Firmly established only at prescription strength, where lithium prevents the return of severe mood episodes and reduces deaths among people who have them. Slower memory loss, fewer dementia diagnoses, and longer life rest on population comparisons and small studies that disagree. Prescription harms center on thyroid, kidneys, and calcium; at over-the-counter amounts harms appear rare but unstudied over decades. (Full Review)
| Marker | Target | Why |
|---|---|---|
| Serum lithium, 12-hour trough | 0.25–0.5 mmol/L cognitive; 0.6–1.0 mmol/L mood; undetectable on trace doses | The only direct measure of exposure; toxicity begins just above the therapeutic range |
| Estimated glomerular filtration rate | >90 mL/min/1.73 m² | Determines lithium clearance and therefore exposure at any given dose |
| Cystatin C | 0.6–1.0 mg/L | Kidney filtration marker independent of muscle mass |
| Urine osmolality, first morning | >600 mOsm/kg | Detects loss of urinary concentrating ability, the earliest renal effect of lithium |
| Thyroid-stimulating hormone | 0.5–2.0 mIU/L | Detects the most common lithium-associated endocrine effect before symptoms appear |
| Free T4 | 1.0–1.5 ng/dL | Distinguishes mild from overt hypothyroidism when thyroid-stimulating hormone rises |
| Thyroid peroxidase antibodies | Negative | Identifies before starting who is most likely to become hypothyroid on lithium |
| Serum calcium, albumin-corrected | 2.20–2.45 mmol/L | Detects lithium-associated hyperparathyroidism, whose symptoms mimic cognitive decline |
| Parathyroid hormone | 15–45 pg/mL | Confirms the mechanism when calcium rises; can be elevated before calcium leaves range |
| Serum sodium | 138–142 mmol/L | Low sodium raises lithium retention; screens for the dilutional effect of excess water |
| Complete blood count | Within reference range, with a modest expected rise in neutrophils | Lithium reliably causes a benign white cell rise that would prompt an infection workup |
| Body weight | Stable within 2 kg of baseline | Common reason for discontinuation and may signal thyroid suppression |
| Plasma phospho-tau 217 | Below the assay’s positivity threshold; trajectory matters more than a single value | The most practical blood measure of the pathology the proposed mechanism targets |
| Neurofilament light chain | Age-adjusted; a rising value over time is the signal | Non-specific marker of ongoing neuronal injury, a secondary endpoint in lithium trials |
Cadence: Prescription doses: serum lithium 5–7 days after initiation and after every dose change, then every 3 months for the first year and every 3–6 months thereafter, with kidney, thyroid, and calcium panels at 3, 6, and 12 months and annually. Trace supplement doses: kidney, thyroid, and calcium panels every 12 months, moving to 6-monthly if any value drifts.