This blog is to accompany a past series release titled, "Antidepressants - Going Backwards" with British-turned-Australian psychiatrist, neuropharmacologist, and clinical researcher, Dr. Ken Gillman. Moving forward, I will post transcripts of my conversations with guests under each episode heading and a blog post with SOURCES (at the bottom) on the first episode of the installment. Here is a link to Ken Gillman's website (https://www.psychotropical.com/), as well as a brief bio at the bottom of this post. I highly encourage you to check it out as it provides a wealth of knowledge, whether you're a clinician, patient, or anywhere in between.
This series is about MAOIs, or MonoAmine Oxidase Inhibitors. It tells a story about the evolution of how we diagnose and treat depression over the last 70 years. From the emergence of MAOIs in the 1950's and the concepts of biologic vs neurotic depression, to the transition to the TCAs and eventually, the SSRIs in the 1990's. The separation of how we used to classify depression into biologic and neurotic subtypes was very useful for guiding treatment. The changing nomenclature has been extremely detrimental to our conceptualization and treatment of depression (and anxiety, and other forms of mental illness).
Biologic depression tends to run in families and has predominant symptoms of low energy, low motivation, and anhedonia, or the inability to derive pleasure from things that normally give you pleasure. If you've ever seen Winnie-the-Pooh, the character Eeyore provides an appropriate example of what a biologically depressed person looks like; they move slowly, they speak slowly, they may lay in bed for hours without actually sleeping, ruminating and perseverating internally on the same issues exhaustively (though it's not all bad as these patients tend to be more realistic, and less susceptible to exploitation, such as by 'snake oil salesmen'). These symptoms indicate a major role for the neurotransmitter Dopamine in treating the condition, and ultimately and most importantly, reducing people's risk of suicide. There is a biologic, or genetic, component to this type of depression; it tends to run in families, and carries a high risk of suicide. This form of depression used to fall into the category of 'manic-depressive' illness, which was also a more appropriate conceptualization. Patients with this condition (which now has been separated into bipolar disorder and 'unipolar' depression aka major depressive disorder) are considered generally to have a 'mood disorder,' with weekly to monthly fluctuations in their mood. It could range from manic (high energy, low sleep, goal-directed, grandiose, creative and imaginative but also at its severe end potentially psychotic and delusional) to euthymic ('normal' mood) to depressed (as described above), but any given patient did not have to experience all three. They simply fluctuate periodically BETWEEN at least 2 of the 3, including patients who experienced mania followed by euthymia OR depression followed by euthymia OR mania followed by euthymia followed by depression.
This distinction is SO important as it guides our treatments. Mood stabilizers like Lithium and Lamotrigine can be very effective at preventing relapses and minimizing these fluctuations. Dopaminergic agents like MAOIs and stimulants can be much more effective than serotonergic agents (most well-known and common being the SSRIs like Prozac, Zoloft, Lexapro, PAxil, etc.) during the depressive fluctuations. This distinction also helped us to label the conditions and thereby the patients who are most likely to die by suicide.
None of this is to say that treating what's sub-typed as NEUROTIC depression is not important. We all have exacerbations of our mood state based on what we experience in life (and the crazy amount of information our minds are exposed to that makes us constantly feel like we are responding to threats OR not doing everything we can imagine, what I call the proactive-survival parts of our mind). But, these exacerbations based on things happening in our lives that we just don't like OR can't tolerate require a different form of treatment. Typically, this starts with THERAPY, and in my opinion and experience, is more driven by anxiety and feelings of being overwhelmed, than by a biologic shutting down mechanism. The symptoms, and therefore the treatment, are different. They are more likely to respond to medications like SSRIs, which are much more effective in alleviating symptoms of anxiety due to their numbing effects.
Whereas the biologically depressed person that is considering suicide and starts an SSRI may experience emotion-numbing effects that can reduce their anxiety about attempting suicide enough to allow them to engage in an attempt. This watering down of the diagnosis and pushing SSRIs as a first-line treatment option for everyone is inevitably doing more harm than good, but it's done a hell of a lot of good for the pockets of big pharmaceutical company executives and shareholders.
This is the shit, as a psychiatric provider and a person that cares about other human beings and the general positive progress and evolution of our society, that really pisses me off; when the greed of a few impacts the longevity and fulfillment of the society.
Ken Gillman has been fighting this fight for a long time. I'm relatively new to it. In this series, he also reveals some of the fraudulent practices that go into 'making research work,' or appear efficacious, with clinical anecdotes and outcomes not correlating to what the research claims. He understands that the way the system operates is driven by monetary goals, that oftentimes the promise of HOPE is used on consumers to consume more drugs and medications. He emphasizes the need for empowering conscientious physicians and researchers to have the final word and say on what is safe and effective and gives several historically relevant examples of data manipulation and fraud. He shares the same disdain for some of the ways our system operates as I do, but has decades more experience working within its' constraints.
I stumbled across Dr. Gillman's work by listening to David Puder's podcast, "Psychiatry and Psychotherapy" and was immediately drawn to his brazen nature about the shortcomings of our field. When he appropriately labeled an excess of serotonin as a toxicity rather than a syndrome, I knew he could be trusted as a critical thinker and wanted to hear more about his professional views. He is very well-known and respected throughout the field and I have already learned so much from he and his associates, including the MAOI Roundtable, an email chain of researchers and clinicians that use MAOIs, and also discuss numerous other aspects of our field.
I hope you enjoy the series and learn a little about how our medical and research system works here in America, so you are educated to make the best possible decisions with your doctors/providers as possible in this very uncertain world we live in.
-Ethan P. Short, MD
SOURCES for this episode (in no particular order):
https://journals.sagepub.com/doi/10.1177/0141076813486262
Depression and Anxiety in Babylon, Edward Reynolds
https://journals.sagepub.com/doi/10.1177/070674377902400811
Depression and Loss: a theme in Robert Burton’s “Anatomy of Melancholy”, Brink
https://pubmed.ncbi.nlm.nih.gov/16594840/
Ben Franklin and shock-induced amnesia, Finger and Zaromb
https://www.verywellmind.com/who-discovered-depression-1066770
The History of Depression: Accounts, Treatments, and Beliefs Through the Ages, Nancy Schimelpfening, medically reviewed by Amy Morin, LCSW
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136031/
Antidepressants: From MAOIs to SSRIs and more, Ramachandraih
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949440/
Gordon Parker, Is Depression Overdiagnosed? Yes
-in response to article titled, Is depression overdiagnosed? No
https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00113/full
Antidepressant Use in Medicaid-insured youth: Trends, Covariates, and Future Research Needs, Zito, 2020, shows 1987 figures of 0.2%
https://www.cdc.gov/nchs/products/databriefs/db283.htm
Antidepressant Use Among Persons aged 12 and over, US, Pratt, 2017
https://pubmed.ncbi.nlm.nih.gov/27940701/
National Trends in the Prevalence and Treatment of Depression in Adolescents and Young Adults, Mojtabai
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30385-3/fulltext
Comparative Efficacy and Tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis, Cipriani, Zhou, 2016
Healy, D., Le Noury, J., & Jureidini, J. Paediatric antidepressants: Benefits and risks. International Journal of Risk & Safety in Medicine, (Preprint), 1-7
Outside the Black Box: Re-assessing Pediatric Antidepressant Prescription, Duncan
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702701/
Suicidal events in the Treatment for Adolescents with Depression Study (TADS), Vitiello 2009
-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
https://doi.org/10.1136/bmj.h4320
Restoring Study 329: efficacy and harms of paroxetine and imipramine in the treatment of major depression in adolescence, 2015, LeNoury, BMJ
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC539828/
FDA to review “missing” drug company documents, Lezner, 2005
More information about Dr. Ken Gillman:
https://www.psychotropical.com/
I am Dr Ken Gillman, a psychiatrist and clinical neuro-pharmacologist. My website provides free expert analysis and information about psychotropic drugs, based on my peer reviewed publications. I am the founder of the International MAOI Expert Group , the chairman of its Presiding Council and the senior author of the new MAOI guidelines.
Current professional status
- Principal investigator and director at ‘PsychoTropical Research’
- Chairman of the presiding council of the International MAOI expert group
My team and I publish papers in my areas of special expertise in the peer-reviewed scientific literature. (See google Scholar)
I am regarded as a world authority on serotonin toxicity, monoamine oxidase inhibitor (MAOI) antidepressant drugs and related topics.
Research publication information
I have an H-index of 29 and a cumulative total of more than 4,500 citations. I have about fifteen major single-author review papers that have been extensively cited (between 100-500 times).
I am the founder and convener of the International MAOI Expert Group; I am also the chairman of its presiding council.
I am an invited expert-participant in the Malignant Hyperthermia Association of the US (MHAUS) expert group.