Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.
Lithium: The Misunderstood Mineral
Whether you’ve been taking lithium for years, or wondering whether it’s right for you, you’re going to learn a lot about this misunderstood mineral in this podcast. That’s right, lithium is a mineral – it was the third element to enter the universe – after hydrogen and helium. So that means lithium has more in common with other supplements that people take – like calcium, magnesium, and zinc – then it does with medications. And, like those other minerals, lithium is found in the human body in trace amounts – we get lithium in the diet from potatoes, tomatoes, cereals, cabbage, and drinking water.
KN: OK So lithium is part of the human body – so do people with depression and bipolar have a lithium deficiency?
CA: Not exactly – we don’t really understand what lithium does in the trace amounts that are in the human body, but it must serve some function because when animals are deprived of lithium they don’t grow as well and have reproductive problems. We also know this. Some parts of the world have more lithium in the drinking water, And it’s clear that people who grow up with more lithium in their drinking water are much more mentally healthy – they have lower rates of crime, suicide, drug addiction.
KN: What parts of the world have more lithium?
CA: They’ve found this association in over a thousand regions and cities – in Europe, Japan, Texas, and where we’re podcasting from today – North Carolina. Much of the lithium that’s been used in medicine was mined from the Appalachian mountains.
KN: And a hundred years ago people flocked to these mountain to drink lithium water at health resorts. One of them – Lithia springs in Lithia Georgia – was recognized by native Americans for its healing properties long before the Americans found it. Roman physicians too recommended lithium water for healing the nerves. In fact, lithium was so popular as a health supplement before 1940 that 2 U.S. presidents had it shipped to the white house, and it was added as an ingredient to beer and soda. 7UP was originally marketed as a “lithiated soda” and the reason it’s called 7UP is that lithium’s molecular weight is 7. We see a similar thing today with omega-3 fatty acids – or fish oil – today. Look around the grocery store and you’ll see milk, peanut butter, eggs, chocolates supplemented with omega-3’s. And like lithium, omega-3’s help in depression and bipolar disorder, so why don’t we see lithium in the grocery store anymore?
CA: Lithium is a salt, and in the 1940’s someone had the idea to use it as a salt substitute. People did not know at the time that lithium can be toxic when you take too much, and a few people died in those days from too much lithium salt. That put a damper on the lithium springs, and companies stopped including lithium in their products.
KN: Shortly after, in 1949, doctors made the discovery that therapeutic doses of lithium could treat bipolar disorder and depression. That discovery was made by a doctor in my home country of Australia – John Cade – but it took about 10 years for the finding to catch on in the rest of the world.
CA: And when it did, lithium became classified as a medicine, which is why you can’t get lithium over the counter like you can calcium, magnesium and zinc.
KN: Some companies still try to market lithium as a supplement called lithium orotate, but we don’t recommend taking that. Doctors study medicines in animals before they study them in people, and they gave up on lithium orotate in the animal phase because it was causing a high rate of kidney damage.
CA: Yes just because lithium is naturally found in the human body does not mean that its safe. In fact any supplement is unsafe in large amounts. An overdose of calcium can cause renal stones and death. We know a lot about lithium today because doctors have been studying it for 70 years. Lithium has risks and benefits – so let’s get into that. Why would anyone want to take lithium?
KN: Lithium has 2 main uses in psychiatry:
- In bipolar disorder, it treats mania and depression, and – on average – it prevents bipolar disorder better than any other treatment we have.
- In regular, non-bipolar depression, lithium can make antidepressants work better. For many patients, antidepressants don’t work all the way, and doctors add in other medicines to “augment” them or make them work better. Lithium is actually the best studied one of these “augmentation” medicines. Actually it’s tied for first place in that category with the atypical antipsychotics like aripiprazole, olanzapine, quetiapine.
Less commonly, lithium is also used for problems with anger, aggression, or to make antipsychotics work better in schizophrenia. Let’s look closer at those two main uses – bipolar disorder and depression – as there is a lot of misunderstanding around those.
CA: The reason for some of that misunderstanding is that lithium has always been a generic medication. You can’t copyright lithium, which means pharmaceutical companies cannot make any profit off it. A study from Dartmouth university found that in 2016 the pharmaceutical industry spent 30 billion dollars on marketing. Much of that marketing money is spent to educate doctors and patients about their drug.
KN: Educate might be a stretch there Dr. Aiken….
CA: The government does regulate a lot of that education, but the overall effect is to make their drugs seem safer than they are. And we’re all impacted by it. Even if you’ve never seen a pharmaceutical ad for – say – Latuda which is another treatment for bipolar and depression – it’s likely that someone you know has, and they may influence you indirectly if the ad made a favorable impression on them.
KN: So there’s never been an ad for lithium – not even when it was first released. So this podcast aims to fill that gap. What are some of the most common misunderstandings people have about lithium?
CA: First is that lithium is for mania. Mania part of bipolar disorder, and it is a state of mind that’s the opposite of depression, when people are hyped up instead of slowed down, they feel energized, hyper, racing thoughts, talking faster, full of ideas and plans, well that’s the good side of mania. If it goes on too long all of that hyped up energy turns into heightened anxiety. The mind races with every worse-case-scenario, you feel paranoid like you can’t trust anyone, agitated, tired and wired and can’t sleep, and your emotions swing in all directions from sadness to irritability to excitement. There are two types of mania – there’s full mania which happens in bipolar I and hypomania – or mild mania. Both of them have the same symptoms. The main difference is in how impulsive people get during them. In hypomania people get a little impulsive. They may spend too much money, argue with colleagues at work, or drive aggressively…. But they can usually apologize, take back the things they bought – it doesn’t lead to permanent damage. In mania the consequences are harder to rebound from, like buying a car, starting a business, ending relationships, quitting work, bankruptcy, breaking the law.
In psychiatry, we’ve had lots of treatments for depression but not as many for mania, so historically lithium has been used for mania more often than depression. That is why it’s associated with bipolar disorder, and that has also lead to two misunderstandings. First, many people with mania are not aware that they have a problem and so don’t want to take medication, so they are likely to complain about the med. Second, we use a higher dose of lithium to treat mania than depression, and it has more side effects at the higher dose.
KN: In reality, lithium is one of the better tolerated anti-manic treatments, even at the higher doses. The chance of being tired on lithium is 1 in 28, while for other anti-manic meds it’s around 1 in 5. Lithium is also less likely to cause weight gain and concentration problems than other anti-manic medications. In the doses for depression, which are about 30% lower, it is even better tolerated.
Four Levels of Lithium
CA: So how does this one mineral have so many conflicting reputations? It helps to think of lithium as 4 different medications, because how it acts is going to depend on the dose. Lithium is dosed based on the blood level, which makes its dosing very scientific – when you take it your doctor will check the level to make sure it’s just right.
KN: That’s actually the main reason doctors use genetic testing in psychiatry, by the way. The only genes that the FDA considers useful for in psychiatric genetic testing are the ones that influence the blood level of the drugs. With lithium, you don’t need a genetic test, because we can check your blood level directly. If you did have genetic testing done, it still won’t tell us anything about your lithium dose because the genes they test for are in the liver, and lithium is one of few medications that does not pass through the liver. Here are the four types of lithium:
LEVEL 1: low-dose lithium. This is the range in 7UP and lithium water. These micro doses of lithium prevent dementia, suicide, mental illness, and have some anti-aging effects, but they don’t actually treat anything in psychiatry. Here we’re talking about doses from 10mg to 150 mg a day, and the blood level would not be
LEVEL 2: Medium dose lithium. This is the dose for depression – both bipolar and regular depression. The ideal blood level here is 0.6-0.8, although it needs to be personalized. Older adults, for example, may do well with lower levels because their brain absorbs lithium more easily.
LEVEL 3: High dose lithium. This is the dose for mania – with levels around 0.8-1.2
LEVEL 4: Toxic lithium. Lithium generally becomes toxic at levels above 1.2, although older adults may experience symptoms of toxicity a little below that. Symptoms of lithium toxicity include: severe tremor, trouble walking from imbalance and poor coordination, vomiting, diarrhea, mental confusion and trouble talking.
CA: Lithium toxicity is the most important danger to understand if you take lithium. So why would lithium reach a toxic level? The main way is through drug interactions. Lots of drugs can raise lithium levels, particularly medicines for blood pressure, antibiotics, and pain medications called non-steriodalantiinflammatories or NSAIDs. That last category is the only one that’s available over the counter, and it includes common pain medicines like Ibuprofen, naproxyn, Alleve, and prescription ones like celecoxib (Celebrex), diclofenac voltaren, and indomethacin. So if you’re taking over the counter medications while you are on lithium, acetaminophen – Tylenol – and aspirin are OK – most others are not.
KN: This doesn’t mean you can’t take those other medications with lithium, it just means you’d need to let your doctor know so they can adjust the dose and check your level more often. Other things that can cause lithium toxicity are dehydration – so drink plenty of water if you’re having a fever, are out in the heat, or having diarrhea or vomiting. Outside of those scenarios you are not likely to get a high level, unless you double up on your dose so use a pill box if you’re taking lithium so you don’t forget if you took it or not. But let’s get into the good levels of lithium. Dr. Aiken why would someone want to take lithium for depression?
CA: Lithium can be very powerful for two types of depression. In bipolar depression, lithium can work on its own. In regular depression, it can make antidepressants work better. And in both cases, lithium does something that no other mood medication does: It prevents suicide. Now, even if you don’t struggle with suicidal thoughts, that gives you an idea of how powerful its antidepressant effects are.
KN: We are all at risk for suicide. Suicide is the 10th leading cause of death in the U.S., and for people with mood disorders that risk is 10-20 times higher. When they take lithium, that risk falls dramatically – so that it’s close to the rate in the general population. No other medication does that. I’ve seen patients who have struggled with suicidal thoughts their entire life, and it’s a real struggle when your mind leaps to that option every time you’re under stress. Then when these patients take lithium they no longer have those dark thoughts – it’s very liberating.
CA: In regular, non-bipolar depression lithium should be considered in people who haven’t had a meaningful response to two antidepressants. At that point, it’s very unlikely that a third antidepressant trial is going to work, and people get better results by adding on a medication like lithium. Or they could try a non-medicine approach, such as electroconvulsive therapy, transcranial magnetic stimulation, lightbox, or psychotherapy.
KN: Lithium can work for anyone with bipolar disorder, and when it does it tends to keep working so you don’t have to keep readjusting medications a lot. This month we interviewed one of the pioneers of lithium research, Janusz K. Rybakowski, and he has found that one in 3 patients with bipolar disorder have excellent response to lithium and can stay well for many years on it. We don’t know exactly who they are, so the best way to tell if you’re a lithium responder it to try it, but there are a few signs that lithium will be a good fit. People who have the textbook case of bipolar disorder – where they have clear episodes of depression, clear episodes of mania or hypomania, and return to their normal selves in between those episodes, tend to respond well to it. There are many other signs that point to a good response, but that is the main one.
And here’s what I see in my patients. They feel more stable, and more in control of their lives. They sleep better – lithium actually helps repair the circadian rhythm system – that’s the part of the brain that regulates sleep and energy on a 24 hours cycle, and problems in this system are one of the main causes of bipolar disorder. People like lithium when it works. A few years ago google asked people with bipolar disorder what was most helpful to them – and lithium came out on top above all other medications as the most helpful. Doctors agree – many experts in bipolar disorder consider lithium the gold standard in treatment.
Lithium’s Side Effects
CA: The most common side effects with lithium are nausea, tremor, and thirst. People tend to drink more and pee more on lithium, and you want to stick with water because caloric beverages – and diet drinks – are going to cause weight gain. Lithium is not a big weight gainer – in the short term it tends to cause a little weight loss. But over long term there can be an increase in weight with lithium. The nausea gets better by taking it after a meal, or using ginger capsules or another medicine for nausea. Nausea shouldn’t be a stopping point for lithium because it usually goes away after a few weeks, and if you can push through that lithium can be life changing. The tremor with lithium does not go away with time, but there are many treatments for tremor and it also improves with lowering the dose. Other side effects are less common: Acne, taste changes, muscle weakness, sexual dysfunction.
As we said earlier, lithium is not a heavy sedative, but about 1 in 10 people feel like their mind is slowed down on it or their emotions are suppressed – they feel flat. That usually improves with lowering the dose. In terms of concentration, there is some evidence that people with bipolar disorder have better concentration and memory over the long term if they take lithium, but on the other hand it can cause some cognitive side effects like mental slowing, so that can cut both ways. In the very long term, people who take lithium have a much lower risk of developing dementia, and there’s a reason for that. Lithium is neuroprotective, which means it protects brain cells from damage and even helps them grow and repair. Most psychiatric medications are neuroprotective actually, but they do so in just a small area of the brain, while lithium’s neuroprotective effects are stronger and more widespread throughout the entire brain.
Lithium is not addictive, but there is a risk of mood getting worse if it is stopped abruptly. If you plan to go off lithium, let your doctor know so they can show you the safest way to do that.
CA: All of the medications for bipolar disorder have some medical risks, and with lithium there are two that you need to know about: Thyroid and kidneys.
If you took lithium your entire life, you’d have a one in 10 chance of developing hypothyroidism – or low thyroid – on lithium. Low thyroid is a common medical problem and easy to correct with replacement hormone. Most people’s thyroid returns to normal if they come off the lithium. Low thyroid makes people feel depressed – sluggish, tired, high appetite – so it’s important to check your thyroid while on lithium particularly if you have a new depression.
The other risk is with the kidneys. This problem is much more rare than the thyroid one, but it is more serious. As you age, your kidneys tend to slow down, and lithium can make them slow down a little more. Very rarely that could lead to kidney failure, but your doctor would be able to catch the problem before it got out of hand and stop the lithium. There is some evidence that people don’t develop renal problems on lithium if their level is kept low at or below 0.8 range
Unlike other treatments for bipolar disorder, lithium does not cause diabetes, liver problems, or unwanted muscle movements like tardive dyskinesia.
KN: While lithium has two clear medical risks, it also has many medical benefits that are relevant to bipolar and depression. The leading cause of death in bipolar disorder is stroke, and lithium reduces the risk of stroke. Heart attacks are also more common in people with bipolar and depression – lithium prevents heart attacks and even helps the heart repair itself after damage, called cardiac remodeling. On the other hand, people with heart disease may want to get approval from their heart doctor before starting lithium because it can cause problems in people with certain kinds of arrhtymias.
CA: People live longer when they take lithium – actually people live longer when they take just about any psychiatric medicine as long as it works – because a health mind is part of a healthy body. But specifically with lithium, there is some evidence that even mentally well people live longer when taking it – as we age the ends of our DNA crumble a bit like the pages of an old book, and lithium protects the DNA from that damage. Lithium also lowers the risk of cancer, possibly by protecting the DNA.
KN: Another medical benefit of lithium is that it prevents viral infections. Herpes flare ups go down when people take lithium, and lithium has strong anti-viral properties that have been shown against over a dozen viruses. Lithium also improves the immune system – and that’s a little fact you need to know because it might raise your white blood or neutrophile count – and you’d want your primary doctor to know that that’s a harmless and possibly helpful effect of lithium when they review your labs.
CA: The bottom line. Lithium is a powerful medicine for both bipolar disorder and depression. Some people have life-changing results with it, and it’s hard to know who they are in advance – so if other options haven’t worked for you it’s worth giving this a try. It’s better tolerated than people think, and most of the side effects can be managed by working closely with your doctor. If you take lithium, you need to be careful about drug interactions, dehydration, and accidentally taking too much – like most things in life, lithium is good at the right dose, but too much is a problem.