Lithium is widely recognised today as a key component of rechargeable battery. Yet few people realise that lithium is also one of the most important medicines in the history of psychiatry.
From forgotten discovery to psychiatry breakthrough
The use of lithium in psychiatric treatment dates back to the mid-19th century. However, its therapeutic potential was largely forgotten until it was rediscovered by Dr John Cade, an Australian psychiatrist, who demonstrated its effectiveness in mania.
A cornerstone treatment for bipolar disorder
Today, lithium remains a cornerstone treatment to prevent recurrence and to treat manic and depressive episodes in bipolar disorder. In addition, lithium can be prescribed as an add-on treatment for individuals with depression who do not respond adequately to standard antidepressant medications.
Lithium and suicide prevention
One particularly interesting property of lithium is its ability to reduce impulsivity in both humans and animals, a key factor linked to suicidal behaviour. A pooled analysis of multiple studies has shown that lithium treatment is associated with a reduction in suicide risk, potentially through its stabilising effects on impulsivity.
Why is lithium used less today
Despite strong scientific evidence supporting its benefits, lithium use in clinical practice has declined in recent years. Global data suggest that lithium remains underutilised in bipolar disorder, even though clinical guidelines continue to recommend it as a first-line treatment.
Several factors may explain this trend. Lithium requires regular monitoring through blood tests, and concerns about adverse effects may discourage both clinicians and patients. Furthermore, the increasing availability of newer treatments, particularly antipsychotics, has shifted prescribing preferences.
Balancing safety and effectiveness
However, it is important to recognise that many adverse effects associated with lithium can be effectively managed through appropriate monitoring and clinical supervision. With proper knowledge and regular testing, lithium can be used safely and effectively. Notably, other treatments such as antipsychotics also carry their own side effect profile, which also require regular monitoring.
Investigating lithium’s effects on the brain
To better understand how lithium works in the brain, we conducted a study at the University of Oxford investigating its effect on emotional processing and impulsivity. The study involved healthy volunteers who received a short course of lithium treatment.
Participants received lithium and placebo in a randomised order. There was a washout period to ensure that the first treatment was fully eliminated before the second phase began.
What our study revealed?
We found that lithium influenced how people processed emotional information. Specifically, participants became less sensitive to negative emotional cues, such as sad facial expressions. They also took longer time to respond to negative self-related words.
Rebalancing emotional processing
These findings suggest that lithium may help rebalance emotional processing by shifting it away from negative towards a more neutral or positive processing of emotional information.
This is important because negative emotional bias is commonly reported in depression, including treatment-resistant depression, and is recognised as an early marker of treatment response. Previous research has shown that effective antidepressants can change emotional processing patterns even before patients feel symptom improvement or clinicians observe significant clinical changes.
Beyond impulsivity finding
While our study did not find substantial evidence that lithium reduced impulsivity in a laboratory-based task, its broader clinical benefits in reducing suicide risk remain well supported by other studies.
Why lithium still matters today
In Malaysia, conversations about mental health are becoming more open. Awareness is improving, but stigma and misunderstanding still exist. As we continue to strengthen mental health services and promote evidence-based treatment, it is important not to overlook medications that have stood the test of time.
An old medicine worth rediscovering
Lithium may not be new and trendy, but remains one of the most evidence-based medications we have in treating bipolar and difficult-to-treat depression. Sometimes, the most valuable solutions are not the newest ones, but the ones we have quietly relied on for decades
Author summary
Dr Fitri Fareez Ramli is a Medical Lecturer at the Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia and holds a DPhil in Psychiatry from the University of Oxford. His research focuses on neuropsychopharmacology and emotional processing in mood disorders.