No, Serotonin Levels Don’t Cause Depression. Yes, SSRIs Are Still Valuable.
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August 5, 2022A recent study review shook the foundations of what we thought we knew about clinical depression, stating that it found no reason to believe low serotonin levels lead to depression.
The new umbrella review — an overview of existing meta-analyses and systematic reviews — published in Molecular Psychiatry, suggests that depression is not likely caused by a chemical imbalance, and calls into question what antidepressants do. Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), which were originally said to work by correcting abnormally low serotonin levels. There is no other accepted pharmacological mechanism by which antidepressants affect the symptoms of depression.
People have been quick to condemn the medical establishment and accuse big pharma of fabricating the whole SSRI situation for money (which, in fairness, would be totally on brand and isn’t necessarily NOT happening).
Now, let me begin by saying that I am a fan of Tucker Carlson and I adore Tulsi Gabbard. But imma need them to stay in their lanes on this one.
Hi, I’m Rachel S. I am an SSRI user. I’ve been on an antidepressant since I was 18, and I need people to not demonize these drugs that have helped me, and many other people, feel better.
Let me start by addressing the study review that I referenced at the start of this article. It seems very cut and dry, right? Low serotonin levels don’t seem to cause depression (and anxiety), therefore medications designed to increase serotonin levels aren’t actually treating depression (or anxiety).
But here’s the thing: The scientific community is still trying to figure out how SSRIs actually work. An influential study (published in Molecular Psychiatry, yes, the same one as the review) from 2020 aimed to unravel some of that mystery, and they found that the key to SSRI effectiveness lies not in increasing serotonin levels, but activating certain genes:
Using a combination of behavioral tests and real-time RNA analysis, the researchers were able to monitor changes in the animals’ behavior and gene expression as they responded to the [SSRI]. Things started to get interesting on the ninth day of treatment: The activity of a gene called c-Fos began to increase markedly, and by day 14 the mice were showing telltale behavioral changes—they were moving around more, for example, and took an interest in food even after being moved to a new environment. The timing was remarkable, [senior research associate Revathy Chottekalapanda] says, because it aligned with well-established milestones in the treatment of human patients.
. . .
As it turns out, c-Fos helps create a so-called transcription factor, AP-1, which activates specific genes by binding to their DNA. . . AP-1 then switches on several genes that promote neuronal plasticity and remodeling, allowing the brain to reverse the neurological damage associated with depression. After two to three weeks, the regenerative effects of those changes can be seen—and felt.
So, look. No, I’m not a molecular scientist, psychologist, or literally any specialist who has any particular insight into these very complex issues. I think it’s enough for us to know that they ARE complex and actively being unraveled.
Is depression caused by a lack of serotonin? It doesn’t seem that way, no. Do SSRIs work by increasing serotonin levels? Well, they certainly do, but it looks like that’s not the key to their effectiveness. Do SSRIs work for everyone? Nope, and Chottekalapanda is working on figuring out why only two-thirds of users respond positively to them.
(On a side note, while some people just don’t respond to SSRIs full stop, it is entirely possible that people who have negative experiences with them just aren’t on the right one. In Tucker Carlson’s clip, he describes the reality of being on an SSRI as “[becoming] numb,” “[losing] a part of one’s self,” and being robbed of “[experiencing] deep joy.” The first antidepressant I took made me feel that way, so I switched to a different one. Alakazam! I am a functioning human.)
The reality is that we’re facing an unprecedented crisis in terms of mental health, the medicalization of normal behaviors, and a culture that is not designed to facilitate mental well-being. Yes, big pharma is unbelievably corrupt. Yes, far too many children are on mood stabilizers. Yes, many aspects of mental disorders and the drugs we use to treat them are still poorly understood. Certainly, there are many connections to be drawn between these intertwining issues.
But turning SSRIs into Public Enemy No. 1 is not a useful one. The drugs are not the problem, doctors who overprescribe them are. Pharmaceutical companies who market them as a cure-all are. Parents who prefer to medicate their child into submission are. But the drugs themselves, while not right for everyone, save lives. Mine included.
And if I see one more “hur durr libz r stupid cuz SSRIs” tweet imma lose my sh*t, y’all, do not test me.
5 Comments
Your doctor gives advice. It is up to you to choose whether you want to follow it. Informed consent includes the bad as well as the good. I have run into a surprising number of doctors who are quite arrogant. I suspect their motivation for entering the field of medicine is financial gain rather than serving their patients. My long-time doctor retired a couple years ago so I scheduled my annual physical with a new doc. When I made the appointment, I said that I thought I was in A-fib. Ho Hum was the response. At the exam I told the doc I thought I was in A-fib. Ho Hum. His thought was that we try to control my heart rate with pills. Then I checked with a cardiologist in Texas. I told him that I was coming from Alaska, and he set me up with three days for him, testing, and cardio ablation. At the exam he said that yep, ablation. Did the scan and stress test the next day, cryoablation the next day and I have been in sinus rhythm since then with a heart rate 0f 64 to 73. the first doc was quite young, and I was 80. With Obama care the standard is age over 70, palliative care only. Keep us happy and let us die. Be skeptical of medical advice and do your homework. I’m looking for a primary care physician, 60 or older. So, I agree with you, young lady.
I’m so glad those are working for you. If you need them, stay put. Mine are a different category, but I’m betting they aren’t sure about them either.
This is an area where people get incredibly arrogant, incredibly fast. Patients need to be very careful. Many people talk about the unconscious as if they have lunch with it every week, but while the idea helps, it is more a matter of faith than the soul. A bunch of theories, such as all the current ones about trans and various other alphabet people, have no actual research or studies, or even serious observation, behind them at all.
If someone is having a hard time finding good help, Focus on the Family has both Christian counselors on the phone and will help you find a Christian psychiatrist or counselor that you can get to: no demanding that you abandon your marriage, parents (non-abusive) or children…… or “gender”.
Agreed, we as patients need to be our own strongest advocates!
First, Rachel, I’m glad that your meds are working for you. I’m no expert either but I am a retired medic and in my experience all meds have different effects on different people. Results can speak to the effectiveness of any drug or the lack thereof. One thing to think about, all drugs are poison and have side effects. A balance between the benefits vs the harm is the basis for the choice and levels of medications for a positive rather than a negative effect. That being said, I have concerns with companies like Pfizer that would not release the jab until granted immunity from civil suit. I’ll have to research the statement that they spend more on advertising than research. If true, that also concerns me. I don’t think a ban on your meds is in the future but there are some legitimate questions that should be answered.
I completely agree, not every med will work for everyone and it’s our responsibility as patients to make an informed choice. That’s why I think it’s so criminal for doctors and pharmaceutical companies to misrepresent themselves and their products. I certainly share your concerns about Pfizer and their ilk; personally, I think the only legitimate role of the FDA is to make sure pharmaceutical companies are being truthful and leave the decision-making up to individuals.
I don’t anticipate any bans either, and I’m eager to learn what researchers like Chottekalapanda find out in the future. I just worry about this particular issue becoming politicized the way climate change and COVID have; that’s a surefire way to rob a scientific pursuit of its legitimacy.