Lithium
(revised 12/2005; minor update 11/2012)

If the whole idea of lithium scares you, you might want to start with some comments from the world's expert on how lithium works, Dr. Manji.  Then come back here for basic information people who are going to take it will need, which follows. Finally, if you want some serious detail on the risks, you'll find a link for more at the bottom of the page.   

Lithium, an naturally occurring mineral like sodium, was found to have effects on mood problems in the 1940ís. It has been the main medication for Bipolar Disorder (formerly "manic-depressive disorder") for many years. Lithium is still the best researched medication for this condition; no other medication has been shown to be superior in controlling depression, suicidal thoughts, or long-term mood stability. It also has been shown to decrease anger and sudden impulse decisions in people who do not have bipolar disorder.

Lithium is like two different medications:  low doses are pretty easy to manage and produce few side effects.  High doses are tricky to manage, require close monitoring to stay safe, and can cause side effects which make people want to consider alternative treatments. 

How does it work?

The exact way this medication works is not known. It affects a several stages in the process by which nerve cells communicate with one another (at least three steps from the receptor to the nucleus). This is an area of very active research.

How much is enough?

Most people require at least 900 mg to reach the "therapeutic range" (see "blood levels", below). However, lower doses can often be of benefit, especially when used with another mood stabilizer. Such a "combination strategy" allows for lower doses of both medications, thus avoiding side effects.

A simple blood test can show exactly how much of the medication is in the blood. When you are first starting this medication there may be several such tests done, because high levels of lithium can be dangerous and your doctor will be working to make sure you will not get that high a level in your bloodstream.

What are the common side effects?

Many people get no side effects at all.  The list here is to tell you what occasionally happens to some people. (If you have psoriasis or kidney problems, however, put it at the bottom of your list of options; it can make these worse).

Because lithium is very similar to sodium (a "salt"), taking lithium is like taking small salt tablets: it makes you thirsty. If you donít drink more water than usual, you can have dry mouth. But when you do drink more, you will also urinate more. During the day this is usually not a problem, but some people have to get up at night to urinate when they did not need to before. Most people taking lithium will notice these effects somewhat, more so at higher doses.

Some people can have nausea from lithium. The slow-release versions (Lithobid, Eskalith) are much less likely to cause this but can cost you more (not generic). After you have been taking lithium without nausea, becoming nauseous is a dangerous sign: your level may have become too high; get a lithium level if this does not get better, or if you get other lithium side effects.

As the dose and blood level go up, some other side effects can occur. Tremor (usually seen as shaky hands) is common. It can often be controlled with low doses of "propanolol", a blood pressure medication, if you and your doctor decide to continue lithium at this dose.

Weight gain can occur with lithium. At first almost everyone will gain a few pounds as their body hangs on to more water (salt effect). Some people can continue to gain weight, though. This is much less of a problem with lithium than with valproate, both in how often it happens and how much weight is gained. Usually at this point we will switch medications, but some people can control the weight issue with regular exercise, wise eating, and avoiding alcohol entirely -- all good health habits anyway.

Some people can have "edema", when your body has too much water, which shows up as ankle swelling or feeling "bloated". High doses can cause dry skin. At higher doses, loose stool or even diarrhea are frequently noted. Most of the other side effects you will see reported are uncommon.

Too high a dose causes nausea, feeling very unsteady or "wobbly", slurring of speech, and confusion. If you notice these, call the on-call physician (she or he may arrange for a lithium blood test, and may lower your dose until the test shows what to do). It is dangerous to continue lithium if you have these side effects.

Are there any serious side effects? (revised 5/05)

For a very detailed look at lithium risks, take that link.  Here's a shorter overview: 

Very high lithium levels, such as in overdose or continuing to take too much, can be fatal or cause kidney damage or other problems. Rarely a person can get very high levels when taking the right dose: this usually involves interactions with another medicine such as ibuprofen (Motrin, Advil) or blood pressure medications; or becoming severely dehydrated (losing fluids through vomiting and/or diarrhea is the most common; if you are sick, taking no lithium until you can drink--and keep!-- plenty of water can avoid this); or making a mistake with the dosing.

Lithium can decrease thyroid hormone in about one out of 10 people taking lithium (common). The gland is generally okay and recovers its usual function if lithium is stopped; the only exception to this may be in families where there are relatives with thyroid problems. Thyroid levels need to be checked at least once a year while on lithium, but several times in the first year. (Some references recommend routine checks twice a year, and a few even more often than that; this is a matter for discussion with your doctor). We usually check your lithium level as well at that time.

Long-term lithium treatment, for a decade or two, can lead to a steady lowering in kidney function. The higher the dose, the greater will be this risk.Presne  It is routine to monitor kidney function while people are taking lithium, and this is important to insure long-term safety.  I've had two patients who had done so well on lithium, for decades, that we were reluctant to switch treatment, even as their kidney test slowly worsened.  I now realize I was too slow to get them off it, and as a result they have to get up several times a night to urinate (this condition is called diabetes insipidus; unrelated, except in frequent urination, to the diabetes you hear about all the time, which is a sugar problem--diabetes mellitus). Make sure your doctor is watching this kidney test, called "creatinine".  When your creatinine goes over 1.0 or 1.2, it's time to have a discussion about switching medications. 

In addition to the slow decrease in kidney function, there is a risk of "kidney failure", requiring dialysis.  In most cases this has been associated with "lithium toxicity", that is, getting much too high a blood level of lithium.e.g. AlaskaCase As you can see, there are many reasons to be careful with lithium, especially if your blood levels are in the range of 1.0 or higher.  

What about pregnancy?

This medication can definitely cause abnormalities in unborn children. Becoming pregnant while taking any medication for bipolar disorder is a tricky issue that requires discussion with a specialist in this disorder. Tell your doctor how you will avoid becoming pregnant.

How do I start?

Each pill is 300 mg. There is also a smaller dose if this size causes too much nausea at first -- call your doctor to discuss how to handle this (the pills lose their slow-release properties if broken).

Start with one tablet at bedtime. Increase by one tablet at bedtime every four days until:

a) your "target symptoms" improve: continue that dose or

b) side effects you cannot tolerate: decrease by one tablet and continue or

c) you reach 900 (3 pills per night).

You may split the dose (one in the morning, two in the evening), to decrease minor side effects.

When you have been taking the same dose for more than 4 days, you are ready for a blood test that will show your lithium level. Ask your doctor for instructions on going to the lab. We always check your level before your morning dose ("trough level") so that we can compare one result with another accurately. Carry your morning dose with you and swallow it after your blood is drawn. It is ok to have breakfast before your lab test.

Does lithium interact with other medications?

Lithium itself does not cause major interaction problems. Other medications may change how the kidney is getting rid of lithium and lead to increased levels. Some blood pressure medications (diuretics, ACE inhibitors) and most "non-steroidal anti-inflammatories" like ibuprofen (Motrin, Advil) have strong effects on lithium levels; careful lab testing is usually required with these combinations.

Is this addictive?

There is no "addiction": if you stop, there is no "craving. However, there is good evidence that stopping lithium suddenly can cause a rapid return of symptoms. It is important to taper slowly off lithium, taking at least several weeks to do so, unless there are reasons to go faster. Stopping over several months is much wiser.


For more detailed information about the risk side of the lithium picture (same info' as above, but with more details, see my Lithium Risks: Thyroid, Kidney, and Weight Gain Problems page.

For a brief history of lithium as an anti-manic agent, starting with its discovery in 1817, through the mid-1900's, to FDA approval in 1970, see my History of Lithium page, which borrows heavily from an essay by Robert Howland, M.D.

Lithium levels go down when manic? sometimes, yes.