Lithium as a Disease-Modifying Drug

September 22, 2026by Chris Aiken, MD0

Robert Post, MD runs Bipolar Network News, a resource for new research that inspired this blog

A leading scientist finds new research to support lithium.

STUDY: Post RM, Expert Review of Neurotherapeutics 2026

STUDY TYPE: Expert opinion / narrative review

FUNDING: Independent

Background

Robert Post developed the kindling theory of bipolar disorder. Working at NIMH, he hypothesized that bipolar follows a progressive, self-perpetuating course. Untreated, the episodes become increasingly frequent, autonomous, and less dependent on external triggers.

Here he gathers new evidence on lithium, suggesting it works as a disease-modifying drug, altering the course of the illness, tempering the vicious cycle of progressive episodes.

Summary
  • Underutilized. Less than 20% of US bipolar outpatients take lithium, versus about half on antidepressants, which have questionable efficacy and can worsen cycling. Lithium is rarely used in children with bipolar disorder despite positive trials and FDA approval to age 7.
  • Renal. A study of 17,740 patients found no excess kidney-disease risk with lithium versus other mood stabilizers, though other studies find problems, particularly at levels above 0.8.
  • Weight. A meta-analysis found lithium is weight-neutral versus placebo, contrary to its reputation for causing weight gain.
  • Suicide. Lithium is the only mood stabilizer with a proven anti-suicide effect.
  • Dementia prevention. In mice fed a low-lithium diet, brain lithium deficiency caused cognitive decline resembling that in patients with mild cognitive impairment or Alzheimer’s disease; a novel formulation, lithium orotate, reversed it in the animal model.
Disease Modifying

A disease modifying treatment addresses underlying causes and improves long-term outcomes. Dr. Post summarized the recent research, and I’ve added a few other highlights:

  • Underlying causes. Lithium corrects the expression of circadian rhythm genes, the genes with the closest link to bipolar. It normalizes the hyepr-excitability of pleuripotent bipolar neurons.
  • Other biological benefits. Lithium is linked to longer telomeres (related to aging of the DNA) and preserved brain volume, with more neuroprotective effects than any other psychiatric medication.
  • Outcomes. Lithium lowers mortality, both from suicide and medical causes. Functional outcomes are greater on lithium compared to antipsychotics, and in some studies it prevents future episodes better than other mood stabilizers like valproate.
Practice Implications
  1. Bipolar and recurrent depression are long-term illnesses. Aim for treatments that address underlying causes, increase the lifespan, and prevent future episodes.
  2. One in three people with bipolar have the classic type, with euphoric hypomanias or manias, followed by depressions, and full, sustained recovery between episodes. They can be bipolar I or II, and are very responsive to lithium.

—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report

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