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Meta-Analysis
. 2007 Jul 18;2007(3):CD004186.
doi: 10.1002/14651858.CD004186.pub2.

Amitriptyline for depression

G Guaiana, C Barbui, M Hotopf
Meta-Analysis

Amitriptyline for depression

G Guaiana et al. Cochrane Database Syst Rev. .

Abstract

Background: For many years amitriptyline has been considered one of the reference compounds for the pharmacological treatment of depression. However, new tricyclic drugs, heterocyclic compounds and selective serotonin reuptake inhibitors have been introduced on the market with the claim of a more favourable tolerability/efficacy profile.

Objectives: The aim of the present systematic review was to investigate the tolerability and efficacy of amitriptyline in comparison with the other tricyclic/heterocyclic antidepressants and with the selective serotonin reuptake inhibitors.

Search strategy: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies) was searched on 28-11-2005. Reference lists of all included studies were checked.

Selection criteria: Only randomised controlled trials were included. Study participants were of either sex and any age with a primary diagnosis of depression. Included trials compared amitriptyline with another tricyclic/heterocyclic antidepressant or with one of the selective serotonin reuptake inhibitors.

Data collection and analysis: Data were extracted using a standardised form. The number of patients undergoing the randomisation procedure, the number of patients who completed the study and the number of improved patients were extracted. In addition, group mean scores at the end of the trial on Hamilton Depression Scale or any other depression scale were extracted. In the tolerability analysis, the number of patients failing to complete the study and the number of patients complaining of side-effects were extracted.

Main results: A total number of 194 studies were included in the review. The estimate of the overall odds ratio (OR) for responders showed that more subjects responded to amitriptyline in comparison with the control antidepressant group (OR 1.12 to 95% confidence interval (CI) 1.02 to 1.23, number needed to treat to benefit (NNTB) = 50). The estimate of the efficacy of amitriptyline and control agents on a continuous outcome revealed an effect size which also significantly favoured amitriptyline (Standardised Mean Difference (SMD) 0.13, 95% CI 0.04 to 0.23). Whilst these differences are statistically significant, their clinical significance is less clear. When the efficacy analysis was stratified by drug class, no difference in outcome emerged between amitriptyline and either tricyclic or selective serotonin reuptake inhibitor comparators. The dropout rate in patients taking amitriptyline and control agents was similar; however, the estimate of the proportion of patients who experienced side-effects significantly favoured control agents in comparison with amitriptyline (OR 0.66, 95% CI 0.59 to 0.74). When the tolerability analysis was stratified by drug class, the dropout rate in patients taking amitriptyline and the selective serotonin reuptake inhibitors significantly favoured the latter (OR 0.84, 95% CI 0.75 to 0.95, number needed to treat to harm (NNTH) = 40). When the responder analysis was stratified by study setting amitriptyline was more effective than control antidepressants in inpatients (OR 1.22, 95% CI 1.04 to 1.42, NNTB = 24), but not in outpatients (OR 1.01, 95%CI 0.88 to 1.17, NNTB = 200).

Authors' conclusions: This present systematic review indicates that amitriptyline is at least as efficacious as other tricyclics or newer compounds. However, the burden of side-effects in patients receiving it was greater. In comparison with selective serotonin reuptake inhibitors amitriptyline was less well tolerated, and although counterbalanced by a higher proportion of responders, the difference was not statistically significant.

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Conflict of interest statement

None.

Figures

1.1
1.1. Analysis
Comparison 1 overall efficacy, Outcome 1 responders (int‐to‐treat).
1.4
1.4. Analysis
Comparison 1 overall efficacy, Outcome 4 mean scores at endpoint.
2.1
2.1. Analysis
Comparison 2 overall tolerability, Outcome 1 drop‐outs.
2.2
2.2. Analysis
Comparison 2 overall tolerability, Outcome 2 patients with side‐effects.
3.3
3.3. Analysis
Comparison 3 efficacy against TCA and related antidepressants, Outcome 3 responders (int‐to‐treat).
3.4
3.4. Analysis
Comparison 3 efficacy against TCA and related antidepressants, Outcome 4 mean scores at endpoint.
4.3
4.3. Analysis
Comparison 4 tolerability against TCA and related antidepressants, Outcome 3 drop‐outs.
4.4
4.4. Analysis
Comparison 4 tolerability against TCA and related antidepressants, Outcome 4 patients with side‐effects.
5.3
5.3. Analysis
Comparison 5 efficacy against SSRIs, Outcome 3 responders (int‐to‐treat).
5.4
5.4. Analysis
Comparison 5 efficacy against SSRIs, Outcome 4 mean scores at endpoint.
6.1
6.1. Analysis
Comparison 6 tolerability against SSRIs, Outcome 1 drop‐outs.
6.2
6.2. Analysis
Comparison 6 tolerability against SSRIs, Outcome 2 patients with side‐effects.
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    1. Lennox IG, Asbury JF, Couldrick WG, Beswick KB. Viloxazine and amitriptyline in depressive illness. A double‐blind controlled trial in general practice. The Practitioner 1978;220:153‐6. - PubMed
Levin 1974 {published data only}
    1. Levin A. Maprotiline and amitriptyline in the treatment of depressive illness. A double‐blind comparison. South African Medical Journal 1974;48:47‐9. - PubMed
Lipsedge 1971 {published data only}
    1. Lipsedge MS, Rees WL. A double‐blind comparison of dothiepin and amitriptyline for the treatment of depression with anxiety. Psychopharmacologia 1971;19:153‐62. - PubMed
Loga 1992 {published data only}
    1. Loga S, Milovanovic D, Eric LJ. A double‐blind, parallel‐group comparative study of dothiepin and amitriptyline in the treatment of depression in a yugoslavian population. Journal of Drug Development 1992;4:213‐8.
Loo 1988 {published data only}
    1. Loo H, Malka R, Defrance R, Benard JY, Niox‐Riviere H, Raab A, et al. Tianeptine and amitriptyline. Controlled double‐blind trial in depressed alcoholic patients. Neuropsychobiology 1998;19:79‐85. - PubMed
Lopez‐Ibor 1979 {published data only}
    1. Lopez‐Ibor Alino JJ, Ayuso Gutierrez JL, Montejo Iglesias ML, Ramos JL. Estudio clinico comparativo entre el nomifensin y la amitriptilina en el tratamiento de la depresion endogena. Actas Luso Espanolas de Neurologia, Psiquiatria y Ciencias Afines 1979;7:123‐32. - PubMed
Lydiard 1997 {published data only}
    1. 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;58:484‐91. - PubMed
Magnus 1977 {published data only}
    1. Magnus RV, Schiff AA. Once‐daily treatment for mixed anxiety/depressive states: a comparison of slow release amitriptyline and fluphenazine with notriptyline. Journal of International Medical Research 1977;5:109‐13. - PubMed
Marais 1974 {published data only}
    1. Marais GF. Clinical evaluation of the antidepressants maprotiline and amitriptyline. A double‐blind controlled trial. South African Medical Journal 1974;48:1530‐2. - PubMed
Marchesi 1998 {published data only}
    1. Marchesi C, Ceccherininelli A, Rossi A, Maggini C. Is anxious‐agitated major depression responsive to fluoxetine? A double‐blind comparison with amitriptyline. Pharmacopsychiatry 1998;31:216‐21. - PubMed
Mariategui 1978 {published data only}
    1. Mariategui J, Chavez H, Olivares A. Lofepramina: estudio clinico comparativo con amitriptilina. Acta Physiologica Latinoamericana 1978;24:201‐9. - PubMed
Marneros 1979 {published data only}
    1. Marneros A, Philipp M. A double‐blind trial with amitriptyline and lofepramine in the treatment of endogenous depression. International Pharmacopsychiatry 1979;14:300‐4. - PubMed
Masco 1985 {published data only}
    1. Masco HL, Sheetz MS. Double‐blind comparison of fluoxetine and amitryptyline in the treatment of major depressive illness. Advances in Therapy 1985;2:275‐84.
Mason 1990 {published data only}
    1. Mason BJ, Kocsis JH, Frances AJ, Mann JJ. Amoxapine versus amitriptyline for continuation therapy of depression. Journal of Clinical Psychopharmacology 1990;10:338‐43. - PubMed
McCallum 1975 {published data only}
    1. McCallum P, Meares R. A controlled trial of maprotiline (Ludiomil) in depressed outpatients. Medical Journal Australia 1975;2:392‐4. - PubMed
McClelland 1979 {published data only}
    1. McClelland HA, Kerr TA, Stephens DA, Howell RW. The comparative antidepressant value of lofepramine and amitriptyline. Results of a controlled trial with comments on the scales used. Acta Psychiatrica Scandinavica 1979;60:190‐8. - PubMed
McConaghy 1965 {published data only}
    1. McConaghy N, Kingston WR, Stevenson HG, Atkinson I, Cole E, Fennessy LA. A controlled trial comparing amitriptyline and protriptyline in the treatment of out‐patient depressives. Medical Journal of Australia 1965;ii:403‐5. - PubMed
Melo de Paula 1977 {published data only}
    1. Melo de Paula AJ, Heckert U, Abizaid W, Sotto Maior M. Amoxapina e amitriptilina ‐ Um estudio duplo‐cego em pacientes deprimidos. Folha Médica 1977;75:165‐9.
Mendels 1968 {published data only}
    1. Mendels J. Comparative trial of nortriptyline and amitriptyline in 100 depressed patients. American Journal Psychiatry 1968;124:59‐62. - PubMed
Mendlewicz 1980 {published data only}
    1. Mendlewicz J, Linkowski P, Rees JA. A double‐blind comparison of dothiepin and amitriptyline in patients with primary affective disorder: serum levels and clinical response. British Journal Psychiatry 1980;136:154‐60. - PubMed
Mendlewicz 1982 {published data only}
    1. Mendlewicz J, Pinder RM, Stulemeijer SM, Dorth R. Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline. Journal of Affective Disorders 1982;4:219‐26. - PubMed
Metha 1980 {published data only}
    1. Metha BM, Spear FG, Whittington JR. A double‐blind controlled trial of mianserin and amitriptyline in depression. Current Medical Research Opinion 1980;7:14‐22. - PubMed
Mindham 1977 {published data only}
    1. Mindham BA. A comparison of maprotiline (Ludiomil) and amitriptyline. Journal of International Medical Research 1977;5 Suppl 4:25‐33. - PubMed
Moises 1981 {published data only}
    1. Moises HW, Kasper S, Beckmann H. Trazodone and amitriptyline in treatment of depressed inpatients. A double‐blind study. Pharmacopsychiatry 1981;14:167‐71. - PubMed
Moller 1993 {published data only}
    1. Moller HJ, Berzewski H, Eckmann F, Gonzalves N, Kissling W, Knorr W, et al. Double‐blind multicenter study of paroxetine and amitriptyline in depressed patients. Pharmacopsychiatry 1993;26:75‐8. - PubMed
Moller 1995 {published data only}
    1. Moller HJ, Kasper S, Muller H, Kissling W, Fuger J, Ruhrmann S. A controlled study of the efficacy and safety of mianserin and amitriptyline in depressive inpatients. Pharmacopsychiatry 1995;28:249‐52. - PubMed
Moller 1998 {published data only}
    1. Moller HJ, Gallinat J, Hegerl U, Arato M, Janka Z, Pflug B, et al. Double‐blind, multicenter comparative study of sertraline and amitriptyline in hospitalized patients with major depression. Pharmacopsychiatry 1998;31:170‐7. - PubMed
Moller 2000 {published data only}
    1. Moller HJ, Glaser K, Leverkus F, Gobel C. Double‐blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression. Pharmacopsychiatry 2000;33:206‐12. - PubMed
Molnar 1977 {published data only}
    1. Molnar G. Maprotiline ‐ a double‐blind study of a new tetracyclic antidepressant in severe depression. Canadian Psychiatric Association Journal 1977;22:19‐23. - PubMed
Montbrun 1976 {published data only}
    1. Montbrun F, Obermair W. Lofepramine versus amitriptyline. A double‐blind study [Doppelblindstudie lofepramin versus amitriptylin]. Therapiewoche 1976;26:8722‐6.
Monteleone 1994 {published data only}
    1. Monteleone P, Fabrazzo M. Blood levels of mianserin and amitriptyline and clinical response in aged depressed patients. Pharmacopsychiatry 1994;27:238‐41. - PubMed
Montgomery 1980 {published data only}
    1. Montgomery SA, McAuley R, Montgomery DB, Dawling S, Braithwaite RA. Pharmacokinetics and efficacy of maprotiline and amitriptyline in endogenous depression: a double‐blind controlled trial. Clinical Therapeutics 1980;3:292‐310. - PubMed
Muller‐Oerlingh 1979 {published data only}
    1. Muller‐Oerlinghausen B, Ruther E, Adam HK. Clinical profile and serum concentration of viloxazine as compared to amitriptyline. Pharmakopsychiatry 1979;12:321‐37. - PubMed
Murasaki 1990 {published data only}
    1. Murasaki M, Kurihara M, Takahashi R, Mori A, Hasegawa K, Endo S, et al. Clinical Effects of Trazodone (KB‐831) on depression. Clinical Evaluation 1990;18:279‐313.
Murphy 1978 {published data only}
    1. Murphy JE, Bridgman KM. A comparative clinical trial of mianserin (Norval) and amitriptyline in the treatment of depression in general practice. Journal of International Medical Research 1978;6:199‐206. - PubMed
Murphy 1980 {published data only}
    1. Murphy JE, Ankier SI. An evaluation of trazodone in the treatment of depression. Neuropharmacology 1980;19:1217‐8. - PubMed
Naftulin 1972 {published data only}
    1. Naftulin DH, Ware JE. A behavioural and clinical evaluation of two psychotropic agents: doxepin‐hydrochloride & pherphenazine‐amitriptyline hydrochloride. Psychosomatics 1972;XIII:125‐30. - PubMed
Nelson 1982 {published data only}
    1. Nelson WH, Orr WW, Stevenson JM, Shane SR. Hypothalamic‐pituary‐adrenal axis activity and tricyclic response in major depression. Archives of General Psychiatry 1982;39:1033‐6. - PubMed
Nieto 1973 {published data only}
    1. Nieto D, Rincon HP. A new antidepressive agent: C 34,276‐Ba or maprotyline, 1st tetracyclic thymoanaleptic Clinical study [Un nuevo antidepresivo: el C 34,276‐Ba o maprotilina, primer timoanaleptico tetraciclico]. Prensa Medica Mexicana 1973;38(11):429‐34. - PubMed
Nugent 1979 {published data only}
    1. Nugent D. A double‐blind study of viloxazine and amitriptyline in depressed geriatric patients. Clinical Trials Journal 1979;16:13‐7.
Okasha 1976 {published data only}
    1. Okasha A, Sadek A. A controlled, double‐blind clinical trial between maprotiline and imipramine in depressive illness. Journal of the Egyptian Medical Association 1976;59:557‐62. - PubMed
Peters 1990 {published data only}
    1. Peters UH, Lenhard P, Metz M. Therapy of depression in the psychiatrist's office ‐ A double‐blind multicenter study [Ambulante therapie der depression mit fluoxetin ‐ eine multizentrische doppelblindstudie]. Nervenheihunde 1990;9:28‐31.
Petrie 1982 {published data only}
    1. Petrie WM, Ban TA, Wilson WH, Jamieson RC, Guy W. Viloxazine in the treatment of endogenous depression. A standard (amitriptyline) controlled clinical study. International Pharmacopsychiatry 1982;17:280‐6. - PubMed
Preskorn 1991 {published data only}
    1. Preskorn SH, Silkey B, Beber J, Dorey C. Antidepressant response and plasma concentrations of fluoxetine. Annals of Clinical Psychiatry 1991;3:147‐51.
Prusoff 1981 {published data only}
    1. Prusoff B, Weissman MM, Charney J, Dockerty J, Kleber H, Rounsavill BJ, et al. Speed of symptom reduction in depressed outpatients treated with amoxapine and amitriptyline. Current Therapeutic Research 1981;30:843‐55.
Pugh 1982 {published data only}
    1. Pugh R, Bell J, Cooper AJ, Dunstan R, Greedharry D, Pomeroy J, et al. Does lofepramine have fewer side effects than amitriptyline?. Journal of Affective Disorders 1982;4:355‐63. - PubMed
Quadri 1980 {published data only}
    1. Quadri AA, Shalini K, Channabasavanna SM. d‐Amphetamine as a predictor for response to imipramine and amitriptyline. Indian Journal of Psychiatry 1980;22:182‐4. - PMC - PubMed
Querol 1970 {published data only}
    1. Querol M. Double blind studies with antidepressive drugs [Estudio doble ciego con antidepresivos]. Revista de Neuro‐Psiquiatria 1980;XXXIII:251‐70. - PubMed
Rabkin 1984 {published data only}
    1. Rabkin JG, McGrath PJ, Quitkin FM, Fyer A, Stewart JW, Liebowitz MR, et al. Mianserin versus amitriptyline for depression: a double‐blind 6‐week trial. Neuropsychobiology 1984;12:224‐8. - PubMed
Rampello 1995 {published data only}
    1. Rampello L, Nicoletti G, Raffaele R, Drago F. Comparative effects of amitriptyline and amineptine in patients affected by anxious depression. Pharmacopsychiatry 1995;31:130‐4. - PubMed
Rees 1976 {published data only}
    1. Rees JA, Cryer PC. A single‐blind comparative study of once daily dothiepin (Prothiaden) and divided daily doses of amitriptyline. Current Medical Research Opinion 1976;6:416‐21. - PubMed
Rego 1974 {published data only}
    1. Rego A, Sanchez De Vega J. Single‐blind comparative study between patients with ludiomil (Ciba 34,276‐Ba) and its evaluation with Hamilton's scale [Estudio comparativo simple‐ciego entre pacientes con Ludiomil (Ciba 34, 276‐Ba) y su valoraciòn con la escala de Hamilton]. Archivos Neurobiologica 1974;37:475‐84. - PubMed
Reimherr 1990 {published data only}
    1. Reimherr FW, Chouinard G, Cohn CK, Cole JO, Itil T, Lapierre YD. 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. - PubMed
Remick 1994 {published data only}
    1. Remick RA, Reesal R, Oakander M, Allen J, Claman J, Ramirez CE, et al. Comparison of fluvoxamine and amitriptyline in depressed outpatients. Current Therapeutic Research 1994;55:243‐50.
Richmond 1964 {published data only}
    1. Richmond PW, Roberts AH. A comparative trial of imipramine, amitriptyline, isocarboxazid and tranylcypromine in out‐patient depressive illness. British Journal of Psychiatry 1964;110:846‐50. - PubMed
Rickels 1970 {published data only}
    1. Rickels K, Gordon PE, Weise CC, Bazilian SE, Feldman HS, Wilson DA. (1970) Amitriptyline and trimipramine in neurotic depressed outpatients: A collaborative study. American Journal of Psychiatry 1970;127:126‐218. - PubMed
Rickels 1972 {published data only}
    1. Rickels K, Hutchinson JC, Weise CC, Csanalosi I, Chung HR, Case WG. Doxepin and amitriptyline‐perphenazine in mixed anxious‐depressed neurotic outpatients: a collaborative controlled study. Psychopharmacologia 1972;23:305‐18. - PubMed
Rickels 1974 {published data only}
    1. Rickels K, Weise CC, Csanalosi I, Chung HR, Feldman HS, Rosenfeld H, et al. Clomipramine and amitriptyline in depressed outpatients. A controlled study. Psychopharmacology 1974;34:361‐76. - PubMed
Rickels 1982 {published data only}
    1. Rickels K, Case WG. Trazodone in depressed outpatients. American Journal of Psychiatry 1982;139:803‐6. - PubMed
Rickels 1982a {published data only}
    1. Richels K, Csanalosi I, Werblowsky J, Weise CC, Weinstock R, Brown AS, et al. Amitriptyline‐perphenazine and doxepin in depressed outpatients: a controlled double‐blind study. Journal of Clinical Psychiatry 1982;43:419‐22. - PubMed
Rickels 1985 {published data only}
    1. Richels K, Feighner JP, Smith WT. Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Archives of General Psychiatry 1985;42:134‐41. - PubMed
Rose 1965 {published data only}
    1. Rose JT, Leahy MR, Martin IC, Westhead TT. A comparison of nortriptyline and amitriptyline in depression. British Journal of Psychiatry 1985;III:1101‐3. - PubMed
Rush 1988 {published data only}
    1. Rush AJ, Weissenburger J, Vasavada N, Orsulak PJ, Fairchild CJ. Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline. Journal of Clinical Psychopharmacology 1988;8:421‐5. - PubMed
Rush 1989 {published data only}
    1. Rush AJ, Giles DE, Jarret RB, Feldman‐Koffler F, Debus JR, Weissenburger J, et al. Reduced REM latency predicts response to tricyclic medication in depressed outpatients. Biological Psychiatry 1989;26:61‐72. - PubMed
Rybakowski 1991 {published data only}
    1. Rybakowski J, Matkowski K, Linka M. Monitoring of the treatment of endogenous depression with imipramine and amitriptyline (preliminary report) [Monitorowane leczenie depresji endogennej imipramina i amitryptylina]. Psychiatria Polska 1991;25:111‐8. - PubMed
Sacchetti 2002 {published data only}
    1. Sacchetti E, Casano GB, Penati G, Pavan L, Nardini M, Casacchia M, et al. Paroxetine versus amitriptyline in patients with recurrent major depression: a double‐blind trial. International Journal of Psychiatry in Clinical Practice 2002;6:23‐29. - PubMed
Sandifer 1965 {published data only}
    1. Sandifer MG, Wilson IC, Gambill JM. The influence of case selection and dosage in an antidepressant drug trial. British Journal of Psychiatry 1965;III:142‐8. - PubMed
Sedman 1977 {published data only}
    1. Sedman G. Double‐blind trial of sustained‐release amitriptyline compared with viloxazine in moderate to severe depressive illness. Current Medical Research and Opinion 1977;5:217‐25. - PubMed
Sethi 1979 {published data only}
    1. Sethi BB, Sharma I, Singh H, Metha UK. Amoxapine and amitriptyline: a double‐blind study in depressed patients. Current Therapeutic Research 1979;25:726‐37.
Shaw 1986 {published data only}
    1. Shaw DM, Thomas DR, Briscoe MH, Watkins SE, Crimmins R, Harris B, et al. A comparison of the antidepressant action of citalopram and amitriptyline. British Journal of Psychiatry 1986;149:515‐7. - PubMed
Shipley 1985 {published data only}
    1. Shipley JE, Kupfer DJ, Griffin SJ, Dealy RS, Coble PA, McEachran AB, et al. Comparison of effects of desipramine and amitriptyline on EEG sleep of depressed patients. Psychopharmacology 1985;85:14‐22. - PubMed
Silverstone 1977 {published data only}
    1. Silverstone JT. A comparison of maprotiline and amitriptyline in the treatment of depression in general practice. The Practitioner 1977;218:279‐82. - PubMed
Sims 1980 {published data only}
    1. Sims AC. Comparison of the efficacy of sustained‐release amitriptyline with maprotiline in the treatment of depressive illness. Current Medical Research and Opinion 1980;6:534‐9. - PubMed
Sinclair 1975 {published data only}
    1. Sinclair JM, Walsh MR, Valle‐Jones JC, Schiff AA. Treatment of anxiety/depressive conditions in the elderly: a double‐blind comparative study of motival and amitriptyline. Age and Ageing 1975;4:226‐31. - PubMed
Solis 1970 {published data only}
    1. Solis HG, Molina GB, Pineyro A. Clinical evaluation of doxepin and amitriptyline in depressed patients. Current Therapeutic Research 1970;12:524‐7. - PubMed
Staner 1995 {published data only}
    1. Staner L, Kerkhofs M, Detroux D, Leyman S, Linkowski P, Mendlewicz J. Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double‐blind randomized trial in major depression. Sleep 1995;18:470‐7. - PubMed
Stier 1982 {published data only}
    1. Stier CS, Neumann M, Elizur A. Comparative double‐blind study between maprotiline and amitriptyline in one fixed nightly dose in major depressive disorder. Current Therapeutic Research 1982;32:447‐56.
Stott 1993 {published data only}
    1. Stott PC, Blagden MD, Aitken CA. Depression and associated anxiety in primary care: a double‐blind comparison of paroxetine and amitriptyline. European Neuropsychopharmacology 1993;3:324‐5.
Straker 1966 {published data only}
    1. Straker M, Davanloo H, Moll A. A double‐blind comparison of a new antidepressant, protryptiline, with imipramine and amitriptyline. Canadian Medical Association Journal 1966;94:1220‐2. - PMC - PubMed
Stuppaeck 1994 {published data only}
    1. Stuppaeck CH, Geretsegger C, Whitworth AB, Schubert H, Platz T, Konig P, et al. A multicentre double‐blind trial of paroxetine versus amitriptyline in depressed inpatients. Journal Clinical Psychopharmacology 1994;14:241‐6. - PubMed
Toru 1972 {published data only}
    1. Toru M, Takamizawa M, Kariya T, Kobayashi K, Takahashi R. A double‐blind sequential comparison of doxepin with amitriptyline in depressed patients. Psychosomatics 1972;XIII:241‐50. - PubMed
Trappe 1973 {published data only}
    1. Trappe B. Doxepin and amitriptyline‐chlordiazepoxide combination in neurotic states. Psychiatria Fennica 1973;4:269‐75.
Trick 1975 {published data only}
    1. Trick KL. Double‐blind comparison of maprotiline (Ludiomil) with amitriptyline in the treatment of depressive illness. Journal of International Medical Research 1975;3 Suppl 2:67‐70.
Tsaras 1981 {published data only}
    1. Tsaras G, Ambrus J. Comparative clinical trial of chlordiazepoxide plus amitriptyline against maprotiline in depression with a component of anxiety [Etude clinique comparative de l'association chlordiazepoxide‐amitriptyline et de la maprotiline chez des patients souffrant de dépression à composante anxieuse]. Revue Medicale de la Suisse Romande 1981;101:483‐6. - PubMed
Upward 1988 {published data only}
    1. Upward JW, Edwards JG, Goldie A, Waller DG. Comparative effects of fluoxetine and amitriptyline on cardiac function. British Journal of Clinical Pharmacology 1988;26:399‐402. - PMC - PubMed
Van Amerongen 1979 {published data only}
    1. Amerongen P. Double‐blind clinical trial of the antidepressant action of amineptine. Current Medical Research and Opinion 1979;6:93‐100. - PubMed
Veith 1983 {published data only}
    1. Veith RC, Bielski RJ, Bloom V, Fawcett JA, Narasimhachari N, Friedel RO. Urinary MHPG excretion and treatment with desipramine or amitriptyline: prediction of response, effect of treatment, and methodological hazards. Journal of Clinical Psychopharmacology 1983;3:18‐27. - PubMed
Versiani 1999 {published data only}
    1. Versiani M, Ontiveros A, Mazzotti G, Ospina J, Davila J, Mata S, et al. Fluoxetine versus amittriptyline in the treatment of major depression with associated anxiety (anxious depression): a double‐blind comparison. International Clinical Psychopharmacology 1999;14:321‐7. - PubMed
Von Bauer 1969 {published data only}
    1. Bauer G, Nowak H. Doxepin, a new antidepressant: comparison of effects with amitriptyline [Doxepin, ein neues antidepressivum: wirkungsvergleich mit amitriptylin]. Arzneimittezforschung 1969;19:1642‐6. - PubMed
Waite 1986 {published data only}
    1. Waite J, Grundy E, Arie T. A controlled trial of antidepressant medication in elderly in‐patients. International Clinical Psychopharmacology 1986;1:113‐26. - PubMed
Watanabe 1978 {published data only}
    1. Watanabe S, Yokoyama S, Kubo S, Iwai H, Kuyama C. A double‐blind controlled study of clinical efficacy of maprotiline and amitriptyline in depression. Folia Psychiatrica et Neurologica Japonica 1978;32:1‐31. - PubMed
Weissman 1975 {published data only}
    1. Weissman MM, Lieb J, Prusoff B, Bothwell S. A double‐blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients. Acta Psychiatrica Scandinavica 1975;52:225‐36. - PubMed
Wheatley 1975 {published data only}
    1. Wheatley D. Controlled clinical trial of a new antidepressant (ORG.GB 94) of novel chemical formulation. Current Therapeutic Research 1975;18:849‐54. - PubMed
Wheatley 1992 {published data only}
    1. Wheatley D. MInaprine in depression: a controlled trial with Amitriptlyline. British Journal of Psychiatry 1992;161:113‐5. - PubMed
Wilcox 1994 {published data only}
    1. 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;9:271‐9. - PubMed
Wright 1976 {published data only}
    1. Wright S, Hermann L. Double‐blind comparative study on the effects of lofepramine and amitriptyline in depressive outpatients [Doppelblindversuch zum wirkungsvergleich von lofepramin und amitriptylin bei ambulant behandelten patienten mit depressiven zustandsbildern]. Arzneimittezforschung 1976;26:1167‐69. - PubMed
Yamhure 1977 {published data only}
    1. Yamhure A, Villalobos A. Amoxapine: a double‐blind comparative clinical study of amoxapine and amitriptyline in depressed, hospitalised patients. Current Therapeutic Research 1977;21:502‐6.
Young 1987 {published data only}
    1. Young JPR, Coleman A, Lader MH. A controlled comparison of fluoxetine and amitriptyline in depressed outpatients. British Journal of Psychiatry 1987;151:337‐40. - PubMed
Ziegler 1977 {published data only}
    1. Ziegler VE, Clayton PJ, Biggs JT. A comparison study of amitriptyline and nortriptyline with plasma levels. Archives of General Psychiatry 1977;34:607‐12. - PubMed

References to studies excluded from this review

Anonimous 1971 {published data only}
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Branconnier 1981 {published data only}
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Hackett 1967 {published data only}
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Hollister 1964 {published data only}
    1. Hollister LE, Overall JE, Johnson M, Pennington V, Katz G, Shelton J. Controlled comparison of amitriptyline, imipramine and placebo in hospitalised depressed patients. Journal of Nervous and Mental Disease 1964;139:370‐5. - PubMed
Hutchinson 1963 {published data only}
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Kiebach 1982 {published data only}
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Lambourn 1974 {published data only}
    1. Lambourn J, Rees JA. A general practitioner study of dothiepin and amitriptyline. Journal of International Medical Research 1974;2:210‐3.
Lloyd 1981 {published data only}
    1. Lloyd C, Zisook S, Click M, Jaffe KE. Life events and response to antidepressants. Journal of Human Stress 1981;7:2‐15. - PubMed
Maier 1989 {published data only}
    1. Maier W, Philipp M, Schlegel S, Heuser I, Wiedemann K, Benkert O. Diagnostic determinants of response to treatment with tricyclic antidepressants: a polydiagnostic approach. Psychiatry Research 1989;30:83‐93. - PubMed
Marjerrison 1969 {published data only}
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