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Lithium for bipolar disorder
1949; US approval 1970· Therapy or method
Well replicatedStrong, repeated evidence.
A simple salt that steadies mood in bipolar disorder, the first drug shown to keep a mental illness from returning.
See it on the Psychology map →What it says
In 1949 Australian psychiatrist John Cade, at a Melbourne veterans' hospital, gave lithium to ten manic patients; most calmed dramatically. Danish psychiatrist Mogens Schou's trials in the 1950s and 60s showed it prevents relapses. US approval lagged until 1970, partly because a lithium salt substitute had poisoned heart patients in the late 1940s. Effective doses sit close to toxic levels, so blood tests are needed, and kidney and thyroid effects are monitored. It also lowers suicide risk.
Why it matters
It showed a medicine could target a specific mental illness, and it remains a first-line treatment, though it is cheap and unpatentable, so little marketed.
The evidence
Cade's 1949 report in the Medical Journal of Australia, Schou's controlled trials, and meta-analyses showing fewer relapses and suicides among patients taking lithium.
Open questions
How lithium works is still unknown. A 2025 Harvard mouse study linked low brain lithium to Alzheimer's disease; whether that applies to people is unclear.
Connections (2)
▸Lithium for bipolar disorder stabilizes mood in Bipolar disorderWell replicated
The connection
Lithium dampens manic highs and, to a lesser degree, depressive lows, and taken long term it prevents many future episodes. It is particularly good at preventing mania and suicide. About a third of patients respond very well; others respond partly or not at all.
Who showed it and when
John Cade, Melbourne, 1949; Mogens Schou's trials in Denmark from 1954; US FDA approval for mania in 1970.
The evidence
Randomized trials and meta-analyses show lithium reduces relapses and suicides compared with placebo and with several other drugs.
Open questions
How it works is unknown, and why some patients respond dramatically while others do not is being studied genetically.
▸Lithium for bipolar disorder launched the modern era of Psychiatric medicine: drugs and brain treatmentsWell replicated
The connection
Cade's 1949 discovery was the first time a drug clearly treated a specific mental illness rather than simply sedating patients. With chlorpromazine (1952) and the first antidepressants (1957), it launched modern psychopharmacology and the idea that mental disorders have treatable biology.
Who showed it and when
Melbourne, Australia, 1949; little noticed until Mogens Schou's Danish trials in the 1950s–60s won wider acceptance.
The evidence
Cade's published report and histories of psychiatry, such as Edward Shorter's, document lithium as the first modern psychiatric drug.
Open questions
Some historians give chlorpromazine more credit, since it spread worldwide within a few years while lithium took two decades to be widely adopted.