For many years now, I have been extremely confused, bewildered, taken aback, floored, (insert shocked emoji here) about an aspect of taught psychiatric practice that makes zero sense to me on a very basic level.  Yes, you can show me pharma-sponsored studies and you can tell me it is the first-line treatment and the 'standard of care,' but it makes NO SENSE.  Yes, you can tell me they're SAFE and EFFECTIVE, while the alternative is DANGEROUS and TOXIC, but that's not reflected by what I see in my own clinical practice.  Of course, I'm talking about what I'm told by the system to do for my depressed patients contemplating suicide... prescribe an SSRI, or Serotonin-Reuptake Inhibitor (some of which really aren't very 'Selective').

But wait, don't the SSRIs carry a black box warning for children and adolescents?  That they increase the risk of suicide in the first two weeks of starting or increasing their dose?  Wait... haven't their been hundreds of legal cases and lawsuits against the makers of these drugs due to implications of them contributing to suicides, homicides, or violent crimes?  Wait... isn't there another medicine that has proven benefits in reducing the risk of suicide... that has 20-year follow up studies revealing up to 10x protective effect against the worst outcome in all of psychiatry, suicide?  That has proven impact in reducing impulsivity... that is EXTREMELY safe at low doses and offers dozens of other potential mental and physical health benefits?  Of course, I'm talking about lithium, which I was taught only to do as 3rd or 4th line, after trialing multiple SSRIs and alternatives.  Of course, I'm talking about lithium, a drug which still does not have FDA approval for treatment of unipolar depression, despite having some of (in my opinion, the best) the best evidence of a protective role against future biologic depressive episodes and suicide.  Of course, I'm talking about lithium, a drug that has been used medically since the 1870s, and long before that by ancient cultures who recognized its' beneficial properties without the aid of modern scientific tools.

It's almost as if SSRIs were developed and researched at a time when older antidepressant drug classes, TCAs and MAOIs, were running out of exclusivity patents, something no company has ever had on lithium due to its status as a natural element existing in the Earth and seas all around us.  Maybe this was another big pharma push to replace one class of (most would argue more effective) drugs, in the TCAs, with a newer, more profitable class of drugs, that, like so many other pharmaceutical rollouts, appeared 100% safe and adequately effective, per their marketing.  Now, many of those patents have run out... and companies aren't spending as much time or money fighting the stigma around this class of meds due to the vast majority of them going generic.  Companies continue to create 'novel antidepressants' that don't work significantly differently than the older ones.

The suicide side effect is the most serious potential side effect of SSRIs.  When the various companies researching and later promoting drugs like Prozac, Zoloft, Lexapro, Paxil, and others, did their clinical trials seeking FDA approval, many of them had to do way more than the 2 required trials due to initial trials failing to separate significantly from placebo.  Additionally, there were some clinical trial gymnastics occurring in later trials, due to a pesky problem that kept emerging: there were too many clinical trial participants thinking about or trying to kill themselves in the SSRI arms.  A few cartwheels and somersaults later, these pesky suicidal patients were deemed to have a 'concurrent illness,' determining they were undiagnosed bipolar disorder patients after-the-fact, and therefore should not be included in the final clinical trial results, allowing the companies to claim a comparable number of suicidal events in both SSRI and placebo arms of the trials.  This way, they can publicly state there was no difference in the # or severity of suicidal events in both trials.

Some will argue that the SSRIs only cause this type of suicidal reaction in adolescents.  I firmly stand by my scientific opinion that the drug doesn't know and doesn't care when someone turns 18 years old... with so many court cases involving adults (both young and old) between the time of this class of drugs' emergence and now, implicating them as contributing factors in suicides, homicides, and other crimes, and the prerogative of pharmaceutical companies to settle these cases (as opposed to any sort of public trial), it pretty much solidifies my opinion on this lifeline industry opinion.

Others, including those removing 'concurrent illness' patients from the original clinical trial data, will argue that SSRIs only cause a 'manic-type' reaction with potential suicidal action, in bipolar patients, and you simply need to avoid, or be very careful, prescribing them to this population.  Unfortunately, there's not some biologic or blood marker of folks who are bipolar.  They are not easily identified, and sometimes, they are only identified BY HAVING these types of reactions to SSRIs or other psychiatric medications.  The term 'bipolar disorder' itself is a pharmaceutical promotion and is not even consistent with the scientific understanding of what it is, with manic-depressive illness spectrum better conceptualizing what biologic depression is, only requiring patients to have significant fluctuations in their mood interspersed with periods of normal mood, not mandating they have both manic AND depressive episodes.  I've seen and heard of these reactions occurring in patients with major depressive disorder (some of which, again, would have previously been diagnosed as manic-depressive, though many with neurotic, or anxiety-driven depression being included in this newer classification system, muddying the waters of who would respond better to antidepressants vs anti-anxiety meds for their condition) without any history of mania or hypomania.  And, the average age of onset of bipolar disorder (which mandates having a manic or hypomanic episode, usually occurring after the onset of multiple depressive episodes) is 22 in males and 27 in females.  Bipolar, or Manic Depression, is a neuro-developmental condition that most often emerges after puberty and it is impossible to be 100% correct and accurate in diagnosing it versus major depression. 

So, these arguments fail to convince me that I should be using more SSRIs, especially as a first-line agent.  And, I haven't even talked about the 50+% rates of sexual side effects, some of which persist for months to years in a condition called PSSD, or Post-SSRI Sexual Dysfunction.  I have seen patients develop severe gambling addictions, worsening alcoholism, and pornography addictions after being started on SSRIs, though drawing a causative link is incomplete and difficult.  We're just scraping the surface of possible problems, from visual impairments, to metabolic syndrome, to extreme apathy and emotional numbing, to name a few.  Not to mention there is not robust, independent, and reliable data proving long-term efficacy of SSRIs, and there's even some data indicating irreversible cellular changes that worsen the long-term courses of depression and anxiety.

I'm not saying these medications have no clinical utility, but they need to be used with extreme caution and in neurotic, not biologic, depression, as they function more like anti-anxiety meds than antidepressants (though anti-anxiety meds had a bad rap at the time of SSRIs emergence, coming off the Valium and benzo disasters of the 1960s, 70s, and 80s).  If 1/10 patients started on an SSRI becomes suicidal (Dr. Healy would argue it's even higher than that), and I'm putting 10% of my patients started on this class of drugs at risk of killing themselves... is it worth it?  What if that number was 5%?  1%?  Of course, depressed patients are going to at higher risk for suicide per the natural course of their illness, but why wouldn't I prescribe an anti-suicide drug (LITHIUM) right off the bat... even if I need to pair it with a faster-acting agent?  A drug that can have potent anti-suicide effects even at low, and extremely safe, doses.  A drug that all of us are exposed to at minute levels on a daily basis through our food and water supply, therefore we know there is some level of tolerance to it.  These are very straightforward and basic concepts... use the anti-suicide drug for patients that are suicidal... don't use the pro-suicide drug for patients that may be at risk of suicide... yet these concepts are not widely taught as part of psychiatric dogma.  And that is fucking crazy.  It's almost as if the system prioritizes profits over patient care and scientific progress... that despite rising rates of suicide, drug overdoses, obesity, etc, we continue to peddle the pharmaceutical drivel they call 'quality data,' AT THE EXPENSE OF OUR PATIENT'S WELL-BEING. 

Now, moving forward, big pharma doesn't give as much of a damn about this class of drugs anymore as they're not nearly as lucrative as in the past.  They will undoubtedly give way to a new class of antidepressants... right now that appears to be psychedelics, which will undoubtedly be most effective in neurotic, or anxiety-driven depressed patients (who, in the past, were not considered depressed, had a low risk of suicide, and tended to improve with non-pharmacologic therapy... which was not very lucrative for big pharma).  They will likely also cause psychotic reactions in undiagnosed bipolar patients, and us providers on the front lines will be responsible for determining their long-term efficacy and impact on reducing suicide risk (part of pharma's playbook is to gather subjective data in asking patients how suicidal they are after getting the drug treatment, but failing to follow up with long-term objective data comparing the # of suicides in the treatment vs placebo group 1-10 years down the road).  And lastly, their highest benefit/risk ratio likely will exist with periodic use (limiting risks of dependence and tolerance) to help expedite the therapy process and overcome mental blocks in life... but this is not conducive to making money and I don't doubt the companies backing these treatments will try to promote a daily use of psilocybin and related compounds.

Again, how many times will we see similar stories playing out over and over again?  I think we are less trusting of big industry than in the past, but I hope we start engaging in action, demanding change at a government regulatory level, or demanding overhaul of our politicians only concerned with funding their next big campaign push.  At the end of the day, THIS promotion of antidepressants needs to be viewed in a very skeptical light.  We have got to STOP buying into the idea that there is a silver bullet for psychiatric illnesses, that every new drug that comes out is safe and effective for everybody, so we can actually what patient symptoms, characteristics and genetic profiles respond best to which class of medications, a more phenomenologic and considerate approach than we engage in now.  Otherwise, psychiatry will continue to be laughed at and mocked by other speciality providers, with gradually worsening outcomes in its patient populations.  Mic Drop.


Antidepressant Use in Medicaid-insured youth: Trends, Covariates, and Future Research Needs, Zito, 2020, shows 1987 figures of 0.2%

Antidepressant Use Among Persons aged 12 and over, US, Pratt, 2017

National Trends in the Prevalence and Treatment of Depression in Adolescents and Young Adults, Mojtabai

Comparative Efficacy and Tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis, Cipriani, Zhou, 2016

            -34 trials with n 5260, 14 antidepressants, showing fluoxetine only one statistically significantly more effective than placebo

            -Interpretation: “risk-benefit profile of antidepressants in the acute treatment of MDD, do not seem to offer a clear advantage for children and adolescents”


Healy, D., Le Noury, J., & Jureidini, J. Paediatric antidepressants: Benefits and risks. International Journal of Risk & Safety in Medicine, (Preprint), 1-7

-All 20 trials b/w 1990 and 2005 were negative on primary outcome measures. 2 fluoxetine trials that had provided the foundation for the drug’s regulatory approval and whose outcomes had typically been considered positive, were found to be negative upon review, with an “excess of suicidality on active treatment.”

            -Also included AEs, genital numbing, obstruction of growth velocity, WG, hard time discontinuing, AKITHISIA (a/w violence/suicide)

            -Do endorse some pediatric antiDEP trials in OCD and ‘other anxiety states’ have produced some positive primary outcome results… aka emotional numbing

-15 studies since 2006 were nearly all negative on primary outcome measures

Outside the Black Box: Re-assessing Pediatric Antidepressant Prescription, Duncan


Suicidal events in the Treatment for Adolescents with Depression Study (TADS), Vitiello 2009, 36-week RCT n 439

-MIA: NIMH study known as TADs study, 22% vs 6.7% with a suicide event on SRIs vs placebo, 17/18 who attempted were taking an antiDEP

-Initially unclear based on looking at TADS, however, with 44 “suicidal events” (other times reported as “suicidal ideation” or “suicidal behavior”; I had to count the number of filled in squares vs not-filled-in squares to get MIA’s 17/18 on an SSRI at time of “suicidal behavior,” which I think is an “attempt.”

            -Of 26 “suicidal ideations,” 19 a/w SRI tx

-Author’s conclusion: “most suicidal events occurred in the context of persistent depression and insufficient improvement, without evidence of medication-induced behavioral activation as a precursor.


-Robert Whitaker, Anatomy of an Epidemic, pages 229-246


2012 Cochrane review of SRI use in children/adolescents concludes evidence of increased risk of suicide in patients treated with antidepressants