Lithium Augmentation Therapy in Refractory Depression: Clinical Evidence and Neurobiological Mechanisms

Canadian Journal of Psychiatry

Volumn 48, Issue 7, 2003, Pages 440-448

  Bauer, Michael ^a,d   Adli, Mazda ^a   Baethge, Christopher ^b   Berghöfer, Anne ^a   Sasse, Johanna ^a   Heinz, Andreas ^a   Bschor, Tom ^c  

^a HUMBOLDT UNIVERSITY   (Germany)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^d CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Cortisol; DEX CRH test; Lithium; Lithium augmentation; Major depression; Neuroendocrine tests; Refractory depression; Serotonin; Treatment resistant depression

Indexed keywords

ANTIDEPRESSANT AGENT; DEXAMETHASONE; HYDROCORTISONE; LITHIUM; NORADRENALIN; NORADRENALIN UPTAKE INHIBITOR; PLACEBO; SEROTONIN; SEROTONIN UPTAKE INHIBITOR;

ADJUVANT THERAPY; ANIMAL EXPERIMENT; CLINICAL TRIAL; COCHRANE LIBRARY; DEPRESSION; DEXAMETHASONE SUPPRESSION TEST; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; HUMAN; MAJOR DEPRESSION; MEDLINE; NEUROBIOLOGY; NEUROENDOCRINE SYSTEM; NEUROTRANSMISSION; NORADRENERGIC SYSTEM; PATHOPHYSIOLOGY; PROSPECTIVE STUDY; PUBLICATION; REFRACTORY DEPRESSION; REVIEW; SEROTONINERGIC SYSTEM; TREATMENT RESISTANT DEPRESSION;

EID: 0142026828     PISSN: 07067437     EISSN: None     Source Type: Journal    
DOI: 10.1177/070674370304800703     Document Type: Review

References (79)

1. Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of unipolar depressive disorders, part 1: acute and continuation treatment of major depressive disorder. World J Biol Psychiatry 2002;3:5-43.
2. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000; 157 (Suppl):1-45.
3. Crismon ML, Trivedi M, Pigott TA, Rush AJ, Hirschfeld RM, Kahn DA, and others. The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder. J Clin Psychiatry 1999;60:142-56.
4. De Montigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders. Br J Psychiatry 1981;138:252-56.
5. Heninger GR, Charney DS, Sternberg DE. Lithium carbonate augmentation of antidepressant treatment. Arch Gen Psychiatry 1983;40:1335-42.
6. Kantor D, McNevin S, Leichner P, Harper D, Krenn M. The benefit of lithium carbonate adjunct in refractory depression - fact or fiction? Can J Psychiatry 1986;31:416-8.
7. Zusky PM, Biederman J, Rosenbaum JF, Manschreck TC, Gross CC, Weilberg JB, and others. Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study. J Clin Psychopharmacol 1988;8:120-4.
8. Schöpf J, Baumann P, Lemarchand T, Rey M. Treatment of endogenous depressions resistant to tricyclic antidepressants or related drugs by lithium addition. Results of a placebo-controlled double-blind study. Pharmacopsychiatry 1989;22:183-7.
9. Browne M, Lapierre YD, Hrdina PD, Horn E. Lithium as an adjunct in the treatment of major depression. Int Clin Psychopharmacol 1990;5:103-10.
10. Joffe RT, Singer W, Levitt AJ, MacDonald C. A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiatry 1993;50:387-93.
11. Stein G, Bernadt M. Lithium augmentation therapy in tricyclic-resistant depression. A controlled trial using lithium in low and normal doses. Br J Psychiatry 1993;162:634-40.
12. Katona CLE, Abou-Saleh MT, Harrison DA, Nairac BA, Edwards DRL, Lock T, and otheres. Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine. Br J Psychiatry 1995;166:80-6.
13. Baumann P, Nil R, Souche A, Montaldi S, Baettig D, Lambert S, and others. 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; 16:307-14.
14. De Montigny C, Cournoyer G, Morisette R. Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression: correlations with the neurobiologic actions of tricyclic antideoressant drugs and lithium on the serotonin system. Arch Gen Psychiatry 1983;40:1327-34.
15. De Montigny C, Elie R, Caille G. Rapid response to the addition of lithium in iprindole-resistant unipolar depression: a pilot study. Am J Psychiatry 1985;142:220-3.
16. Price LH, Charney DS, Henninger GR. Variability of response to lithium augmentation in refractory depression. Am J Psychiatry 1986;143:1387-92.
17. Delgado PL, Price LH, Charney DS Heninger GR. Efficacy of fluvoxamine in treatment refractory depression. J Affect Disorder 1988;15:55-60.
18. Fontaine R, Ontiverod A, Elie R, Vézina M. Lithium carbonate augmentation of desipramine and fluoxetine in refractory depression. Biol Psychiatry 1991;29:946-8.
19. Dinan TG. Lithium augmentation in sertraline-resistant depression: a preliminary dose-response study. Acta Psychiatr Scand 1993;88:300-1.
20. Flint AJ, Rifat SL. A prospective study of lithium augmentation in antidepressant-resistant geriatric depression. J Clin Psychopharmacol 1994;14:353-6.
21. Hawley CJ, Roberts AG, Baldwin DS. Tolerability of combined treatment with lithium and fluoxetine: 14 cases treated under open conditions. Int Clin Psychopharmacol 1994;9:31-3.
22. Hawley CJ, Roberts AG, Walker MH. Tolerability of combined treatment with lithium and paroxetine: 19 cases treated under open conditions. Int Clin Psychopharmacol 1994;8:266-7.
23. Uehlinger C, Nil R, Amey M, Baumann P, Dufour H. Citalopram-lithium combination treatment of elderly depressed patients: a pilot study. Int J Ger Psychiatry 1995;10:281-7.
24. Sluzeska A, Sobieska M, Rybakowski JK. Changes in acute-phase proteins during lithium potentiation of antidepressants in refractory depression. Biol Psychiatry 1997;35:123-7.
25. Hoencamp E, Haffmans PMJ, Dijken WA, Huijbrechts IPAM. Lithium augmentation of venlafaxine: an open-label trial. J Clin Psychiatry 2000;20:538-43.
26. Hoencamp E, Haffmans PMJ, Dijken WA. Brofaromine versus lithium addition to maprotiline: a double blind study in maprotiline refractory depressed outpatients. J Affect Disord 1994;30:219-27.
27. Fava M, Alpert J, Nierenberg A, Lagomasino I, Sonawalla S, Tedlow J, and others. Double-blind study of high-dose fluoxetine versus lithium or desipramine augmentation of fluoxetine in partial responders and nonresponders to fluoxetine. J Clin Psychopharmacol 2002;22:379-87.
28. Dinan TG, Barry S. A comparison of electroconvulsive therapy with a combined lithium and tricyclic combination among depressed tricyclic nonresponders. Acta Psychiatr Scand 1989;80:97-100.
29. Fava M, Rosenbaum JF, McGrath PJ, Stewart JW, Amsterdam JD, Quitkin FM. Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: a double-blind, controlled study. Am J Psychiatry 1994;151:1372-4.
30. Bauer M, Bschor T, Kunz D, Berghöfer A, Ströhle A, Müller-Oerlinghausen B. Double-blind, placebo-controlled trial of the use of lithium to augment anti-depressant medication in continuation treatment of unipolar major depression. Am J Psychiatry 2000;157:1429-35.
31. Bauer M, Döpfmer S. Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin Psychopharmacol 1999;19:427-34.
32. Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol 1992;45:255-65.
33. Bschor T, Berghöfer A, Ströhle A, Kunz D, Adli M, Müller-Oerlinghausen B, and others. How long should the lithium augmentation strategy be maintained? A 1-year follow-up of a placebo-controlled study in unipolar refractory major depression. J Clin Psychopharmacol 2002;22:427-30.
34. Hardy BG, Shulman KI, Zucchero C. Gradual discontinuation of lithium augmentation in elderly patients with unipolar depression. J Clin Psychopharmacol 1997;17:22-6.
35. Fahy S, Lawlor BA. Discontinuation of lithium augmentation in an elderly cohort. Int J Geriatr Psychiatry 2001;16:1004-9.
36. Maes M, Meltzer HY. The serotonin hypotheses of major depression. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: the fourth generation of progess. New York: Raven Press; 1995. p 933-44.
37. Schatzberg AF, Garlow SJ, Nemeroff CB. Molecular and cellular mechanisms in depression. In: Davis KL, Charney D, Coyle JT, Nemeroff C, editors. Neuropsychopharmacology: the fifth generation of progress. American College of Neuropsychopharmacology. Philadelphia (PA): Lippincott Williams and Wilkins; 2002. p 1039-50.
38. Blier P, De Montigny C. Short-term lithium administration enhances serotonergic neurotransmission: electrophysiological evidence in the rat CNS. Eur J Pharmacol 1985;133:66-77.
39. Price LH, Charney DS, Delgado PL, Heninger GR. Lithium and serotonin function: implications for the serotonin hypothesis of depression. Psychopharmacology (Berl) 1990;100:3-12.
40. Müller-Oerlinghausen B. Lithium long-term treatment - does it act via serotonin? Pharmacopsychiatry 1985;18:214-7.
41. Price LH, Charney DS, Delgado PL, Goodman WK, Krystal JH, Woods SW, and others. Clinical studies of 5-HT function using IV L-tryptophan. Prog Neuropsychopharmacol Biol Psychiatry 1990;14:459-72.
42. De Montigny C. Lithium addition in treatment-resistant depression. Int Clin Psychopharmacol 1994;9 (Suppl 2):31-5.
43. Grahame-Smith DG, Green AR. The role of brain 5-hydroxytryptamine in the hyperactivity produced by lithium and monoamine oxidase inhibition. Br J Pharmacol 1974;52:19-26.
44. Treiser SL, Cascio CS, O'Donohue TL, Keilar K. Lithium increases serotonin release and decreases serotonin receptors in the hippocampus. Science 1981;213:1529-31.
45. Broderick P, Lynch V. Behavioral and biochemical changes induced by lithium and L-tryptophan in muridical rats. Neuropharmacology 1982;21:671-9.
46. De Montigny C, Aghajanian GK. Tricyclic antidepressants: long-term treatment increases responsivity of rat forebrain neurons to serotonin. Science 1978;202:1303-6.
47. Chaput Y, De Montigny C, Blier P. Presynaptic and postsynaptic modifications of the serotonin system by long-term administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. Neuropsychopharmacology 1991;5:219-29.
48. De Montigny C. Lithium addition in treatment-resistant depression: evidence for the involvement of the serotonin system. In: Racagni G, Brunello N, Fukuda T, editors. Biological psychiatry. Volume 1. Amsterdam: Elsevier Science Publishers BV; 1991. p 243-4.
49. Okamoto Y, Motohasi N, Hayakawa H, Muraoka M, Yamawaki S. Addition of lithium to chronic antidepressant treatment potentiates presynaptic serotonergic function without changes in serotonergic receptors in the rat cerebral cortex. Neuropsychobiology 1996;33:17-20.
50. Wegener G, Bandpey Z, Heiberg IL, Mork A, Rosenberg R. Increased extracellular serotonin level in rat hippocampus induced by chronic citalopram is augmented by subchronic lithium: neurochemical and behavioural studies in the rat. Psychopharmacology (Berl) 2003;166:188-94.
51. Cowen PJ, McCance SL, Ware CJ, Cohen PR, Chalmers JS, Julier DL. Lithium in tricyclic-resistant depression. Correlation ofincreased brain 5-HT function with clinical outcome. Br J Psychiatry 1991;159:341-6.
52. McCance-Katz E, Price LH, Charney DS, Heninger GR. Serotonergic function during lithium augmentation of refractory depression. Psychopharmacology 1992;108:93-7.
53. Dinan TG. Psychoneuroendocrinology of mood disorders. Curr Opin Psychiatry 2001;14:51-5.
54. Steckler T, Holsboer F, Reul JM. Glucocorticoids and depression. Baillieres Best Pract Res Clin Endocrinol Metab 1999;13:597-614.
55. Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000;23:477-501.
56. Holsboer-Trachsler E, Hemmeter U, Hatzinger M, Seifritz E, Gerhard U, Hobi V. Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment-neurobiological and psychometric assessment of course. J Psychiatr Res 1994;28:381-99.
57. Heuser IJE, Schweiger U, Gorthardt U, Schmider J, Lammers CH, Dettling M, and others. Pituitary-adrenal-system regulation and psychopathology during amitriptyline treatment in elderly depressed patients and normal comparison subjects. Am J Psychiatry 1996;153:93-9.
58. Bschor T, Adli M, Baethge C, Eichmann U, Ising M, Uhr M, and others. Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression. Neuropsychopharmacology 2002;27:470-8.
59. Bschor T, Baethge C, Adli M, Eichmann U, Ising M, Uhr M, and others. Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression. Depress Anxiety 2003;17:43-8.
60. Platman SR, Fieve RR. Lithium carbonate and plasma cortisol response in the affective disorders. Arch Gen Psychiatry 1968;18:591-4.
61. Platman SR, Hilton JG, Koss MC, Kelly WG. Production of cortisol in patients with manic-depressive psychosis treated with lithium carbonate. Dis Nerv Syst 1971;32:542-4.
62. Sugawara M, Hashimoto K, Hattori T, Takao T, Suemaru S, Ota Z. Effects of lithium on the hypothalamo-pituitary-adrenal axis. Endocrinol Jpn 1988;35:655-63.
63. Zatz M, Reisine TD. Lithium induces corticotropin secretion and desensitization in cultured anterior pituitary cells. Proc Natl Acad Sci USA 1985;82:1286-90.
64. Reisine T, Zatz M. Interactions among lithium, calcium, diacylglycerides, and phorbolesters in the regulation of adrenocorticotropin hormone release from AtT-20 cells. J Neurochem 1987;49:884-9.
65. Bschor T, Baethge C, Adli M, Eichmann U, Ising M, Uhr M, and others. Association between response to lithium augmentation and the combined DEX/CRH test in major depressive disorder. J Psychiatr Res 2003;37:135-43.
66. Holsboer F, Lauer Ch J, Schreiber W, Krieg JC. Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology 1995;62:340-7.
67. Amsterdam JD, Winokur A, Abelman E, Lucki I, Rickels K. Cosyntropin (ACTH alpha 1-24) stimulation test in depressed patients and healthy subjects Am J Psychiatry 1983;140:907-9.
68. Barden N, Reul JM, Holsboer F. Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? Trends Neurosci 1995;18:6-11.
69. Zobel AW, Yassouridis A, Frieboes RM, Holsboer F. Prediction of medium-term outcome by cotisol response to the combined dexamethasone-CRH test in patients with remitted depression. Am J Psychiatry 1999;156:949-51.
70. Zobel AW, Nickel T, Sonntag A, Uhr M, Holsboer F, Ising M. Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression: a prospective study. J Psychiatr Res 2001;35:83-94.
71. Souza FG, Goodwin GM. Lithium treatment and prophylaxis in unipolar depression: a meta-analysis. Br J Psychiatry 1991;158:666-75.
72. Adli M, Bschor T, Canata B, Döpfmer S, Bauer M. Lithium in the treatment of acute depression. [Article in German] Fortschr Neurol Psychiatr 1998;66:435-41.
73. Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, Gray N, and others. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 2003;53:707-42.
74. Manji HK, Moore GJ, Chen G. Bipolar disorder: leads from the molecular and cellular mechanisms of action of mood stabilizers. Br J Psychiatry 2001;178(Suppl 41):107-19.
75. Lenox RH, Hahn CG. Overview of the mechanism of action of lithium in the brain: fifty-year update. J Clin Psychiatry 2000;61 (Suppl 9):5-15.
76. Manji HK, Lenox RH. Protein kinase C signaling in the brain: molecular transduction of mood stabilization in the treatment of manic-depressive illness. Biol Psychiatry 1999;46:1328-51.
77. Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK. Enhancement of hippocampal neurogenesis by lithium. J Neurochem 2000;75:1729-34.
78. Huang X, Wu DY, Chen G, Manji H, Chen DF. Support of retinal ganglion cell survival and axon regeneration by lithium through a Bcl-2-dependent mechanism. Invest Ophthalmol Vis Sci 2003;44:347-54.
79. Phiel CJ, Wilson CA, Lee VM, Klein PS. GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature 2003;423:435-9.