Tag: lithium

Categories : Mental HealthTags :

Why Lithium is Still the Gold Standard in Treating Bipolar Disorder

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Julia E. Marquez Arrico, Universitat de Barcelona

According to recent data from the Global Bipolar Cohort, only 29% of people with bipolar disorder are prescribed lithium. Despite being the “gold standard” for treating this mental health condition, we often prioritise perceptions over scientific reality, and neglect the best available treatment.

Lithium is not some complex molecule synthesised in a state-of-the-art laboratory. It is just an element, the third in the periodic table, and ever since the Australian psychiatrist John Cade discovered its therapeutic properties in 1949, it has maintained a relevance that no other psychotropic drug has been able to match.

This longevity is not a relic of the past, but a reflection of its clinical robustness. Despite decades of research and the constant emergence of new drugs, no alternative has shown comparable efficacy in the long-term prevention of manic and depressive episodes in bipolar disorder.

According to a review published in 2024, lithium is still “the mainstay treatment of mood disorders in general and in bipolar disorder specifically”. It is also the benchmark against which all other treatment options are compared, both for stabilising mood and reducing the risk of relapse.

It is the only mood stabiliser with proven efficacy in treating mania and depression, as well as in preventing relapses. Furthermore, recent studies confirm that it may also have neuroprotective properties, from the modulation of cellular pathways involved in neural plasticity to potential effects in preventing mild cognitive impairment and dementia.

These characteristics explain why international guidelines still rank it as the first-line treatment for bipolar disorder. A consensus published in 2025 stated that it should be prescribed more frequently, contrary to the unfounded reservations that still persist in clinical practice.

Suicide reduction

Above all, there is one aspect that sets lithium apart from other psychopharmaceutical drugs: its ability to reduce the risk of suicide. No other medication has demonstrated such a consistently protective effect.

A 2024 review highlighted that, despite the methodological difficulties in studying this statistically rare event, the body of evidence from clinical trials, observational studies and meta-analyses all points in the same direction: lithium reduces mortality and suicide attempts.

This is likely due to its ability to reduce impulsivity, stabilise extreme mood swings and prevent depressive relapses, all of which create the moments of greatest risk.

Beyond episodic treatment

Current research is also looking into lithium’s ability to alter the course of bipolar disorder. Not only does it stop episodes, but it also protects the brain, and evidence suggests that, unlike some antipsychotics, it improves brain connectivity and preserves verbal fluency.

In fact, there is very interesting data suggesting that it could reduce the risk of dementia by up to 50%. Even residual levels in drinking water appear to have a protective effect at a population level. Lithium is, in short, a molecule with exceptional neuroprotective potential.

But the neuroprotective effects do not stop there. Recent studies also suggest that lithium stimulates the production of brain-derived neurotrophic factor, a protein essential for neuronal survival and growth that is often reduced in patients with bipolar disorder.

In other words, it doesn’t just prevent the brain from deteriorating – it actively helps it to heal.

Blood monitoring and ‘precision medicine’

It is often argued that the need for blood tests to monitor lithium levels (the optimal therapeutic range is 0.6-0.8 millimoles per litre) is an inconvenience. However, from a rigorous clinical perspective, this monitoring is a safeguard, not a risk. It is what allows the dose to be adjusted to the exact biology of each patient, a form of “precision medicine” that we were already practising long before the term became fashionable.

We should also remember that many commonly used medicines – from anticoagulants to immunosuppressants – require the same kind of laboratory monitoring, yet they are not considered dangerous for that reason.

What lithium management requires is not fear, but rigour. So why is it prescribed less often? The answer is complex. It is partly due to pressure from the pharmaceutical industry to promote new, patentable molecules – lithium, being a natural element, cannot be patented. There is also a degree of clinical reluctance due to its narrow therapeutic window – it needs to be carefully controlled to ensure a safe yet effective dose.

However, international guidelines are clear: lithium should be the first choice. We cannot overlook it in favour of less effective alternatives simply because they appear more modern. This kind of mistake should not influence clinical practice.

Newer is not always better

Good psychopharmacology is not a question of chasing the latest developments, but of using the most appropriate treatment for each individual at every stage of their illness.

Lithium has a proven track record that spans decades, across areas that no other mood stabiliser can address simultaneously. It controls manic and depressive episodes, prevents suicide, and provides active neuroprotection. Three areas, in one single drug.

This does not mean it is right for absolutely everyone. Good psychopharmacology should always push back against fads and dogma alike, but discarding lithium’s use without ever seriously considering it deprives patients of an option that is, according to the evidence, categorically the best therapeutic option.

Our challenge today is not to reinvent the wheel, but to understand how best to use the therapeutic tools we already have. A drug doesn’t become outdated just because time has passed; it becomes outdated when new evidence emerges and supersedes it. In the case of lithium, new evidence only confirms its value.

Julia E. Marquez Arrico, Professora Lectora, Universitat de Barcelona

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : COVID NeurologyTags :

Higher Doses of Lithium might Relieve Long COVID, Research Suggests

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Photo by Andrea Piacquadio

A small University at Buffalo clinical trial has found that at low doses, lithium aspartate is ineffective in treating the fatigue and brain fog that is often a persistent feature of long COVID; however, a supplemental dose-finding study found some evidence that higher doses may be effective.

Published in JAMA Network Open, the study was led by Thomas J. Guttuso, Jr., MD, professor of neurology in the Jacobs School of Medicine and Biomedical Sciences at UB and a physician with UBMD Neurology.

“It’s a negative study with a positive twist,” Guttuso concludes.

Because long COVID is believed to stem from chronic inflammation and lithium has known anti-inflammatory actions, Guttuso had recommended that a patient of his try low-dose lithium for persistent long COVID symptoms. He was surprised when this patient reported a near full resolution of fatigue and brain fog within a few days of initiating lithium aspartate at 5mg a day.

Relief from symptoms

Based on this single case, Guttuso became interested in lithium aspartate as a potential treatment for long COVID and recommended it to other such patients.

According to Guttuso, 9 of 10 long COVID patients he treated with lithium aspartate 5-15mg a day saw very good benefit in terms of improvements to their fatigue and brain fog symptoms.

“Based on those nine patients, I had high hopes that we would see an effect from this randomized controlled trial,” says Guttuso. “But that’s the nature of research. Sometimes you are unpleasantly surprised.”

The randomised controlled trial showed no benefit from 10-15mg a day of lithium aspartate compared to patients receiving a placebo.

After one patient from the study subsequently increased the lithium aspartate dosage to 40mg a day and experienced a marked reduction in fatigue and brain fog symptoms, Guttuso decided to then conduct a dose-finding study designed to explore if a higher dose of lithium aspartate may be effective.

The three participants who completed the dose-finding study reported greater declines in fatigue and brain fog with the higher dose of 40-45mg per day. This was especially true in the two patients with blood lithium concentrations of 0.18 and 0.49mmol/L compared to one patient with a level of 0.10mmol/L who saw partial improvements.

“This is a very small number of patients, so these findings can only be seen as preliminary,” says Guttuso. “Perhaps achieving higher blood levels of lithium may provide improvements to fatigue and brain fog in long COVID.”

Dosage may be too low

He notes that it is possible the randomized controlled trial was ineffective because the dose of lithium aspartate that was used was too low.

“The take-home message is that very low dose lithium aspartate, 10-15 milligrams a day, is ineffective in treating the fatigue and brain fog of long COVID,” says Guttuso. “Perhaps we need to do another randomised controlled trial that uses higher lithium aspartate dosages that achieve blood lithium levels of 0.18-0.50mmol/L to determine if they could be effective.”

An estimated 17 million people have long COVID in the US, and worldwide the number is estimated at 65 million.

“There currently are no evidence-based therapies for long COVID,” says Guttuso. He hopes that the National Institutes of Health will view lithium as worth studying through a trial with higher dosages; the NIH is allocating an additional $500 million to study long COVID therapies that appear to be promising.

Guttuso adds that if a subsequent randomised controlled trial finds that higher dosages of lithium aspartate are effective, long COVID patients would still need to discuss taking it with their health care providers; in addition, he says, if they do begin taking it at higher dosages, blood lithium levels should be monitored.

Source: University at Buffalo

Categories : Neurodegenerative DiseasesTags :

Lithium May Prevent Dementia in Elderly Patients

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Old man
Photo by Kindel Media on Pexels

A University of Cambridge study appears to show that older adults who received lithium were less likely to develop dementia. The findings, which appear in the journal PLOS Medicine, are in agreement with other recent studies and could pave the way for larger investigations.

Dementia, the most common form of which is Alzheimer’s, currently represents the leading cause of death in elderly Western populations, but there are no preventative treatments available.

“The number of people with dementia continues to grow, which puts huge pressure on healthcare systems,” said Dr Shanquan Chen from Cambridge’s Department of Psychiatry, the paper’s first author. “It’s been estimated that delaying the onset of dementia by just five years could reduce its prevalence and economic impact by as much as 40 percent.”

In previous studies have proposed, lithium was proposed as a possible treatment for those with a dementia diagnosis or early cognitive impairment, but it is unclear whether it can delay or even prevent the development of dementia altogether, as these studies were limited in size.

Lithium is a mood stabiliser usually prescribed for conditions such as bipolar affective disorder and depression. “Bipolar disorder and depression are considered to put people at increased risk of dementia, so we had to make sure to account for this in our analysis,” said Dr Chen.

The researchers analysed data from 29 618 NHS patients who accessed mental health services between 2005 and 2019. Patients were all over 50 years of age, with a mean age just under 74, had received at least a one-year follow-up appointment, and had not been previously diagnosed with either mild cognitive impairment or dementia.

Of these patients, 548 had been treated with lithium and 29 070 had not. For the group that had received lithium, 53, or 9.7%, were diagnosed with dementia. For the group that had not received lithium, 3,244, or 11.2%, were diagnosed with dementia.

After controlling for factors such as smoking, other medications, and other physical and mental illnesses, lithium use was associated with a lower risk of dementia, both for short and long-term users. However, since the overall number of patients receiving lithium was small and this was an observational study, larger clinical trials would be needed to establish lithium as a potential treatment for dementia.

Another limitation of the study was the number of patients who had been diagnosed with bipolar disorder, which is normally associated with an increased risk of dementia. “We expected to find that patients with bipolar disorder were more likely to develop dementia, since that is the most common reason to be prescribed lithium, but our analysis suggested the opposite,” said Dr Chen. “It’s far too early to say for sure, but it’s possible that lithium might reduce the risk of dementia in people with bipolar disorder.”

Additional research is now needed to see if lithium really does have a benefit in these conditions.

Source: University of Cambridge

Categories : Mental Health NeurologyTags :

Lithium Brain Variations Play Role in Depression

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New research into depression has uncovered a previously unknown role played by the trace element lithium appears to play a role, which has been shown to be different in healthy and depressive people. 

Image source: Pixabay

Lithium is widely known from rechargeable batteries but is also known in psychiatry as a first-line mood stabiliser for bipolar disorders. lithium is present in drinking water in trace amounts. Studies have shown that a higher natural lithium content in drinking water is associated with a lower suicide rate among the population. However, the exact role lithium that plays in the brain is still not known.

Forensic medical experts at Ludwig-Maximilians-Universitaet (LMU) in Munich teamed up with physicists and neuropathologists at the Technical University of Munich (TUM) and an expert team from the Research Neutron Source Heinz Maier-Leibnitz (FRM II) to develop a technique which can be used to precisely map the distribution of lithium in the brain.

Neutrons probe for lithium

The scientists investigated the brain of a patient who was a suicidal and compared it with two control persons. The investigation focused on the ratio of the lithium concentration in white brain matter to the concentration in the gray matter of the brain.

In order to determine where how much lithium is present in the brain, the researchers analysed 150 samples from various brain regions—for example those regions which are presumably responsible for processing feelings. At the FRM II Prompt Gamma-Ray Activation Analysis (PGAA) instrument the researchers irradiated thin brain sections with neutrons.

“One lithium isotope is especially good at capturing neutrons; it then decays into a helium atom and a tritium atom,” explains Dr. Roman Gernhäuser of the Central Technology Laboratory of the TUM Department of Physics. The two decay products are picked up by detectors which provide lithium’s location in the brain sections. 

Since the lithium concentration in the brain is usually very low, it is also very difficult to ascertain. “Until now it wasn’t possible to detect such small traces of lithium in the brain in a spatially resolved manner,” said Dr Jutta Schöpfer of the LMU Munich Institute for Forensic Medicine. “One special aspect of the investigation using neutrons is that our samples are not destroyed. That means we can repeatedly examine them several times over a longer period of time,” Gernhäuser points out.

Significant differences

“We saw that there was significantly more lithium present in the white matter of the healthy person than in the gray matter. By contrast, the suicidal patient had a balanced distribution, without a measurable systematic difference,” Dr Roman Gernhäuser summarised.

“Our results are fairly groundbreaking, because we were able for the first time to ascertain the distribution of lithium under physiological conditions,” Schöpfer said

“Since we were able to ascertain trace quantities of the element in the brain without first administering medication and because the distribution is so clearly different, we assume that lithium indeed has an important function in the body.”

Only the beginning

“Of course the fact that we were only able to investigate brain sections from three persons marks only a beginning,” Gernhäuser said. “However, in each case we were able to investigate many different brain regions which confirmed the systematic behaviour.”

“We would be able to find out much more with more patients, whose life stories would also be better known,” said Gernhäuser, adding that then the question of whether lithium distribution was a cause or a result of depression.

Source: Medical Xpress