Dr. Douglas Berger’s response to “Lithium for Alzheimer Prevention: What Are We Waiting for?” Psychiatric Times, October 07, 2016


http://www.psychiatrictimes.com/bipolar-disorder/lithium-alzheimer-prevention-what-are-we-waiting#comment-49925

The answer to Dr. Phelps’ “what are we waiting for” is a large prospective study of Alzheimer’s patients with a long-term follow up (the studies linked in his comment below are not this kind of study).

The study Dr. Phelps is excited about only had 55 persons in each arm with only a 1.5 year follow up (a short follow up for Alzheimer’s), the treatment effect maintained but did not improve further in the final 3-month evaluation term:

https://www.researchgate.net/publication/228098677_Microdose_Lithium_Treatment_Stabilized_Cognitive_Impairment_in_Patients_with_Alzheimer’s_Disease

Looking at the graph of MMSE score changes, assuming these results in this small sample would be valid in a large group, MMSE differences of about 5 points began to seem come out by 12 months and held up to 18 months, but there was no further improvement from month 15 to month 18 in the treatment group, and no deterioration in the control group. Will this modest level of improvement persist in large samples for many months, and how does 5 points on the MMSE translate into meaningful clinical differences over the following few years is a crucial piece of information before we start thumping our prescription pads with lithium prescriptions.

I encourage Dr. Phelps to look more carefully at the design and results of this study and change his call from prescribing lithium to promoting a bigger and longer trial. We don’t want people running to lithium if it doesn’t work very much or for too long, perhaps taking larger doses in a fever to treat dementia knowing larger doses are routinely used for mood disorders (no matter what people are told some will still try to take more), and avoiding other treatments, i.e., memantine for which lithium would need a head-to-head comparison.

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