Informed Consent: SSRIs

About 50 million Americans take antidepressants; are they provided an accurate risk/benefit breakdown?

Feb 14, 2024

Disclaimer:

I am not a doctor, much less your doctor; don’t consider this article medical advice. Although I have criticisms of SSRIs, I have also worked with many patients who reported life-changing benefits from them, and these experiences are valid.

Don’t let anyone tell you that you need to be on an SSRI for the rest of your life, but know that stopping abruptly can be a disaster, even deadly. The process of reducing or stopping an SSRI can take several months to years. If your prescriber doesn’t understand this, find a new prescriber who is familiar with hyperbolic tapering or is willing to learn.

Summary

In clinical trials, SSRIs are, at best, only marginally more effective than placebo
SSRIs are more effective at causing sexual dysfunction than they are at treating depression, and sexual side effects can be permanent (called PSSD - post-SSRI sexual dysfunction)
The overall side effect profile of SSRIs parallels depression itself, creating a situation where patients harmed by their medications are sometimes dismissed by prescribers for being “mentally ill, “somatic,” or “dramatic”
Withdrawal from SSRIs can be prolonged, horrific, and misunderstood as a “return of the illness”

In Depth

Common SSRIs:

Citalopram (Celexa)
Escitalopram (Lexapro)
Paroxetine (Paxil)
Sertraline (Zoloft)
Fluoxetine (Prozac)

When Prozac hit the market in 1988, it wasn’t the first SSRI, but it became part of a cultural phenomenon. Through a brilliant marketing campaign by Eli Lilly, the “chemical imbalance” hypothesis of depression became mainstream. It changed American society.

Serotonin became commonly understood as the “happy chemical.” 80% of the general public still believe this.

It gave new validity to a specialty in medicine that was of bad repute by characterizing depression as a medical condition with a medical solution. Psychiatry has long been looked down upon by “real” medical doctors.
About fifty million Americans are currently taking an antidepressant

How valid is the science behind the “happy chemical” narrative? There are true sources of chemical imbalances that cause depressive symptoms, including:

Hormonal

Thyroid
Estrogen, progesterone
Testosterone (yes, women too)

Vitamins

B12, B6
Folate
Vitamin D

These are all objectively measurable chemical sources of depressive symptoms; how does serotonin compare? Three and a half decades after Prozac hit the market:

Rates of depression and suicide have been going up for decades, especially amongst youth
Suicide remains a top cause of death for working age adults

If SSRIs are effective, and increasing numbers of people are taking them, why are suicide rates climbing? What’s the state of the science around SSRIs?

Let’s begin by looking at the FDA’s Page Packet Inserts (these are required to be distributed with bottles of antidepressants for reference by prescribers and pharmacists); surely they will explain that SSRIs fix a chemical imbalance that is causing your depression, just like the commercials said, right?

From the FDA website - Page Packet Inserts, 2024

Mechanism of Action:

Prozac
Although the exact mechanism of PROZAC is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.
Paxil
The mechanism of action of PAXIL in the treatment of MDD, SAD, OCD\, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT).
Citalopram
The mechanism of action of citalopram HBr as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).

“Unknown,” “presumed to be…” Not exactly brimming with confidence, are they? Keep in mind, the serotonin hypothesis originated roughly 70 years ago - long enough to generate some evidence of its validity, right?

Well, apparently not:

The serotonin theory of depression: a systematic umbrella review of the evidence

Journal of Molecular Psychiatry, 2022, Moncrieff et al., University College London

This umbrella review looked through an enormous body of evidence, including studies on:

Serotonin
Serotonin metabolite 5-HIAA
Concentrations in body fluids
Serotonin 5-HT1A receptor binding
Serotonin transporters
Brain imaging studies
Post-mortem studies
Tryptophan depletion studies
Gene associations studies
Environment interactions studies

Their conclusions?

Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.

Ouch. Has the marketing team at Eli Lilly been notified? The authors go on:

The chemical imbalance theory of depression is still put forward by professionals. …
The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs.
This review suggests that the huge research effort based on the serotonin hypothesis has not produced convincing evidence of a biochemical basis to depression. This is consistent with research on many other biological markers. We suggest it is time to acknowledge that the serotonin theory of depression is not empirically substantiated.

This language is how authors of clinical research kindly call out their colleagues for being full of shit.

Let’s apply what we’ve learned to a real-world scenario:

John is a 24 year old man who had the good fortune of scheduling two clinic appointments on the same day. First, he sees a doctor in urology:

“Doc, it’s embarrassing, but I’m having trouble in the bedroom,” he explains. “I finish way too fast. I’m not happy, she’s not happy… is there anything that can help?”

“Absolutely,” says Dr. Glaxo. “I have a highly effective medication for that. If you take it an hour before you head into the bedroom, it will cause genital numbing and should help with your problem.”

After a brief discussion about possible side effects, John makes his way to his next appointment.

“Thanks for seeing me,” John says to his PCP (Primary Care Provider), Dr. Lilly. “The waitlist to see a psychiatrist was months long, and I’m not sure I can wait.”

John explains how he has had worsening symptoms of depression: anxiety, insomnia, disengagement from previously enjoyable activities, emotional blunting, even some gastrointestinal issues. It’s not his doctor’s usual wheelhouse, but luckily he has a tool: the PHQ-9 Depression Scale. John scores high enough to make his doctor comfortable making a tentative diagnosis of depression, landing John into the prescribing algorithm.

“We’ve got some effective medications for depression that have been around a long time,” Dr. Lilly explains.

John receives a Patient Education Handout and is a little bothered by the list of side effects, because they sound remarkably similar to his depression itself: GI issues, headaches, sleep issues, emotional blunting, weight gain - even suicidal thoughts. These side effects can happen right away, but it takes at least a few weeks for it to help with depression; weird. There was also a separate section specifically about sexual side effects that just included a vague statement “if you experience sexual side effects, talk to your doctor.”

If you haven’t figured it out yet, yes, John was prescribed the exact same medication by both doctors. SSRIs can often cause the same side effects of depression itself, and are particularly effective at causing sexual dysfunction. To their manufacturers, this is a marketing opportunity, not a red flag, because they always prioritize profits over outcomes. Yay, we can sell our medication for multiple diagnoses! Cha-ching!

Hey John, now that you’ve started an SSRI, put on weight, lost sleep, have headaches, and been numbed both sexually and emotionally, how’s your depression?

The PHQ-9

Let’s discuss the depression scale John completed, the PHQ-9. Where would you assume this originated? A panel of respected psychiatrists? That was my assumption, and I’m already cynical about the mental health establishment.

Howard Kroplick was a marketing man for Pfizer who came up with the PHQ-9 shortly after they released the SSRI Zoloft in 1991. The purpose? With a shortage of psychiatrists available to prescribe their new antidepressant, Pfizer wanted to make PCPs comfortable prescribing psych meds. Voila, a screening tool was born in the marketing department of a corporation repeatedly convicted of fraud and racketeering.

How well is this strategy working? For Pfizer, it’s working great:

Patient Health Questionnaire-9 scores do not accurately estimate depression prevalence: individual participant data meta-analysis

Journal of Clinical Epidemiology, February 2020, Levis et al.

Conclusion: PHQ-9 ≥10 substantially overestimates depression prevalence.

Pfizer, the company that holds the record for the largest felony criminal fine in history, developed an SSRI that their own clinical trials showed was (at best) marginally better than placebo. Then their marketing team developed a biased questionnaire, the PHQ-9, to supercharge prescriptions for it by making primary care doctors more comfortable making a diagnosis of depression. As tens of millions of prescriptions were being written and tens of billions in profits were being made, their clinical trial data was not publicly available to the patients taking it or the doctors prescribing it until a Freedom of Information Act request forced its release. Many in the mental health establishment remain woefully ignorant to this day that the efficacy of SSRIs is comparable to harmless placebos while the side effects are grossly under-researched.

Does this ring of “informed consent” to you?

At my former hospital, our vendor for patient education materials was a company owned by Merck, who has a criminal history only rivaled by their pharma competitors and a death count that would make Mexican drug lords blush. The cause of depression, according to Merck? A “chemical imbalance.”

Here’s how I would change the patient education handouts on SSRIs if I were in charge:

1. Sexual dysfunction

Sexual dysfunction is currently separated from other side effects and very vague - this topic needs to be detailed and include the fact that it can be permanent. Voices of those affected by PSSD need to be amplified.

Here’s what a Patient Education Handout should say about SSRIs:

Common sexual symptoms include:
Genital numbing
Loss of interest in sex (low libido)
Erectile dysfunction (men)
Vaginal dryness (women)
Weak orgasms or inability to orgasm
There are also other side effects that are less common.
For some people, side effects only start after they stop taking an antidepressant. The sexual side effects of antidepressants can be long-lasting (even if you stop taking the medication). There is no known cure.
It can be difficult to know exactly how common sexual side effects are, because depression itself can also impact sexual function.

2. Protracted withdrawal

The term “discontinuation syndrome” was invented because of the negative connotations around the word “withdrawal.” If people thought that SSRIs were addictive, they might be hesitant to generate profits for Pfizer, Lilly, and Merck. Protracted withdrawal is often misidentified as a relapse of original symptoms, which then reinforces the “chemical imbalance” narrative that “you will need to stay on this medication or your depression will return.” Mental health professionals have become more aware of acute withdrawal, but much of the mental health establishment remains ignorant about protracted withdrawal, which can last years and has very little research dollars devoted to it

3. The placebo effect

The efficacy of SSRIs is high - patients often report that they work. But according to the clinical trials for these medications, so do the patients taking an inert placebo - which don’t carry the risks of suicide or permanent sexual dysfunction.

How can a prescriber explain to their patient that their belief that a medication will work is often the only way it can work?

This issue was laid out in damning detail back in 2004 by Irving Kirsch, author of The Emperor’s New Drugs:

Abstract:
Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by the drug companies reveal that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close to any theory in the history of science having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.

On the topic of informed consent and a detailed risk/benefit analysis between a patient and a prescriber, here’s where we’ve landed:

The narrative behind SSRIs is rife with fraud, life-changing side effects, and life-ending side effects (violence towards self and violence towards others). The scope of this disaster is shamefully under-recognized within the mental health establishment. The disinformation playbook being run to promote SSRIs is predictable and has been used effectively for decades with other products, including cigarettes, vaccines, and a multitude of medications. Mental health professionals have a responsibility to their patients to both spot fraud and teach about issues like permanent sexual dysfunction, protracted withdrawal, and the placebo effect. As medical professionals, we must never allow our own ignorance to be a path towards patient harm and pharma profits.

The Good News

I recognize that this article hasn’t exactly been an uplifting read, but there is a paradigm shift happening right now as more mental health professionals recognize the following:

Mental health is metabolic health. Metabolic health is mental health.

Ever heard of the “gut-brain connection?” 90% of your serotonin is in your gut; more and more psychiatrists are turning towards metabolic treatments for their patient’s mental wellness.

To learn more, read Brain Energy by Dr. Chris Palmer, a well respected Harvard psychiatrist.

The Brain Energy theory of depression:

Mental disorders are metabolic disorders of the brain
Metabolic treatments may lead to better outcomes than are currently possible
The “chemical imbalance” hypothesis is far too reductionist - mental health involves massively complex interactions between a person’s nutrition, gene expression, trauma history, and many other factors.

A high-fat, low carb diet used to be the standard treatment for epilepsy, and it was very effective. Now, people diagnosed with bipolar disorder are prescribed… epilepsy meds.

Green Monkeys

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