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Amitriptyline versus placebo for major depressive disorder

  1. Claudia Leucht*,
  2. Maximilian Huhn,
  3. Stefan Leucht

Editorial Group: Cochrane Common Mental Disorders Group

Published Online: 12 DEC 2012

Assessed as up-to-date: 30 AUG 2012

DOI: 10.1002/14651858.CD009138.pub2


How to Cite

Leucht C, Huhn M, Leucht S. Amitriptyline versus placebo for major depressive disorder. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD009138. DOI: 10.1002/14651858.CD009138.pub2.

Author Information

  1. Technische Universität München Klinikum rechts der Isar, Klinik und Poliklinik für Psychiatrie und Psychotherapie, München, Germany

*Claudia Leucht, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, Ismaningerstrasse 22, München, 81675, Germany. Claudia.Leucht@lrz.tu-muenchen.de. claudialeucht@gmx.de.

Publication History

  1. Publication Status: New
  2. Published Online: 12 DEC 2012

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. Additional references
Amsterdam 1986 {published data only}
  • Amsterdam JD, Case WG, Csanalosi E, Singer M, Rickels K. A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression. Pharmacopsychiatry 1986;19(3):115-9.
Bakish 1992 {published data only}
  • Bakish D, Bradwejn J, Nair N, McClure J, Remick R, Bulger L. A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicentre study. Psychopharmacology 1992;106(Suppl):S98-101.
  • Bakish D, Wiens A, Ellis J, Alda M, Lapierre Y. A double-blind placebo-controlled comparison of moclobemide and amitriptyline in the treatment of depression. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 1992;37(Suppl 1):12-7.
Bhatia 1991 {published data only}
  • Bhatia SC, Hsieh HH, Theesen KA, Townley RG, Andersen JM, Weiss S, et al. Platelet alpha-2 adrenoreceptor activity pre-treatment and post-treatment in major depressive disorder with melancholia. Research Communication in Chemical Pathology and Pharmacology 1991;74(1):47-57.
Blashki 1971 {published data only}
  • Blashki TG, Mowbray R, Davies B. Controlled trial of amitriptyline in general practice. British Medical Journal 1971;1(741):133-8.
  • Blashki TG, Mowbray RM, Davies BM. A controlled trial of an antidepressant (amitriptyline) in general practice. V World Congress of Psychiatry, Ciudad de Mexico, 28 November - 4 December 1971. [CN-00216475]
  • Blashki TG, Mowbray RM, Davies BM. A controlled trial of an antidepressant (amitriptyline) in general-practice. V World Congress of Psychiatry, Ciudad de Mexico, 28 November - 4 December 1971:409.
Bremner 1995 {published data only}
  • Bremner JD. A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression. Journal of Clinical Psychiatry 1995;56(11):519-25.
  • Bremner JD. Double-blind comparison of mirtazapine, amitriptyline and placebo in major depression. Nervenheilkunde 1996;15(8):533-40.
Carman 1991 {published data only}
  • Carman JS, Ahdieh H, Wyatt-Knowles E, Warga E, Panagides J. A controlled study of mianserin in moderately to severely depressed outpatients. Psychopharmacology Bulletin 1991;27(2):135-9.
Claghorn 1983 {published data only}
  • Claghorn J, Gershon S, Goldstein BJ. Zimeldine tolerability in comparison to amitriptyline and placebo: findings from a multicentre trial. Acta Psychiatrica Scandinavica 1983;68(Suppl 308):104-14.
  • Claghorn J, Gershon S, Goldstein BJ, Behrnetz S, Bush DF, Huitfeldt B. A double-blind evaluation of zimelidine in comparison to placebo and amitriptyline in patients with major depressive disorder. Progress in Neuro-Psychopharmacological and Biological Psychiatry 1983;7(2-3):367-82.
Feighner 1979 {published data only}
  • Feighner JP, Brauzer B, Gelenberg AJ, Gomez W, Kiev A, Kurland ML, et al. A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness. Psychopharmacology 1979;61(2):217-25.
Gelenberg 1990 {published data only}
  • Gelenberg AJ, Wojcik JD, Falk WE, Spring B, Brotman AW, Galvin Nadeau M. Clovoxamine in the treatment of depressed outpatients: a double-blind, parallel-group comparison against amitriptyline and placebo. Comprehensive Psychiatry 1990;31(4):307-14.
  • Spring B, Gelenberg AJ, Garvin R, Thompson S. Amitriptyline, clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients. Psychopharmacology 1992;108(3):327-32.
Georgotas 1982 {published data only}
Hicks 1988 {published data only}
Hormazabal 1985 {published data only}
Hoschl 1989 {published data only}
Jacobson 1990 {published data only}
  • Bech P. Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression. International Journal of Neuropsychopharmacology 2001;4:337-45. [DOI: 10.1017/S1461145701002565]
  • Jacobson AF, Dominguez RA, Goldstein B, de la Gandara J. Comparison of ORG-3770 and amitriptyline in depressed outpatients. Psychopharmacology 1990;30:851.
Katz 1993 {published data only}
  • Katz RJ, Lott M, Landau P, Waldmeier P. A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant. Biological Psychiatry 1993;33:261-6.
Katz 1993a {published data only}
  • Katz RJ, Lott M, Landau P, Waldmeier P. A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant. Biological Psychiatry 1993;33:261-6.
Klieser 1988 {published data only}
  • Klieser E, Lehmann E. Experimental comparison between the effect of standardized trazodone-amitriptyline and placebo treatment in vitalized depressive patients. Psychopharmacology 1988;95(Suppl):3-5.
  • Klieser E, Lehmann E. Experimental examination of trazodone. Clinical Neuropharmacology 1989;12(Suppl 1):18-24.
Kupfer 1979 {published data only}
Kusalic 1993 {published data only}
Langlois 1985 {published data only}
Lydiard 1997 {published data only}
  • Lydiard RB, Stahl SM, Hertzman M, Harrison WM. A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. Journal of Clinical Psychiatry 1997;58(11):484-91.
McNair 1984a {published data only}
  • McNair DM, Kahn RJ, Frankenthaler LM, Faldetta LL. Amoxapine and amitriptyline II Specificity of cognitive effects during brief treatment of depression. Psychopharmacology 1984; Vol. 83, issue 2:134-9.
  • McNair DM, Kahn RJ, Frankenthaler LM, Faldetta LL. Amoxapine and amitriptyline. I. Relative speed of antidepressant action. Psychopharmacology 1984;83(2):129-33.
Mynors-Wallis 1995 {published data only}
Organon 3-020 unpublished {unpublished data only}
  • Bech P. Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression. International Journal of Neuropsychopharmacology 2001;4:337-45. [DOI: 10.1017/S1461145701002565]
  • Organon 3-020. [personal communication from the pharmaceutical company]
Organon 84062 unpublished {published data only}
  • Organon 84062. [personal communication from the pharmaceutical company]
Paykel 1988a {published data only}
  • Hollyman JA, Freeling P, Paykel ES, Bhat A, Sedgwick P. Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice. Journal of the Royal College of General Practitioners 1988;38(314):393-7.
  • Organon 84062.
  • Paykel ES, Freeling P, Hollyman JA. Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. Pharmacopsychiatry 1988;21(1):15-8.
  • Paykel ES, Hollyman JA, Freeling P, Sedgwick P. Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. Journal of Affective Disorders 1988;14(1):83-95.
Preskorn 1983 {published data only}
Raft 1981 {published data only}
  • Raft D, Davidson J, Wasik J, Mattox A. Relationship between response to phenelzine and MAO inhibition in a clinical trial of phenelzine, amitriptyline and placebo. Neuropsychobiology 1981;7(3):122-6.
Reimherr 1990 {published data only}
  • Lapierre YD. Controlling acute episodes of depression. International Clinical Psychopharmacology 1991; Vol. 6, issue Suppl 2:23-35.
  • Reimherr FW, Byerley WF, Ward MF, Lebegue BJ, Wender PH. Sertraline, a selective inhibitor of serotonin uptake, for the treatment of outpatients with major depressive disorder. Psychopharmacology Bulletin 1988;24(1):200-5.
  • Reimherr FW, Chouinard G, Cohn CK, Cole JO, Itil TM, LaPierre YD, et al. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. Journal of Clinical Psychiatry 1990;51(Suppl B):18-27.
Rickels 1982 {published data only}
Rickels 1985 {published data only}
Roffman 1982 {published data only}
  • Roffman M, Gould E, Brewer S, Lau H, Sachais B, Dixon N, et al. Comparative anticholinergic activity of oxaprotiline and amitriptyline. Drug Development Research 1983;3(6):561-6.
  • Roffman M, Gould EF, Brewer SJ, Lau H, Sachais B, Dixon RB, et al. A double blind comparative study of oxaprotiline with amitriptyline and placebo in moderate depression. Current Therapeutic Research, Clinical and Experimental 1982;32(2):247-56.
  • Stassen HH, Angst J, Delina-Stula A. Delayed onset of action of antidepressant drugs? Survey of recent results. European Psychiatry 1997; Vol. 12, issue 4:166-76.
  • Stassen HH, Delini-Stula A, Angst J. Time course of improvement under antidepressant treatment: a survival-analytical approach. European Neuropsychopharmacology 1993;3:127-35.
Rowan 1980 {published data only}
Shipley 1981 {published data only}
  • Shipley JE, Kupfer DJ, Spiker DG, Shaw DH, Coble PA, Neil JF, et al. Neuropsychological assessment and EEG sleep in affective disorders. Biological Psychiatry 1981;16(10):907-18.
Smith 1990 {published data only}
  • Smith WT, Glaudin V, Panagides J, Gilvary E. Mirtazapine vs amitriptyline vs placebo in the treatment of major depressive disorder. Psychopharmacology Bulletin 1990;26(2):191-6.
Stratas 1984 {published data only}
  • Stratas NE. A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder. Journal of Clinical Psychiatry 1984;45(11):466-9.
Thomson 1982 {published data only}
  • Thomson J, Rankin H, Ashcroft GW, Yates CM, McQueen JK, Cummings SW. The treatment of depression in general-practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo. Psychological Medicine 1982;12(4):741-51.
van de Merwe 1984a {published data only}
  • van de Merwe TJ, Silverstone T, Ankier SI, Warrington SJ, Turner P. A double-blind non-crossover placebo-controlled study between group comparison of trazodone and amitriptyline on cardiovascular function in major depressive disorder. Psychopathology 1984;17(Suppl 2):64-76.
Wilcox 1994 {published data only}
  • Wilcox CS, Cohn JB, Katz BB, Mijares CP, Guarino JJ, Panagides J, et al. A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients. International Clinical Psychopharmacology 1994;9(4):271-9.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. Additional references
Anon 1971 {published data only}
  • Anon. Multihospital controlled comparison of the therapeutic effects of four antidepressants. Activitas Nervosa Superior 1971;13(3):166-7.
Barton 1972 {published data only}
  • Barton JL, Snaith RP. A clinical assessment of a sustained release preparation of amitriptyline. Current Medical Research and Opinion 1972;1(3):123-9.
Beasley 1990 {published data only}
Bellack 1981 {published data only}
  • Bellack AS, Hersen M, Himmelhoch J. Social skills training compared with pharmacotherapy and psychotherapy in the treatment of unipolar depression. American Journal of Psychiatry 1981;138(12):1562-7.
Bente 1974 {published data only}
  • Bente D, Feder J, Helmchen H, Hippius H, Rosenberg L. Double blind test of three antidepressants. 3. Methodical problems. Arzneimittelforschung 1974;24(2):205-7.
Bergener 1968 {published data only}
Branconnier 1982 {published data only}
  • Branconnier RJ, Cole JO, Ghazvinian S, Rosenthal S. Treating the depressed elderly patient: the comparative behavioral pharmacology of mianserin and amitriptyline. Advances in Biochemical Psychopharmacology 1982;32:195-212.
Browne 1963 {published data only}
Bruck 1974 {published data only}
  • Bruck J, Söllner E, Tschabitscher H. Results of the clinical testing of amitriptylin and C 34,276-Ba (dibenzobicyclooctadiene derivative) in a double-blind study. Der Nervenarzt 1974;45(9):492-6.
Burrows 1980 {published data only}
  • Burrows GD, Norman TR, Davies BM. A comparative study of amoxapine and amitriptyline for depressive illness. Australian Family Physician 1980;9(11):762-6.
Claghorn 1984 {published data only}
  • Claghorn JL, Schroeder J, Goldstein BJ, 2nd. Comparison of the electrocardiographic effect of dothiepin and amitriptyline. Journal of Clinical Psychiatry 1984;45(7):291-3.
Coble 1981 {published data only}
Cosyns 1974 {published data only}
  • Cosyns P. A single daily dose of a sustained release form of amitriptyline in depressive illness. Acta Psychiatrica Belgica 1974;74(4):430-6.
Davis 1967 {published data only}
  • Davis WG. Treatment of anxiety and depression. A double-blind study of a perphenazine and amitriptyline in combination. Rocky Mountain Medical Journal 1967;64(11):73-6.
DiMascio 1974 {published data only}
  • DiMascio A. Drug therapy of depressed outpatients. Psychopharmacology Bulletin 1974;10:57.
Downing 1972 {published data only}
Downing 1973 {published data only}
Downing 1979 {published data only}
Downing 1983 {published data only}
  • Downing RW, Rickels K. Physician prognosis in relationship to drug and placebo response in anxious and depressed psychiatric outpatients. Journal of Nervous and Mental Disease 1983;171(3):182-5. [CN-00030322]
Ellingson 1973 {published data only}
  • Ellingson. BC-105 vs amitriptyline vs placebo. Psychopharmacology Bulletin 1973;9:78-82.
Fisch 1992 {published data only}
Friedman 1974 {published data only}
  • Friedman AS. Drug and family therapy in depressed outpatients. Psychopharmacology Bulletin 1974;10:18-9.
Friedman 1975 {published data only}
Friedman 1976 {published data only}
  • Friedman AS. Drug and family therapy in depressed outpatients. Psychopharmacology Bulletin 1976;12(3):82-3. [0048-5764]
Friedman 1980 {published data only}
  • Friedman J, McCallum P, Meares R. Stimulus intensity control in depression: a study of the comparative effect of doxepin and amitriptyline on cortical evoked potentials.. Australian and New Zealand Journal of Psychiatry 1980;14(2):115-9.
Garry 1963 {published data only}
Gomez 1968 {published data only}
  • Gomez JR, Gomez G. The treatment of anxiety and depression in general-practice using an amitriptyline-perphenazine preparation. British Journal of Clinical Practice 1968;22(3):105-9.
Guy 1982 {published data only}
  • Guy W, Ban TA, McEvoy JP, Petrie WM, Wilson WH, Schaffer JD. A collaborative study of a new antidepressant, viloxazine, in neurotic and endogenous depressives. International Pharmacopsychiatry 1982;17(1):36-42.
Hazell 1995 {published data only}
Hecht 1986 {published data only}
  • Hecht Orzack M, Cole JO, Friedman L, Bird M, McEachern J. Weight changes in antidepressants: a comparison of amitriptyline and trazodone. Neuropsychobiology 1986;15(Suppl 1):28-30.
Hollister 1964 {published data only}
  • Hollister LE, Overall JE, Johnson M, Pennington V, Katz G, Shelton J. Controlled comparison of imipramine, amitriptyline and placebo in hospitalised depressed patients. Journal of Nervous and Mental Disease 1964;139(4):370-5.
Houston 1983 {published data only}
  • Houston J, Berg I, Butler A, McGuire R. Amitriptyline for depressed women with young children in general practice. British Journal of Psychiatry 1983;142:103-4.
Hussain 1970 {published data only}
  • Hussain Z. Drugs in depressive illness. British Medical Journal 1970;1(707):482.
Imlah 1985 {published data only}
Itil 1972 {published data only}
  • Itil TM, Cora R, Hsu W, Gig E, Saletu B. Clinical, toxicological and electroencephalographical effects of a new tricyclic antidepressant, OI-77. Arzneimittelforschung 1972;22(12):2063-6.
Jacobson 1978 {published data only}
  • Jacobson AF. Doctor-patient concordance in a placebo-controlled trial of limbitrol versus its components. Psychopharmacology Bulletin 1978;14(3):61-3.
Kasper 1995 {published data only}
  • Kasper S. Clinical efficacy of mirtazapine: a review. 8th European College of Neuropsychopharmacology Congress, Venice, Italy. 30th September - 4th October. 1995.
Kasper 1997 {published data only}
  • Kasper S. Mirtazapine vs amitriptyline and placebo in the treatment of severely depressed patients. 10th European College of Neuropsychopharmacology Congress, Vienna, Austria. 13th - 17th September. 1997.
Kasper 1997a {published data only}
Kiev 1974 {published data only}
Klerman 1974 {published data only}
Laakmann 1995 {published data only}
  • Laakmann G, Faltermaier-Temizel M, Bossert-Zaudig S, Baghai T, Lorkowski G. Treatment of depressive outpatients with lorazepam, alprazolam, amitriptyline and placebo. Psychopharmacology 1995;120(1):109-15.
  • Laakmann G, Faltermaier-Temizel M, Bossert-Zaudig S, Baghai T, Lorkowski G. Treatment of mild to moderate depressive syndrome. A placebo-controlled double-blind trial on therapy with benzodiazepines or antidepressants. Munchener Medizinische Wochenschrift 1996; Vol. 138, issue 5:39-44.
Lipsedge 1970 {published data only}
Malitz 1971 {published data only}
Master 1963 {published data only}
McCallum 1975 {published data only}
McDonald 1966 {published data only}
  • McDonald IM, Perkins M, Marjerrison G, Podilsky M. A controlled comparison of amitriptyline and electroconvulsive therapy in the treatment of depression. American Journal of Psychiatry 1966;122(12):1427-31.
McLean 1992 {published data only}
Moll 1990 {published data only}
  • Moll E, Hetzel W. Moclobemide (Ro 11-1163) safety in depressed patients. Acta Paediatrica Scandinavica. Supplement 1990;82(360):69-70. [CN-00187843]
Möller 1993 {published data only}
  • Möller HJ, Berzewski H, Eckmann F, Gonzalves N, Kissling W, Knorr W, et al. Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. Pharmacopsychiatry 1993;26:75-8.
Montgomery 1980b {published data only}
  • Montgomery SA, McAuley R, Montgomery DB. Pharmacokinetics and efficacy of maprotiline and amitriptyline in endogenous depression: a double-blind controlled trial. Clinical Therapy 1980;3(4):292-310.
Montgomery 1998 {published data only}
  • Montgomery SA, Reimitz PE, Zivkov M. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study. International Clinical Psychopharmacology 1998;13(2):63-73.
Morakinyo 1970 {published data only}
  • Morakinyo VO. Amytriptyline and chlordiazepoxide (Limbitrol) in depressive states in Nigerians - a double-blind study. African Journal of Medical Sciences 1970;1(4):409-14.
Othmer 1983 {published data only}
Othmer 1988 {published data only}
  • Othmer SC, Thmer E, Preskorn SH, Mac D. Differential effect of amitriptyline and bupropion on primary and secondary depression: a pilot study. Journal of Clinical Psychiatry 1988;49(8):310-2.
Paykel 1973c {published data only}
Podobnikar 1966 {published data only}
Prusoff 1974 {published data only}
  • Prusoff B. Drug treatment of depressed outpatients. Psychopharmacology Bulletin 1974;10:59-60.
Rampello 1995 {published data only}
Rickels 1970 {published data only}
Rickels 1970b {published data only}
Rickels 1974 {published data only}
Rickels 1981 {published data only}
Rockliff 1971 {published data only}
Rosenberg 1974 {published data only}
Schou 1979 {published data only}
Skarbek 1962 {published data only}
Skarbek 1963 {published data only}
Spiker 1988 {published data only}
Stabl 1989 {published data only}
  • Stabl M, Biziere K, Schmid-Burgk W, Amrein R. Review of comparative clinical trials. Moclobemide vs tricyclic antidepressants and vs placebo in depressive states. Journal of Neural Transmission. Supplementum 1989;28:77-89.
Stahl 1997 {published data only}
  • Stahl SM, Wingard P. Meta-analysis of randomized, double-blind, placebo-controlled studies of mirtazapine vs amitriptyline. Sixth World Congress of Biological Psychiatry, Nice, France. June 22-27. 1997.
Stein 1980 {published data only}
Taverna 1969 {published data only}
  • Taverna P, Ferrari G. Comparative evaluation of nortriptyline, amitriptyline and of a placebo in the treatment of anxiety and depressive disorders. Minerva Medica 1969;60(49):2417-31.
Taylor 1993 {published data only}
Wallerstein 1967 {published data only}
Warner 1988 {published data only}
Welner 1980 {published data only}
Wilson 1982 {published data only}
Zis 1980 {published data only}
  • Zis AP, Grof P, Webster MA, Goodwin FK. Prediction of relapse in recurrent affective disorder. Psychopharmacology Bulletin 1980;16:47-9.
Zivkov 1995 {published data only}

References to studies awaiting assessment

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. Additional references
Kahn 2008 {published data only}
  • Kahn AY, Catterson ML, Preskorn SH. Double-blind cross-over study of mirtazapine, amitriptyline and placebo in patients with major depressive disorder. Directions in Psychiatry 2008;28:15-20.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. Additional references
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