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Mood Stabilizers: Lithium: 10 Things All Clinicians Need to Know

Mardoche Sidor, MD and Karen Dubin, PhD, LCSW

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“Ron continues to ask me questions about Lithium and the effects on his kidneys and thyroid. I have no idea what he is talking about, but I want to help.” Lily articulated these words to Dawn, as they were getting ready for the weekly talk on Mood Stabilizers. “There is a lot to know about Lithium, and we could spend days just talking about it.

Let us dedicate this time to learning more, so you can be ready to answer Ron’s questions when you see him next,” Dawn replied with a smile.

This is the fourth article in the series on Mood Stabilizers. I provided an overview, with an outline of five essential points to know about Mood Stabilizers, and I gave a brief description of ten of the most commonly used Mood Stabilizers. Lithium was one of them, the first known Mood Stabilizer, the oldest, and the most effective, and to which, this current article is dedicated. Like Lily, your patients and clients may have asked you several questions.

Below are Ten things all clinicians need to know about Lithium.

Lithium has been used long before our first antipsychotic

In the mid nineteenth century, around 1843, Lithium carbonate was used for the treatment of bladder stones, and 16 years later, in 1859, it was recommended for the treatment of gout, kidney stones, mania, depression, and headaches. However, it was not until Dr. John Cade discovered its effectiveness for the treatment of symptoms of mania, in 1948, that it was first used to treat Bipolar Disorder. This information is important for us to remind our patients and clients that Lithium is one of the most studied of all our psychotropic medications.

Its mechanism of action is partly simple and partly an enigma

The messages carried to the cells (smallest structural and functional unit) of the brain travel and become intensified through ion transport (atom or molecule with a net electric charge). As you may know, there is an irregular increase in brain activity in mania, and Lithium interferes with the ion transport processes to decrease this irregularity of an increased brain processing activity. This is the clearest part related to the macro view of Lithium’s mechanism of action (how it produces its effect). However, the details of the micro view remain an enigma.

This is good news for all of us and for our patients and clients with Bipolar Disorder, who have 10% risk of attempting and dying from suicide. If you remember, in our article series on Antipsychotics, Clozapine also has this property, and an entire article has been dedicated to it, as well.

It may take weeks for Lithium to start working

When our patients or clients arrive at the emergency room because of mania, for example, they will likely receive a dose of Haloperidol (Haldol) or Olanzapine (Zyprexa), because of the immediate effect, a property Lithium does not share. Lithium achieves optimal effectiveness when at a constant level in the body. This mostly happens only after a few weeks. As a consequence, it also means we should strongly recommend that our patients and clients not skip their Lithium dose, especially in the beginning of treatment.

Lithium can affect the thyroid gland

When our patients or clients take Lithium, they will need to have regular blood tests done for thyroid function. Baseline testing, before the first dose, is also recommended. The prescribing physician should be expected to help the patient or client pay attention to symptoms suspicious for hypothyroidism. This requires astute clinical attention, because many of these symptoms may simply be related to medication side effects or even underlying depression.  Blood testing and discontinuing the Lithium—should it be the culprit—should solve the problem. At times, the symptoms of hypothyroidism do not resolve even when Lithium has been discontinued. In this case, a thyroid supplement, like Synthroid would be the ultimate answer.

Lithium can affect the kidneys

This does not happen with short-term use of Lithium but only after many years, on the order of ten years or more. Nonetheless, there is a lot that can be done to prevent renal (kidney) involvement, and you can help your patients and clients have this conversation with their prescribing physician. Once again, obtaining baseline levels and paying attention to other prescribed medications and monitoring Lithium blood levels all provide measure for successful ways to decrease the likelihood of insult or damage to the kidneys.

Lithium can cause weight gain

“I heard Topamax makes patients and clients lose weight, while Lithium and Depakote results in weight gain.” Lily, the clinician, articulated these words to Dawn. While Topiramate helps with weight loss, its mood stabilizing effect is no better than placebo. Lithium causes weight gain, and it is a good mood stabilizer. How do we achieve a common ground? The good news, there are things that can be done to avoid the weight gain caused by Lithium. As stated above, Lithium can cause hypothyroidism, which causes weight gain, and taking measures to prevent hypothyroidism or control thyroid function can be a great way to prevent Lithium induced weight gain. Further, as I mentioned in a previous article, since increased thirst is a side effect of Lithium, many of our patients and clients respond by consuming sugary drinks. Reminding them to have plain water instead of sugary drinks will help them avoid weight gain and other physical health conditions that may come with sugar consumption, like diabetes. Lastly, the weight gain with Lithium tends to be slow, unlike that related to Olanzapine, for example, and it is less common in men. The weight gain is also more likely in patients or clients who were already overweight prior to starting Lithium. Like any weight gain from any other medication use, in general, lifestyle modification is key, and we can help our patient and clients in this area.

Lithium can cause birth defects

Women exposed to Lithium during pregnancy are twice as likely to have a spontaneous abortion. About 6 percent of them will have children born with cardiovascular anomalies, with an increased risk during the first trimester. The use of anticonvulsant Mood Stabilizers, like Valproic acid (Depakote) and Carbamazepine (Tegretol) is contraindicated during pregnancy, because of significant risks for fatal birth defects. Lithium also causes birth defects, though less fatal than the anticonvulsant Mood Stabilizers, and its use during pregnancy remains a challenge, due to lack of better options. However, very important for all of us to pay attention to, should any of our patients or clients absolutely need to be on Lithium while pregnant, a high dose of folate, close fetal monitoring through regular ultrasounds and fetal echocardiogram are highly recommended. More importantly, anyone on Lithium should be encouraged to be on some form of contraceptive methods or to undergo other medication trials should there be plans for pregnancy.

Lithium can cause acne

Acne may happen in up to one third of our patients and clients taking Lithium. The good news is that the acne tends to disappear on its own after some time. Otherwise, a decrease in dose, under close monitoring of the prescribing physician or a consultation with a dermatologist, when a dose decrease is not possible, are some of the recommendations.

Lithium can cause mental slowness

“A young, bright college student, with Bipolar Disorder, was studying for her final exam and was experiencing some mental slowness. She, therefore, decided to stop her Lithium with the results of staying up late and studying better. However, this student was absent for her final exams, because, sadly, she had been admitted to the hospital for a suicide attempt.” Dawn told Lily and her colleagues this story to illustrate that Lithium can cause mental slowness and many times, as a result, our patients and clients will decide to stop their medication. This often results in sad outcomes; the patients or clients de-stabilize and whatever they were focusing on that prompted them to stop taking their medication becomes lost in the process. Even sadder, Lithium may become less effective after such an episode of lapse and the resulting mania. This phenomenon is known as kindling.

“I feel confident speaking with my clients about antipsychotics. But now, Ron, who is on Lithium is asking me lots of questions, and I want to help him.” Lily articulated these words to Dawn, the team psychiatrist, who has been working with the HOPE ACT team, helping them with tools to help educate the clients. “You and your colleagues have shown confidence and knowledge about antipsychotics; Lithium is a Mood Stabilizer and this is a good opportunity to start talking about them,” responded Dawn.

Dawn went on and gave an overview to Lily and her colleagues on Mood Stabilizers and on five things that all clinicians need to know about them. I outlined these five essentials, summarized as:

  1. Mood Stabilizers should be used as a last resort in “rapid and short mood changes;”

  2. They are divided into three main categories;

  3. Lithium and most of the anticonvulsant mood stabilizers are contraindicated in pregnancy;

  4. All mood stabilizers are not created equal; and

  5. Lithium has been shown to be the most effective mood stabilizer.

After this overview and these five essential points, Lily wanted more.  She said, “I am starting to have an idea about the mood stabilizers. There are so many of them. How do I break them down to learn the basics about each one?” “Lily, let us move on to the next step and discuss the specific Mood Stabilizers,” responded Dawn. She then provided a description of ten of the most commonly used Mood Stabilizers, outlined as:

Lily, in her dedication to show the most support possible to her patients and clients, spoke to Dawn once again, “Ron continues to ask me questions about Lithium and the effects on his kidneys and thyroid. I have no idea what he is talking about, but I want to help.” “There is a lot to know about Lithium, and we could spend days just talking about it. Let us dedicate this time to learning more, so you can be ready to answer Ron’s questions when you see him next,” Dawn replied with a smile.

And there it went; 10 things all clinicians need to know about Lithium:

  1. It has been used long before our first antipsychotic;

  2. Its mechanism of action is partly simple and partly an enigma;

  3. It can significantly reduce suicide;

  4. It may take weeks for it to start working;

  5. It can affect the thyroid gland;

  6. It can affect the kidneys;

  7. It can cause weight gain;

  8. It can cause birth defects;

  9. It can cause acne; and

  10. It can cause mental slowness.

Knowledge is meant to empower, and not to prevent us from making decisions. I often speak about risk-benefit analysis as part of any decision-making process. For example, while none of our patients or clients should have to choose between freedom from acne and receiving good treatment for Bipolar Disorder, we are a long way from using medications that have no side effects. This is where we, the clinicians, come in, to help support our patients and clients, to help them with this risk-benefit analysis exercise, and to help empower them to make an informed decision. We can help educate and support them in making lifestyle modifications that will further decrease the likelihood of most of the side effects from Lithium and many of the other mood stabilizers.

You are doing meaningful work. Each time you empower yourself with knowledge like this, more than you realize, you increase the likelihood of making an even more meaningful difference in the lives of your patients and clients. You are also arming yourself to prevent the chances of making mistakes that might cause patients and clients to be hospitalized after decompensating.

References:

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  2. Manji HK, Moore GJ, Chen G. Lithium at 50: Have the neuroprotective effects of this unique medication been over-looked? Boil Psychiatry. 1999;46:929–940.

  3. Goodwin FK, Fireman B, Simon GE, Hunkeler EM, Lee J, Revicki D. Suicide risk in bipolar disorder during treatment with Lithium and divalproex. JAMA. 2003;290:1467–147.

  4. Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J. Decreased risk of suicides and attempts during long-term Lithium treatment: A meta-analytic review. Bipolar Disord. 2006;8:625–639.

  5. Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J Aust. 1949;2:349–352.

  6. Moore GJ, Cortese BM, Glitz DA, et al. A longitudinal study of the effects of Lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients. J Clin Psychiatry. 2009 [Epub ahead of print]; doi 10.4088/JCP.07m03745.

  7. Moore GJ, Bebchuk JM, Hasanat K, et al. Lithium increases N-acetyl-aspartate in the human brain: In vivo evidence in support of bcl-2’s neurotrophic effects? Boil Psychiatry. 2000;48:1–8.

  8. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK. Lithium-induced increase in human brain grey matter. Lancet. 2000;356:1241–1242.

  9. Jope RS. A bimodal model of the mechanism of action of Lithium. Mol Psychiatry. 1999;4:21–25.

  10. Gould TD, Chen G, Manji HK. In vivo evidence in the brain for Lithium inhibition of glycogen synthase kinase-3. Neuropsychopharmacology. 2004;29:32–38.

  11. Ikeda A, Kato T. Biological predictors of Lithium response in bipolar disorder. Psychiatry Clin Neurosci. 2003;57:243–250.

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