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Rediscovering Low-Dose Lithium for Mood Disorders

Lithium is prescribed for bipolar disorder. Side effects are scary! Could low-dose lithium be safer for mood disorders or Alzheimer's?

Lithium is a chemical element that is widespread in nature. You can find it in the earth’s crust, in water and even in the food you eat. Depending upon where you live, there is a good chance that there are trace amounts of lithium in your drinking water. Could this mineral be beneficial for the brain? Might low-dose lithium help some people overcome depression? What are the risks?

From Batteries to the Brain:

Most people these days are aware of lithium-ion batteries. They power our cell phones, laptop computers and other portable electronic devices. In addition, heart pacemakers are powered by lithium-containing batteries. Electric vehicles, including high-end Teslas, run on lithium-ion batteries as well.

Lithium has been called “white gold.” That’s because this silvery metal has been in great demand for all the obvious reasons. Of course, prices soared. But high prices in 2021 and 2022 led to huge lithium mining ventures. That led, in turn, to a glut in 2023 and a surplus at the start of 2024. On the other hand, the story of lithium goes far back before cell phones or electric vehicles.

Lithium for Gout?

Of course, it’s quite a jump from batteries that power computers or cars to medicine. Initially, physicians began using this element in the mid-nineteenth century. A British internist, Dr. Alfred Baring Garrod, figured out that gout was caused by elevated uric acid levels in the body. In 1859 he reported using lithium to lower uric acid levels and ease the symptoms of gout, including something he called “brain gout” (Bipolar Disorders, June, 2009).

There was some suggestion that high levels of uric acid in the bloodstream might trigger manic episodes. Would lithium calm the heightened arousal that we now call bipolar disorder?

Lithium for Bipolar Disorder:

Psychiatrists and neurologists began using lithium salts to control seizures and calm nervous patients in the 1870s.

In 1871, Dr. William Hammond of the Bellevue Hospital Medical College in NYC wrote in his book, A Treatise on Diseases of the Nervous System:

“Latterly I have used the bromide of lithium in cases of acute mania, and have more reason to be satisfied with it than with any other medicine calculated to diminish the amount of blood in the cerebral vessels, and to calm any nervous excitement that may be present.”

Within a decade or two, Danish physicians began using lithium carbonate to treat depression.

“Crazy Water” (aka Low-Dose Lithium) in Mineral Wells, Texas:

On this side of the ocean, the town of Mineral Wells, Texas, developed a reputation for its unique water. According to legend, a “crazy old lady” would regularly drink the well water in town. Gradually, her dementia seemed to lift and she had less of the “crazies.” Soon, people from all over the country were flocking to Mineral Wells to drink from the “Crazy Well.”

By 1909 there were seven wells, four bath houses featuring the mineral water and nearly 50 boarding houses or hotels. Some of the wells in Mineral Wells had measurable amounts of lithium. The Crazy Water Company continues to this day and lists lithium as one of the minerals in its Crazy Water #4.

Hangover Remedy?

You may be amused but possibly not surprised to learn that lithium found a place in patent medicines. During the early part of the 20th century, entrepreneurs sold such products to treat hangovers and other health concerns. In 1929, Bib-Label Lithiated Lemon-Lime Soda was a new soft drink. The marketing slogan was: “It takes the ouch out of the grouch.”

The product became 7Up Lithiated Lemon Soda and was eventually renamed 7 Up in 1936, presumably for the atomic weight of lithium (6.9). After 1948, however, the lithium citrate was removed. That was because the government banned the use of lithium in soft drinks.

The Resurgence of Lithium:

For most of the early twentieth century, the medical community lost interest in lithium. It might have remained forgotten had it not been for an Australian physician who reported that lithium citrate and lithium carbonate could relieve “psychotic excitement” (Medical Journal of Australia, Sept. 3, 1949). Other Australian researchers reported that this element was helpful against what was then called mania (Medical Journal of Australia, Aug. 18, 1951).

United States Lags in Lithium:

For reasons that remain somewhat mysterious, American physicians were extremely slow to adopt lithium therapy. Denmark, Britain, France, Germany and many other countries approved the use of lithium for patients with depression and mania. By the time the FDA gave it the green light in 1970, fifty other countries had approved it for the treatment of manic depression.

Bipolar Disorder:

Most health professionals now refer to manic depression as bipolar disorder. Lithium is considered a key treatment. Because the dose of lithium used to treat this condition is very high, patients and their families are warned to be alert for symptoms of toxicity such as diarrhea, vomiting, trouble walking, muscle weakness or drowsiness.

Lithium can also reduce kidney function. Patients should be monitored for that potential adverse effect. Thyroid function should also be monitored, since chronic lithium intake can impair the thyroid gland (Environmental Health Perspectives, June 2011).

Low-Dose Lithium for Depression?

Here is a recent question from a reader of our syndicated newspaper column about low-dose lithium:

Q. My young adult daughter has been taking Zoloft for depression. She recently weaned off it and her new doctor put her on 5 mg of lithium orotate.

She first tried to take bupropion but couldn’t tolerate the higher 300 mg dose. What’s more, her pills smelled like rotten eggs. I think it’s interesting that one pharmacist said this smell is normal and another said it is not. Your article confirmed the bad smell is not normal for this pill. I hope you can give us some information about lithium orotate.

A. There is growing interest in low-dose lithium for both mood disorders and cognitive impairment. This mineral was introduced in the US as a treatment for bipolar disorder in 1970. That condition was called manic depression in those days.

The problem with lithium treatment has been its toxicity. At the high doses that have been used (900 to 1,800 mg of lithium carbonate daily), there are several serious side effects. They include thyroid disorders, kidney damage, hand tremor, digestive upset, heart rhythm changes, confusion and visual difficulties.

The low-dose lithium orotate your daughter is now taking has not been studied as carefully, but it appears to be safe (Brain and Behavior, Aug. 2021). The limited evidence that exists suggests that low-dose lithium may be helpful for depression or bipolar disorder (Neuroscience and Biobehavioral Reviews, Jan. 2023).The dose of lithium orotate your daughter is taking (5 mg) is very low. As long as she is being monitored by her physician, this should pose little risk.

Lithium Side Effects:

  • Hand tremor
  • Thirst, dry mouth
  • Frequent urination
  • Digestive distress, nausea, vomiting, loss of appetite, diarrhea
  • Weight gain

Signs of Lithium Toxicity:

  • Drowsiness, fatigue, lethargy, cognitive dysfunction
  • Muscle weakness
  • Coordination problems
  • Giddiness, unsteadiness walking difficulties
  • Blurred vision
  • Ringing in the ears
  • Excessive urination
  • Muscle twitching (fasciculations), uncontrollable muscle movements
  • Slurred speech, blackouts, seizures, vertigo, confusion
  • Incontinence
  • Irregular heart rhythms, low blood pressure
  • Kidney damage
  • Thinning hair, hair loss
  • Acne
  • Thyroid disorders (goiter, hypothyroidism)
  • Diabetes insipidus

Drug Interactions with Lithium-Containing Medications:

There are a great many medications that can interact dangerously with lithium. They include:

  • Amiloride
  • Benazepril
  • Captopril
  • Chlorothiazide
  • Chlorpromazine
  • Chlorthalidone
  • Desmopressin
  • Diltiazem
  • Enalapril
  • Fluphenazine
  • Fosinopril
  • Furosemide
  • Hydrochlorothiazide
  • Indapamide
  • Lisinopril
  • Losartan
  • Moexipril
  • Promethazine
  • Ramipril
  • Spironolactone
  • Trandolapril
  • Triamterene
  • Valsartan
  • Verapamil

This is not a complete list. Always check with your pharmacist about all potential drug interactions!

Low-Dose Lithium: A Different Ballgame

Many of the very serious adverse reactions mentioned above are associated with the high doses of lithium that have been approved by the Food and Drug Administration. The agency has not considered low-dose therapy.

Despite the long list of side effects and drug interactions, low-dose lithium is an idea that is starting to resurface. A fascinating article in the New York Times (Sept. 13, 2014) was titled:

“Should We All Take a Bit of Lithium?”

It was written by Dr. Anna Fels, a psychiatrist and faculty member at Weill Cornell Medical College.

Dr. Fels pointed out in her article that:

“…people whose water had the least amount of lithium had significantly greater levels of suicide, homicide and rape than the people whose water had the higher levels of lithium. The group whose water had the highest lithium level had nearly 40 percent fewer suicides than that with the lowest lithium level.

“Almost 20 years later, a Japanese study that looked at 18 municipalities with more than a million inhabitants over a five-year period confirmed the earlier study’s finding: Suicide rates were inversely correlated with the lithium content in the local water supply.

“More recently, there have been corroborating studies in Greece and Austria.”

The idea that low doses of lithium might be linked to less depression and suicide is intriguing. There is even some evidence that it might be neuroprotective.

Dr. Fels goes on to suggest that:

“…its efficacy in mood disorders and suicide prevention has been documented as well as or better than virtually any other psychotropic medication. But it retains a grim and undeserved reputation, perhaps because it was originally associated in the public mind with serious mental illness and because, like many medications, lithium can have serious side effects if not monitored properly. As a psychiatrist, I can tell you that because of its stigma, lithium as a medication is a hard sell to patients with serious mood disorders who could clearly benefit from treatment. But there are undoubtedly other reasons for its neglect. Pharmaceutical companies have nothing to gain from this cheap, ubiquitous element.”

Low-Dose Lithium vs. Alzheimer’s Disease?

The FDA recently approved two new drugs to treat Alzheimer’s disease: aducanumab (Aduhelm) and lecanemab (Leqembi). We have written extensively about these monoclonal antibodies (mabs). A third drug in this class is poised for FDA approval. It is known as donanemab. We discuss all three drugs at this link. They are very pricey and they come with some very serious side effects.

There is a lot of money and reputation riding on these “mabs” or “mAbs.” Given that nearly 7 million people in the US suffer from Alzheimer’s disease, everyone is desperate for an effective treatment.

I was fascinated to stumble across a study from Japan comparing all three of the mAbs above to lithium (Ageing Research Reviews, Jan. 2024). It was titled:

“Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer’s disease: a systematic review and network meta-analysis”

The authors introduce their review this way:

“Lithium is a promising disease-modifying treatment for MCI [mild cognitive impairment] and AD [Alzheimer’s disease] because it modulates the inositol triphosphate cascade, autophagy, glycogen synthase kinase-3 beta, protein kinase beta/phosphoinositide 3-kinase, micro-RNA homeostasis, neurotransmission, neurogenesis, mitochondrial function, inflammation and oxidation (including the reduction of Aβ accumulation via these mechanisms), all of which are assumed to be the etiology of AD. A previous meta-analysis of randomized controlled trials (RCTs) reported that lithium was significantly more effective than placebo for cognitive decline in MCI and AD, with no significant difference in rates of discontinuation due to adverse effects or any cause.”

OK, I know that was a lot of technical neuroscientist-speak. I left it in to demonstrate that there is science here.

The conclusions of this low-dose lithium comparison study:

“Although it is yet to be determined which is more effective between lithium or lecanemab or donanemab, lithium may be more effective than aducanumab. Aducanumab, lecanemab and donanemab do not appear to differ in their effectiveness on cognitive function. Low-dose lithium may be safer than aducanumab, lecanemab and donanemab.”

This will, of course, not be welcome news from either the drug companies involved or the FDA. The idea that low-dose lithium might be safer and more effective than very expensive new drugs from the pharmaceutical industry will make many neuroscientists cringe.

OTC Lithium?

Lithium is available as a dietary supplement, and people are taking it. Researchers have reported that lithium, zinc or magnesium at nutritional levels may help ease anxiety or depression (Pharmacological Reports, Aug. 2014).  Lithium supplementation (at a dose of 400 micrograms) improved energy, friendliness and happiness in a very small placebo-controlled study with former drug users (Biological Trace Element Research, Jan. 1994). Please note the emphasis on “micro.” We are not talking about milligrams!

That helps explain the renewed interest in this compound as a dietary supplement. Who wouldn’t want to increase their happiness, however that might be measured?

As Dr. Fels wrote, some studies of lithium levels in drinking water suggest that suicide rates are lower where natural levels of lithium are higher (International Journal of Environmental Research and Public Health, Nov. 12, 2013; International Clinical Psychopharmacology, Jan. 2015).

Is Lithium Helpful for Depression?

Some psychiatrists are now prescribing lithium orotate or lithium citrate at low doses (10 or 20 mg) for depression. In fact, certain psychiatrists believe that it can be helpful, after electroconvulsive therapy, for treatment-resistant depression (Revue Medicale de Bruxelles, 2017). To put the low dose of 10 to 20 mg into perspective, you have to realize that the official FDA prescribing information lists doses of lithium carbonate in the range of 900 to 1,200 mg daily.

What About ADHD?

Dr. James Greenblatt reports that very low-dose lithium can be helpful for children with attention difficulties, especially those for whom irritability, anger and aggression are an important part of the picture (Greenblatt & Gottlieb, Finally Focused, Harmony Books, 2017). You can listen to an interview we did with Dr. Greenblatt at this link (Show # 1107). We also recorded a nationally syndicated radio show titled #1118: What You Should Know About Lithium at this link.

Parents who would like to consider such an approach for their children must discuss this possibility with the pediatrician first. They may also wish to consult ConsumerLab.com for the results of tests the organization has conducted on lithium orotate supplements. (There is a charge for an annual subscription to ConsumerLab.com to access their full reports.)

Needless to say, no one should ever consider taking lithium, low-dose or standard dose, without knowledgeable medical supervision! We firmly believe that this drug/mineral must be monitored by a health-care professional to watch out for serious side effects!

Your Thoughts?

We welcome your thoughts about low-dose lithium. If you have ever used this approach, please share your experience in the comment section below. Of course, if you have experienced toxicity from this mineral, we would also like to hear your story.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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  • Terao, I. and Kodama, W., "Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer's disease: a systematic review and network meta-analysis," Ageing Research Reviews," Jan. 2024, doi: 10.1016/j.arr.2024.102203
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