Lithium: The Depressing Case of Misrepresented Monitoring Data V
The thrilling conclusion!
This is the conclusion of my collaborative series with
on the topic of lithium monitoring.It's on lithium, the third element on the periodic table, and a star of my recent book—Inessential Pharmacology. (amazon affiliates link). The prior articles are:
and now, the conclusion…
“We prefer to always give lithium once a day.”
Mistakes are understandable and forgivable. Even the most experienced academics can and do make relatively simple mistakes or misjudgments. I do all the time – including quite possibly in this piece. It isn’t the potential mistakes of Dr Meyer that have caused this grating feeling at my core. It is the arrogance.
I understand that part of a clinician’s job is to inspire confidence in a patient. However, throughout my psychiatric treatment, I have observed the line between confidence and arrogance being crossed far more prevalently than in other walks of my life. As a patient, it has grown many seeds of mistrust, often making me feel powerless. When I started to look through psychiatric academic literature, I couldn’t believe how many researchers seemed to care more about being right instead of figuring out what was true.
After I published an article about my personal story of taking lithium, Dr Nassir Ghaemi, a psychiatrist with an interest in lithium, published a blog post refuting a claim I never made1. I felt horrified that my article could have been misinterpreted as a treatment recommendation. But now? Looking back at Dr Ghaemi’s blog post, it reads like someone full of arrogance. I would encourage you to read his blog posts and make up your own mind – maybe my biases have gotten the better of me?
Then there is the case of Joanna Moncrieff, who seems to have focused most of their academic work on a single vague research question: do psychotropic medications work? With the answer usually “no”. In my opinion, this suggests someone with an agenda. I don’t believe this is an isolated case. Factionalism (or dogmatism) within psychiatry [1], [2] seems to be a lot more rife than in physics.
I couldn’t believe how many researchers seemed to care more about being right as opposed to figuring out what was true.
Science is supposed to humble you, not embolden you! While writing any scientific article, I try to be aware of how little I know/understand. My knowledge and understanding of statistical methods, for instance, is poor at best. I am beset with doubt. That doubt seems to be lacking in a cohort of psychiatric researchers. For example, take a gander at a quote from an earlier video by Dr. Meyer in the webinar series introduced in part 1:
The lithium package insert, which was created in 1970 still says to use it 2 to 3 times a day, we now know this is absolutely incorrect.
How can one possibly make the statement that using lithium two to three times per day is “absolutely incorrect,” therefore meaning that lithium should be preferably “always” given once per day, based on seemingly one single retrospective study?
When I took lithium, I tried both a single daily dose regimen and a multiple daily dose regimen. The multiple dose regimen allowed me to take a lower daily dose of lithium, which according to Schoot et al. [3] seems to be associated with less long term renal dysfunction risk. A 1992 paper by Abraham et al. [4] describes another example where twice-daily dosing might have been a better option than Single Daily Dosing (SDD) for a patient:
[The patient] became very drowsy and was unable to carry out his usual daily activities 1 week after he was switched from twice to once daily. He lost confidence in himself, his mouth became dry and he developed a distressing tremor in the morning.
I want to emphasize that I do not have the requisite training/knowledge/understanding to make any recommendations. Please keep this in mind when I present the following information. The British National Formulary (BNF) recommends starting lithium by dividing doses throughout the day until the patient is stabilized on the lowest possible effective dose. The BNF then recommends switching patients to a SDD regimen.
The same recommendation is made by Carter et al. [5]:
Because lithium serum [12 hour] levels are based on BID2 dosing, patients should be started on BID dosing to determine an appropriate daily dosage in the therapeutic range, and then switched to SDD
In terms of risk, this makes sense to my ignorant brain. Current evidence suggests that it usually takes over 10 years of lithium exposure2 for end-stage kidney disease to develop [6] and the most predominant risk on initiation of lithium is acute toxicity symptoms [7]. Given the limited and arguably poor [8] available evidence on optimal lithium serum concentrations, wouldn’t using a twice-daily regimen to produce a more “level” serum lithium concentration limit the risk of acute toxicity on initiation of therapy? Once an effective, stable dose is found, switching to an SDD regimen could then possibly reduce the long-term renal risk.
Ultimately, from a patient’s perspective, it depends. I would have loved to have had a conversation with my psychiatrist about the benefits and risks of different dosing regimens.
Alex was hoping for a conversation with a psychiatrist. Should he get his wish? This is a leading question. Here is a prior article co-authored by Alex and Awais Aftab on the topic.
Our patients have opinions that we need to consider. Some of them have analytical skills that we lack. Often, they have more buy-in to the outcomes of our research because they suffer when it is inaccurate in ways that physicians don't. Or at least, some of us don’t. I am deeply grateful to
for sharing his experience, analysis, and frank feedback with us all. We must hold ourselves accountable for the consequences of our decisions, good and bad.Updates:
My new book is available! Inessential Pharmacology—It’s even got a snazzy new cover.
I’m proud to announce I’m now a strategic advisor for Psyrin, Yung Therapist Sidekick, and Videra Health.
The 2025 physician fee schedule has an open comment period. I’m excited to encourage perusal and open comments, and I'll post more soon.
Fermata has a new landing page.
Rapid Acting Mental Health Treatment 2025 is coming in January!
My newest song on Spotify is a Tracey Chapman cover…
[1] W. R. Smith and D. A. Sisti, “Rapprochement and Reform: Overcoming Factionalism in Policy Making for Serious Mental Illness,” Psychiatr. Serv., vol. 73, no. 5, pp. 539–546, May 2022, doi: 10.1176/appi.ps.202100450.
[2] K. Atterbury and N. Jones, “Overcoming Factionalism in Serious Mental Illness Policy Making: A Counter-Perspective,” Psychiatr. Serv., vol. 73, no. 5, pp. 574–576, May 2022, doi: 10.1176/appi.ps.202100613.
[3] T. S. Schoot, T. H. J. Molmans, K. P. Grootens, and A. P. M. Kerckhoffs, “Systematic review and practical guideline for the prevention and management of the renal side effects of lithium therapy,” Eur. Neuropsychopharmacol., vol. 31, pp. 16–32, Feb. 2020, doi: 10.1016/j.euroneuro.2019.11.006.
[4] G. Abraham, N. Delva, J. Waldron, J. S. Lawson, and J. Owen, “Lithium treatment: a comparison of once- and twice-daily dosing,” Acta Psychiatr. Scand., vol. 85, no. 1, pp. 65–69, Jan. 1992, doi: 10.1111/j.1600-0447.1992.tb01444.x.
[5] L. Carter, M. Zolezzi, and A. Lewczyk, “An updated review of the optimal lithium dosage regimen for renal protection,” Can. J. Psychiatry Rev. Can. Psychiatr., vol. 58, no. 10, pp. 595–600, Oct. 2013, doi: 10.1177/070674371305801009.
[6] A. C. Wiuff, C. Rohde, B. D. Jensen, A. A. Nierenberg, S. D. Østergaard, and O. Köhler-Forsberg, “Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder,” Bipolar Disord., vol. 26, no. 1, pp. 71–83, 2024, doi: 10.1111/bdi.13356.
[7] N. Murphy, L. Redahan, and J. Lally, “Management of lithium intoxication,” BJPsych Adv., vol. 29, no. 2, pp. 82–91, Mar. 2023, doi: 10.1192/bja.2022.7.
[8] W. A. Nolen et al., “What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium,” Bipolar Disord., vol. 21, no. 5, pp. 394–409, Aug. 2019, doi: 10.1111/bdi.12805.
specifically, I never made a recommendation for twice daily dosing of lithium.
To clarify, I mean that for those who were unlucky enough to develop end stage renal disease, it usually took over ten years of lithium exposure. To my current understanding, most people don’t develop serious renal problems over the long term when taking lithium.
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This has been a great series! Thank you so much for sharing your experience, Alex, and also pointing out these methodological flaws which have been propagated down the line (and continue to be). Not to sound obtuse, but if I was understanding correctly, and Owen please chime in here as an expert, if a patient is on a SDD regimen, the “trough”, aka point where lithium levels are theoretically at the lowest serum concentration, should be measured roughly 24 hours after the most recent dose?
Also, based on the studies provided, is it then recommended that providers initiate patients on MDD dosing until the optimal therapeutic dose is discovered, and then switch to the equivalent dose on an SDD regimen?
In any case, thank you again for your contribution and look forward to reading more!
"I have observed the line between confidence and arrogance being crossed far more prevalently than in other walks of my life." This is so incredibly common in our field. I tell my residents, "Believe nothing, fact check everything."
I am curious to hear your thoughts on adherence of SDD vs MDD dosing. I know for me and my family, it's hard enough to remember to take every dose of an antibiotic prescription, and that's only 7-10 days worth. I try to put myself in the shoes of my patients and I wonder how realistic it is for me to expect consistent adherence to MDD, especially in folks that I see with minimal psychosocial support, homeless, etc. Maybe I underestimate them, but I worry that sending them home with MDD regimens may set them up for failure.
Either way, I loved the series. Great read as always.