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A Placebo-Controlled Comparison of Lithium and Triiodothyronine Augmentation of Tricyclic Antidepressants in Unipolar Refractory Depression

A Placebo-Controlled Comparison of Lithium and Triiodothyronine Augmentation of Tricyclic... Abstract Objective: To directly compare the efficacy of lithium carbonate and liothyronine sodium (triiodothyronine) in the augmentation of therapeutic response in antidepressant nonresponders. Design: A randomized, double-blind, placebocontrolled study of 2 weeks' duration. Setting: The Mood Disorders Program, Clarke Institute of Psychiatry and the University of Toronto, Ontario. Patients: Fifty outpatients, males and females, with unipolar, nonpsychotic major depression who had failed to respond to treatment with desipramine hydrochloride or imipramine hydrochloride. Results: Both liothyronine and lithium were more ef- fective than placebo in reducing scores on the Hamilton Rating Scale for Depression. However, the antidepressant augmenting effect of these two compounds did not differ from each other. When response was defined as a 50% or more reduction in the Hamilton Rating Scale for Depression scores and a final score less than 10, we found that 10 of 17 subjects responded to liothyronine, nine of 17 responded to lithium and three of 16 responded to placebo. Conclusions: Our study suggests that both lithium and liothyronine may be considered as alternatives in augmenting antidepressant response in patients who do not respond to treatment with a tricyclic antidepressant. References 1. Klein DE, Gittelman R, Quitkin F. Diagnosis and Drug Treatment of Psychiatric Disorders . 2nd ed. Baltimore, Md: Williams & Wilkins; 1980. 2. Schou M. Lithium and treatment-resistant depressions: a review . Lithium . 1990; 1:3-8. 3. Price LH. Lithium augmentation and tricyclic-resistant depression . In: Extein I, ed. Treatment of Tricyclic-Resistant Depression . Washington, DC: American Psychiatric Press; 1988:51-79. 4. DeMontigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug nonresponders . Br J Psychiatry . 1981;138:252-256.Crossref 5. DeMontigny C, Cournoyer G, Morisette R, Langlois R, Caille G. Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression: correlations with the neuro-biologic actions of tricyclic antidepressant drugs and lithium ion on the serotonin system . Arch Gen Psychiatry . 1983;143:1387-1334. 6. Price LH, Charney DS, Heninger GR. Variability of response to lithium augmentation and refractory depression . Am J Psychiatry . 1986;143:1387-1392. 7. Louie AK, Meltzer HY. Lithium potentiation of antidepressant treatment . J Clin Psychopharmacol . 1984;4:316-321.Crossref 8. Heninger GR, Charney DS, Sternberg DE. Lithium carbonate augmentation of antidepressant treatment: an effective prescription for treatment-refractory depression . Arch Gen Psychiatry . 1983;40:1335-1342.Crossref 9. Cournoyer G, DeMontigny C, Ouellette J, Leblanc G, Langlois R, Elie R. Lithium addition in tricyclic-resistant unipolar depression: a placebo-controlled study. Abstracts of Collegium Internationale Neuropsychopharmacologicum, Florence, Italy, June 19-23, 1984;179. 10. 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;31:416-418. 11. Stein G, Bernadt M. Double-blind trial of lithium carbonate in tricyclic resistant depression . In: Birch NJ, ed. Lithium: Inorganic Pharmacology and Psychiatric Use . Oxford, England: IRL Press; 1988:35-36. 12. Zusky PM, Biederman J, Rosenbaum JF, Manschreck TC, Gross CC, Weilberg JB, Gastfriend DR. Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study . J Clin Psychopharmacol . 1988;8:120-124.Crossref 13. Schopf J, Baumann P, Lemarchand T, Ray 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;22:183-187.Crossref 14. Austin MPV, Souza FGN, Goodwin GM. Lithium augmentation in antidepressantresistant patients: a quantitative analysis . Br J Psychiatry . 1991;159:510-514.Crossref 15. Earle BV. Thyroid hormone and tricyclic antidepressants in resistant depression . Am J Psychiatry . 1970;126:1667-1669. 16. Banki CM. Triiodothyronine in the treatment of depression . Orv Hetil . 1975; 116:2543-2547. 17. Banki C. Cerebrospinal fluid amine metabolites after combined amitriptylinetriiodothyronine treatment of depressed women . Eur J Clin Pharmacol . 1977; 11:311-315.Crossref 18. Ogura C, Okuma T, Uchida Y, lmai S, Yogi H, Sunami Y. Combined thyroid (triiodothyronine)—tricyclic antidepressant treatment in depressed states . Folia Psychiatr Neurol Jpn . 1974;28:179-186. 19. Tsutsui S, Yamazaki Y, Nanba T, Tsushima M. Combined therapy of T3 and antidepressants in depression . J Int Med Res . 1979;7:138-146. 20. Goodwin FK, Prange AJ Jr, Post RM, Muscettola G, Lipton MA. Potentiation of antidepressant effects by L-triiodothyronine tricyclic nonresponders . Am J Psychiatry . 1982;139:34-38. 21. Schwarcz G, Halaris A, Baxter L, Escobar J, Thompson M, Young M. Normal thyroid function in desipramine nonresponders compared to responders by the addition of L-triiodothyronine . Am J Psychiatry . 1984;141:1614-1616. 22. Thase ME, Kupfer DJ, Jarrett DB. Treatment of imipramine-resistant recurrent depression, I: an open clinical trial of adjunctive L-triiodothyronine . J Clin psychiatry . 1989;50:385-388. 23. Gitlin MJ, Winer H, Fairbanks L, Hershman JM, Friedfeld N. Failure of T3 to potentiate tricyclic antidepressant response . J Affective Disord . 1987;13:267-272.Crossref 24. Joffe RT, Singer W. A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants . Psychiatry Res . 1990;32:241-252.Crossref 25. Garbutt JC, Mayo JP Jr, Gillette GM, Little KY, Mason GA. Lithium potentiation of tricyclic antidepressants following lack of T3 potentiation . Am J Psychiatry . 1986;143:1038-1039. 26. Joffe RT. T3 and lithium potentiation of tricyclic antidepressants . Am J Psychiatry . 1988;145:1317-1318. 27. Hamilton M. A rating scale for depression . J Neurol Neurosurg Psychiatry . 1960;23:56-62.Crossref 28. Price LH. What is the duration for augmentation with T3 or lithium in resistant depression? J Clin Psychopharmacol . 1989;9:73.Crossref 29. Keppel G, Zedeck S. Data Analysis for Research Designs . New York, NY: WH Freeman & Co; 1989. 30. Rhoades HM, Overall JE. The Hamilton Depression Scale: factor scoring and profile classification . Psychopharmacol Bull . 1983;19:91-96. 31. Garbutt J, Malekpour B, Brunswick D, Jonnalagadda MR, Jolliff L, Poddak R, Wilson I, Prange AJ Jr. Effects of triiodothyronine on drug levels and cardiac function in depressed patients treated with imipramine . Am J Psychiatry . 1979; 136:980-982. 32. 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.Crossref 33. Stern RA, Nevels CT, Shelhorse ME, Prohaska ML, Mason GA, Prange AJ Jr. Antidepressant and memory effects of combined thyroid hormone treatment and electroconvulsive therapy: preliminary findings . Biol Psychiatry . 1991;30: 623-627.Crossref 34. Nemeroff CB. Augmentation regimens for depression . J Clin Psychiatry . 1991; 52( (suppl) ):21-27. 35. Schopf J. Treatment of depressions resistant to tricyclic antidepressants, related drugs or MAO-inhibitors by lithium addition: review of the literature . Pharmacopsychiatry . 1989;22:174-182.Crossref 36. Fontaine R, Ontiveros A, Elie R, Vezina M. Lithium carbonate augmentation of desipramine and fluoxetine in refractory depression . Biol Psychiatry . 1991;29: 946-948.Crossref 37. Bartko JJ, Pulver AE, Carpenter WT Jr. The power of analysis: statistical perspectives: part 2 . Psychiatry Res . 1988;23:301-310.Crossref 38. Pigott TA, Pato MT, L'Heureux F, Hill JL, Grover JN, Bernstein SE, Murphy DL. A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder . J Clin Psychopharmacol . 1991;11:242-248.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

A Placebo-Controlled Comparison of Lithium and Triiodothyronine Augmentation of Tricyclic Antidepressants in Unipolar Refractory Depression

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Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1993.01820170065008
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Abstract

Abstract Objective: To directly compare the efficacy of lithium carbonate and liothyronine sodium (triiodothyronine) in the augmentation of therapeutic response in antidepressant nonresponders. Design: A randomized, double-blind, placebocontrolled study of 2 weeks' duration. Setting: The Mood Disorders Program, Clarke Institute of Psychiatry and the University of Toronto, Ontario. Patients: Fifty outpatients, males and females, with unipolar, nonpsychotic major depression who had failed to respond to treatment with desipramine hydrochloride or imipramine hydrochloride. Results: Both liothyronine and lithium were more ef- fective than placebo in reducing scores on the Hamilton Rating Scale for Depression. However, the antidepressant augmenting effect of these two compounds did not differ from each other. When response was defined as a 50% or more reduction in the Hamilton Rating Scale for Depression scores and a final score less than 10, we found that 10 of 17 subjects responded to liothyronine, nine of 17 responded to lithium and three of 16 responded to placebo. Conclusions: Our study suggests that both lithium and liothyronine may be considered as alternatives in augmenting antidepressant response in patients who do not respond to treatment with a tricyclic antidepressant. References 1. Klein DE, Gittelman R, Quitkin F. Diagnosis and Drug Treatment of Psychiatric Disorders . 2nd ed. Baltimore, Md: Williams & Wilkins; 1980. 2. Schou M. Lithium and treatment-resistant depressions: a review . Lithium . 1990; 1:3-8. 3. Price LH. Lithium augmentation and tricyclic-resistant depression . In: Extein I, ed. Treatment of Tricyclic-Resistant Depression . Washington, DC: American Psychiatric Press; 1988:51-79. 4. DeMontigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug nonresponders . Br J Psychiatry . 1981;138:252-256.Crossref 5. DeMontigny C, Cournoyer G, Morisette R, Langlois R, Caille G. Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression: correlations with the neuro-biologic actions of tricyclic antidepressant drugs and lithium ion on the serotonin system . Arch Gen Psychiatry . 1983;143:1387-1334. 6. Price LH, Charney DS, Heninger GR. Variability of response to lithium augmentation and refractory depression . Am J Psychiatry . 1986;143:1387-1392. 7. Louie AK, Meltzer HY. Lithium potentiation of antidepressant treatment . J Clin Psychopharmacol . 1984;4:316-321.Crossref 8. Heninger GR, Charney DS, Sternberg DE. Lithium carbonate augmentation of antidepressant treatment: an effective prescription for treatment-refractory depression . Arch Gen Psychiatry . 1983;40:1335-1342.Crossref 9. Cournoyer G, DeMontigny C, Ouellette J, Leblanc G, Langlois R, Elie R. Lithium addition in tricyclic-resistant unipolar depression: a placebo-controlled study. Abstracts of Collegium Internationale Neuropsychopharmacologicum, Florence, Italy, June 19-23, 1984;179. 10. 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;31:416-418. 11. Stein G, Bernadt M. Double-blind trial of lithium carbonate in tricyclic resistant depression . In: Birch NJ, ed. Lithium: Inorganic Pharmacology and Psychiatric Use . Oxford, England: IRL Press; 1988:35-36. 12. Zusky PM, Biederman J, Rosenbaum JF, Manschreck TC, Gross CC, Weilberg JB, Gastfriend DR. Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study . J Clin Psychopharmacol . 1988;8:120-124.Crossref 13. Schopf J, Baumann P, Lemarchand T, Ray 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;22:183-187.Crossref 14. Austin MPV, Souza FGN, Goodwin GM. Lithium augmentation in antidepressantresistant patients: a quantitative analysis . Br J Psychiatry . 1991;159:510-514.Crossref 15. Earle BV. Thyroid hormone and tricyclic antidepressants in resistant depression . Am J Psychiatry . 1970;126:1667-1669. 16. Banki CM. Triiodothyronine in the treatment of depression . Orv Hetil . 1975; 116:2543-2547. 17. Banki C. Cerebrospinal fluid amine metabolites after combined amitriptylinetriiodothyronine treatment of depressed women . Eur J Clin Pharmacol . 1977; 11:311-315.Crossref 18. Ogura C, Okuma T, Uchida Y, lmai S, Yogi H, Sunami Y. Combined thyroid (triiodothyronine)—tricyclic antidepressant treatment in depressed states . Folia Psychiatr Neurol Jpn . 1974;28:179-186. 19. Tsutsui S, Yamazaki Y, Nanba T, Tsushima M. Combined therapy of T3 and antidepressants in depression . J Int Med Res . 1979;7:138-146. 20. Goodwin FK, Prange AJ Jr, Post RM, Muscettola G, Lipton MA. Potentiation of antidepressant effects by L-triiodothyronine tricyclic nonresponders . Am J Psychiatry . 1982;139:34-38. 21. Schwarcz G, Halaris A, Baxter L, Escobar J, Thompson M, Young M. Normal thyroid function in desipramine nonresponders compared to responders by the addition of L-triiodothyronine . Am J Psychiatry . 1984;141:1614-1616. 22. Thase ME, Kupfer DJ, Jarrett DB. Treatment of imipramine-resistant recurrent depression, I: an open clinical trial of adjunctive L-triiodothyronine . J Clin psychiatry . 1989;50:385-388. 23. Gitlin MJ, Winer H, Fairbanks L, Hershman JM, Friedfeld N. Failure of T3 to potentiate tricyclic antidepressant response . J Affective Disord . 1987;13:267-272.Crossref 24. Joffe RT, Singer W. A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants . Psychiatry Res . 1990;32:241-252.Crossref 25. Garbutt JC, Mayo JP Jr, Gillette GM, Little KY, Mason GA. Lithium potentiation of tricyclic antidepressants following lack of T3 potentiation . Am J Psychiatry . 1986;143:1038-1039. 26. Joffe RT. T3 and lithium potentiation of tricyclic antidepressants . Am J Psychiatry . 1988;145:1317-1318. 27. Hamilton M. A rating scale for depression . J Neurol Neurosurg Psychiatry . 1960;23:56-62.Crossref 28. Price LH. What is the duration for augmentation with T3 or lithium in resistant depression? J Clin Psychopharmacol . 1989;9:73.Crossref 29. Keppel G, Zedeck S. Data Analysis for Research Designs . New York, NY: WH Freeman & Co; 1989. 30. Rhoades HM, Overall JE. The Hamilton Depression Scale: factor scoring and profile classification . Psychopharmacol Bull . 1983;19:91-96. 31. Garbutt J, Malekpour B, Brunswick D, Jonnalagadda MR, Jolliff L, Poddak R, Wilson I, Prange AJ Jr. Effects of triiodothyronine on drug levels and cardiac function in depressed patients treated with imipramine . Am J Psychiatry . 1979; 136:980-982. 32. 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.Crossref 33. Stern RA, Nevels CT, Shelhorse ME, Prohaska ML, Mason GA, Prange AJ Jr. Antidepressant and memory effects of combined thyroid hormone treatment and electroconvulsive therapy: preliminary findings . Biol Psychiatry . 1991;30: 623-627.Crossref 34. Nemeroff CB. Augmentation regimens for depression . J Clin Psychiatry . 1991; 52( (suppl) ):21-27. 35. Schopf J. Treatment of depressions resistant to tricyclic antidepressants, related drugs or MAO-inhibitors by lithium addition: review of the literature . Pharmacopsychiatry . 1989;22:174-182.Crossref 36. Fontaine R, Ontiveros A, Elie R, Vezina M. Lithium carbonate augmentation of desipramine and fluoxetine in refractory depression . Biol Psychiatry . 1991;29: 946-948.Crossref 37. Bartko JJ, Pulver AE, Carpenter WT Jr. The power of analysis: statistical perspectives: part 2 . Psychiatry Res . 1988;23:301-310.Crossref 38. Pigott TA, Pato MT, L'Heureux F, Hill JL, Grover JN, Bernstein SE, Murphy DL. A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder . J Clin Psychopharmacol . 1991;11:242-248.Crossref

Journal

Archives of General PsychiatryAmerican Medical Association

Published: May 1, 1993

References