Readers of The Frontier Psychiatrists are aware— because they can't help it— that when there isn't breaking news about United Healthcare, Owen Muir, MD, DFAACAP is excited to write about chemistry. Particularly, organic chemistry. Today is a huge disappointment. Magnesium, as an element on the periodic table, contains no carbon. Carbon-containing molecules? That's what organic chemistry is made of! This is general chemistry at best. However, it gets over the hump to get into this newsletter by virtue of “data to evaluate, related to its efficacy in the treatment of depression.” Welcome to my daily newsletter about health-related topics.
Programing Notes:
1. May 5th, 6-9 PM is Rapid Acting Mental Health Treatment NYC LIVE. Get Those Tickets!
I’m a practicing psychiatrist. Psychiatric appointments are available at Fermata, in Brooklyn, NY by clicking here.
I also work at Acacia Clinics in Sunnyvale.
My boss there, David Carreon, M.D., just wrote a book—The Opposite of Depression, which you can buy here (affiliate link).
I pried open the paywall on a lot of the older content for now, so please, read and enjoy 200+ more articles now available to share.
Magnesium plays important roles in biological systems—those that contain carbon! I'm a carbon fan-human over here.
For example, if you're at risk of a cardiac arrhythmia, for example, torsade de pointes, magnesium can help stabilize cardiac membranes1, so you don't die. Its utility in this role was recently featured in an article by one of my favorite co-authors, Kirsten Cherian, Ph.D.2, in which it was combined with Ibogaine3.
The introduction in a review on magnesium in depression reads like the intro for a keynote speaker at a conference on narcissism:
Magnesium, one of the most essential minerals in the human body, a co-factor of many enzymatic reactions [43, 54], is known to be involved in proper functioning of cardiovascular, alimentary, endocrine and osteoarticular systems4
Stop, stop, you are embarrassing magnesium!
The initial observations related to magnesium’s role in depression related to the amount of magnesium in red blood cells (otherwise known as erythrocytes, to doctors who want to sound like we are talking about science to anyone listening on the sly).
[authors] found an inverse relationship between magnesium intake and depressive symptoms in community-dwelling adults. However, the authors wonder if the poor quality of depressives’ diet was a causative factor or a consequence of their mental disorder.
Humans don’t have a lot of magnesium in our body at baseline:
An adult contains about 24 grams of magnesium, of which more than 50 percent is localized in bones while the rest is found in soft tissues and plasma/serum.5
Today’s article will go beyond the theoretical review and feature a remarkable paper published in 2017 in PLOS ONE:
Role of magnesium supplementation in the treatment of depression: A randomized clinical trial
It is also an opportunity to write my favorite kind of study design: the randomized crossover trial. In this study, by Tarleton, et. al.6, every participant got magnesium or a placebo. But they randomized was the time point at which they were assigned to either magnesium or placebo. They either started with magnesium, or started with placebo, and then switched over. This allows subjects to serve as their own controls—and when you're acting as your own control, statistical power is improved.
This was done at the University of Vermont, and for a single center trial of 12 weeks, enrolled a lot of participants!
An open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male) diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment).
Similar to the previously evaluated lavender trial (brand name Silexan), this was a study in a very challenging population (for research) of mild to moderate depression.
Digging into…Table One usually lets us know if there are baseline differences (here it is moved to something titled “Table Two”— recall, the subjects are the controls):
Looking at our friend the “CONSORT Diagram”:
The randomization is described…and…everyone gets Magnesium sooner or later. Let’s see how they did on depression scores:
And now, looking at anxiety (as measured on the GAD-7):
When the data is subgrouped, it holds up across various slices of the sample:
Looking at age, baseline depression, baseline anxiety, gender, or adherence? It works across all subgroups! This is a well-done trial of a salt (MgCl) in the treatment of depression that is mild, using my favorite study design!
Other Times to Catch Me Live:
May 7th at ATA Nexus in Phoenix!
May 15-16, Miami Beach + Virtual
Join me as I proudly co-chair the Summit on Breakthrough Therapies for Addiction, taking place May 15-16 at Mount Sinai Medical Center Miami Beach and live-streamed online. We will share research and expertise on treatments like psychedelics, non-hallucinogenic compounds, interventional brain medicine, neuromodulation, VR, EMDR, GLP-1s, and more.
Use discount code OM15 for 15% off today by visiting https://bit.ly/3vgLlZy.GP
And then…A Virtual, on June 5-7th!
Neurodiversity: A Conference for and About Doctors Who Think Differently (this is an affiliate link)
Tzivoni, D., Banai, S., Schuger, C., Benhorin, J., Keren, A., Gottlieb, S., & Stern, S. (1988). Treatment of torsade de pointes with magnesium sulfate. Circulation, 77(2), 392-397.
Cherian, Kirsten PhD1; Shinozuka, Kenneth BA2,3,*; Tabaac, Burton J. MD, FAHA4,5; Arenas, Alejandro MD6; Beutler, Bryce D. MD7; Evans, Viviana D. BA8; Fasano, Chelsey BA9; Muir, Owen S. MD, DFAACAP10,11. Psychedelic Therapy: A Primer for Primary Care Clinicians—Ibogaine. American Journal of Therapeutics 31(2):p e133-e140, March/April 2024. | DOI: 10.1097/MJT.0000000000001723
Cherian, K. N., Keynan, J. N., Anker, L., Faerman, A., Brown, R. E., Shamma, A., Keynan, O., Coetzee, J. P., Batail, J., Phillips, A., Bassano, N. J., Sahlem, G. L., Inzunza, J., Millar, T., Dickinson, J., Rolle, C. E., Keller, J., Adamson, M., Kratter, I. H., . . . Williams, N. R. (2024). Magnesium–ibogaine therapy in veterans with traumatic brain injuries. Nature Medicine, 30(2), 373-381. https://doi.org/10.1038/s41591-023-02705-w
Serefko, A., Szopa, A., Wlaź, P., Nowak, G., Radziwoń-Zaleska, M., Skalski, M., & Poleszak, E. (2013). Magnesium in depression. Pharmacological Reports, 65(3), 547-554.
Derom, M. L., Sayón-Orea, C., Martínez-Ortega, J. M., & Martínez-González, M. A. (2013). Magnesium and depression: a systematic review. Nutritional neuroscience, 16(5), 191-206.
Tarleton, E. K., Littenberg, B., MacLean, C. D., Kennedy, A. G., & Daley, C. (2017). Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLOS ONE, 12(6), e0180067. https://doi.org/10.1371/journal.pone.0180067