Lithium has hidden health benefits against stroke, cancer, dementia, and even the coronavirus.
Published On: 11/10/2022
Duration: minutes, seconds
Kellie Newsome: Today on Throwback Thursday: A surprise finding on lithium in the elderly gets us rethinking the medical side of lithium.
Chris Aiken: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, and I’m Kellie Newsome and we’re about to take you back in time to our June 2019 podcast on lithium. Stay tuned to the end and we’ll update the podcast with new research.
This month's issue featured a new study, and I'm not going to go into all the details, but the bottom line is it suggests that older patients with non bipolar depression may respond more favorably to lithium. This is not what I've been taught. In fact, I'm holding an article from 2016 in my hands that's titled Lithium in the Elderly Demands, Caution, and Vigilance. So how do I put that together?
Chris Aiken: Well, lithium does have serious risks and side effects, and the elderly are both more sensitive and more vulnerable to those risks. Those include, of course, hypothyroidism which occurs about 15% of the time if someone were to take lithium for their whole. SIADH, also known as diabetes insipidus and that occurs on a spectrum from drinking a lot and peeing a lot to the full clinical syndrome that needs to be evaluated and tested with a urine analysis. Lithium can also cause extrapyramidal symptoms like stiffness in the muscles, and parkinsonian symptoms, and those are more common in the elderly. There's also heart problems we need to worry about, like EKG changes, specifically T wave flattening, SA node dysfunction, bradycardia, and premature ventricular contractions. So anyone with an arrhythmia we might worry about lithium.
Kellie Newsome: But what about the kidneys?
Chris Aiken: Yes, the kidneys are the biggest risk and there's new data about that that makes us reconsider it a bit. Overall, it seems like about 1 to 5% of people who use lithium over a 20 year period will have some renal problems, but a lot of the studies are suggesting that this doesn't actually go on to renal failure at any greater rate. So there's a slowing of the kidneys more than renal failure.
Chris Aiken: And then there's this study from Israel that came out a few years ago. They took people who are developing renal problems on lithium, and some were switched to a different mood stabilizer, usually an anticonvulsant, and they looked at the outcomes. Now you'd assume that if you switch them off lithium, their kidneys are going to do better. But in this study, which was not controlled, but it was very large, it was the opposite. People actually fared worse in their renal function when they were switched to an anticonvulsant, and there is some data linking anticonvulsant use to kidney problems as well. As wel as bipolar can influence the kidney function. So there's multiple reasons why someone with bipolar disorder might develop kidney problems as they age, and lithium is just one of them, and the other drugs may have problems as well.
Kellie Newsome: Another reason I would avoid lithium in the elderly is the toxicity and taking their medications wrong can lead to toxicity.
Chris Aiken: Yes, and the elderly who can be forgetful and have memory problems might be more likely to double up on their dose, so that's a big concern. Also, older patients are going to be more likely to take blood pressure medicines that can interact with lithium and as those doses get changed, toxicity can develop. They're also prone to electrolyte problems like low sodium hyponatremia, and that itself can cause lithium levels to rise. And of course, as you age, your kidneys tend to slow, which can make lithium levels rise, so there's a lot of reasons why we'd worry about using lithium in the elderly.
Kellie Newsome: Is the dosage different in the older folks?
Chris Aiken: Well, you do aim for lower blood levels of lithium when used in the elderly, and that would be like anyone over 60. In the general population we look for a level of .6 to .8 for depression and in the elderly it would be more like .4 to .6.
Kellie Newsome: Why is that? Is that to avoid side effects?
Chris Aiken: Sort of, but actually it's because they just don't need as high a level, so they're not compromising any of the benefits of lithium by lowering their levels. And the reason is quite interesting as people age the brain becomes more porous so it can absorb more of the lithium with a lower blood level. Specifically, it takes 2 doses of lithium to get one into the brain if you're younger. But if you're older, it only takes one dose of lithium to get one into the brain. It's a one to one ratio, so in general you need to cut the dose about in half for an older person. So instead of a 1.0 level, they might need a .5 level, say for treating mania. Now those numbers are of course very approximate. You have to individualize it for the patient. But the bottom line is you might expect them to actually respond to a lower level as well, as of course have fewer side effects on a lower level.
Kellie Newsome: So there are a lot of medical risks, but this month Carlat report also mentioned a medical benefit with lithium and it may have a lower risk of stroke.
Chris Aiken: Yes, and that's no small matter. I mean, stroke is the leading cause of death in bipolar disorder and I'm going to get a little preachy about this now, because when doctors treat, say, diabetes, they don't just look at the blood glucose, right? They look at the ocular health because diabetes can affect the eyes and cognition because it can affect the brain. They look at infections and feet because of neuropathy. They basically look at the whole body, but when we treat bipolar disorder, what do we look for?
Kellie Newsome: Mania and depression.
Chris Aiken: Right, and that's just two things. We don't actually look for stroke, which is the biggest risk of death for people with bipolar disorder.
Chris Aiken: Bipolar disorder affects the entire body. They have greater risks of heart attack, and that's been associated with the number of manic episodes they've had. They have greater risks of diabetes and metabolic problems, so all this business about monitoring physical health isn't just about monitoring medication side effects, it's about looking at the health of the whole person. So I'm off my soapbox now and I'll just say that stroke is no small matter in bipolar disorder and what we're finding in that recent study is that most medications for bipolar disorder actually raise the risk of strokes. That's not a good thing. In that list lithium had the lowest risk of stroke, and there's other studies showing that lithium may actually reduce the risk of stroke for people with bipolar disorder.
Kellie Newsome: Are there any other medical benefits of lithium?
Chris Aiken: Yeah, there's quite a few, and these are the things we need to think about as we balance the medical risks in older patients. Lithium is cardioprotective. There's been a lot of new studies on that, showing that it can help in cardiac remodeling so in recovery after a heart attack. It also helps prevent heart attacks. Lithium is neuroprotective and what that means is a lower risk of dementia, and that's been pretty firmly established that even in small small dosages, lithium can lower that risk. Lithium also causes what we call a benign elevation of the neutrophil count. Basically it raises white blood counts and through that and other mechanisms it improves immunity so people have a lower risk of infection. Lithium also has antiviral properties specifically against HIV and herpes virus. And here's an interesting finding lithium increases the telomere length.
Kellie Newsome: What does that mean?
Chris Aiken: Well, as we age the ends of our telomeres shorten a bit. That's part of why we look different as we age and why we have greater risks of cancer. And lithium prevents that shortening.
Kellie Newsome: Where did you find all this?
Chris Aiken: A lot of this comes from Dr. Robert Post, who was a former head of the NIMH. He's retired now, but publishing a lot on these lithium findings and I'm just going to read this quote from him. It's from an article called the New News About Lithium. “Telomeres are shortened by childhood stressors, greater number of depressive episodes, and implacable anger. Whereas they are lengthened by exercise, a good diet, mindfulness meditation, and having positive and altruistic goals in life."
So it's a good thing that lithium is on the side of lengthening the telomeres, and I don't know for certain, but that might be part of why we see lower risks of cancer in people who take lithium. They seem to lower the overall cancer rate by about 20%. Lithium also lowers the risk of numerous neurologic illnesses. Including seizures and amyotrophic lateral sclerosis. And finally, there's some small studies both in humans and animals, showing that lithium might increase overall longevity. Now we know for sure that patients with bipolar who take lithium tend to live longer, because that seems to be that bipolar is shortening the lifespan, but I'm talking about everyday people as well it may increase longevity.
Kellie Newsome: OK, so here's a common problem. A patient gets better on lithium, and I've seen this, it really can treat depression even when it's not bipolar. But then as they age, their creatinine starts to rise. What do you do?
Chris Aiken: That's a tough one, and it's a really sad one because I've seen these patients. I've seen people who start lithium when they're 60 or 65, and they've struggled with depression or mood symptoms their whole life, and finally they get cured on lithium and then they need to come off of it because their creatinine is rising now. In those cases, I don't know if they're creatinine is rising because of the lithium or just because of age or other factors. But in that case it's always a good idea to lower the dose down as low as it can go because we do know that the rise in creatine is associated with the lithium level itself. The other step is to consult a nephrologist specifically if the creatinine goes to 1.5 or above. I would definitely consult with the nephrologist on what to do.
Kellie Newsome: There's not a lot. Is there anything else we can do?
Chris Aiken: Well, there are two other strategies, neither of which are very well reearched. The first is N- acetylcysteine also called NAC and a lot of people know this as an antioxidant that's become popular in psychiatry because it treats trichotillomania, addictions, bipolar depression, and possibly OCD and memory problems. So people are starting to use NAC. Well, it turns out that in animal research NAC actually helps restore kidney function after lithium toxicity. So they took mice and gave them renal impairment through lithium, and then we gave half of them in NAC and the ones who got the NAC had better renal function, less tubular necrosis, so less cell death, and less obstruction in their tubular lumens. So NAC was not just preventing kidney problems, it was actually helping to treat the kidney problems caused by lithium. So Dr. Michael Burke recommends using NAC for that reason, even though it's just animal data we know that NAC is pretty safe. There can be constipation, but not many other side effects. We know that it has benefits for bipolar depression and that's from a handful of controlled trials.
Kellie Newsome: How do you dose it?
Chris Aiken: Well for the mice they gave about 700 milligrams a day in human equivalents. So for our body size it would be 700 milligrams a day. For people with bipolar depression we use 2000 milligrams a day. And that's the dose we usually use for trichotillomania and other psychiatric conditions. So I'm very comfortable with the NAC strategy if you're not able to get that patient off of lithium and certainly I've seen patients where I've tried and tried, but the depression is too severe off of it. The other strategy is not one that I'm recommending as strongly, but there are papers on it. Its Amiloride. Amiloride is a diuretic that's been used successfully to treat diabetes insipidus, including on lithium. Now it's thought that diabetes insipidus itself is a risk factor for renal problems on lithium. So just treating that and preventing it might be a strategy, but separate of that there is an article from the journal Nephrology in 2016 that suggested that Amiloride may have a preventative effect on renal interstitial fibrosis on lithium. This wasn't a human study. This was preclinical data so it's not something we can jump on, and my concern is that Amiloride is relatively contraindicated in people with renal disease. Because, among other things, it can cause high levels of potassium. Another way to prevent renal problems on lithium is to give the dose all at night. For reasons we don't understand, the kidneys do better when they're exposed to a pulse of lithium in the evening rather than twice a day dosing, and this actually makes pharmacologic sense as well, because lithium's half life is 18 to 24 hours.
Chris Aiken: To learn more and read the full articles, check out the Carlat report …
Kellie Newsome: We recorded that podcast in June of 2019. Six months later, on December 30th, the Wuhan Municipal Health Commission issued an emergency notice to local hospitals alerting them to patients with unexplained pneumonia. Three weeks later, the first US case of coronavirus was confirmed on January 21, and as the virus spread globally we began to wonder if lithium’s antiviral effects would be of any help.
Chris Aiken: We spoke with Janusz Rybakowski that Spring, who did the original studies on lithium and herpes virus. Since then, lithium had been tested against 12 viruses, and killed all of them, including several coronavirus variants. Janusz thought lithium was promising for the epidemic, and we observed a trend in our own practice that patients on lithium seemed less likely to get infected. One man who was taking lithium went to a party where all 9 people got infected, but he did not.
But all of that was theoretical, until this summer of 2022, when the first randomized controlled trial of lithium in COVID 19 came out. The little mineral worked. It was tested against placebo in 30 patients admitted to the ICU for COVID 19. After 7-10 days of treatment, all outcomes were significantly better in the lithium group – shorter hospital stay, fewer ICU admissions, and lower levels of inflammatory markers. The study also looked for long COVID symptoms 1 month later, and lithium cut those down in half compared to placebo. The dose of lithium was similar to what we use in mood disorders, with a target blood level of 0.6-1.2.
Kellie Newsome: Lithium carries a lot of stigma, and patients who take it appreciate this story – knowing that the drug is not just for psychiatry, but helps fight one of the most serious health problems around. But if your patient is already taking lithium and develops COVID, watch out for toxicity. Lithium levels can go high when patients are dehydrated, have fever, or take NSAIDs to control viral symptoms.
Kellie Newsome: Thank you for joining us on throwback Thursdays. If you’d like to earn CME credits, follow the link in the show notes ... and follow us online where Dr. Aiken is releasing a daily dose of psychiatric research on his linked in and twitter feeds, @ChrisAikenMD.
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