Both are equal after successful TMS, but one is better tolerated
STUDY: Noda Y et al, JAMA Network Open 2025
STUDY TYPE: Randomized, single-blind, noninferiority trial
FUNDING: Teijin Pharma (they distribute Neurostar TMS in Japan)
Background
Lithium is one of the best studied options for prevention of depression, not just for bipolar but for unipolar, as these stats show:
- Lithium prevented depression in 21 randomized trials averaging 2 years
- Lithium lowers the risk of relapse after ECT by 50%
- Lithium lowers re-hospitalization for depression by 50% (non-randomized data)
This trial tested this gold-standard strategy against maintenance TMS in patients who responded to TMS.
The Study
- 75 adults with treatment-resistant depression who’d responded to acute bilateral rTMS in Japan.
- Randomized to 24 weeks of maintenance rTMS or lithium, added to existing venlafaxine.
- Primary outcome was depression severity at 24 weeks; secondary, time to relapse.
Results
Depression scores at 24 weeks didn’t differ between rTMS and lithium (difference 0.3 points, 95% CI -2.7 to 3.3, p=.84). Relapse occurred in 18% of each group (p=.92).
Side Effects
Lithium produced more adverse events than rTMS (16 versus 3, odds ratio 7.10, p=.005), including tremor, headache, dizziness, and one case of pancreatitis. One patient was hospitalized for worsening depression; only 3 of 37 tolerated a full dose.
Limitations
The sample was enriched with TMS responders. Industry sponsoreship. Randomization balanced age, sex, and severity, but not illness duration, and the lithium group had roughly two years longer illness by chance. Only raters were blinded. The lack of a placebo arm means both treatments could be ineffective, and we wouldn’t know.
Practice Implications
- For a patient who’s responded to acute TMS, weekly maintenance rTMS is a reasonable alternative to lithium, with similar protection and fewer side effects.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
