Lithium

Lithium is the best mood stabilizer we have for bipolar I, and we don't use it nearly enough. That's the whole post, more or less. The rest is detail.

Sections

1. What it does
2. The blood draw thing, which is what guys actually hate
3. What’s nice to hear about it
4. Dosing, in plain language
5. Side effects, in the order they come up
6. Who it’s actually for
7. The kind of patient who tends to make the switch and not look back
8. What not to do
9. How it stacks up against the alternatives in bipolar 1
10. Where I land
11. Sources

Lithium is the original mood stabilizer and it’s borderline overpowered. It’s been the best tool we’ve got for bipolar 1 since before most of us were born, and we still don’t use it nearly enough, and the only real reason we don’t is that it’s a hassle, not that it doesn’t work. That’s the whole post, more or less. The rest is detail.

It’s been around since the 1940s, it’s a simple metal salt, you can’t patent it, no drug company has any reason to market it, which means there’s no sales rep showing up at the office handing out pens and lunch… which honestly explains a lot about our industry, because newer drugs with worse track records get prescribed more often just because somebody paid for the pens. Lithium has a sales rep budget of zero dollars. It’s also the only mood stabilizer with solid data showing it cuts suicide in bipolar patients, probably partly by steadying mood and possibly by taking the edge off impulsive decisions. Nothing else has that data. Nothing.

Quick definitions before we go further, because “bipolar” gets thrown around like everybody already knows the fine print. Bipolar 1 is the big version: full-blown manic episodes where a person doesn’t sleep for days, spends money they don’t have, talks a mile a minute, and sometimes ends up in the hospital or in handcuffs. Bipolar 2 is the quieter cousin: the highs are milder (energized and a little reckless, but not off the rails), and it’s really the crushing lows that drag the person down. Short version, bipolar 1 is mania plus depression, bipolar 2 is mild highs plus heavy depression. That difference matters for what drug you reach for, and I’ll come back to it.

What it does

The honest answer is that we don’t fully know, and anybody who tells you otherwise is selling something. There are theories. One says it tamps down an overactive enzyme inside brain cells. Another says it drains a chemical the cells use to pass signals around, so the signaling calms down. Another says it nudges up a protein that helps brain cells stay healthy and repair themselves. Researchers have a half-dozen more they like to argue about at conferences. And if you’re wondering what some or all of those mean, don’t feel bad about it, I had to google it too. It’s not really that interesting. None of it matters for what we’re doing here. What matters: it calms mood in both directions of bipolar, it holds back the highs more reliably than it pulls people out of the lows, it cuts how often episodes come back, and it lowers suicide. That last one is the kicker. Untreated bipolar 1 carries a suicide risk many times higher than the general population, high enough that a real share of these patients end up taking a road they can’t turn back from. Lithium drops that a lot. That’s not just some shit I’m saying, that’s the most solid finding in the whole bipolar literature, and there isn’t a close second.

The blood draw thing, which is what guys actually hate

Here’s the catch, and it’s the only real one. Lithium has a narrow safe zone. Too low and it doesn’t work. Too high and it’s poisonous, and lithium toxicity is a real medical emergency that can kill you or leave you with permanent nerve damage, which is a fact your prescriber shouldn’t be shy about telling you up front. The maintenance target is roughly 0.6 to 0.8 on the blood test for most people, sometimes a bit higher during an active manic stretch. It’s a tighter zone than most drugs, which is exactly why it gets a reputation it half deserves.

This means blood draws. At first every week or two while we dial in the dose, then every three months for the first year, then every six to twelve months once things are quieter. We’re checking three things: the lithium level itself, the thyroid (because lithium slowly drags it down in a chunk of patients), and the kidneys (because the kidneys clear lithium out of the body, and they get worn on a little over decades). Most long-term lithium patients will at some point need a daily thyroid pill, which is easy to manage and not the disaster it sounds like. The kidney effects are slower and usually mild but they’re real, which is the kind of thing you’d want a prescriber to sit down and walk you through honestly instead of skipping over.

The blood draws are what guys hate about lithium and what makes them refuse it before trying it, and I get it, nobody’s first choice for a hobby is getting stuck with a needle on a schedule. It’s also why we end up sending plenty of bipolar patients home on Depakote (valproate, a different mood stabilizer with worse long-term math) or Lamictal (lamotrigine, also a different mood stabilizer, mostly good for the depression side of bipolar 2) when they would’ve done better on lithium, because lithium asks you to take part in your own treatment in a way the others don’t. The labs are the price of admission, and the price is real but the drug is worth it.

What’s nice to hear about it

I’m going to lead with the upside for once, because the lithium conversation usually opens with all the lab stuff and then patients tune out before anybody gets to the part where the drug actually works. For the right patient, it works in a way nothing else really does. The highs quiet down in a few weeks. The mood swings slow. Sleep evens out. The relationship and the job stop getting periodically blown up by episodes nobody saw coming. The patients who do well on lithium tend to describe it not as feeling better in some chemical-vibes way but as their life finally being something they can plan for, which doesn’t go on a rating scale, and which is the part the drug delivers that the newer stuff mostly doesn’t.

Dosing, in plain language

Start at 300mg twice a day, or 600mg at night. Check a level five to seven days in, which is when the drug has settled to a steady level in the blood and the number actually means something instead of just being a random reading you paid for. Adjust from there. Most adults end up between 900 and 1500mg total a day, taken once or twice daily. Once a day at night is fine for most people and cuts some of the daytime side effects.

Hydration matters a lot, more than people expect. Getting dehydrated spikes your lithium level, so does ibuprofen and naproxen (the over the counter pain pills) because they cut how fast the kidneys clear it, so does the kind of stomach bug where you can’t keep fluids down. Any of those, hold the dose and call. That sounds like a lot to track. In practice it comes up once or twice a year, you drink water like you actually like it because you’re going to need it, and you learn to manage it without thinking about it much. Tylenol (acetaminophen) is fine for pain because it doesn’t run through the same kidney route, ibuprofen and naproxen are the problem.

One more thing on Tylenol, and this one’s mostly for couples planning a pregnancy. Lithium is actually one of the few mood stabilizers that’s relatively safe to stay on while pregnant, which is a big deal, because the usual alternative, valproate (Depakote), is one of the worst things you can take while pregnant and can seriously harm the baby. So a lot of pregnant women on a mood stabilizer end up on lithium specifically. The catch is that Tylenol, which is the go-to pain and fever option in pregnancy since ibuprofen and naproxen are off the table, has had some recent question marks raised about heavy use during pregnancy. Nobody’s saying never touch it, and a one-off dose for a fever isn’t the concern. The practical guidance is just don’t reach for it on autopilot, use the lowest amount that does the job, for the shortest stretch, and loop in your OB before making it a daily habit. If you’re pregnant and on lithium, that’s a conversation worth having out loud rather than guessing at.

Side effects, in the order they come up

Tremor first. A slight hand shake, usually mild, often fades over the first few months. Caffeine makes it worse, which is its own issue for the guys who run on coffee like it’s a food group. Propranolol (a blood pressure pill that also kills tremor) knocks it down if it’s bothersome.

Gut stuff in the first weeks… nausea, sometimes loose stools, occasionally a metallic taste in the mouth that makes everything taste like you’ve been chewing on a battery. Mostly settles down. Taking it with food helps.

Thirst and peeing more. Lithium changes how the kidney holds onto water, so you pee more and you drink more, and some guys barely notice while some find it genuinely disruptive (the get-up-twice-a-night version is the most common complaint). Worth knowing going in.

Weight gain, modest, maybe five to ten pounds over a year, less than Depakote or Zyprexa, more than Lamictal, so not nothing but not a catastrophe either.

The cognitive thing is the one that bothers smart, high functioning guys the most, and it’s the complaint I take most seriously. Some patients on lithium describe feeling slightly less sharp, slightly out of it, slightly less themselves in a way that’s hard to put a finger on. Sometimes dropping the dose fixes it. Sometimes the trade off just isn’t worth it for that particular person and we move to Lamictal or something else. The framing I try to use here’s that the goal isn’t to feel exactly the way you did before, the goal is to keep your life from blowing up every couple of years… but I take the cognitive complaint seriously when patients raise it, because it’s real and brushing it off is how people end up quietly stopping their drug and not telling you until the next episode lands them somewhere bad.

Acne and psoriasis (a scaly, itchy skin rash) can flare in people already prone to either. Not common, real when it happens. Thyroid suppression over time, manageable with a daily pill, expected enough that we’re checking labs anyway.

Who it’s actually for

Bipolar 1, the classic version with full manic episodes… that’s the textbook fit, the one lithium was basically built for. Mixed states, where the highs and lows show up jumbled together. Bipolar with a family history that responded to lithium, because lithium-responsive bipolar tends to run in families (a brother or dad who did well on it tends to be one of the better signs this patient will too). Bipolar with suicide risk, which is most of bipolar, which is the whole point about underuse.

For bipolar 2, where the highs are mostly mild and the lows are the real problem, Lamictal is usually the better first move. Lithium works for bipolar 2, it’s just a heavier tool than the situation usually needs, like bringing a chainsaw to prune a houseplant.

For ordinary depression that’s failed multiple antidepressants, adding a low dose of lithium on top (300 to 600mg, way below bipolar dosing) is one of the best-proven ways to give the antidepressant a boost (Crossley and Bauer 2007), and almost nobody uses it because of the lab thing. Real shame, the data goes back to the 80s, it’s been sitting there working the whole time.

The kind of patient who tends to make the switch and not look back

Picture a guy in his late thirties who’s been carrying a bipolar 1 diagnosis since his mid-twenties, started after one big manic episode that involved buying something he couldn’t afford and driving somewhere he shouldn’t have. He’s been on Depakote for years and is tired of the weight and the thinning hair, and he has a brother who’s done well on lithium for a long stretch. He comes in willing to try the switch as long as somebody walks him through the trade offs honestly… the labs, the hydration thing, the painkiller rule.

The switch from one drug to the other takes about six weeks. He lands somewhere around 1200mg of lithium at night with a level in the 0.7 range. Six months in he’s sharper than he’s been in a while, he’s lost most of the Depakote weight, his wife is asking him what’s different. Two years later he’s still on it, has had one mild blip during a stretch of bad sleep with a newborn (which is just bipolar telling on itself, losing sleep is the most reliable trigger for mood trouble in these patients), tightened up his sleep and rechecked the level, no full episode. He’s also alive, which the suicide data suggests is part of what the drug is doing for him in a way nothing else really can. That last sentence is the one I’ve got to say out loud to patients sometimes, because it lands differently than the abstract version.

Lithium has a sales rep budget of zero dollars. Newer drugs with worse track records get prescribed more because somebody is handing out pens at the office, which honestly explains a lot about our industry.

What not to do

Don’t take ibuprofen or naproxen without checking with the prescriber, the kidney thing is real… Tylenol is fine because it works through a different route, the rest of the over the counter pain shelf is a problem. Don’t get dehydrated, hot Saturday hike means you drink water like you actually like it because you’re going to need it, stomach bug means hold the dose for a day and call. Don’t skip the labs, the monitoring is the price of admission and the drug is worth it. Don’t stop cold turkey, especially in the first year, because lithium-responsive bipolar that gets stopped and restarted sometimes doesn’t respond the same way the second time around… this is one of the few drugs where the choice to stop has lasting consequences, which is worth knowing before you stop on a whim.

How it stacks up against the alternatives in bipolar 1

Depakote (valproate) is the most prescribed alternative because the monitoring feels less involved and the side effects feel more familiar to general medicine. It works for active mania, sometimes works for keeping things steady long-term, doesn’t have the suicide-cutting effect, and the long-term picture (weight, hair loss, tremor, liver effects, and the fact that it can seriously harm a baby, which makes it a bad idea for any woman who might get pregnant) is worse than lithium for most patients. Depakote is fine when it’s working. Lithium is better when both would work, which is most of the time in bipolar 1.

The atypical antipsychotics (Abilify, Seroquel, Latuda, Vraylar, a class of drugs used at lower doses to keep bipolar steady) have real data for maintenance and are easier to start because there aren’t any labs and no slow dose ramp. The catch is the metabolic side effects (weight, blood sugar, cholesterol drifting the wrong way) stack up over decades, and being on one of these for twenty years isn’t free, the bill just shows up later. For active mania we’ll often use Seroquel or Zyprexa to get a patient down quickly while lithium builds up in the background.

Lamictal is great for bipolar 2 where the depression is the problem. It does close to nothing for the manic side of bipolar 1, so if you’ve got bipolar 1, Lamictal alone isn’t enough. Lamictal combined with lithium or an atypical is reasonable.

Where I land

Lithium is underused in modern American psychiatry, and the reasons are mostly about money and habit rather than medicine, which is a polite way of saying the drug got benched for reasons that have nothing to do with whether it works. Nobody is marketing it because there’s no money in marketing it, the lab thing scares off prescribers who’d rather pick a drug without monitoring, and most patients haven’t been told that the boring metal salt is the one with the best long-term math for bipolar 1. If you’ve got bipolar 1 and you’ve never been offered lithium, the question to ask your prescriber is why not, and “we usually start with something newer” isn’t actually an answer.

If you want the prescription, you get the prescription. I’m a provider, not a parent. My job is the honest take, your job is the choice. With lithium specifically my honest take is more enthusiastic than with most things… not because it’s painless, it isn’t, but because for the patient who actually has bipolar 1 it’s the drug with the cleanest claim to keeping you alive, and the lab burden is a tax I’ll happily help you pay for a payoff like that.

Sources

1. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013;346:f3646. PMID 23814104. (Suicide-reduction meta-analysis)
2. Geddes JR, Burgess S, Hawton K, Jamison K, Goodwin GM. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry. 2004;161(2):217-222. PMID 14754766.
3. Yatham LN, Kennedy SH, Parikh SV, et al. CANMAT and ISBD 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. PMID 29536616.
4. Crossley NA, Bauer M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized- placebo-controlled trials. J Clin Psychiatry. 2007;68(6):935-940. PMID 17592920. (Lithium augmentation in depression)
5. Sheard MH, Marini JL, Bridges CI, Wagner E. The effect of lithium on impulsive aggressive behavior in man. Am J Psychiatry. 1976;133(12):1409-1413. PMID 984241.
6. Smith KA, Cipriani A. Lithium and suicide in mood disorders: Updated meta-review of the scientific literature. Bipolar Disord. 2017;19(7):575-586. PMID 28895269.