CC BY-NC-ND 4.0 · Pharmacopsychiatry 2023; 56(05): 188-196
DOI: 10.1055/a-2117-5200
Original Paper

Lithium Therapy in Old Age: Recommendations from a Delphi Survey

Julia Christl
1   Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
Bruno Müller-Oerlinghausen
2   Charité Universitätsmedizin Berlin, Berlin, Germany
3   Brandenburg Medical School Theodor Fontane, Faculty of Medicine and Psychology, Neuruppin, Germany
Michael Bauer
4   Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
Daniel Kamp
1   Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
Fabian Fußer
5   Klinik für Gerontopsychiatrie, Psychosomatik und Psychotherapie, Pfalzklinikum Klingenmünster, Klingenmünster, Germany
Jens Benninghoff
6   Zentrum für Altersmedizin und Entwicklungsstörungen, kbo-Isar-Amper-Klinikum München-Ost, Haar, Germany
7   LVR-Universitätsklinik Essen, Kliniken und Institut der Universität Duisburg-Essen, Essen, Germany
Rosa A. Fehrenbach
8   Saarland-Heilstätten GmbH, SHG-Kliniken Sonnenberg, Klinik für Gerontopsychiatrie, Saarbrücken, Germany
Christian Lange-Asschenfeldt
1   Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
9   Oberberg Fachklinik Düsseldorf Kaarst, Kaarst, Germany
Michael Rapp
10   University of Potsdam, Research Area Cognitive Sciences, Division of Social and Preventive Medicine, Potsdam, Germany
Bernd Ibach
11   Zentrum für Alterspsychiatrie und Privé, Clienia Littenheid AG, Littenheid und Universität Zürich, Zürich, Schweiz
Rainer Schaub
12   Klinik für Gerontopsychiatrie und Psychotherapie, Klinikum am Weissenhof, Weinsberg, Germany
Axel Wollmer
13   Klinik für Gerontopsychiatrie und Psychotherapie, Asklepios Klinik Nord-Ochsenzoll, Hamburg, Germany
Timm Strotmann-Tack
14   Klinik für Gerontopsychiatrie und Psychotherapie, LVR-Klinik Viersen, Viersen, Germany
Michael Hüll
15   Zentrum für Psychiatrie Emmendingen, Emmendingen, Germany
Susanne Biermann
16   LWL-Klinik Lengerich, Lengerich, Germany
Katharina Roscher
17   Psychiatrische Klinik Lüneburg, Lüneburg, Germany
Bernd Meissnest
18   LWL-Klinikum Gütersloh, Gütersloh, Germany
Alexander Menges
19   Klinikum Freudenstadt, Freudenstadt, Germany
Bernd Weigel
20   Bezirksklinikum Mainkofen, Mainkofen, Deggendorf, Germany
Dorothee Maliszewski-Makowka
21   LVR-Klinik Bedburg-Hau, Bedburg-Hau, Germany
Christian Mauerer
22   Bezirkskrankenhaus Bayreuth, Bayreuth, Germany
Martin Schaefer
23   Klinik für Psychiatrie, Psychotherapie, Psychosomatik und Suchtmedizin, Evang. Kliniken Essen-Mitte, Essen, Germany
Beate Joachimsmeier
24   LWL Klinik Paderborn, Paderborn, Germany
Sarah Kayser
25   Klinik für Allgemeine Psychiatrie und Psychotherapie mit Poliklinik Universitätsklinikum Tübingen, Tübingen, Germany
Lars Christian Rump
26   Department of Nephrology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Tillmann Supprian
1   Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
› Author Affiliations


Introduction While lithium (Li) has been well established for the treatment of bipolar disorder, geriatric patients require special attention when it comes to issues of drug safety. Declining renal function, amongst other medical conditions, and polypharmacy may pose increased risks. Only a few previous studies have addressed the management of Li in geriatric patients.

Methods Twenty-four German medical experts on geriatric medicine and Li treatment participated in a Delphi survey, consisting of two rounds of questionnaires and a final formulation of treatment recommendations. Three major issues of Li therapy were outlined: initiation of treatment, monitoring of ongoing therapy, and withdrawal due to medical reasons. Final recommendations were consented to at a threshold of at least 80% expert agreement.

Results Final consensus was achieved on 21 clinical recommendations. The approved recommendations covered aspects of necessary laboratory checks, concomitant medication, and target Li serum concentration in geriatric patients. Concerning the termination of Li therapy, an agreement was reached on the appropriate time span for tapering and on potential alternatives to Li. No consensus was achieved on whether concomitant dementia or frailty should be considered contraindications for Li treatment and the appropriate threshold of the estimated glomerular function rate for withdrawing Li.

Conclusion According to the view of German experts, Li may be used in geriatric patients, but it should be monitored carefully. However, the lack of consent in several specific treatment situations underlines the need for research on specific issues of Li therapy.

Publication History

Received: 25 April 2023
Received: 13 June 2023

Accepted: 16 June 2023

Article published online:
28 July 2023

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  • References

  • 1 NICE-2014. Bipolar Disorder: Assessment and Management (NICE2014). Available at: https :// nce/cg185
  • 2 Yatham LN, Kennedy SH, Parikh SV. et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord 2018; 20: 97-170
  • 3 DGBS e.V, DGPPN e.V. S3-Leitlinie zur Diagnostik und Therapie Bipolarer Störungen. Langversion. 2019
  • 4 Tondo L, Alda M, Bauer M. et al. Clinical use of lithium salts: Guide for users and prescribers. Int J Bipolar Disord 2019; 7: 16
  • 5 Sajatovic M, Strejilevich SA, Gildengers AG. et al. A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar Disord 2015; 17: 689-704
  • 6 Sajatovic M, Gyulai L, Calabrese JR. et al. Maintenance treatment outcomes in older patients with bipolar I disorder. Am J Geriatr Psychiatry 2005; 13: 305-311
  • 7 Young RC, Mulsant BH, Sajatovic M. et al. GERI-BD: A randomized double-blind controlled trial of lithium and divalproex in the treatment of mania in older patients with bipolar disorder. Am J Psychiatry 2017; 174: 1086-1093
  • 8 Kok RM, Vink D, Heeren TJ. Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly: an open, randomized controlled trial. J Clin Psychiatry 2007; 68: 1177-1185 DOI: 10.4088/jcp.v68n080.3.
  • 9 Wilkinson D, Holmes C, Woolford J. et al. Prophylactic therapy with lithium in elderly patients with unipolar major depression. Int J Geriatr Psychiatry 2002; 17: 619-622
  • 10 Forlenza O, Hajek T, Almeida OP. et al. on behalf of the GAGE-BD initiative. Demografic and clinical characteristics of Lithium-treated older adults with bipolar disorder. Acta Psychiatr Scand 2022; 146: 442-455
  • 11 Velosa J, Delgado A, Finger E. et al. Risk of dementia in bipolar disorder and the interplay of lithium: A systematic review and meta-analyses. Acta Psychiatr Scand 2020; 141: 510-521 DOI: 10.1111/acps.13153.
  • 12 Shulman KI, Rochon P, Sykora K. et al. Changing prescription patterns for lithium and valproic acid in old age: Shifting practice without evidence. BMJ 2003; 326: 960-961
  • 13 Shulman KI, Almeida OP, Herrmann N. et al. Delphi survey of maintenance lithium treatment in older adults with bipolar disorder: An ISBD task force report. Bipolar Disord 2019; 21: 117-123
  • 14 Dols A, Kessing LV, Strejilevich SA. et al. International Society for Bipolar Disorders Task Force for Older Adults with Bipolar Disorder. Do current national and international guidelines have specific recommendations for older adults with bipolar disorder? A brief report. Int J Geriatr Psychiatry 2016; 31: 1295-1300
  • 15 US Food and Drug Administration. Lithium carbonate
  • 16 Lahteenvuo M, Tanskanen A, Taipale H. et al. Real-world effectiveness of pharmacologic treatments for the prevention of rehospitalization in a Finnish nationwide cohort of patients with bipolar disorder. JAMA Psychiatry 2018; 75: 347-355
  • 17 Bauer M, Adli M, Bschor T. et al. Lithium’s emerging role in the treatment of refractory major depressive episodes: Augmentation of antidepressants. Neuropsychobiology 2010; 62: 36-42
  • 18 Buspavanich P, Behr J, Stamm T. et al. Treatment response of lithium augmentation in geriatric compared to non-geriatric patients with treatment-resistant depression. J Affect Disord 2019; 215: 136-140
  • 19 Cooper C, Katona C, Lyketsos K. et al. A systematic review of treatments for refractory depression in older people. Am J Psychiatry 2011; 168: 681-688
  • 20 Abou-Saleh MT, Müller-Oerlingshausen B, Copper AJ. Lithium in the episode and suicide prophylaxis and in augmenting strategies in patients with unipolar depression. Int J Bipolar Disord 2017; 5: 11
  • 21 Cipriani A, Hawton K, Stockton K. et al. Lithium in the prevention of suicide in mood disorders: Updated systematic review and meta-analysis. BMJ 2013; 346: f3646
  • 22 Song J, Sjölander A, Joas E. et al. Suicidal behavior during Lithium and Valproate treatment: A within-individual 8-year prospective study of 50.000 patients with bipolar disorder. Am J Psychiatry 2017; 174: 795-802
  • 23 Vallée A, Vallée JN, Lecarpentier Y. Parkinson's disease: Potential actions of lithium by targeting the WNT/β-catenin pathway, oxidative stress, inflammation and glutamatergic pathway. Cells 2021; 25: 230 DOI: 10.3390/cells10020230.
  • 24 Lazzara CA, Kim YH. Potential application of lithium in Parkinson’s and other neurodegenerative diseases. Front Neurosci 2015; 9: 403
  • 25 Haukvik UK, Gurholt TP, Nerland S. et al.; In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group. Hum Brain Mapp 2022; 43(1): 385-398 DOI: 10.1002/hbm.25249.
  • 26 Nolen WA, Licht RW, Young AH. 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: 394-409 DOI: 10.1111/bdi.12805.
  • 27 Rej S, Beaulieu S, Segal M. et al. Lithium dosing and serum concentrations across the age spectrum: from early adulthood to the tenth decade of life. Drugs Aging 2014; 31: 911-916 DOI: 10.1007/s40266-014-0221-1.
  • 28 Sproule BA, Hardy BG, Shulman KI. Differential pharmacokinetics of lithium in elderly patients. Drugs Aging 2000; 16: 165-177
  • 29 Rej S, Herrmann N, Shulman K. The effects of lithium on renal function in older adults–a systematic review. J Geriatr Psychiatry Neurol 2012; 25: 51-61 DOI: 10.1177/0891988712436690.
  • 30 Singh LK, Nizamie SH, Akhtar S. et al. Improving tolerability of lithium with a once-daily dosing schedule. Am J Ther 2011; 18: 288-291 DOI: 10.1097/MJT.0b013e3181d070c3.
  • 31 Meeusen JW, Rule AD, Voskoboev N. et al. Performance of cystatin C- and creatinine-based estimated glomerular filtration rate equations depends on patient characteristics. Clin Chem 2015; 61: 1265-1272 DOI: 10.1373/clinchem.2015.243030.
  • 32 Grubb A, Nyman U, Björk J. Improved estimation of glomerular filtration rate (GFR) by comparison of eGFRcystatin C and eGFRcreatinine. Scand J Clin Lab Invest 2012; 72: 73-77
  • 33 Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-198
  • 34 Nasreddine ZS, Phillips NA, Bedirian V. et al. The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 53: 695-699
  • 35 Fillenbaum GG, Mohs R. CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychology assessment battery: 35 years and counting. J Alzheimers Dis 2023; 13 DOI: 10.3233/JAD-230026.
  • 36 Enudi W, Lawlor B, O'Connell HP. A survey of patients' knowledge about lithium therapy in the elderly. Prim Care Companion CNS Disord 2014; 16 PCC.13m01550 DOI: 10.4088/PCC.13m01550.
  • 37 Volkmann C, Bschor T, Köhler S. Lithium treatment over the lifespan in bipolar disorders. Front Psychiatry 2020; 11: 377
  • 38 Ross J. Discontinuation of Lithium augmentation in geriatric patients with unipolar depression: A systematic review. Can J Psychiatry 2008; 53: 117-120
  • 39 Müller-Oerlinghausen B, Berghöfer A, Ahrens B. The antisuicidal and mortality-reducing effect of lithium prophylaxis: Consequences for guidelines in clinical psychiatry. Can J Psychiatry 2003; 48: 433-439
  • 40 Bowden CL, Calabrese JR, Sachs G. et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003; 60: 392-400
  • 41 Geddes JR, Goodwin GM, Rendell J. et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. The Lancet 2010; 375: 385-395
  • 42 Sajatovic M, Calabrese JR, Mullen J. Quetiapine for the treatment of bipolar mania in older adults. Bipolar Disord 2008; 10: 662-671