Lithium and its effects: does dose matter?
BDNF
Drinking water
GSK-3Beta
Micro-dose
Suicide
Journal
International journal of bipolar disorders
ISSN: 2194-7511
Titre abrégé: Int J Bipolar Disord
Pays: Germany
ID NLM: 101622983
Informations de publication
Date de publication:
24 Jun 2024
24 Jun 2024
Historique:
received:
07
02
2024
accepted:
18
06
2024
medline:
25
6
2024
pubmed:
25
6
2024
entrez:
24
6
2024
Statut:
epublish
Résumé
Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations. This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections. Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.
Sections du résumé
BACKGROUND
BACKGROUND
Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.
CONTENT
BACKGROUND
This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.
CONCLUSIONS
CONCLUSIONS
Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.
Identifiants
pubmed: 38914810
doi: 10.1186/s40345-024-00345-8
pii: 10.1186/s40345-024-00345-8
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
23Informations de copyright
© 2024. The Author(s).
Références
Aggarwal SP, Zinman L, Simpson E, McKinley J, Jackson KE, Pinto H, et al. Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(5):481–8.
pubmed: 20363190
pmcid: 3071495
doi: 10.1016/S1474-4422(10)70068-5
Ahrens B, Müller-Oerlinghausen B. Does Lithium exert an independent Antisuicidal Effect? Pharmacopsychiatry. 2001;34(4):132–6.
pubmed: 11518473
doi: 10.1055/s-2001-15878
Alda M. Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol Psychiatry. 2015;20(6):661–70.
pubmed: 25687772
pmcid: 5125816
doi: 10.1038/mp.2015.4
Alda M, Manchia M. Personalized management of bipolar disorder. Neurosci Lett. 2018;669.
Andrade Nunes M, Araujo Viel T, Sousa Buck H. Microdose Lithium Treatment Stabilized Cognitive Impairment in patients with Alzheimer’s Disease. Curr Alzheimer Res. 2013;10(1):104–7.
Araya P, Martínez C, Barros J. Lithium in Drinking Water as a Public Policy for Suicide Prevention: Relevance and Considerations. Frontiers in Public Health [Internet]. 2022 [cited 2024 Jan 30];10. https://www.frontiersin.org/articles/ https://doi.org/10.3389/fpubh.2022.805774 .
Baastrup PC, Poulsen JC, Schou M, Thomsen K, Amdisen A. Prophylactic lithium: double blind discontinuation in manic-depressive and recurrent-depressive disorders. Lancet (London England). 1970;2(7668):326–30.
pubmed: 4194439
doi: 10.1016/S0140-6736(70)92870-9
Baldessarini RJ, Tondo L. Testing for Antisuicidal effects of Lithium Treatment. JAMA Psychiatry. 2022;79(1):9–10.
pubmed: 34787652
doi: 10.1001/jamapsychiatry.2021.2992
Barjasteh-Askari F, Davoudi M, Amini H, Ghorbani M, Yaseri M, Yunesian M, et al. Relationship between suicide mortality and lithium in drinking water: a systematic review and meta-analysis. J Affect Disord. 2020;264:234–41.
pubmed: 32056756
doi: 10.1016/j.jad.2019.12.027
Beurel E, Grieco SF, Jope RS. Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther. 2015;0:114–31.
doi: 10.1016/j.pharmthera.2014.11.016
Boll M-C, Alcaraz-Zubeldia M, Rios C, González-Esquivel D, Montes S. A phase 2, double-blind, placebo-controlled trial of a valproate/lithium combination in ALS patients. Neurologia (Engl Ed). 2022;S2173-5808(22)00089-X.
Chatterjee D, Beaulieu JM. Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity. Front Mol Neurosci. 2022;15:1028963.
pubmed: 36504683
pmcid: 9731798
doi: 10.3389/fnmol.2022.1028963
Cheng Z, Han T, Yao J, Wang K, Dong X, Yu F, et al. Targeting glycogen synthase kinase-3β for Alzheimer’s disease: recent advances and future prospects. Eur J Med Chem. 2024;265:116065.
pubmed: 38160617
doi: 10.1016/j.ejmech.2023.116065
Chiò A, Borghero G, Calvo A, Capasso M, Caponnetto C, Corbo M, et al. Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial. Neurology. 2010;75(7):619–25.
pubmed: 20702794
doi: 10.1212/WNL.0b013e3181ed9e7c
Chiu C-T, Chuang D-M. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders. Pharmacol Ther. 2010;128(2):281–304.
pubmed: 20705090
pmcid: 3167234
doi: 10.1016/j.pharmthera.2010.07.006
Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ (clinical research ed.). 2013;346:f3646.
Coppen A, Noguera R, Bailey J, Burns BH, Swani MS, Hare EH, et al. Prophylactic lithium in affective disorders. Controlled trial. Lancet (London England). 1971;2(7719):275–9.
pubmed: 4104974
doi: 10.1016/S0140-6736(71)91331-6
Cundall RL, Brooks PW, Murray LG. A controlled evaluation of lithium prophylaxis in affective disorders. Psychol Med. 1972;2(3):308–11.
pubmed: 4562449
doi: 10.1017/S0033291700042616
Dawson EB, Moore TD, McGanity WJ. The mathematical relationship of drinking water lithium and rainfall to mental hospital admission. Dis Nerv Syst. 1970;31(12):811–20.
pubmed: 5497853
De-Paula VJ, Gattaz WF, Forlenza OV. Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at subtherapeutic concentrations. Bipolar Disord. 2016;18(8):692–5.
pubmed: 27882645
doi: 10.1111/bdi.12449
Devanand DP, Crocco E, Forester BP, Husain MM, Lee S, Vahia IV, et al. Low dose Lithium treatment of behavioral complications in Alzheimer’s Disease: Lit-AD Randomized Clinical Trial. Am J Geriatr Psychiatry. 2022;30(1):32–42.
pubmed: 34059401
doi: 10.1016/j.jagp.2021.04.014
Duthie AC, Hannah J, Batty GD, Deary IJ, Starr JM, Smith DJ, et al. Low-level lithium in drinking water and subsequent risk of dementia: Cohort study. Int J Geriatr Psychiatry. 2023;38(3):e5890.
pubmed: 36747488
doi: 10.1002/gps.5890
Ercis M, Ozerdem A, Singh B. When and how to use Lithium Augmentation for treating major depressive disorder. J Clin Psychiatry. 2023;84(2):23ac14813.
pubmed: 36883886
doi: 10.4088/JCP.23ac14813
Eyre-Watt B, Mahendran E, Suetani S, Firth J, Kisely S, Siskind D. The association between lithium in drinking water and neuropsychiatric outcomes: a systematic review and meta-analysis from across 2678 regions containing 113 million people. Aust N Z J Psychiatry SAGE Publications Ltd. 2021;55(2):139–52.
doi: 10.1177/0004867420963740
Fajardo VA, Fajardo VA, LeBlanc PJ, MacPherson REK. Examining the relationship between Trace Lithium in drinking Water and the Rising Rates of Age-Adjusted Alzheimer’s Disease Mortality in Texas. J Alzheimers Dis. 2018;61(1):425–34.
pubmed: 29103043
doi: 10.3233/JAD-170744
Fenech RK, Hamstra SI, Finch MS, Ryan CR, Marko DM, Roy BD, et al. Low-dose Lithium supplementation influences GSK3β activity in a Brain Region specific manner in C57BL6 male mice. J Alzheimers Dis. 2023;91(2):615–26.
pubmed: 36463453
doi: 10.3233/JAD-220813
Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011;198(5):351–6.
pubmed: 21525519
doi: 10.1192/bjp.bp.110.080044
Forlenza OV, Radanovic M, Talib LL, Gattaz WF. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. Br J Psychiatry. 2019;215(5):668–74.
pubmed: 30947755
doi: 10.1192/bjp.2019.76
Fornai F, Longone P, Cafaro L, Kastsiuchenka O, Ferrucci M, Manca ML, et al. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2008;105(6):2052–7.
pubmed: 18250315
pmcid: 2538879
doi: 10.1073/pnas.0708022105
Gelenberg AJ, Kane JM, Keller MB, Lavori P, Rosenbaum JF, Cole K, et al. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med. 1989;321(22):1489–93.
pubmed: 2811970
doi: 10.1056/NEJM198911303212201
Giotakos O, Tsouvelas G, Nisianakis P, Giakalou V, Lavdas A, Tsiamitas C, et al. A negative association between lithium in drinking water and the incidences of homicides, in Greece. Biol Trace Elem Res. 2015;164(2):165–8.
pubmed: 25556933
doi: 10.1007/s12011-014-0210-6
Gould TD. Targeting glycogen synthase kinase-3 as an approach to develop novel mood-stabilising medications. Expert Opin Ther Targets. 2006;10(3):377–92.
pubmed: 16706678
doi: 10.1517/14728222.10.3.377
Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, et al. Association between maternal fluoride exposure during pregnancy and IQ scores in offspring in Canada. JAMA Pediatr. 2019;173(10):940–8.
pubmed: 31424532
pmcid: 6704756
doi: 10.1001/jamapediatrics.2019.1729
Hamm JP, Peterka DS, Gogos JA, Yuste R. Altered cortical ensembles in mouse models of Schizophrenia. Neuron. 2017;94(1):153–e1678.
pubmed: 28384469
pmcid: 5394986
doi: 10.1016/j.neuron.2017.03.019
Hamm JP, Shymkiv Y, Mukai J, Gogos JA, Yuste R. Aberrant cortical ensembles and Schizophrenia-like sensory phenotypes in Setd1a+/- mice. Biol Psychiatry. 2020;88(3):215–23.
pubmed: 32143831
pmcid: 7363535
doi: 10.1016/j.biopsych.2020.01.004
Harari F, Bottai M, Casimiro E, Palm B, Vahter M. Exposure to Lithium and Cesium through drinking water and thyroid function during pregnancy: a prospective cohort study. Thyroid. 2015;25(11):1199–208.
pubmed: 26332132
pmcid: 4652143
doi: 10.1089/thy.2015.0280
Herrera-Rivero M, Adli M, Akiyama K, Akula N, Amare AT, Ardau R et al. Exploring the genetics of lithium response in bipolar disorders. Res Sq. 2023;rs.3.rs-3677630.
Johnson G, Gershon S, Burdock EI, Floyd A, Hekimian L. Comparative effects of lithium and chlorpromazine in the treatment of acute manic states. Br J Psychiatry: J Mental Sci. 1971;119(550):267–76.
doi: 10.1192/bjp.119.550.267
Keller MB, Lavori PW, Kane JM, Gelenberg AJ, Rosenbaum JF, Walzer EA, et al. Subsyndromal symptoms in bipolar disorder. A comparison of standard and low serum levels of lithium. Arch Gen Psychiatry. 1992;49(5):371–6.
pubmed: 1586272
doi: 10.1001/archpsyc.1992.01820050035005
Kessing LV, Gerds TA, Knudsen NN, Jørgensen LF, Kristiansen SM, Voutchkova D, et al. Association of Lithium in drinking Water with the incidence of Dementia. JAMA Psychiatry. 2017;74(10):1005–10.
pubmed: 28832877
pmcid: 5710473
doi: 10.1001/jamapsychiatry.2017.2362
Kleindienst N, Severus WE, Miller H-J, Greil W. Is polarity of recurrence related to serum lithium level in patients with bipolar disorder? Eur Arch Psychiatry Clin Neurosci. 2005;255(1):72–4.
pubmed: 15711896
doi: 10.1007/s00406-005-0574-x
Kleindienst N, Severus WE, Greil W. Are serum lithium levels related to the polarity of recurrence in bipolar disorders? Evidence from a multicenter trial. Int Clin Psychopharmacol LWW. 2007;22(3):125–31.
doi: 10.1097/01.yic.0000224788.21406.c8
Kumar R, Joseph B, Pazdernik VM, Geske J, Nuñez NA, Pahwa M, et al. Real-world clinical practice among patients with bipolar disorder and chronic kidney disease on long-term Lithium therapy. J Clin Psychopharmacol. 2023;43(1):6–11.
pubmed: 36584244
pmcid: 10590216
doi: 10.1097/JCP.0000000000001632
Licht RW, Lithium. Still a major option in the management of bipolar disorder. CNS Neurosci Ther. 2012;18(3):219–26.
pubmed: 22070642
doi: 10.1111/j.1755-5949.2011.00260.x
Licht RW, Vestergaard P, Rasmussen NA, Jepsen K, Brodersen A, Hansen PE. A lithium clinic for bipolar patients: 2-year outcome of the first 148 patients. Acta Psychiatrica Scandinavica. 2001;104(5):387–90.
pubmed: 11722321
doi: 10.1111/j.1600-0447.2001.00389.x
Liew Z, Meng Q, Yan Q, Schullehner J, Hansen B, Kristiansen SM, et al. Association between estimated Geocoded residential maternal exposure to Lithium in drinking Water and Risk for Autism Spectrum disorder in offspring in Denmark. JAMA Pediatr. 2023;177(6):617–24.
pubmed: 37010840
pmcid: 10071398
doi: 10.1001/jamapediatrics.2023.0346
Luca A, Luca M. Comment to the letter to the editor entitled Lithium in drinking water and suicide risk by Tomoyuki Kawada. EXCLI J. 2022;21:1066–7.
pubmed: 36172069
pmcid: 9489887
Manchia M, Hajek T, O’Donovan C, Deiana V, Chillotti C, Ruzickova M et al. Genetic risk of suicidal behavior in bipolar spectrum disorder: analysis of 737 pedigrees. Bipolar Disord. 2013;15(5).
Manji HK, Moore GJ, Chen G. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry. 1999;46(7):929–40.
pubmed: 10509176
doi: 10.1016/S0006-3223(99)00165-1
Masterton G, Warner M, Roxburgh B. Supervising lithium. A comparison of a lithium clinic, psychiatric out-patient clinics, and general practice. Br J Psychiatry: J Mental Sci. 1988;152:535–8.
doi: 10.1192/bjp.152.4.535
McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721–8.
pubmed: 22265699
doi: 10.1016/S0140-6736(11)61516-X
Memon A, Rogers I, Fitzsimmons SMDD, Carter B, Strawbridge R, Hidalgo-Mazzei D, et al. Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies. Br J Psychiatry. 2020;217(6):667–78.
pubmed: 32716281
doi: 10.1192/bjp.2020.128
Meyer JM. Pharmacotherapy of psychosis and mania. In: Brunton LL, Hilal-Dandan R, Knollmann BC, editors. Goodman & Gilman’s: the pharmacological basis of therapeutics, 13e. New York, NY: McGraw-Hill Education; 2017.
Meyer JM, Stahl SM. The Lithium Handbook: Stahl’s Handbooks [Internet]. Cambridge: Cambridge University Press; 2023 [cited 2024 May 24]. https://www.cambridge.org/core/books/lithium-handbook/321B19975C691428C015AB43F6F0E5ED .
Morris G, Berk M. The putative use of Lithium in Alzheimer’s Disease. Curr Alzheimer Res. 2016;13(8):853–61.
pubmed: 26892287
doi: 10.2174/1567205013666160219113112
Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (trial 144). Bipolar Disord. 2013;15(1):100–9.
pubmed: 23228201
doi: 10.1111/bdi.12027
Nolen WA, Licht RW, Young AH, Malhi GS, Tohen M, Vieta E, et al. What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium. Bipolar Disord. 2019;21(5):394–409.
pubmed: 31112628
pmcid: 6688930
doi: 10.1111/bdi.12805
Nunes MA, Schöwe NM, Monteiro-Silva KC, Baraldi-Tornisielo T, Souza SIG, Balthazar J, et al. Chronic Microdose Lithium Treatment prevented memory loss and neurohistopathological changes in a transgenic mouse model of Alzheimer’s Disease. PLoS ONE. 2015;10(11):e0142267.
pubmed: 26605788
pmcid: 4659557
doi: 10.1371/journal.pone.0142267
Osher Y, Bersudsky Y, Belmaker RH. The New Lithium Clinic. Neuropsychobiology. 2010;62(1):17–26.
pubmed: 20453531
doi: 10.1159/000314306
Pallaskorpi S, Suominen K, Ketokivi M, Valtonen H, Arvilommi P, Mantere O, et al. Incidence and predictors of suicide attempts in bipolar I and II disorders: a 5-year follow-up study. Bipolar Disord. 2017;19(1):13–22.
pubmed: 28176421
doi: 10.1111/bdi.12464
Parker WF, Gorges RJ, Gao YN, Zhang Y, Hur K, Gibbons RD. Association between Groundwater Lithium and the diagnosis of bipolar disorder and dementia in the United States. JAMA Psychiatry. 2018;75(7):751–4.
pubmed: 29799907
pmcid: 6145675
doi: 10.1001/jamapsychiatry.2018.1020
PLATMAN SR. A Comparison of Lithium Carbonate and Chlorpromazine in Mania. Am J Psychiatry. 1970;127(3):351–3.
pubmed: 4917856
doi: 10.1176/ajp.127.3.351
Prien RF, Caffey EM. Relationship between dosage and response to lithium prophylaxis in recurrent depression. Am J Psychiatry. 1976;133(5):567–70.
pubmed: 1267063
doi: 10.1176/ajp.133.5.567
Prien RF, Caffey EM, Klett CJ. Relationship between serum lithium level and clinical response in acute mania treated with lithium. Br J Psychiatry: J Mental Sci. 1972;120(557):409–14.
doi: 10.1192/bjp.120.557.409
Rybakowski JK. Response to Lithium in Bipolar Disorder: clinical and genetic findings. ACS Chem Neurosci. 2014;5(6):413–21.
pubmed: 24625017
pmcid: 4063501
doi: 10.1021/cn5000277
Schaeffer EL, Catanozi S, West MJ, Gattaz WF. Stereological investigation of the CA1 pyramidal cell layer in untreated and lithium-treated 3xTg-AD and wild-type mice. Ann Anat. 2017;209:51–60.
pubmed: 27777112
doi: 10.1016/j.aanat.2016.10.002
Schou M. Lithium in psychiatric therapy and prophylaxis. J Psychiatr Res. 1968;6(1):67–95.
pubmed: 4876759
doi: 10.1016/0022-3956(68)90047-2
Schrauzer GN, Shrestha KP. Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biol Trace Elem Res. 1990;25(2):105–13.
pubmed: 1699579
doi: 10.1007/BF02990271
Severus WE, Lipkovich IA, Licht RW, Young AH, Greil W, Ketter T et al. In search of optimal lithium levels and olanzapine doses in the long-term treatment of bipolar I disorder. A post-hoc analysis of the maintenance study by Tohen 2005. Eur. psychiatr. 2010;25(8):443–9.
Severus WE, Kleindienst N, Evoniuk G, Bowden C, Möller HJ, Bohus M, et al. Is the polarity of relapse/recurrence in bipolar-I disorder patients related to serum lithium levels? Results from an empirical study. J Affect Disord. 2009;115(3):466–70.
pubmed: 19019453
doi: 10.1016/j.jad.2008.10.009
Severus E, Bauer M, Geddes J. Efficacy and effectiveness of Lithium in the long-term treatment of Bipolar disorders: an update 2018. Pharmacopsychiatry. 2018;51(05):173–6.
pubmed: 29898463
doi: 10.1055/a-0627-7489
Shopsin B, Gershon S, Thompson H, Collins P. Psychoactive drugs in mania. A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol. Arch Gen Psychiatry. 1975;32(1):34–42.
pubmed: 1089401
doi: 10.1001/archpsyc.1975.01760190036004
Smith KA, Cipriani A. Lithium and suicide in mood disorders: updated meta-review of the scientific literature. Bipolar Disord. 2017;19(7):575–86.
pubmed: 28895269
doi: 10.1111/bdi.12543
Solomon DA, Ristow WR, Keller MB, Kane JM, Gelenberg AJ, Rosenbaum JF, et al. Serum lithium levels and psychosocial function in patients with bipolar I disorder. Am J Psychiatry. 1996;153(10):1301–7.
pubmed: 8831438
doi: 10.1176/ajp.153.10.1301
SPRING G, SCHWEID D, GRAY C, STEINBERG J. A double-blind comparison of Lithium and Chlorpromazine in the treatment of Manic States. Am J Psychiatry. 1970;126(9):1306–10.
pubmed: 4905019
doi: 10.1176/ajp.126.9.1306
Stokes PE, Shamoian CA, Stoll PM, Patton MJ. Efficacy of lithium as acute treatment of manic-depressive illness. Lancet (London England). 1971;1(7713):1319–25.
pubmed: 4103395
doi: 10.1016/S0140-6736(71)91886-1
Stokes PE, Kocsis JH, Arcuni OJ. Relationship of lithium chloride dose to treatment response in acute mania. Arch Gen Psychiatry. 1976;33(9):1080–4.
pubmed: 17642108
doi: 10.1001/archpsyc.1976.01770090070006
Strawbridge R, Kerr-Gaffney J, Bessa G, Loschi G, Freitas HLO, Pires H, et al. Identifying the neuropsychiatric health effects of low-dose lithium interventions: a systematic review. Neurosci Biobehavioral Reviews. 2023;144:104975.
doi: 10.1016/j.neubiorev.2022.104975
Swash M. Lithium time-to-event trial in amyotrophic lateral sclerosis stops early for futility. Lancet Neurol. 2010;9(5):449–51.
pubmed: 20363191
doi: 10.1016/S1474-4422(10)70085-5
Takahashi R, Sakuma A, Itoh K, Itoh H, Kurihara M. Comparison of efficacy of lithium carbonate and chlorpromazine in mania. Report of collaborative study group on treatment of mania in Japan. Arch Gen Psychiatry. 1975;32(10):1310–8.
pubmed: 1101844
doi: 10.1001/archpsyc.1975.01760280108010
Taylor DM, Barnes TRE, Allan HY. The Maudsley Prescribing Guidelines in Psychiatry (The Maudsley Prescribing Guidelines Series). Wiley. Kindle Edition.; 2021. https://onlinelibrary.wiley.com/doi/book/10.1002/9781119870203 .
Terao I, Kodama W. Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer’s disease: a systematic review and network meta-analysis. Ageing Res Rev. 2024;94:102203.
pubmed: 38253184
doi: 10.1016/j.arr.2024.102203
Terao I, Honyashiki M, Inoue T. Comparative efficacy of lithium and aducanumab for cognitive decline in patients with mild cognitive impairment or Alzheimer’s disease: a systematic review and network meta-analysis. Ageing Res Rev. 2022;81:101709.
pubmed: 35961514
doi: 10.1016/j.arr.2022.101709
Tondo L, Baldessarini R. Antisuicidal effects in Mood disorders: are they unique to Lithium? Pharmacopsychiatry. 2018;51(05):177–88.
pubmed: 29672801
doi: 10.1055/a-0596-7853
Toricelli M, Evangelista SR, Buck HS, Viel TA. Microdose Lithium Treatment Reduced Inflammatory Factors and neurodegeneration in organotypic hippocampal culture of Old SAMP-8 mice. Cell Mol Neurobiol. 2021;41(7):1509–20.
pubmed: 32642922
doi: 10.1007/s10571-020-00916-0
Velosa J, Delgado A, Finger E, Berk M, Kapczinski F, de Azevedo Cardoso T. Risk of dementia in bipolar disorder and the interplay of lithium: a systematic review and meta-analyses. Acta Psychiatr Scand. 2020;141(6):510–21.
pubmed: 31954065
doi: 10.1111/acps.13153
Viel T, Chinta S, Rane A, Chamoli M, Buck H, Andersen J. Microdose lithium reduces cellular senescence in human astrocytes - a potential pharmacotherapy for COVID-19? Aging. 2020;12(11):10035–40.
pubmed: 32534451
pmcid: 7346079
doi: 10.18632/aging.103449
Wilson EN, Do Carmo S, Iulita MF, Hall H, Ducatenzeiler A, Marks AR, et al. BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology. Transl Psychiatry. 2017;7(8):e1190.
pubmed: 28763060
pmcid: 5611736
doi: 10.1038/tp.2017.169
Yoon H, Bak MS, Kim SH, Lee JH, Chung G, Kim SJ, et al. Development of a spontaneous pain indicator based on brain cellular calcium using deep learning. Exp Mol Med. 2022;54(8):1179–87.
pubmed: 35982300
pmcid: 9385425
doi: 10.1038/s12276-022-00828-7
Yuryev M, Andriichuk L, Leiwe M, Jokinen V, Carabalona A, Rivera C. In vivo two-photon imaging of the embryonic cortex reveals spontaneous ketamine-sensitive calcium activity. Sci Rep. 2018;8(1):16059.
pubmed: 30375447
pmcid: 6207746
doi: 10.1038/s41598-018-34410-x
Zall H, Therman PG, Myers JM. Lithium carbonate: a clinical study. Am J Psychiatry. 1968;125(4):549–55.
pubmed: 5711819
doi: 10.1176/ajp.125.4.549
Zhao L, Gong N, Liu M, Pan X, Sang S, Sun X, et al. Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer’s disease mouse model. Neurobiol Aging. 2014;35(12):2736–45.
pubmed: 25018109
doi: 10.1016/j.neurobiolaging.2014.06.003
Zhuo C, Tian H, Zhu J, Fang T, Ping J, Wang L, et al. Low-dose lithium adjunct to quetiapine improves cognitive task performance in mice with MK801-induced long-term cognitive impairment: evidence from a pilot study. J Affect Disord. 2023;340:42–52.
pubmed: 37506773
doi: 10.1016/j.jad.2023.07.104