Fluoxetine, trade-name Prozac, was the first selective serotonin reuptake inhibitor (SSRI)1. Welcome to the Frontier Psychiatrists newsletter. It is a health-themed publication written by a child and adult psychiatrist. I'm doing a series of essays on individual medications, as I have decided not to use them as the mainstay of my psychiatric practice anymore.
I’m focusing on neuromodulation as a first-line treatment. I think it's a better first-line treatment. I didn't learn how to use medication by not thinking about them, prescribing them, or reading primary literature voraciously. Thus, I have spare thoughts to share! I am a thinking process enthusiast—over thought content, any day.
Dr. Faust: I was tempted by the devil, and I know no temptation is tempting unless the devil tells you so….
What the hell did you want my soul for? How do you know I have a soul?…everybody knows the devil is all lies.
It's been a while since Prozac was introduced in 1987. It is easy to forget why it was an exciting medication for Psychiatry. Prozac will not kill you if you take too much of it most of the time. It is not particularly toxic in overdose. The same cannot be said of prior psychiatric medications for depression. Former stars of the pharmacopeia included tricyclic antidepressants (imipramine, desipramine, nortriptyline, etc.).
Prozac is the most popular antidepressant on earth:
Since [1988], fluoxetine has become the most widely prescribed antidepressant drug in the world.
The toxic nature of prior antidepressants is a horrible stroll down bad memory lane, but it is necessary to understand why Prozac was such a big deal.
The older monoamine oxidase inhibitors can—and did2—kill people. Monoamine oxidase inhibitors could do so, accidentally, with a slice of errant pizza3. The wrong ingestion of a common food, like aged cheese, could lead to a hypertensive crisis and death.
Tricyclic antidepressants can cause irreversible heart block in overdose4. This means you have a cardiac arrest and die. The amount of medicine you need for a lethal dose is less than a month's supply. I'm being non-specific for obvious reasons. However, plenty of people did their homework. Often, those people had depression.
Before Prozac, every depressed person who came to see a psychiatrist — if they didn’t spend a decade on the couch as the only treatment— walked out the door with a bottle of pills that could be used to complete suicide. This was not a medical specialty for the meek5. They were EKGs to read. They were serious side effects to manage. There were medical comorbidities. A whole generation of psychiatrists trained as real physicians—a whole year of internal medicine used to be the standard in residency. Now, it is four months. Many did psychoanalytic training, not using medicine at all, and just sitting there for an hour a day, four days a week, with people crippled by suicidal ideation and depression, relatively powerless, no miracle drugs, and the few medication's they did have? It will be like handing every suicidal person a gun and telling them never to use it for anything but hunting as the only option.
Psychiatry was a hard-core medical discipline. Psychiatrists must be comfortable with bad outcomes, ambiguity, and human suffering with limited options.
Lobotomy was a Nobel Prize-winning procedure and surgery at that. A Psychiatrist like Dr. Arthur Sackler, M.D., had to perform it. Yes, one of those Sackler brothers.
He was a Psychiatrist; he worked as the Director of Research at Creedmoor State Psychiatric Hospital, just down the street from where I did my adult psychiatric training. Psychiatrists were specialists who dealt with serious problems and used challenging treatments, which scared other unfamiliar doctors. To themselves anyway. They were odd ducks to other doctors, I’ll wager.
Prozac changed this. It was safe. According to the FDA, fluoxetine has the following approved uses:
Fluoxetine is FDA-approved for major depressive disorder (for patients eight years and older), obsessive-compulsive disorder, panic disorder, bulimia, binge eating disorder, premenstrual dysphoric disorder, and bipolar depression as well as treatment-resistant depression when used in combination with olanzapine.
Prozac didn't work especially well. On average, it didn't work better than any prior medications. In some individuals, it worked well. In others, it didn't do much. To break the narrative fourth wall for a moment, if the argument is over whether antidepressants are better than placebo, then as a bare minimum, we might agree these are not overwhelmingly potent drugs—the defense of barely better than placebo vs. no better? It is a fight where patients are the losers, no matter the outcome.
But…it didn't kill you. The old medicines did. Overnight, the Psychiatrist didn’t need to be quite as terrified of causing the death of anyone they were treating. More tolerable medications that were non-fatal came. Pretty soon, Psychiatrists were referring to themselves as psychopharmacologists. They would…muddle with meds. None of these new medicines worked very well6. What were they? Myriad. Experts needed to ponder receptor occupancy and try one or the other, and then another, and another.
Soon, there were enough barely different medications to fumble, allowing psychiatrists to change how they introduced themselves at fashionable parties. Every newly psychopharmacologist-identified psychiatrist was a triumph of the will…of one man’s copywriting genius. Arthur Sackler, M.D. paid for medical school by copywriting at an advertising agency.7. He almost single-handedly created modern psychopharmacology advertising. General medical doctors started treating people with Prozac. Sometimes, it worked. It didn't kill people.
The dawn of the mental healthification of Psychiatry.
Psychologists— or their professional organization, the American Psychological Association—decided they should also prescribe medicine. Prozac was so safe. People who prescribe medicine get paid a little bit more. The American Psychological Association agreed to work with the US military to develop torture—sorry, interrogation— techniques for prisoners at Gitmo8. The American Psychiatric Association was asked and declined to have its members participate:
Pentagon officials said . . . they would try to use only psychologists, not psychiatrists, to help interrogators devise strategies to get information from detainees at places like Guantánamo Bay, Cuba. The new policy was followed by little more than two weeks, an overwhelming vote by the American Psychiatric Association discouraging its members from participating in those efforts (Lewis, 2006).
The American Psychological Association decided to partner on the torture of prisoners to get the support of the US military in their efforts to get the right to prescribe Prozac and make a little bit more money for its members. There have been extensive reports thereafter, but as the AMA put it in the 2005 Journal of Ethics report:
There was even a small program in the 1990s that allowed DoD psychologists to have prescribing privileges9—a contentious, long-standing scope-of-practice issue between psychologists and psychiatrists.
Prozac and the rest were so exciting (financially) that psychology sold its soul for the privilege. Like most deals with the devil, the rewards were less than one might imagine. Faust, for his part, held out for more than:
In those states [6 thus far— ED.]10, appropriately trained psychologists can be granted the right to prescribe medications. If needed, patients can work with one healthcare provider for psychological testing, psychotherapy, and medication management.
Mental health nurse practitioners could safely prescribe Prozac. Almost anyone can safely prescribe Prozac. It's not going to kill you. The harms it causes, although not trivial, aren't death. They are subtle and common but not too common. It reduces libido. It can cause anorgasmia. People don’t love to talk about those things. Talking about sexual function is for perverts and, maybe, psychoanalysts. It can interact with other medicines. These are risks you can overlook. It's also easy to overlook how frequently it doesn't work well.
Prozac has another important feature, compared to other medicines, which is that it has an extremely long half-life. The drug takes two weeks to build up in your system for one half-life, and five half-lives is ten weeks. If you abruptly stop Prozac, it takes ten weeks until it's out of your system. It is among the least harmful drugs to discontinue abruptly. It’s a slow medicine. Time-lapse, things got better, and the depression got quite a bit better because somebody cared.
That's powerful medicine, no matter what the pill is. Even if you stop Prozac because you feel better, there are few acute withdrawal symptoms with a long half-life. When Prozac came to market, no patient was treated for over a year. A series of discontinuation syndromes— least pronounced with Prozac—was unknowable. Since Prozac was the first of its kind, the severity of discontinuation syndromes was under-recognized11. The rest of the SSRIs12 and SNRIs13 would rectify this excellent pharmacokinetic profile with shorter-acting formulations and more vicious withdrawal syndromes.
Prozac was so safe. Gone were grave discussions about the risk of death by suicide if you took the medicine prescribed. You didn't have to be worried about pizza. Psychiatrists can spend less time with patients! They need to do a “med check.” That could be 15 minutes…Hell, it could be one minute14. You’d make a little bit more money that way, anyway.
Prozac was so safe. Human suffering, however, only continued. A generation of health professionals lost the respect they once had for depression, sorrow, anxiety, and dangerousness, which they previously understood. Prozac was here, and with it, the seeds of the “mental health crisis”—absent anyone who knew might understand what was happening.
Mephisto: Of course, you have a soul,
Do not believe them when they say the devil lies…
Please, dear Doctor Faustus, do not say the devil lies.
—Gertrude Stein, Dr. Faustus Lights the Lights
Thank you for reading. Other installments include Xanax, Klonopin, Lurasidone, Olanzapine, Zulranolone, Benzos, Caffeine, Semeglutide, Lamotrigine, Cocaine, Xylazine, Lithium, dextromethorphan/bupropion and Adderall, etc.
Even that “SSRI” term is, to be a reductionist, branding. “Selective” is a relative term. It’s more selective than tricyclics, which are also reuptake inhibitors but therapeutically less selective. Selective sounds good. It sounds precise. We like the story that we are being precise and selective in our care. However, the selective nature of the 5-HT2A receptor is almost absolutely beside the point for the actual mechanism of action, given the drug still works in animal models with a complete genetic knockout of this whole receptor. Selective and serotonin were BRANDING choices to convince psychiatrists to aspire to the mantle of psychopharmacologists and thus focus more on the products sold by Eli Lilly and other Pharma companies….but it’s not the 5HT2A Receptor:
Giroud C, Horisberger B, Eap C, Augsburger M, Ménétrey A, Baumann P, Mangin P. Death following acute poisoning by moclobemide. Forensic Sci Int. 2004 Feb 10;140(1):101-7. doi: 10.1016/j.forsciint.2003.10.021. PMID: 15013171.
Shulman KI, Walker SE. Refining the MAOI diet: tyramine content of pizzas and soy products. J Clin Psychiatry. 1999 Mar;60(3):191-3. PMID: 10192596.
Kerr GW, McGuffie AC, Wilkie S, Tricyclic antidepressant overdose: A review. Emergency Medicine Journal 2001; 18:236-241.
The biological psychiatric revolution almost started with Julius Wagner-Jauregg’s 1917 Malarial Cure for Insanity. This led to the first Nobel in Medicine for Psychiatry in 1927.
This move to a more biological psychiatry had a persuasive champion in Arthur Sackler. But, ever the marketing pro, pharmacology, and, more to the point, persuasive copywriting would win—potency be damned. Cross-over artists in biological psychiatry and psychoanalysis, like Van Ophuijsen, was a personal friend of Arthur Sackler. They coauthored papers on biological psychiatry (along with the rest of the Sackler brothers) in 1951.
Reference for effect sizes in comparison
He was a copywriter in 1942 at William Douglas McAdams, an ad agency specializing in medicine, a company he would buy in 1947 and revolutionize.
Pope KS. Are the American Psychological Association's Detainee Interrogation Policies Ethical and Effective?: Key Claims, Documents, and Results. Z Psychol. 2011;219(3):150-158. doi: 10.1027/2151-2604/a000062. PMID: 22096660; PMCID: PMC3200196.
Bafflingly, the APA on its own website highlights this DoD program as the first step in the “movement” for psychologist prescribing. 1991–1997: The Department of Defense begins a six-year trial program to train 10 psychologists to prescribe medication at assigned military bases. The program was successful, demonstrating that psychologists can be taught to prescribe safely. Some of the psychologists are still prescribing and appropriately trained psychologists may now be credentialed to prescribe in the Defense Department, the U.S. Public Health Service, and the Indian Health Service.
According to the APA (ed: whitewash propaganda) on the issue: All licensed psychologists are highly-trained, healthcare professionals holding a doctorate (Ph.D. or PsyD) and extensive training in the diagnosis and management of mental illness. Graduate school for psychologists takes an average of seven years, with coursework that includes the biological basis for human behavior.
After receiving their doctorate, a psychologist must complete between 1,500 and 6,000 hours of supervised clinical practice and take a national examination to become licensed (rules vary by state). In some states, a jurisprudence exam is also required.
While each state develops its educational requirements, the training for a licensed psychologist to prescribe is rigorous in all the proposed legislation.
In Louisiana, psychologists must complete a postdoctoral master’s degree in clinical psychopharmacology.
New Mexico requires a minimum of 450 hours of didactic instruction and a 400-hour supervised practicum as part of its eligibility criteria.
In Illinois, psychologists seeking prescriptive authority must complete advanced, specialized training in psychopharmacology as well as a full-time prescribing psychology residency of 14 months of supervised clinical medical rotations totaling at least 1,620 hours in various settings such as hospitals, community mental health clinics, and correctional facilities.
For Iowa, psychologists must complete a postdoctoral master of science degree in clinical psychopharmacology, 400 hours of supervised clinical training and practicum (of which 25% must be conducted in a primary care or community mental health setting) as well as two years of supervised practice involving a minimum of 300 patients.
Idaho requires completion of a postdoctoral master of science degree in clinical psychopharmacology from an APA-designated training program, a supervised practicum in clinical assessment and pathophysiology and a two-year supervised provisional prescribing period.
Psychologists seeking to be prescribers must pass a national exam in psychopharmacology.
After completing their formal training, some prescribing psychologists must coordinate care with a patient’s primary care physician and others must obtain a conditional prescribing certificate before they become fully independent prescribers.
Psychologists are also trained to know when to refer patients for the evaluation of other health problems.
When all the training—doctoral and postdoctoral—is completed, prescribing psychologists have more training in diagnosing and treating (including prescribing) mental health disorders than primary care physicians.
Thanks to its superior pharmacokinetics.
Tonks A. Withdrawal from paroxetine can be severe, warns FDA. BMJ. 2002 Feb 2;324(7332):260. doi: 10.1136/bmj.324.7332.260. PMID: 11823353; PMCID: PMC1122195.
Campagne DM. Venlafaxine and serious withdrawal symptoms: warning to drivers. MedGenMed. 2005 Jul 6;7(3):22. PMID: 16369248; PMCID: PMC1681629.
With complexity-based billing, this is factually true and is paid the same as 15 min of time-based medical care, and more per day if you can stand it.
I read your article. I have BiPolar type II. Before that, my diagnosis was Major Depressive Disorder. For that I was prescribed Paxil 50-60mg. After the change in diagnosis 200mg Lamotrigene was added. To make a long story short. I'm 65, and have been living with the above since my early thirties, and probably my adolescence as well. I was prescribed antipsychotics but discontinued due to side effects. I will not consider Lithium, electro-schock etc. due to side effect profiles. I'm able to read the clinical trials, papers, literature, etc. due to my educational background. I find your article a truthful, summary based on your clinical practice, experience and review of applicable data. After living with the above , approximately for my entire life I've come to some realizations. The relief I receive from my Rxs are minimal at best. The cyclic nature, and depth of my depressive syndromes are getting more severe and intense. I have a feeling Psychedelic Rx and therapy in a clinical setting will yield some postive results for a limited amount of time, maybe 6 months to 1 year. So, I'm debating whether to go there. I'm in full agreement with your article. So far, BiPolar Disorder is lifetime, chronic and current medical treatments are at best, yielding some symptomatic relief, and clinically no more effective than placebo. I really have no choice, I have to deal with my mental illness as best I can. So, I'm still searching for symptomatic relief. Any ideas, feel free to email me at: brucedetorres@gmail.com, or call: 786-616-4978. Thanks for your article. You said it with transparent, clear facts and assessment. I think if you're able to get your article out to more widely read outlets, you will be helping many sufferers and people dealing with this terrible illness. Again thanks.