A game changer in the late 1940s,
lithium revolutionized the treatment of bipolar disorder,
offering a beacon of hope for millions of people.
Yet, as decades rolled on,
this miracle compound was gradually nudged off its pedestal,
replaced by newer shiny contenders,
the second-generation antipsychotics.
Why did lithium, once the gold standard,
get pushed off into the shadows?
Is it time for us to reevaluate
the value of this underappreciated hero?
That's what I'm talking about today.
I am Dr. Tracey Marks, a psychiatrist,
and I make mental health education videos.
Lithium has been an essential treatment for bipolar disorder
for more than half a century.
The mineral lithium was discovered in the late 1800s,
but Australian psychiatrist John Cade discovered it
as a treatment for bipolar disorder in the late 1940s.
It was effective in managing manic and depressive episodes
and reducing the risk of suicide.
For decades, lithium remained the gold standard
in the treatment of bipolar disorder.
Then over the years,
lithium usage in the United States started to wane,
with the rise of the second-generation antipsychotics.
These drugs, including olanzapine, quetiapine,
risperidone, and others, came onto the scene in the 1990s.
They promised to be better tolerated with less side effects
compared to the older antipsychotic medications,
like Haldol, and psychiatrists started using them more.
Why? Several factors.
One is the ease of use.
Lithium requires monitoring your blood levels.
It has a narrow therapeutic window,
which means that the range
between the dose of the drug that is effective
or works to treat your symptoms
and the dose that could be harmful or toxic is quite small.
So there's a thin line between the dose that can help
and the dose that can hurt.
This makes dosing and monitoring lithium very important.
You can't just take lithium on autopilot
and never check to see how much of it is in your blood.
The concentration of lithium in your blood
that works for most people
is between 0.6 and 1.2 milliequivalents per liter.
Here's a useful table for lithium levels.
0.1 to 0.4 is a low level for preventative health,
and here's a small aside about preventative health.
Some people believe a little bit of lithium
is good for overall health.
In fact, one of the key ingredients in the drink 7UP,
which is now made by PepsiCo, was lithium citrate.
The FDA made the company, which was not Pepsi at the time,
remove lithium from the drink in 1948.
But back to the table.
0.4 to 0.8 is a medium level that treats depression
and some mood instability.
0.8 to 1.2 is a high level that treats mania.
And then then greater than 1.2 is a toxic level.
Signs of toxicity are confusion, nausea,
and maybe even vomiting,
diarrhea, blurred vision, and severe tremor.
As a non-toxic side effect, lithium can cause a mild tremor
that doesn't interfere with your ability to do things,
but the toxicity tremor is more prominent
and may make it difficult for you to do things,
like hold a cup in your hand without spilling the contents.
So when you take lithium,
you have to be careful about staying hydrated.
If you have any big shifts in your fluid balance,
like from vomiting or diarrhea or heavy sweating,
you have to look out for signs of toxicity.
But toxicity issue aside,
you do have to get regular blood tests,
like every time your dose changes.
Then you can move it out to every three months,
then every six months, and then annually.
For some people, it's hard enough to remember
to take a pill every day,
but then needing to go to the lab regularly
is just too much of a hassle.
A second factor that has made lithium become less popular
is some of the side effects
that affect your organs long-term.
The two main organs are your thyroid and your kidney.
Lithium can interfere with the production
and release of thyroid hormones.
If this happens, you can become hypothyroid,
which can look like tiredness, depression, weight gain,
cold intolerance, and a slow heart rate.
Lithium can also cause inflammation of your thyroid gland.
A 2023 study by Joseph and colleagues
found that a third of people in their study
on long-term lithium treatment developed thyroid disorder.
In this study, the average time on lithium was eight years.
As for your kidney, lithium is metabolized by your kidneys
and can interfere
with the way your kidneys concentrate urine.
You may notice that you have to urinate more frequently.
If you take lithium for a long time, usually years,
you can develop nephrogenic diabetes insipidus,
where the kidneys are no longer able
to concentrate urine effectively.
This issue is reversible if you stop it soon
after you notice these symptoms.
Also, the good news is,
taking lithium all at once at bedtime reduces this problem
and is safer on the kidneys.
So because of these potential effects
on your organs from long-term use,
it's important that in addition to blood level testing,
you also get regular blood tests
to monitor your kidney and your thyroid function.
The last reason that I'll discuss
on why we shifted away from lithium is the perception
that the antipsychotics work faster and better.
It is true that lithium takes longer to see an effect.
It's generally thought that you need to give it a month,
and that's once you get to a dose
that's in the therapeutic range.
Lithium can cause nausea when you first start,
and this is why people will start off with split dosing,
like half the dose in the morning and half in the evening.
Then once your stomach gets used to it,
you can switch to taking it all at night
for the sake of your kidneys.
Every time you change the dose,
you need to get bloodwork to check your new level.
You have to wait a week
after you change the dose to get the bloodwork.
Generally, a 300 milligram capsule
measures out to about a blood level of 0.25.
This is a rough estimate,
as everyone's metabolism is different.
So let's say your doctor starts you out
with 600 milligrams of lithium, and then you get bloodwork.
Your level may be roughly around 0.5,
which is in the low range
and not considered high enough for mania.
So then your doctor will add more lithium
and have you get your level checked again.
So you can see where I'm going here.
This can get tedious.
And if you're manic and in the process
of clearing out your bank account to build a rocket ship
or making plans to sleep with your boss's spouse,
you don't want to wait four to six weeks
for the lithium to take effect.
On the other hand, a good dose of olanzapine, risperidone,
or aripiprazole is like spraying water on that fire
and extinguishing it in a matter of days.
Generally speaking, the antipsychotics can exert
their effects within days to a week.
All of your symptoms may not be gone in that short period,
but you can usually at least feel a little more stable.
Also, with the antipsychotics,
you don't need to monitor blood levels.
So with all this said,
why should we reconsider using lithium
as the first treatment choice for bipolar disorder?
Several reasons.
Unlike antipsychotics, lithium actually addresses
one of the root causes of bipolar disorder.
Recent studies have shown that people with bipolar disorder
have increased sodium and calcium in their cells
due to altered ion transport mechanism.
Lithium actually corrects this by blocking sodium entry
into the cells so that the level is normalized.
So it corrects the problem at the cell level.
Changing how your cells work
changes everything they do downstream.
So lithium corrects the source,
and antipsychotics work at the downstream level,
affecting the chemicals that the cells produce.
An analogy would be, if you have a bleeding wound,
lithium sews up the wound
and the antipsychotics are the gauze
and bandaging that keeps the wound from seeping.
Lithium is one of the few drugs
that is specifically anti-suicidal.
Ketamine is the other juggernaut in that department.
Lithium also stabilizes your body clock
by changing the way your circadian genes work.
It works at the genetic level.
Your body clock affects a lot of body systems,
but the most noticeable are sleep and energy level.
People with bipolar disorder are often night owls,
and if left to their own devices
can end up with a flip sleep schedule
of sleeping during the day and being awake all night.
It can be a struggle to stay on a night sleeping schedule.
Lithium's effects go beyond psychiatric.
Going back to its effect on cells,
lithium has anti-aging properties
because of how it affects telomeres.
Telomeres are the protective caps
on the ends of our chromosomes,
somewhat like the plastic tips on shoe laces.
Each time a cell divides, the telomeres get a bit shorter,
and when they get too short,
the cell can no longer divide and becomes inactive or dies.
This shortening process is associated
with aging, cancer, and other medical disorders.
Researchers have seen that people
with bipolar disorder taking lithium
had longer telomeres than people with
and without bipolar disorder who had not taken lithium.
So the conclusion here is that lithium lengthens telomeres.
Another thing lithium does is it improves brain health
by reducing brain shrinkage.
Antidepressants also do this, but lithium does it more.
Lastly, although lithium does have side effects
that include cognitive slowing and loss of creativity,
it does not cause the weight gain
and metabolic issues that the antipsychotics do.
You can gain weight,
but not as much as with the antipsychotics.
Since lithium can make you thirsty,
you have to be careful not to quench your thirst
with sugary drinks or even diet sodas,
which can still lead to weight gain.
The antipsychotic medications tend to make you crave carbs
and not feel full, but with lithium,
you can end up drinking your calories.
So there's a pretty strong argument
for revisiting lithium if you have bipolar disorder
and especially if you are newly diagnosed.
Lithium is particularly good at keeping episodes away
at the beginning of your illness,
but lithium isn't good for everyone.
It doesn't work as well on people with mixed episodes
or substance use disorder.
For more on this topic, check out this video
on classic versus atypical bipolar disorder
and this other one on managing the metabolic effects
of antipsychotic medications.
Thanks for watching. See you next time.