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Lithium

Database-based evaluation · 1,782 studies in our database, 92 of them controlled human trials · As of · How we work

Lithium is an alkali metal whose salts stabilize mood in medicine; human studies show mixed results depending on the clinical picture.

We evaluated 262 human studies on Lithium, including 29 randomised controlled trials and 56 meta-analyses or systematic reviews; the controlled studies include 2,645 participants in total. As of 24 October 2026.

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1. What Is Lithium? Occurrence, Origin and Forms

Lithium is an alkali metal and the lightest metal; in nature it occurs in rock, mineral springs and drinking water in very small amounts. As a salt it is used in medicine as a mood stabilizer. In addition, very low intake via drinking water is being investigated.

Lithium is found in small amounts in rock, soils, mineral waters and drinking water. In medicine it is given as a salt in solid form or as a solution.

Lithium is obtained from lithium-bearing ores and brines; for medical use these yield salts such as lithium carbonate or lithium citrate. Studies examine different forms, including lithium carbonate, lithium citrate, lithium orotate and the very low intake via drinking water.

Forms and Preparations Studied

  • Lithium carbonate
  • Lithium citrate
  • Lithium orotate
  • Lithium chloride, dissolved in water
  • Trace lithium in drinking water

Not covered on this page:

  • Sodium and potassium, other alkali metals
  • Lithium-ion batteries and other technical uses
  • Other mood stabilizers such as valproate and lamotrigine
  • Brand-name products and finished preparations

2. What Does Lithium Do? Results by Area

AreaResult in controlled studiesStrength of evidenceStudiesParticipants
Dementia and Alzheimer's diseasemostly no differencemoderate15 meta-analyses · 2 controlled · 26 other141
Bipolar disordermixedmoderate11 meta-analyses · 5 controlled · 54 other347
Depressionmixedmoderate6 meta-analyses · 10 controlled · 24 other1,027
Neuroprotectionmostly no differencemoderate11 meta-analyses · 5 controlled · 21 other206
Suicide preventionmostly no differencemoderate8 meta-analyses · 2 controlled · 26 other613
Trace lithium in drinking waterreviews onlylow3 meta-analyses · 0 controlled · 2 other0
Other investigationsmostly no differencehigh10 meta-analyses · 10 controlled · 104 other603

How to read the table: counted are human studies whose results concern the area. “High” means at least one meta-analysis and two controlled studies showing improvement, or at least three controlled studies of which three quarters show improvement, with at least 300 participants in total. “Moderate” means at least two controlled studies showing improvement, as a majority, or one meta-analysis alongside controlled studies. “Low” means one controlled study showing improvement. Where an area has no controlled study, the strength of evidence is at most “low” (result “reviews only” or “observational data only”). Everything else is “unclear”. A study counts as showing improvement when at least half of its outcomes in this area improved. Reviews of combination products do not count as meta-analyses; results that only describe side effects or shares of users do not count as an effect. The same study is counted only once.

3. What the Studies Show in Detail

Lithium, Dementia and Alzheimer's Disease: Human Studies

In mild cognitive impairment, low-dose lithium slowed cognitive decline compared with placebo in a randomized study and lowered phosphorylated tau in the cerebrospinal fluid 8074. Another randomized pilot study with low-dose lithium carbonate in mild cognitive impairment reached none of its primary goals 67. A meta-analysis of randomized studies in Alzheimer's dementia, by contrast, found no established improvement in cognition, everyday function or cerebrospinal fluid biomarkers 20. Reviews show favorable effects on amyloid and tau mainly in animal studies 3038. In observational studies, which several meta-analyses and reviews summarize, lithium treatment was associated with a lower dementia risk 28404458; this shows an association, not proof. In older people with bipolar disorder, a review found no increased risk of neurocognitive disorders with long-term lithium 31.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
8 Terao et al. 2024meta-analysis · 6,547 participantsLithium (low-dose); low-dose; vs. Placebo, donanemab, lecanemab, aducanumabMini-Mental State Examination: improved (significantly outperformed); Alzheimer's Disease Assessment Scale-cognitive subscale: improved (significantly higher than placebo)
17 Matsunaga et al. 2019meta-analysis · 568 participantsLithium (3 RCTs) and tideglusib (2 RCTs) as GSK-3 inhibitors; vs. PlaceboCognitive function scores (lithium subgroup): improved (SMD = -0.41, p = 0.04)
20 Pereira et al. 2026systematic review · 394 participantsLithium (compound not specified); vs. Placebo or standard therapyGlobal cognition (MMSE): no difference (MD -1.61, 95% CI -4.11 to 0.88); Global cognition (ADAS-Cog): no difference (MD -1.82, -3.05 to -0.60); Memory (figure recall): unclear
22 Matsunaga et al. 2015meta-analysis · 232 participantsLithium (compound not specified); vs. PlaceboCognitive performance (ADAS-cog or MMSE): improved (standardized mean difference = -0.41, 95% confidence interval = -0.81 to -0.02, p = 0.04)
27 Deng et al. 2026systematic reviewLithium (as salt, form not specified); low-dose in MCI/AD trials, otherwise not reported; 10 weeks to 3 years; vs. Placebo or other treatment (not further reported)global cognitive deterioration: improved
28 Campedelli et al. 2026meta-analysisLithium (compound not specified); vs. Lithium exposure vs. no exposureDementia risk (pooled hazard ratio): improved (HR 0.633 (95% CI: 0.517-0.775; p = 0.003)); Alzheimer's disease diagnosis (hazard ratio): no difference (HR 0.656 (95% CI: 0.427-1.009; p = 0.052)); Cognitive outcomes (SMD): improved (SMD -0.410 (95% CI: -0.810 to -0.020; p = 0.040))
30 Xiao et al. 2026systematic reviewLithium monotherapy; low-dose, long-term; long-term; vs. no uniform control reportedintracerebral amyloid deposition: unclear (inconsistent effects); AD-related cognitive deficits: unclear (inconsistent effects)
31 Parlapani et al. 2026systematic reviewLithium (long-term treatment); Long-term treatment; vs. No lithium / other treatmentRisk of neurocognitive disorders: no difference (Eight out of nine studies did not support an association)

Further studies in this area: 40 44 50 52 55 56 58 67 74 95 97 99 103 168 169 171 174 190 194 205 216 218 221 224 229 232 235 236 240 249 252 254 257 258 261

Lithium and Bipolar Disorder: Human Studies

In bipolar disorder, lithium alone lowered the risk of new mood episodes compared with placebo in meta-analyses of randomized studies 57, in one of them for manic as well as depressive episodes 5. In children and adolescents with acute mania, more treated participants responded under lithium than under placebo in a network meta-analysis, but the mania symptoms did not decrease more strongly 10. Reviews speak for an effectiveness also in children, around birth and in old age, although larger studies are still pending 615. In adolescents with acute mania, fewer responded under lithium than under quetiapine in a randomized study, the remission rates did not differ 64. In adults with mania under divalproex, additional lithium did not improve the symptoms more strongly than placebo in a small randomized pilot study, and more participants discontinued 70.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
5 Kishi et al. 2021meta-analysis · 9,821 participantslithium, sometimes with valproate/oxcarbazepine or antipsychotics; mean study duration 70.5 ± 36.6 weeks; vs. placebo and other active treatmentsrecurrence/relapse rate of any mood episode: improved; recurrence/relapse rate of depressive episode: improved; recurrence/relapse rate of manic/hypomanic/mixed episode: improved
6 Janiri et al. 2023review · 8,209 participantslithium (form not specified); vs. placebo or non-lithiumefficacy in paediatric bipolar disorder: improved; prevention of mood episodes peripartum: improved; efficacy in bipolar disorder in old age: improved
7 Nestsiarovich et al. 2022meta-analysis · 7,773 participantsLithium, mood stabilizers, antipsychotics, antidepressants; 24-104 weeks follow-up; vs. Placebo or alternative active agentsNew bipolar episodes (lithium vs. placebo): improved (ORs varied 0.19-0.46)
10 Vita et al. 2025meta-analysis · 2,844 participantsLithium (salt form not specified) vs antipsychotics and other mood stabilizers; mean study duration 5.4 weeks; vs. placebo, second-generation antipsychotics, other mood stabilizersmania response vs placebo: improved (RR = 1.35, 95% CI = 1.00, 1.83, p = .049); mania symptom reduction vs placebo: no difference (no mood stabilizer outperformed placebo); all-cause discontinuation vs placebo: no difference (no significant treatment-placebo differences for all-cause discontinuation)
13 Riedinger et al. 2023systematic review · 1,222 participantsLithium (compound not specified); vs. no placebo-controlled RCTs with therapeutic levelsEfficacy in bipolar depression: unclear
15 Janiri et al. 2023systematic review · 857 participantsLithium (compound not specified); vs. Placebo, antipsychotics or other pharmacological agentsEfficacy in manic/mixed episodes vs placebo: improved; Efficacy vs antipsychotics: worsened; Efficacy range: unclear (32% to 82.4%)
19 Kupka et al. 2024systematic review · 403 participantsLithium (compound not specified); vs. Non-discontinuers or continuation vs. discontinuation and restartNon-response to lithium re-treatment: unclear (3.6 to 27.7%, with an average of 17.3%)
27 Deng et al. 2026systematic reviewLithium (as salt, form not specified); low-dose in MCI/AD trials, otherwise not reported; 10 weeks to 3 years; vs. Placebo or other treatment (not further reported)composite cognitive scores: no difference

Further studies in this area: 36 43 48 49 51 53 64 70 72 76 81 98 100 102 104 106 109 110 114 117 120 128 134 139 144 146 152 160 170 173 183 187 191 195 196 197 200 204 205 208 209 210 213 215 218 222 226 228 231 233 234 236 237 239 241 245 246 247 248 249 254 262

Lithium and Depression: Human Studies

In depression the picture is inconsistent. As an add-on to antidepressants, a meta-analysis of placebo-controlled studies found more frequent response with lithium, which was no longer established after correction for publication bias 4. In older people with treatment-resistant depression, adding lithium in a randomized study differed neither in well-being nor in remission from switching to nortriptyline 61. Compared with adding quetiapine, symptoms improved similarly in another randomized study 62. After unsuccessful SSRI, adding lithium in a randomized study brought no established advantage over adjusting the SSRI dose 60, and after unsuccessful imipramine it was weaker in another study than adding citalopram 65. As maintenance treatment after successful magnetic stimulation, lithium prevented relapses in a randomized study similarly to continued magnetic stimulation, with more side effects 69. After ketamine infusions, lithium did not maintain improvement better than placebo in a randomized study 84, and low-dose lithium carbonate as an add-on did not lead more frequently to response in a small placebo-controlled study 92. Systematic reviews report a benefit in treatment-resistant geriatric depression 34 and from low-dose lithium as an add-on 43; a systematic review of direct comparisons considers lithium, quetiapine and esketamine effective, descriptively placing quetiapine somewhat ahead of lithium 33. A systematic review of children, peripartum and older adults found the efficacy in major depression in childhood unclear 6. The strength of evidence is moderate: Many studies are small and compared lithium with other treatments instead of placebo.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
4 Hsu et al. 2026meta-analysis · 13,616 participantsLithium augmentation added to antidepressants; vs. Placebo-controlled RCTsResponse rate (≥50% symptom reduction): improved (OR 2.06; 1.30-3.27); Response rate after bias adjustment (PET-PEESE/selection models): no difference (statistically non-significant)
6 Janiri et al. 2023review · 8,209 participantslithium (form not specified); vs. placebo or non-lithiumefficacy in paediatric major depressive disorder: unclear; efficacy in resistant major depressive disorder in old age: improved
21 Nelson et al. 2014meta-analysis · 237 participantsLithium augmentation of antidepressants (TCA or second generation); vs. Placebo added to antidepressantResponse odds ratio lithium vs. placebo, all contrasts: improved (2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002)); Response with tricyclic antidepressants: improved; Response with second generation antidepressants: improved
33 Eckert et al. 2026systematic reviewLithium augmentation; vs. Quetiapine or esketamineEfficacy in treatment-resistant depression: improved; Descriptive superiority of quetiapine over lithium: no difference
34 Pozuelo et al. 2025systematic reviewLithium (compound not specified); vs. Comparator treatment groupReduction in depressive symptoms post-treatment: improved
43 Strawbridge et al. 2023systematic reviewLow-dose lithium (LDL); Serum level ≤0.6 mmol/L; vs. Placebo or other comparatorDepression (adjunctive therapy): improved (potentially as an adjunctive therapy)
46 Strawbridge et al. 2023systematic reviewLithium (compound not specified); vs. other interventions (ECT, ketamine, bupropion, aripiprazole, quetiapine)Change in pro-inflammatory markers: unclear
60 Pérez et al. 2025randomised controlled · 257 participantsLithium augmentation added to SSRI; 6 weeks; vs. SSRI dose optimisation, nortriptyline combination, venlafaxine switch, problem-solving therapyResponse rate at week 6: unclear (28.2% v. 14.3%, odds ratio = 2.36 [95% CI 1.0-5.6], p = 0.05); Remission rate at week 6: unclear (16.9% v. 12.2%, odds ratio = 1.46, [95% CI 0.57-3.71], p = 0.27); HDRS-17 score reduction: unclear (-2.6 [95% CI -4.9 to -0.4], p = 0.021)

Further studies in this area: 61 63 65 69 79 84 88 91 92 98 122 133 136 145 154 155 193 197 206 225 233 238 239 241 242 243 244 245 250 256 259 260

Lithium and Neuroprotection: Human Studies

In bipolar disorder, systematic reviews report neurotrophic and neuroprotective effects of long-term lithium treatment 3144. A systematic review on low-dose lithium reports less cognitive decline 43, and a randomized controlled study found in young people with a first manic episode a more favorable change in white matter volume in the left internal capsule with lithium compared with quetiapine 86. In contrast, a randomized controlled study in adults with HIV-associated neurocognitive disorder showed no difference in the neuroprotection biomarker panel between lithium and placebo 73, and another randomized controlled study in young people with a first manic episode found no different change in Brain-PAD between the lithium and quetiapine groups 82. The findings come predominantly from reviews and small randomized studies in specific patient groups.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
18 Hamad et al. 2023meta-analysis · 469 participantsLithium, in one study combined with valproate; Doses varied across studies; vs. PlaceboSurvival rate: no difference (hazard ratio = 0.95, 95% confidence interval: 0.65 to 1.37, P = 0.77); Average change of revised ALS functional rating scale: no difference (P = 0.35); Change in forced vital capacity percentage predicted: no difference (P = 0.73)
20 Pereira et al. 2026systematic review · 394 participantsLithium (compound not specified); vs. Placebo or standard therapyCSF biomarkers: no difference
22 Matsunaga et al. 2015meta-analysis · 232 participantsLithium (compound not specified); vs. PlaceboCSF biomarkers (p-tau181, total tau, amyloid-β42): no difference
29 Boere et al. 2026systematic reviewLithium (salt form not specified); vs. Non-lithium bipolar subjects, other treatment, healthy controls, or within-subject baselinesVolume of hippocampus, amygdala, ACC, and PFC: improved; White-matter integrity within frontolimbic circuitry: improved; Amygdala-PFC/ACC connectivity, hippocampal integrity, and volumes: improved
31 Parlapani et al. 2026systematic reviewLithium (long-term treatment); Long-term treatment; vs. No lithium / other treatmentNeurotrophic effects: unclear (accumulating evidence supports Lithium's neurotrophic effects)
37 Hassan et al. 2024systematic reviewLithium (compound not specified); vs. Other neuroprotective strategies or controlStroke volume: unclear; Functional recovery: no difference
41 Solleti et al. 2024systematic reviewLithium (compound not specified); vs. Cross-sectional studies on amygdalar volume with lithiumAmygdalar volume: unclear
43 Strawbridge et al. 2023systematic reviewLow-dose lithium (LDL); Serum level ≤0.6 mmol/L; vs. Placebo or other comparatorCognitive decline: improved (Significant benefits (versus placebo))

Further studies in this area: 44 48 55 56 67 73 82 86 90 191 194 199 200 202 205 208 210 218 224 228 229 233 235 236 248 251 253 257 261

Lithium and Suicide Prevention: Human Studies

In suicide prevention, a mixed picture emerges: observational studies that a systematic review summarizes found fewer suicides under lithium in affective disorders, under long-term treatment more than under short-term 54. Higher lithium levels in drinking water were associated with lower suicide mortality in a meta-analysis of population comparisons and a review 157. In adolescents with bipolar disorder, a review reports fewer suicidal thoughts and self-harm, with a mixed study situation 36. In randomized studies, a protection is not assured: lithium carbonate in addition to usual care did not reduce repeated suicide-related events compared with placebo 59; a re-analysis of the same study in treatment-adherent participants could neither demonstrate nor exclude a protection 89. A meta-analysis of randomized studies found no assured difference in suicides and suicide attempts compared with placebo or usual treatment 11. The strength of evidence is moderate; the studies examined different lithium compounds and populations, and the drinking water findings come from observational studies of entire populations that show associations but not causes. It remains open which salt form and which serum level are decisive for a possible benefit.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
11 Nabi et al. 2022meta-analysis · 2,578 participantsLithium (compound not specified); vs. Placebo or treatment as usualSuicide rate: no difference (OR = 0.41 (95% confidence interval 0.03-2.49), p = 0.45); Non-fatal suicidal behaviour: no difference; Suicide attempts: no difference
14 Ghaemi et al. 2024meta-analysis · 1,203 participantsLithium salts (unspecified); vs. PlaceboSuicides with lithium vs. placebo (complete analysis): improved (two suicides with lithium versus nine with placebo, RR = 0.25); Statistical significance of complete analysis: improved (95% CIs 0.05, 0.83)
35 Waszak et al. 2025systematic reviewLithium (compound not specified); Studies 2014–2024; vs. Valproate and other mood stabilizersSuicide risk: improved
36 Sesso et al. 2024systematic reviewLithium (form not specified); vs. other mood stabilizers, placebo, or no treatmentSuicidal ideation and self-harming behaviors: improved
45 Wilkinson et al. 2023meta-analysisLithium (compound not specified); vs. Placebo/no lithium or active controlsOdds of suicide in bipolar disorder vs. active controls: improved (OR = .58, p = .005); Odds of suicide in bipolar disorder vs. placebo/no lithium: improved (OR = .46, p = .009); Odds of suicide in mixed diagnoses vs. placebo/no lithium: improved (OR = .27, p < .001)
47 Riblet et al. 2022meta-analysisLithium (salt form not specified); vs. Control conditionPeto odds ratio for suicide: no difference (OR = 0.30, 95% CI 0.09-1.02); Incidence rate ratio for suicide: no difference (IRR = 0.22, 95% CI 0.05-1.05)
48 Fountoulakis et al. 2022systematic reviewLithium (monotherapy or combination); vs. other more recently developed agentsSuicidal ideation: improved
51 Ogasawara et al. 2022meta-analysisLithium vs. quetiapine; vs. Quetiapine vs. lithiumSuicide-related events: no difference (OR: 2.35, 95% CI: 0.40-13.65, P = 0.34)

Further studies in this area: 54 59 66 101 107 143 166 171 178 188 200 201 203 205 206 211 212 213 216 217 218 220 222 233 241 248 249 255

Lithium and Trace Lithium in Drinking Water: Human Studies

Higher lithium levels in drinking water were associated with lower suicide mortality in a meta-analysis of population comparisons and a review 157. Two further reviews examine populations and patients with affective disorders. One review tests the assumption that higher lithium levels in drinking water are associated with lower suicide rates 211. The second review considers such an association possible 212. These are observational data from entire populations, not controlled individual studies; they show associations, not causes. The strength of evidence is low; traces of lithium in drinking water were examined, not lithium as a medication.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
1 Barjasteh-Askari et al. 2020meta-analysis · 3,740,113 participantsLithium in drinking water; vs. Regions with higher vs. lower lithium concentrationsuicide mortality: improved (OR= 0.42; 95% CI: 0.27-0.67; p-value <0.01); suicide mortality in men: improved (OR= 0.54; 95% CI: 0.35-0.84; p-value <0.01); suicide mortality in women: no difference (OR= 0.70; 95% CI: 0.48-1.01; p-value =0.057)
57 Vita et al. 2015systematic reviewLithium in drinking water; vs. higher vs. lower lithium levels in drinking watersuicide mortality: improved
58 Mauer et al. 2014systematic reviewLithium in standard and trace doses (various compounds); Standard dose and trace dose (low dose); vs. Placebo in RCTs; ecological/epidemiological comparisonsAssociation between trace-dose lithium and low suicide/homicide/mortality and crime rates: improved (Nine out of 11 epidemiological studies)
211 Tondo et al. 2025reviewLithium salts (carbonate, citrate, orotate, chloride) and lithium in drinking water; vs. Placebo, no treatment, or alternative treatmentSuicide rates: improved
212 Tondo et al. 2024reviewLithium salts (carbonate, citrate, orotate); Long-term treatment; vs. Placebo or alternative treatmentsSuicide rates with higher lithium levels in drinking water: unclear

Lithium: Further Outcomes in Studies

In children and adolescents with conduct disorder, a systematic review found efficacy against aggressive behavior 15. Lithium carbonate in addition to radioiodine increased the cure rate in hyperthyroidism compared with radioiodine alone 12. In Huntington's disease and spinocerebellar ataxia, a systematic review reports improvements, while it saw no difference in amyotrophic lateral sclerosis 55. Against restlessness and aggression in Alzheimer's dementia, low-dose lithium was not superior to placebo in a randomized study 68. Lithium did not prevent nerve damage from chemotherapy better than placebo in a randomized study 83.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
2 Schoretsanitis et al. 2022systematic review · 25,907 participantslithium salts (type not specified); long-term; vs. patients receiving nonlithium treatmentprevalence of impaired kidney function (25.5% (95% CI = 19.8-32.2)); odds ratio for impaired kidney function vs. nonlithium (2.09 (95% CI = 1.24-3.51))
3 Macaron et al. 2026meta-analysis · 17,740 participantsLithium salts (not further specified); long-term use; vs. patients not on lithiumMean estimated glomerular filtration rate (eGFR) (MD = -11.14 ml/min/1.73 m2, 95% CI: -16.61, -5.68); Mean annual eGFR decline (MD = 0.13 ml/min/1.73 m2, 95% CI: 0.06, 0.20); Serum creatinine concentration (MD = 0.05, 95% CI: 0.03, 0.07)
9 Shahraki et al. 2026systematic review · 5,853 participantsLithium salts (compound not specified); chronic therapy; vs. sporadic hyperparathyroidismhypercalcemia prevalence (7.2% (423/5,853)); hyperparathyroidism prevalence (4.8% (156/3,239)); multiglandular disease in surgical cases (25-83%)
12 Abd-ElGawad et al. 2025meta-analysis · 2,047 participantsLithium carbonate (LiCO3) plus radioactive iodine; short-duration intensified vs. diluted doses (subgroups); short duration (subgroup analysis); vs. radioactive iodine alonecure rate: improved (RR 1.12, 95% CI [1.03,1.23], p = 0.01); Free T4 (7 days): improved (MD -4.90, 95% CI [-7.91, -1.89], p = 0.001); Free T4 (most common time point): improved (MD -3.83, 95% CI [-7.45, -0.20], p = 0.04)
15 Janiri et al. 2023systematic review · 857 participantsLithium (compound not specified); vs. Placebo, antipsychotics or other pharmacological agentsEfficacy in conduct disorder, especially aggressive behaviors: improved
16 Sabtiari et al. 2025systematic review · 727 participantsLithium (form not specified); vs. Cognition before vs. after starting lithium (within-subject)Global cognition: unclear (15 studies); Memory: unclear (19 studies); Processing and psychomotor speed: unclear (8 studies)
18 Hamad et al. 2023meta-analysis · 469 participantsLithium, in one study combined with valproate; Doses varied across studies; vs. PlaceboSevere adverse events (odds ratio = 1.13, 95% confidence interval: 0.73 to 1.75, P = 0.58)
20 Pereira et al. 2026systematic review · 394 participantsLithium (compound not specified); vs. Placebo or standard therapySerious adverse events

Further studies in this area: 22 23 24 25 26 32 39 42 48 51 55 56 58 63 68 69 70 71 73 75 77 78 83 85 87 88 93 94 96 97 98 100 105 108 111 112 113 115 116 118 119 121 123 124 125 126 127 128 129 130 131 132 133 135 136 137 138 140 141 142 143 147 148 149 150 151 153 156 157 158 159 160 161 162 163 164 165 167 169 171 172 174 175 176 177 179 180 181 182 184 185 186 189 190 192 197 198 200 206 207 209 210 214 219 221 223 227 229 230 235 241 245 249 250 263 264

4. How Is Lithium Dosed? Preparation, Dose and Duration in Studies

The studies predominantly used lithium salts without a more closely named salt form, in individual studies lithium carbonate, sometimes as an extended-release preparation or at low dose. Lithium citrate, lithium orotate and lithium chloride dissolved in water were not tested as separate forms in the included studies. In many studies, lithium was investigated as an add-on to other active substances such as antidepressants, antipsychotics or anticonvulsants.

Preparation or formDoseDurationStudy
Extended-release lithium carbonate added to usual careStarted at 600 mg/d; levels 0.54 and 0.46 mEq/L—59
Lithium augmentation added to SSRI—6 weeks60
Lithium augmentation of existing antidepressant—approximately 10 weeks61
Lithium (form not specified) vs. quetiapine—12 months63
Lithium (salt form not stated) versus quetiapineLithium target serum level 1.0-1.2 mEq/L; quetiapine 400-600 mg6 weeks64
Lithium augmentation (adjusted to plasma levels) vs. citalopram augmentationLithium: adjusted to plasma levels; citalopram: 30 mg/day10 weeks65
Lithium vs. valproate—2.5 years66
Low-dose lithium carbonate or placebolow dose, exact dose not reported2 years67
Lithium carbonate150–600 mg daily12 weeks68
Lithium maintenance therapy (form not specified) vs. rTMSLithium dose not reported; venlafaxine 150-225 mg/d24 weeks69
Divalproex plus blinded lithium—12 weeks70
Sertraline plus lithium (salt form not stated)—12 weeks71
Lithium added to haloperidolstandard lithium (dose not stated)21 days72
Lithium (salt form not stated)—24 weeks73
Lithium carbonatesubtherapeutic concentrations 0.25–0.5 mEq/L2 years double-blind, then 24 months single-blinded74

5. Is Lithium Safe? Side Effects in Studies

In reviews, lithium salts were associated with impaired kidney function and declining estimated glomerular filtration rate 23; the authors of a meta-analysis consider ongoing monitoring of kidney values essential 3. In older people with mild cognitive impairment, kidney function remained unchanged under low-dose lithium in a randomized study, but more adverse events occurred than under placebo, including weight gain and TSH increase 75. In children and adolescents with mania, more treated participants discontinued lithium because of side effects than under placebo 10. In children and adolescents, no severe lithium-related events were reported 615, but the studies are mostly small and short.

StudyReported side effects
2 Schoretsanitis et al. 2022impaired kidney function (CKD) in 25.5% of lithium patients
3 Macaron et al. 2026worsened kidney function (eGFR, creatinine)
5 Kishi et al. 2021individual adverse events reported, details not in abstract
6 Janiri et al. 2023no serious adverse events in children; low risk of congenital anomalies
8 Terao et al. 2024Lithium may be safer than the antibodies
9 Shahraki et al. 2026hypercalcemia 7.2%, hyperparathyroidism 4.8%, recurrence ~16% at 10 years
10 Vita et al. 2025lithium associated with more adverse event-related drop-outs than placebo
15 Janiri et al. 2023No severe lithium-related adverse events; common side effects similar to adults
16 Sabtiari et al. 2025Concerns about cognition-related side effects; mixed results
17 Matsunaga et al. 2019Tideglusib associated with increased AST elevation; no other significant differences
18 Hamad et al. 2023No difference in severe adverse events
20 Pereira et al. 2026No increased risk of serious AEs; drug-related AEs more frequent but heterogeneous

6. What Remains Open: Limits of the Evidence

  • Most studies do not name the salt form; lithium orotate was not examined in the evaluated studies.
  • Many controlled studies were small and short, tested lithium as an add-on to other active substances, or compared it with other medications instead of placebo.
  • The findings on lithium traces in drinking water come from observational studies of entire populations and show associations, not causes.

7. Bottom Line: What Is Established About Lithium

Lithium is an alkali metal that is used as a salt in medicine as a mood stabilizer. The best-supported use is relapse prevention in bipolar disorder compared with placebo 57; in depression and Alzheimer's dementia, a benefit is not established in randomized studies 420. In suicide prevention, associations from observational and drinking water studies 54157 stand against a randomized study without an established difference 59.

The strength of evidence is moderate in most areas: Many studies were small, tested lithium as an add-on to other active substances, or compared it with other medications instead of placebo. Lithium salts were associated with reduced kidney function 23, and low-dose lithium caused more adverse events than placebo 75.

Frequently Asked Questions

How well has Lithium been studied in humans?

We evaluated 262 human studies on Lithium, including 29 randomised controlled trials and 56 meta-analyses or systematic reviews; the controlled studies include 2,645 participants in total. As of 24 October 2026.

Does Lithium help with dementia and Alzheimer's disease? What the studies show

We evaluated 15 meta-analyses or systematic reviews, 2 controlled studies and 26 further studies; the controlled studies include 141 participants in total. Result of the controlled studies: mostly no difference. Strength of evidence under our published rules: moderate. Sources: 8172022

Does Lithium help with bipolar disorder? What the studies show

We evaluated 11 meta-analyses or systematic reviews, 5 controlled studies and 54 further studies; the controlled studies include 347 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: moderate. Sources: 56710

Does Lithium help with depression? What the studies show

We evaluated 6 meta-analyses or systematic reviews, 10 controlled studies and 24 further studies; the controlled studies include 1,027 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: moderate. Sources: 462133

Does Lithium help with neuroprotection? What the studies show

We evaluated 11 meta-analyses or systematic reviews, 5 controlled studies and 21 further studies; the controlled studies include 206 participants in total. Result of the controlled studies: mostly no difference. Strength of evidence under our published rules: moderate. Sources: 18202229

Does Lithium help with suicide prevention? What the studies show

We evaluated 8 meta-analyses or systematic reviews, 2 controlled studies and 26 further studies; the controlled studies include 613 participants in total. Result of the controlled studies: mostly no difference. Strength of evidence under our published rules: moderate. Sources: 11143536

Does Lithium help with trace lithium in drinking water? What the studies show

We evaluated 3 meta-analyses or systematic reviews and 2 further studies. There are no controlled studies yet, only reviews; the strength of evidence is therefore low at most. Sources: 15758211

What is lithium and how is it used in medicine?

Lithium is an alkali metal and the lightest metal; in nature it occurs in rock, mineral springs and in drinking water in very small amounts. As a salt it is used in medicine as a mood stabilizer. In addition, a very low intake via drinking water is being investigated.

Do human studies show an effect of lithium in bipolar disorder?

Meta-analyses of randomized studies found fewer new mood episodes under lithium alone than under placebo 57; in adolescents with acute mania, quetiapine was more effective in a direct comparison 64.

Is there evidence of an effect of lithium in depression?

The picture is inconsistent: as an add-on to antidepressants, more frequent response in a meta-analysis was no longer assured after correction for publication bias 4, and in randomized comparisons lithium performed similarly to or weaker than other add-on treatments 616265.

What do studies on lithium traces in drinking water show?

Higher lithium levels in drinking water were associated with lower suicide mortality in a meta-analysis of population comparisons and a review 157. Two further reviews examine populations and patients with affective disorders. One review tests the assumption that higher lithium levels in drinking water are associated with lower suicide rates 211, the second considers such an association possible 212. These are observational data from entire populations, not controlled individual studies; they show associations, not causes.

What side effects and safety aspects do the studies report?

In reviews, lithium salts were associated with impaired kidney function and declining estimated glomerular filtration rate 23; the authors of a meta-analysis consider ongoing monitoring of kidney values essential 3. In older people with mild cognitive impairment, kidney function remained unchanged under low-dose lithium in a randomized study, but more adverse events occurred than under placebo, including weight gain and TSH increase 75. In children and adolescents with mania, more treated participants discontinued lithium because of side effects than under placebo 10. In children and adolescents, no severe lithium-related events were reported 615, but the studies are mostly small and short.

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Every statement on this page carries its evidence tier — proven, plausible or hypothesis — and leads to the original work. The decision in the individual case rests with the practitioner; we provide the connections.

International Health Research · https://ih-research.com/en/knowledge/lithium/ · Last updated: 2026-10-24