his strategy would expose 2 out of 3 people to iatrogenic risks and side effects of these “safe” drugs including but limited to suicidality, violent aggression, irreversible sexual dysfunction, mania, and damage to fetal development.

What’s needed to make this happen? An SSRI manufacturer with the courage to engage with the FDA and invest the necessary resources for a prescription-to-OTC switch, a well-trod path that has previously included medicines for allergies, acid reflux, and emergency contraception, among others. This process would primarily involve studies to prove that consumers can understand and follow the medication label, not new clinical trials, because more than three decades of evidence shows that SSRI antidepressants are safe and effective.

Perlis closes with a call to action from pharmaceutical companies, convenient because it absolves him of any downstream responsibility. He also continues to push the thread that depression is just as simple as contraception or acid reflux, even though those ailments occur due to a single, easy-to-explain mechanism. The same cannot be said of depression. Even in a world where biology was the sole explanation, it involves various processes (and apparently, over 100 genes) which means no single antidepressant would be suitable for all.

**Since Monday, this article is making its way around Twitter and I’m now not the only one picking a fight with him. However, in an odd twist, Perlis agreed to an interview with me. We’ll see if that materializes.