Bipolar Disorder and Outcomes of Monotherapy with Lithium, Valproate, Quetiapine, Olanzapine, Venlafaxine, and CitalopramFunding: The authors have received no ﬁnancial support for the research, authorship, and/or publication of this article.
Introduction The aim of this study was to compare the outcomes of monotherapy in individuals with bipolar disorder who are prescribed lithium, valproate, quetiapine, olanzapine, venlafaxine, or citalopram in private psychiatric practices in Germany.
Methods This retrospective study included bipolar disorder patients who had initially started on a monotherapy with lithium, valproate, quetiapine, olanzapine, venlafaxine, or citalopram in 93 private neuropsychiatric practices in Germany between January 2006 and December 2017. Treatment failure was defined as time to discontinuation of medication or addition of another mood stabilizer, antipsychotic, antidepressant, or benzodiazepine.
Results A total of 4990 bipolar patients was examined for the period between 2006 and 2019. Initially, monotherapy with lithium (n=1.098), valproate (n=502), quetiapine (n=927), olanzapine (n=927), venlafaxine (n=574), or citalopram (n=962) was prescribed. Within 24 months, treatment failure had occurred in 76.3% (lithium), 85.1% (valproate), 84.6% (quetiapine), 85.2% (venlafaxine), 92.1% (olanzapine), and 86.6% (citalopram) of patients, respectively. The hazard ratio for treatment failure compared to lithium as reference was highest for olanzapine at 1.66 (1.46–1.88), followed by citalopram 1.27 (1.15–1.39), quetiapine 1.18 (1.07–1.29), valproate 1.18 (1.06–1.33), and venlafaxine 1.14 (1.02–1.27).
Conclusions Our results underline the importance of lithium in the maintenance treatment of bipolar disorders.
Received: 09 November 2020
Received: 15 December 2020
Accepted: 29 December 2020
25 January 2021 (online)
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Bourne C, Aydemir Ö, Balanzá-Martínez V. et al. Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: An individual patient data meta-analysis. Acta Psychiatr Scand 2013; 128: 149-162
- 2 Chen M, Fitzgerald HM, Madera JJ. et al. Functional outcome assessment in bipolar disorder: A systematic literature review. Bipolar Disord 2019; 21: 194-214
- 3 Ferrari AJ, Stockings E, Khoo JP. et al. The prevalence and burden of bipolar disorder: Findings from the Global Burden of Disease Study. Bipolar Disord 2016; 18
- 4 Kessing LV, Hansen HV, Hvenegaar A. et al. Treatment in a specialised out-patient mood disorder clinic v. standard out-patient treatment in the early course of bipolar disorder: Randomised clinical trial. Br J Psychiatry 2013; 202: 212-219
- 5 Hooshmand F, Miller S, Dore J. et al. Trends in pharmacotherapy in patients referred to a bipolar specialty clinic, 2000-2011. J Affect Disord 2014; 155: 283-287
- 6 Olfson M, Kroenke K, Wang S. et al. Trends in office-based mental health care provided by psychiatrists and primary care physicians. J Clin Psychiatry 2014; 75: 247-253
- 7 Hayes JF, Marston L, Walters K. et al. Lithium vs. valproate vs. olanzapine vs. quetiapine as maintenance monotherapy for bipolar disorder: A population-based UK cohort study using electronic health records. World Psychiatry 2016; 15: 53-58
- 8 Quante A, Zeugmann S, Regen F. et al. Psychopharmacological treatment status in outpatients with bipolar disorder: A clinical survey in Germany. Psychiatry Investig 2010; 7: 155-162
- 9 Bohlken J, Bauer M, Kostev K. Drug treatment for patients with bipolar disorders in psychiatric practices in Germany in 2009 and 2018. Psychiatry Res 2020; 289: 112965
- 10 Hayes J, Prah P, Nazareth I. et al. Prescribing trends in bipolar disorder: Cohort study in the United Kingdom THIN primary care database 1995-2009. PLoS One 2011; 6: e28725
- 11 Kendall T, Morriss R, Mayo-Wilson E. et al. Assessment and management of bipolar disorder: Summary of updated NICE guidance. BMJ 2014; 349: g5673
- 12 Bschor T, Baethge C, Grunze H. et al. S3-Leitlinie Bipolare Störungen—1. Update 2019: Was ist neu in der Pharmakotherapie? [German S3 guidelines on bipolar disorders-first update 2019: What is new in pharmacotherapy?]. Nervenarzt 2020; 91: 216-221
- 13 Frye MA, Ketter TA, Leverich GS. et al. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry 2000; 61: 9-15
- 14 Fornaro M, De Berardis D, Koshy AS. et al. Prevalence and clinical features associated with bipolar disorder polypharmacy: A systematic review. Neuropsychiatr Dis Treat 2016; 12: 719-735
- 15 Greene M, Paladini L, Lemmer T. et al. Systematic literature review on patterns of pharmacological treatment and adherence among patients with bipolar disorder type I in the USA. Neuropsychiatr Dis Treat 2018; 14: 1545-1559
- 16 Rhee TG, Olfson M, Nierenberg AA. et al. 20-Year trends in the pharmacologic treatment of bipolar disorder by psychiatrists in outpatient care settings. Am J Psychiatry 2020; 177: 706-715
- 17 Bauer M, Glenn T, Alda M. et al. Drug treatment patterns in bipolar disorder: Analysis of long-term self-reported data. Int J Bipolar Disord 2013; 1: 5
- 18 Kessing LV, Bauer M, Nolen WA. et al. Effectiveness of maintenance therapy of lithium vs other mood stabilizers in monotherapy and in combinations: A systematic review of evidence from observational studies. Bipolar Disord 2018; DOI: 10.1111/bdi.12623.. Epub ahead of print
- 19 Rathmann W, Bongaerts B, Carius HJ, Kruppert S, Kostev K. Basic characteristics and representativeness of the German Disease Analyzer database. Int J Clin Pharmacol Ther 2018; 56: 459-466
- 20 Kostev K, Bohlken J, Jacob L. Analysis of the effects of selective serotonin (and noradrenaline) reuptake inhibitors on the risk of dementia in patients with depression. J Alzheimers Dis 2019; 62: 577-583
- 21 DGBS und DGPPN. 2019. S3-Leitlinie zur Diagnostik und Therapie Bipolarer Störungen. Langversion 2019; www.awmf.org/leitlinien/detail/ll/038-019.html
- 22 Jauhar S, Young AH. Controversies in bipolar disorder; role of second-generation antipsychotic for maintenance therapy. Int J Bipolar Disord 2019; 7: 10
- 23 Gitlin MJ. Antidepressants in bipolar depression: An enduring controversy. Int J Bipolar Disord 2018; 6: 25
- 24 Dell’Osso B, Cremaschi L, Arici C. et al. Differential core pharmacotherapy in bipolar I versus bipolar II disorder and European versus American patients not in a syndromal episode. Int Clin Psychopharmacol 2020; 35: 8-18
- 25 Baldessarini RJ, Leahy L, Arcona S. et al. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv 2007; 58: 85-91
- 26 Kessing LV, Hellmund G, Geddes JR. et al. Valproate v. lithium in the treatment of bipolar disorder in clinical practice: observational nationwide register-based cohort study. Br J Psychiatry 2011; 199: 57-63
- 27 Wingård L, Bodén R, Brandt L. et al. Reducing the rehospitalization risk after a manic episode: A population based cohort study of lithium, valproate, olanzapine, quetiapine and aripiprazole in monotherapy and combinations. J Affect Disord 2017; 217: 16-23
- 28 Wingård L, Brandt L, Bodén R. et al. Monotherapy vs. combination therapy for post mania maintenance treatment: A population based cohort study. Eur Neuropsychopharmacol 2019; 29: 691-700
- 29 Jawad I, Watson S, Haddad PM. et al. Medication nonadherence in bipolar disorder: A narrative review. Ther Adv Psychopharmacol 2018; 8: 349-363