Lithium efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof‑of‑concept study

Machado-Vieira,Rodrigo; Zanetti,Marcus  V.; De Sousa,Rafael  T.; Soeiro‑De‑Souza,Marcio  G.; Moreno,Ricardo  A.; Busatto,Geraldo   F.; Gattaz,Wagner  F.

doi:10.3892/etm.2014.1864

October 2014 Volume 8 Issue 4

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

October 2014 Volume 8 Issue 4

Full Size Image

Article

Lithium efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof‑of‑concept study

Authors:
- Rodrigo Machado-Vieira
- Marcus V. Zanetti
- Rafael T. De Sousa
- Marcio G. Soeiro‑De‑Souza
- Ricardo A. Moreno
- Geraldo F. Busatto
- Wagner F. Gattaz
View Affiliations / Copyright

Affiliations: Laboratory of Neuroscience LIM-27, Department and Institute of Psychiatry, School of Medicine, University of São Paulo (HC-FMUSP), São Paulo, Brazil, Mood Disorders Unit (GRUDA), Department and Institute of Psychiatry, School of Medicine, University of São Paulo (HC-FMUSP), São Paulo, Brazil, Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil
Pages: 1205-1208
|
Published online on: July 24, 2014

https://doi.org/10.3892/etm.2014.1864
Expand metrics +

Abstract

Lithium has a narrow therapeutic index with a subtle balance between effectiveness and adverse effects. Current guidelines recommend the use of lithium as a treatment for acute bipolar depression; however, the therapeutic range for the treatment has not been fully defined. Recently, the adjunctive lower lithium dose in bipolar depression has revealed potential efficacy; however, no study has investigated it predominantly in monotherapy. In this open‑label, proof‑of‑concept study, 31 individuals with bipolar disorder during a depressive episode were randomized and 29 were followed up for six weeks with flexible lithium dosing. All subjects had a 21‑item Hamilton Rating Scale for Depression (HAM‑D) score of ≥18 at baseline. Subjects were divided into two groups, with higher (Li ≥0.5 mEq/l) or lower (Li <0.5 mEq/l) blood lithium levels. Response and remission rates were evaluated using the HAM‑D scores. Following 6 weeks of lithium treatment, the remission rate for all patients was 62.0%. The plasma lithium levels did not impact the clinical response. However, subjects with higher blood lithium levels had an increased prevalence of nausea, restlessness, headaches and cognitive complaints. The results indicate that the lithium dose for the treatment of bipolar depression in an individual should be based on the clinical efficacy and side‑effects. In the context of personalized psychiatric treatments, it is necessary to evaluate the therapeutic action of lithium with individual regimens in order to develop more tolerable and effective treatment approaches.

View Figures

View References

1	Judd LL, Akiskal HS, Schettler PJ, et al: A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 60:261–269. 2003. View Article : Google Scholar : PubMed/NCBI
2	Merikangas KR, Akiskal HS, Angst J, et al: Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 64:543–552. 2007. View Article : Google Scholar : PubMed/NCBI
3	Machado-Vieira R, Manji HK and Zarate CA Jr: The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord. 11(Suppl 2): 92–109. 2009. View Article : Google Scholar : PubMed/NCBI
4	Forlenza OV, de Paula VJ, Machado-Vieira R, et al: Does lithium prevent Alzheimer’s disease? Drugs Aging. 29:335–342. 2012.
5	Haeberle A, Greil W, Russmann S and Grohmann R: Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP. BMC Psychiatry. 12:1532012. View Article : Google Scholar : PubMed/NCBI
6	Yatham LN, Kennedy SH, Parikh SV, et al: Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 15:1–44. 2013. View Article : Google Scholar
7	Gelenberg AJ, Kane JM, Keller MB, et al: Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med. 321:1489–1493. 1989. View Article : Google Scholar : PubMed/NCBI
8	Severus WE, Kleindienst N, Seemüller F, et al: What is the optimal serum lithium level in the long-term treatment of bipolar disorder - a review? Bipolar Disord. 10:231–237. 2008. View Article : Google Scholar : PubMed/NCBI
9	Nierenberg AA, Friedman ES, Bowden CL, et al: Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium. Am J Psychiatry. 170:102–110. 2013. View Article : Google Scholar
10	Perlis RH, Sachs GS, Lafer B, et al: Effect of abrupt change from standard to low serum levels of lithium: a reanalysis of double-blind lithium maintenance data. Am J Psychiatry. 159:1155–1159. 2002. View Article : Google Scholar : PubMed/NCBI
11	Coppen A, Abou-Saleh M, Milln P, et al: Decreasing lithium dosage reduces morbidity and side-effects during prophylaxis. J Affect Disord. 5:353–362. 1983. View Article : Google Scholar : PubMed/NCBI
12	Amsterdam JD and Shults J: Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II major depressive episode: a randomized open-label study. J Clin Psychopharmacol. 28:171–181. 2008. View Article : Google Scholar : PubMed/NCBI
13	Suppes T, Marangell LB, Bernstein IH, et al: A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression. J Affect Disord. 111:334–343. 2008. View Article : Google Scholar : PubMed/NCBI
14	Young AH, McElroy SL, Bauer M, et al: A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I). J Clin Psychiatry. 71:150–162. 2010. View Article : Google Scholar : PubMed/NCBI
15	First MB, Spitzer RL, Gibbon M and Williams J: Structured Clinical Interview for DSM-IV Axis I Disorders. Patient Edition (SCID-I/P). Biometrics Research, New York State Psychiatry Institute; New York, NY: 1995
16	Nolen WA and 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. 15:100–109. 2013. View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Lithium efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof‑of‑concept study

This article is mentioned in:

Abstract

Figure 1

Related Articles