Lithium Therapy in Old Age: Recommendations from a Delphi
                    Survey

Julia Christl; Bruno Müller-Oerlinghausen; Michael Bauer; Daniel Kamp; Fabian Fußer; Jens Benninghoff; Rosa A. Fehrenbach; Christian Lange-Asschenfeldt; Michael Rapp; Bernd Ibach; Rainer Schaub; Axel Wollmer; Timm Strotmann-Tack; Michael Hüll; Susanne Biermann; Katharina Roscher; Bernd Meissnest; Alexander Menges; Bernd Weigel; Dorothee Maliszewski-Makowka; Christian Mauerer; Martin Schaefer; Beate Joachimsmeier; Sarah Kayser; Lars Christian Rump; Tillmann Supprian

doi:10.1055/a-2117-5200

Pharmacopsychiatry, Table of Contents

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

¹Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany

,

Bruno Müller-Oerlinghausen

²Charité Universitätsmedizin Berlin, Berlin, Germany

³Brandenburg Medical School Theodor Fontane, Faculty of Medicine and Psychology, Neuruppin, Germany

,

Michael Bauer

⁴Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany

,

Daniel Kamp

¹Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany

,

Fabian Fußer

⁵Klinik für Gerontopsychiatrie, Psychosomatik und Psychotherapie, Pfalzklinikum Klingenmünster, Klingenmünster, Germany

,

Jens Benninghoff

⁶Zentrum für Altersmedizin und Entwicklungsstörungen, kbo-Isar-Amper-Klinikum München-Ost, Haar, Germany

⁷LVR-Universitätsklinik Essen, Kliniken und Institut der Universität Duisburg-Essen, Essen, Germany

,

Rosa A. Fehrenbach

⁸Saarland-Heilstätten GmbH, SHG-Kliniken Sonnenberg, Klinik für Gerontopsychiatrie, Saarbrücken, Germany

,

Christian Lange-Asschenfeldt

¹Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany

⁹Oberberg Fachklinik Düsseldorf Kaarst, Kaarst, Germany

,

Michael Rapp

¹⁰University of Potsdam, Research Area Cognitive Sciences, Division of Social and Preventive Medicine, Potsdam, Germany

,

Bernd Ibach

¹¹Zentrum für Alterspsychiatrie und Privé, Clienia Littenheid AG, Littenheid und Universität Zürich, Zürich, Schweiz

,

Rainer Schaub

¹²Klinik für Gerontopsychiatrie und Psychotherapie, Klinikum am Weissenhof, Weinsberg, Germany

,

Axel Wollmer

¹³Klinik für Gerontopsychiatrie und Psychotherapie, Asklepios Klinik Nord-Ochsenzoll, Hamburg, Germany

,

Timm Strotmann-Tack

¹⁴Klinik für Gerontopsychiatrie und Psychotherapie, LVR-Klinik Viersen, Viersen, Germany

,

Michael Hüll

¹⁵Zentrum für Psychiatrie Emmendingen, Emmendingen, Germany

,

Susanne Biermann

¹⁶LWL-Klinik Lengerich, Lengerich, Germany

,

Katharina Roscher

¹⁷Psychiatrische Klinik Lüneburg, Lüneburg, Germany

,

Bernd Meissnest

¹⁸LWL-Klinikum Gütersloh, Gütersloh, Germany

,

Alexander Menges

¹⁹Klinikum Freudenstadt, Freudenstadt, Germany

,

Bernd Weigel

²⁰Bezirksklinikum Mainkofen, Mainkofen, Deggendorf, Germany

,

Dorothee Maliszewski-Makowka

²¹LVR-Klinik Bedburg-Hau, Bedburg-Hau, Germany

,

Christian Mauerer

²²Bezirkskrankenhaus Bayreuth, Bayreuth, Germany

,

Martin Schaefer

²³Klinik für Psychiatrie, Psychotherapie, Psychosomatik und Suchtmedizin, Evang. Kliniken Essen-Mitte, Essen, Germany

,

Beate Joachimsmeier

²⁴LWL Klinik Paderborn, Paderborn, Germany

,

Sarah Kayser

²⁵Klinik für Allgemeine Psychiatrie und Psychotherapie mit Poliklinik Universitätsklinikum Tübingen, Tübingen, Germany

,

Lars Christian Rump

²⁶Department of Nephrology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

,

Tillmann Supprian

¹Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany

› Author Affiliations

Abstract

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.

Key words

lithium - old age - maintenance therapy - reference serum level - drug monitoring - geriatric patients - withdrawal - renal function

Full Text

References

References
1 NICE-2014. Bipolar Disorder: Assessment and Management (NICE2014). Available at: https ://www.nice.org.uk/guida 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
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
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 https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017812s027%2C018421s025%2C018558s021lbl.pdf
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
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
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
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
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
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
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
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
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
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