Pharmacopsychiatry 2011; 44(2): 72-74
DOI: 10.1055/s-0030-1268418

© Georg Thieme Verlag KG Stuttgart · New York

Combination of Lithium and Duloxetine in 2 Depressed Patients Refractory to Duloxetine Monotherapy

N. Steffenhagen1 , B. Kürstein1 , K. C. Kirkby2 , H. Himmerich1
  • 1Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany
  • 2Department of Psychiatry, University of Tasmania, Hobart, Tasmania, Australia
Further Information

Publication History

received 30.04.2010 revised 12.09.2010

accepted 01.10.2010

Publication Date:
15 December 2010 (online)

Duloxetine, an inhibitor of both norepinephrine and serotonin transporters (SNRI), is a safe and effective pharmaceutical in acute, adult major depressive disorder [1], but does not exert better effects than standard alternatives [2]. In general, 30–40% of depressed patients do not respond to the first course of drug treatment, and more than 50% of initial non-responders also do not respond to a second, different antidepressant agent [3]. There is good evidence for efficacy of lithium in combination with various antidepressant drugs in therapy-resistant depression. In a recent meta-analysis of 10 randomized placebo-controlled trials, the addition of lithium to an antidepressant therapy had a statistically significant effect compared to the addition of placebo [4]. The therapeutic potential of a combination of an antidepressant with lithium is probably mediated through the serotonergic system [5] and has been demonstrated for tricyclic antidepressants [6], selective serotonin reuptake inhibitors (SSRI) [7] [8] [9] and the selective serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine [8] [10]. Regarding the combination of the SNRI duloxetine and lithium, there are no published data either on efficacy or on safety. This is the first report of the successful addition of lithium to duloxetine in 2 patients with therapy-refractory severe depression.


  • 1 Dugan SE, Fuller MA. Duloxetine: a dual reuptake inhibitor.  Ann Pharmacother. 2004;  38 2078-2085
  • 2 Girardi P, Pompili M, Innamorati M. et al . Duloxetine in acute major depression: review of comparisons to placebo and standard antidepressants using dissimilar methods.  Hum Psychopharmacol. 2009;  24 177-190
  • 3 Adli M, Bauer M, Rush AJ. Algorithms and collaborative-care systems for depression: are they effective and why?.  A systematic review. Biol Psychiatry. 2006;  59 1029-1038
  • 4 Crossley NA, Bauer M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials.  J Clin Psychiatry. 2007;  68 935-940
  • 5 Bschor T, Lewitzka U, Sasse J. et al . Lithium augmentation in treatment-resistant depression: clinical evidence, serotonergic and endocrine mechanisms.  Pharmacopsychiatry. 2003;  36 (S 03) 230-234
  • 6 Fleurence R, Williamson R, Jing Y. et al . A systematic review of augmentation strategies for patients with major depressive disorder.  Psychopharmacol Bull. 2009;  42 57-90
  • 7 Baumann P, Nil R, Souche A. et al . A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation.  J Clin Psychopharmacol. 1996;  16 307-314
  • 8 Katona CL, Abou-Saleh MT, Harrison DA. et al . Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine.  Br J Psychiatry. 1995;  166 80-86
  • 9 Ontiveros A, Fontaine R, Elie R. Refractory depression: the addition of lithium to fluoxetine or desipramine.  Acta Psychiatr Scand. 1991;  83 188-192
  • 10 Bertschy G, Ragama-Pardos E, Ait-Ameur A. et al . Lithium augmentation in venlafaxine non-responders: an open study.  Eur Psychiatry. 2003;  18 314-317
  • 11 Yates WR, Wesner RB, Thompson R. Organic mood disorder: a valid psychiatry consultation diagnosis?.  J Affect Disord. 1991;  22 37-42
  • 12 Frampton JE, Plosker GL. Duloxetine: a review of its use in the treatment of major depressive disorder.  CNS Drugs. 2007;  21 581-609
  • 13 Papakostas GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder.  J Clin Psychiatry. 2009;  70 (S 06) 16-25
  • 14 Hoencamp E, Haffmans J, Dijken WA. et al . Lithium augmentation of venlafaxine: an open-label trial.  J Clin Psychopharmacol. 2000;  20 538-543
  • 15 Adan-Manes J, Novalbos J, Lopez-Rodriguez R. et al . Lithium and venlafaxine interaction: a case of serotonin syndrome.  J Clin Pharm Ther. 2006;  31 397-400
  • 16 Mekler G, Woggon B. A case of serotonin syndrome caused by venlafaxine and lithium.  Pharmacopsychiatry. 1997;  30 272-273
  • 17 Waring WS. Management of lithium toxicity.  Toxicol Rev. 2006;  25 221-230


H. HimmerichMD 

Department of Psychiatry and Psychotherapy

University of Leipzig

Semmelweisstraße 10

04103 Leipzig


Phone: +49/341/97 24490

Fax: +49/341/97 24559