Last updated 3/27/2024
Low-dose lithium is very different from the full-dose lithium used for manic episodes. The low-dose approach described here has no side effects (because if you get one, you’re supposed to lower the dose) and almost no risks. Jump down to the step-by-step description if you’re ready. Otherwise, continue for some Background.
Background
Full doses of lithium are used to treat or prevent a manic episode, but these can also prevent depressive episodes. For people who don’t have manic episodes, lithium might still be useful to prevent or treat depression — but there’s not much research on this.
However, plenty of studies show that lithium can help treat depression when it’s added to an antidepressant. How about when it’s added to something like lamotrigine? And how low a dose might help? Not much research there either. (One study found that low-medium doses were not very helpful, except in lowering exposure to more risky medications).
Risk versus benefit
Speaking from 20+ years treating complex mood problems, I think even very low doses of lithium can help treat and prevent depressions. One of the main reasons to consider low-dose lithium as an add-on to other treatments, or occasionally even by itself, is its very low risk compared to other options.
On the internet you’ll see “lithium” described as risky and full of side effects. But that’s full-dose lithium (perhaps handled poorly by the prescriber). Low-dose lithium, using my approach, has no side effects and has only one risk that must be managed.
So if you can take a month or so to try a low-cost, low-risk strategy, then if it works, great! If it doesn’t, you can move on to another approach. This is why I use low-dose lithium a lot. And used that way, I’ve seen it help. Not every time, but often enough to keep suggesting it.
Step-by-step description
Here’s my approach (as I would describe it to my patient. I’m not telling you or your prescriber what to do).
- The smallest dose of lithium available by prescription is 150 mg. Start there. One capsule nightly. Make sure it doesn’t do anything bad. Some people see some mood improvement even at this dose. If you’re better enough, you could stick with 150 mg.
- If no problems but no better, increase to 300 mg. This could be a week or more later; or in about 4 days if you’re in a hurry to see improvement. If any problems, go back down to 150 mg and we’ll decide what to do from there. Don’t stop, because lithium’s benefits can be subtle and sometimes it takes time to see them.
- After another 4 days to a week or more, if still no better and no problems, increase to 3 capsules nightly (450 mg). Same logic: lower the dose if any problems.
- From here, sometimes we’d pause for a blood test to check the lithium level, in older folks or those with multiple medications or medical problems. Otherwise, I’d instruct younger healthy folks to continue on up to 600 mg, if with 450 mg they were still no better and no worse in any way.
- Then the blood lithium level would tell us what to do. If it’s low (defined below), and still no side effects and no benefits, we might switch to larger pills and continue up to 750 or 900 mg.
Blood levels
Full-dose lithium means enough to prevent a manic episode. Old research suggests this requires a blood level of lithium of 0.5-0.7 (the units are weird, “milliequivalents per liter”, mEq/L ; I won’t use the units, just watch the numbers).
Low-dose lithium, in my view, means a blood level of 0.5 or less. The target is depression, not mania. Where full-dose lithium generally requires 900 or 1200 mg per day, low-dose lithium is more like 450-600 mg/day, or even less.
If the blood level on low-dose lithium is low, and no benefits or problems have been seen, it often makes sense to continue up on the dose. Your prescriber might suggest increasing until something good happens, or some side effect shows up, or a repeat blood test shows lithium is getting up to 0.8 or more. At that level and beyond is when the big risk of lithium (“lithium toxicity”) really increases.
By keeping blood levels below 0.8, we keep lithium’s risks very low. Yes, if some doc’ forgets and adds a blood pressure medication, the level can go way up, and risk too. Likewise if you start taking ibuprofen/Motrin or naproxen/Naprosyn regularly (a few standard doses is okay), as your prescriber should remind you. But otherwise, if your kidney tests look fine (which they nearly always do but have be checked anyway), the main concern with low-dose lithium is thyroid hormone levels.
Thyroid hormone
Even low doses of lithium can lower thyroid hormone. Thyroid sets your metabolic rate, among other things. When it’s low, your energy goes down, weight can go up. Low thyroid can also cause depression, which is ironic — that’s the very thing lithium is supposed to help! And it can, as long as thyroid levels don’t go down.
Changes in thyroid hormone levels caused by lithium can be detected with a blood thyroid test done a month or two after starting lithium (yes, another blood test; it is a downside of using lithium at any dose, I know).
If thyroid hormone has decreased, and lithium has not helped much, then it’s simple: taper off lithium and thyroid hormone should bounce back up. That’s the standard teaching. Unfortunately, I think a few people can become permanently “hypothyroid” requiring a daily dose of oral thyroid to get their levels back up. One study suggests this and supports my hunch that women with a personal or family history of thyroid problems are the ones at greatest risk. I think these people might have become hypothyroid anyway and lithium just got them there sooner, but that’s impossible to really know.
Managing decreased thyroid
If lithium has helped a lot, but thyroid hormone has decreased, you have two choices:
- Taper off lithium and use another treatment; or
- Keep lithium and add thyroid hormone.
If you keep the lithium, how much thyroid to add? Many doc’s will just use enough to get your thyroid back into the normal range. But I prefer to push the thyroid dose to the point where thyroid hormone is in the high-normal range. There’s no risk to being high-normal, whereas being low-normal leaves you more vulnerable to depression. Here’s more detail about thyroid hormone and depression, including how thyroid is measured and what the numbers mean.
What’s the risk?
Full-dose lithium can lower thyroid levels in about 1-person-in-10. Low-dose lithium does this about half as often, more like 1-person-in-20. Women are more likely to be affected, at high or low dose. A family history of thyroid problems also raises the risk. And finally, having low or low-normal thyroid levels before starting lithium also raises the risk. So getting a thyroid test before lithium is a good idea.
Lethargy and “the Blah’s”
About 1 person in 10 will feel awful when taking lithium: slowed down, not interested in things. “Blah”. In my experience, this does not improve with time. In my patients, if this happens, we’d just give up and use another treatment. I’ve seen this happen even at the very lowest 150 mg dose. It doesn’t get better going up, usually it gets worse.
If you see people hating lithium on the internet, it’s often “the Blah’s” they’re talking about. It’s not a thyroid problem, it’s a lithium problem. Darn.
Bonus: low-dose lithium prevents dementia?
Lithium helps brain cells survive stress, even increase in size and number and connections. So, might it help prevent cell deaths in Alzheimer’s and other dementias? Early evidence strongly suggests this could be true. It also looks like very small doses might lead to this benefit.
This doesn’t change depression treatment. But it might really improve lithium’s reputation, if lots of older people start taking it to prevent dementia. This is such an important potential change, I made a 30-minute video summarizing the research. Oh, and I started taking 150 mg/night in 2019. You’ll see why in the video.
Bonus: low-dose lithium prevents suicide?
This benefit of lithium is pretty well accepted. (There was a big VA study that seemed to say no, but an opposite conclusion is more likely. )
So when a person is thinking a lot about suicide, low-dose lithium might be worth considering early. It appears that as little as 150 mg per day might confer this benefit. I’ve had patients report that they simply stopped thinking about suicide shortly after starting lithium, even when their depression hadn’t improved much.