Lithium has been available as a generic since its launch in 1970, but the extended release formulations were once branded, as this 1998 ad shows
Lithium response is better when started earlier
STUDY: Nylander PO et al, Biol Psychiatry Glob Open Sci 2026
STUDY TYPE: Retrospective cohort study
FUNDING: Independent
Background
Guidelines recommend lithium first-line in bipolar, especially early in the course, but people wait years to start it. This study looks at how that delay alters response.
The Study
- 192 adults with bipolar disorder (156 type I, 36 type II) from three Swedish lithium clinics, restrospective covering around 25 years, average of 11.5 years before lithium and 12.6 years on it, given without other mood stabilizers.
- Good response defined as at least a 68% drop in episodes per year on lithium (the median).
Results
The chance of a good response decreased with each step of delay:
- Under 3 years: 69%
- 3 to 8 years: 50%
- 8 to 17 years: 44%
- Over 17 years: 40%
Patients who waited more than 17 years had about one-quarter the odds of a good response (adjusted odds ratio 0.23) compared with those who started within 3 years.
Bipolar II patients waited more than twice as long for lithium (median 15 vs 6 years), but responded about as well as bipolar I. Lithium levels averaged 0.6 mEq/L, slightly lower than the recommended range of 0.6-0.8 mEq/L.
Limitations
Retrospective, no control group, so it can’t prove that delay causes the decline. Poorer responders also had fewer episodes per year before lithium, leaving less room to improve.
Still, the stepwise pattern agrees with Danish registry data favoring lithium after a first mania, and with biological evidence suggesting lithium can change the course of the illness.
Practice Implications
- Learn how to recognize bipolar faster and start lithium earlier in our Carlat Podcast series on Timing.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
