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Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials

Published online by Cambridge University Press:  02 January 2018

Corrado Barbui and
Matthew Hotopf
Corrado Barbui*
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, LondonIstituto di Ricerche Farmacologiche “Mario Negri” MilanDipartimento di Medicina e Sanità Pubblica, Sezione di Psichiatria, Università di Verona, Italy
Matthew Hotopf
Affiliation:
Department of Psychological Medicine, Guy's, King's and St Thomas' Schools of Medicine, and Institute of Psychiatry, London
*
Dr Corrado Barbui, Istituto di Ricerche Farmacologiche “Mario Negri”, Via Eritrea 62, 20157 Milano, Italy. Tel: 0039 02 39014 431; fax: 0039 02 33 2000 49; e-mail: barbui@marionegri.it
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Abstract

Background

Tricyclic antidepressants have similar efficacy and slightly lower tolerability than selective serotonin reuptake inhibitors (SSRIs). However, there are no systematic reviews assessing amitriptyline, the reference tricyclic drug, v. other tricyclics and SSRIs directly.

Aims

To review the tolerability and efficacy of amitriptyline in the management of depression.

Method

A systematic review of randomised controlled trials (RCTs) comparing amitriptyline with other tricyclics/heterocyclics or with an SSRI.

Results

We reviewed 186 RCTs. The overall estimate of the efficacy of amitriptyline revealed a standardised mean difference of 0.147 (95% CI 0.05–0.243), significantly favouring amitriptyline. The overall OR for dropping out was 0.99 (95% CI 0.91–1.08) and that for side-effects was 0.62 (95% CI 0.54–0.70), favouring the control drugs. With drop-outs included as treatment failures, the estimate of the effectiveness of amitriptyline v. tricyclics/heterocyclics and SSRIs showed a 2.5% difference in the proportion of responders in favour of amitriptyline (number needed to treat 40, CI 21–694; OR 1.12 (95%CI 1.01–1.24)).

Conclusions

Amitriptyline is less well tolerated than tricyclics/heterocyclics and SSRIs, but slightly more patients treated on it recover than on alternative antidepressants.

Information

Type
Review Article
Information
The British Journal of Psychiatry , Volume 178 , Issue 2 , February 2001, pp. 129 - 144
Copyright
Copyright © 2001 The Royal College of Psychiatrists 

Amitriptyline is one of the first ‘reference’ tricyclic antidepressants (TCAs). Over the past 40 years a number of newer tricyclics, heterocyclics and selective serotonin reuptake inhibitors (SSRIs) have been introduced (Reference Garattini, Barbui and SaracenoGarattini et al, 1998). Despite several large systematic reviews comparing tricyclics and SSRIs there is no clear agreement over first-line treatment of depression (Reference Song, Freemantle and SheldonSong et al, 1993; Reference Anderson and TomensonAnderson & Tomenson, 1995; Reference Montgomery and KasperMontgomery & Kasper, 1995; Reference Hotopf, Lewis and NormandHotopf et al, 1996; Canadian Coordinating Office for Health Technology Assessment, 1997a ). Grouped as a whole, tricyclics appear to have similar efficacy to SSRIs, but are slightly less well tolerated. If tolerability is measured according to the numbers of drop-outs occurring in randomised controlled trials (RCTs), the number needed to treat (NNT) with SSRIs to prevent one tricyclic-related drop-out is estimated at 33 (Reference Anderson and TomensonAnderson & Tomenson, 1995). This modest advantage has to be set against the increased cost of SSRIs (Canadian Coordinating Office for Health Technology Assessment, 1997b ). A meta-analysis which subdivided TCAs according to whether they were reference compounds (e.g. the oldest TCAs, amitriptyline and imipramine) or newer tricyclics or hetero-cyclics, suggested that the higher drop-out rates associated with tricyclics could be attributed to the effect of amitriptyline and imipramine — newer tricyclics and heterocyclics were no worse than the SSRIs (Reference Hotopf, Hardy and LewisHotopf et al, 1997). However, there have not been any systematic reviews assessing amitriptyline v. other tricyclics and hetero-cyclics directly. We therefore aimed to test the hypothesis that amitriptyline would be less well tolerated than other tricyclics and SSRIs, and also to assess its effectiveness compared with the alternatives.

METHOD

Inclusion criteria

All RCTs comparing amitriptyline with any other tricyclic, heterocyclic or SSRI were included. Crossover studies were excluded. Studies adopting any criteria to define patients suffering from depression were included; a concurrent diagnosis of another psychiatric disorder was not considered an exclusion criterion. Trials in patients with depression with a concomitant medical illness were not included in this review.

Search strategy

Relevant studies were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR). This specialised register is regularly updated by electronic (Medline, Embase, PsycINFO, LILACS, Psyndex, CINAHL, SIGLE) and non-electronic literature searches. The register was searched using the following terms: AMITRIPTYLIN* or AMITRIL or ELATROL or ELAVIL or EMITRIP or ENDEP or ENOVIL or LAROXYL or LENTIZOL or LEVATE or MEVARIL or NOVOTRIPTYN or SAROTEN or TRYPTAL or TRYPTIZOL or TRIPTAFEN*. A specific electronic search was also performed with Medline and Embase from 1966 to 1998. We used the search term: AMITRIPTYLINE and RANDOMISED CONTROLLED TRIAL or RANDOM ALLOCATION or DOUBLE-BLIND METHOD. Reference lists of relevant papers and previous systematic reviews were hand searched for published reports and citations of unpublished research. Finally, attempts were made to obtain data through direct contact with the pharmaceutical industry.

Outcomes

Efficacy was evaluated using the following outcome measures:

  1. (a) Number of patients who responded to treatment out of the total number of randomised patients.

  2. (b) Group mean scores at the end of the trial on Hamilton Depression Rating Scale (HDRS; Reference HamiltonHamilton, 1960), or Montgomery and Åsberg Depression Scale (MADRS; Reference Montgomery and ÅsbergMontgomery & Åsberg, 1979), or any other depression scale.

Tolerability was evaluated using the following outcome measures:

  1. (a) Number of patients failing to complete the study as a proportion of the total number of randomised patients.

  2. (b) Number of patients complaining of side-effects out of the total number of randomised patients.

Data extraction

Using a standard form two reviewers independently extracted information on the year of publication, concealment of allocation, blindness, length of treatment, inclusion criteria, age range, country and setting of the study and type of pharmacological intervention. The number of patients undergoing the randomisation procedure, the number of patients who failed to complete the study (drop-outs) and that of patients complaining of side-effects were recorded. For dichotomous outcomes the number of patients showing a 50% reduction in score on the HDRS or MADRS scale was extracted; if these figures were not available, we extracted the number of patients categorised as ‘much improved’ and ‘improved’ on the Clinical Global Impression scale (CGI; Reference GuyGuy, 1976), or the number of patients in the corresponding categories of any other rating scale if the CGI was not used. For continuous outcomes the mean scores at end-point on the HDRS and the number of patients included in this analysis were recorded. If the HDRS was not employed, we extracted the mean scores at end-point on the MADRS or on any other rating scale. Mean scores were recorded with the standard deviation (s.d.) or standard error (s.e.) of these values. When only the s.e. was reported, it was converted into s.d. according to Altman & Bland (Reference Altman and Bland1996).

Statistical analysis

Efficacy data were analysed in the following way. Responders to treatment were calculated on an intention-to-treat (ITT) basis: drop-outs were always included in this analysis. When data on drop-outs were carried forward and included in the efficacy evaluation (last observation carried forward, LOCF), they were analysed according to the primary studies; when drop-outs were excluded from any assessment in the primary studies they were considered as ‘drug failures’. Scores from continuous outcome scales could not be analysed on an ITT basis. This approach was not feasible as most studies performed only an end-point or LOCF analysis, which inevitably excluded most drop-out patients. Therefore, scores from continuous outcomes were analysed on an end-point basis, including only patients with a final assessment or with an LOCF to the final assessment. Tolerability data were analysed by calculating the proportion of patients who failed to complete the study and who experienced adverse reactions out of the total number of randomised patients. For each outcome measure three separate meta-analyses were planned. The first compared amitriptyline with tricylic/heterocyclic antidepressants, the second amitriptyline with SSRIs and the third analysis summarised the overall comparison of amitriptyline with both tricyclic/heterocyclic drugs and SSRIs.

Dichotomous outcomes were summarised by calculating a Peto-weighted odds ratio for each study, together with the 95% CI. An overall odds ratio was then calculated as a summary measure. The number of patients who need to be treated (NNT) with amitriptyline rather than the control antidepressants for one additional patient to benefit (NNTB) or be harmed (NNTH) was calculated with the 95% CI (Reference AltmanAltman, 1998). Heterogeneity of treatment effects between studies was tested using the χ2 statistic. Continuous outcomes were analysed by calculating a standardised weighted mean difference (SMD) for each study. This measure gives the effect size of an intervention in units of standard deviation so that scores from different outcome scales can be combined into an overall estimate of effect. A random effects model, which takes into consideration any between-study variation, was adopted to combine the effect sizes. Calculations were performed using the RevMan software provided by the Cochrane Collaboration (Review Manager, 1999).

RESULTS

Characteristics of included studies

We identified 352 potentially relevant studies: 186 RCTs met the inclusion criteria and were considered in this review (see Appendix), while 166 studies were excluded for the reasons listed in Table 1. Of the 186 included studies, 146 compared amitriptyline with another TCA or heterocyclic antidepressant and 40 compared amitriptyline with one of the SSRIs. In six studies amitriptyline was administered in combination with perphenazine; in two of these studies the experimental drug was nortriptyline in combination with fluphenazine. One trial compared amitriptyline with nortriptyline plus fluphenazine.

Table 1

Studies identified by the electronic search but excluded from the meta-analysis, and reason for exclusion

Study Reason for exclusion
Abou & Coppen, 1983 Amitriptyline is not one of the randomised treatments
Reference Abou-Saleh and CoppenAbram et al, 1963 Amitriptyline is not one of the randomised treatments
Reference Abram, Kanter and RosenAltamura et al, 1988 Subsample of Altamura et al (1989a )
Reference Altamura, Mauri and ColacurcioAngst, 1963 Not randomised trial
Reference AngstAnonymous, 1971 Efficacy and safety data are not available
Anton & Burch, 1993 Same efficacy/safety of Anton & Burch (Reference Amin, Cooper and Khalid1990)
Reference Anton and BurchArfwidsson et al, 1972 Amitriptyline is not one of the randomised treatments
Reference Arfwidsson, d'Elia and LaurellBagheri et al, 1994 Amitriptyline is not one of the randomised treatments
Reference Bagheri, Picault and SchmittBagheri et al, 1997 Amitriptyline is not one of the randomised treatments
Reference Bagheri, Schmitt and BerlanBaldini & Neary, 1970 Amitriptyline is not one of the randomised treatments
Reference Baldini and NearyBall & Kiloh, 1959 Amitriptyline is not one of the randomised treatments
Reference Ball and KilohBan et al, 1982 People without a primary diagnosis of depression
Reference Ban, Fujimori and PetrieBaumann et al, 1985 Amitriptyline is not one of the randomised treatments
Reference Baumann, Eckmann and StieglitzBercel, 1967 Not randomised trial
Reference BercelBeresewicz et al, 1991 Not randomised trial
Reference Beresewicz, Bidzinska and KoszewskaBergener, 1968 Amitriptyline v. Rd 292
Reference BergenerBialos et al, 1982 Amitriptyline v. placebo
Reference Bialos, Giller and JatlowBlaine, 1975 People without a primary diagnosis of depression
Reference Blaine and MendelsBlashki et al, 1971 Amitriptyline v. amylobarbitone
Reference Blashki, Mowbray and DaviesBolzani & Slivar, 1967 Not randomised trial
Reference Bolzani and SlivarBowden et al, 1987 Same efficacy/safety data of Kocsis et al (Reference Klieser and Lehmann1986)
Reference Bowden, Koslow and MaasBranconnier et al, 1981 Efficacy and safety data are not available
Reference Branconnier, Cole and GhazvinianBrick et al, 1965 Crossover trial
Reference Brick, Doub and PerdueBrown et al, 1980 Efficacy and safety data are not available
Reference Brown, Haier and QuallsBrowne et al, 1963 Amitriptyline v. placebo
Reference Browne, Kreeger and KazamiasBurch et al, 1988 Not randomised trial
Reference Burch, Ahmed and HullinBurgess et al, 1979 Efficacy and safety data are not available
Reference Burgess, Montgomery and WadsworthCasper et al, 1994 Same efficacy/safety data of Kocsis et al (Reference Klieser and Lehmann1986)
Reference CasperChaplan, 1975 People without a primary diagnosis of depression
Reference Chaplan and MendelsCharney et al, 1984a Efficacy and safety data are not available
Reference Charney, Heninger and SternbergCharney et al, 1984b Amitriptyline is not one of the randomised treatments
Reference Charney, Heninger and SternbergClaghorn et al, 1984 Efficacy and safety data are not available
Reference Claghorn, Schroeder and GoldsteinCollard et al, 1978 Crossover trial
Reference Collard, Dufrasne and FraipontCooke et al, 1984 Amitriptyline is not one of the randomised treatments
Reference Cooke, Warsh and StancerCoppen, 1978 Not randomised trial
Reference CoppenCoppen et al, 1976 Efficacy and safety data are not available
Reference Coppen, Gupta and MontgomeryCoppen et al, 1987 Same efficacy/safety data of Coppen et al (Reference Coppen1976)
Reference Coppen, Gupta and MontgomeryCroughan et al, 1988 Efficacy and safety data are not available
Reference CroughanDavidson et al, 1978 Electroconvulsivetherapy v. amitriptyline phenelzine
Reference Davidson, McLeod and LawYoneDe Montigny et al, 1983 Lithium augmentation study
Reference De Montigny, Cournoyer and MorissetteDenker, 1971 Not randomised trial
Reference DenkerElwan et al, 1976 Efficacy and safety data are not available
Reference Elwan, Taher and AllamFernstrom & Kupfer, 1988 Efficacy and safety data are not available
Reference Fernstrom and KupferFriedel et al, 1979 Efficacy and safety data are not available
Reference Friedel, Veith and BloomFriedman et al, 1980 Efficacy and safety data are not available
Reference Friedman, McCallum and MearesGhose et al, 1976 Efficacy and safety data are not available
Reference Ghose, Coppen and TurnerGiedke et al, 1986 Oxaprotiline as the experimental drug
Reference Giedke, Gaertner and Breyer-PfaffGiedke et al, 1987 Oxaprotiline as the experimental drug
Reference Giedke, Heimann and ReinGiller et al, 1985 Amitriptyline v. placebo
Reference Giller, Bialos and HarknessGlassman et al, 1977 Not randomised trial
Reference Glassman, Perel and ShostakGlatzel, 1967 Not randomised trial
Reference GlatzelGoldberg et al, 1981 Same efficacy/safety data of Goldberg & Finnerty (Reference Geretsegger, Stuppaeck and Mair1980) and Rickels & Case (1982)
Reference Goldberg, Rickels and FinnertyGoodwin et al, 1982 Non-responder patients
Reference Goodwin, Prange and PostGuy et al, 1982 Efficacy and safety data are not available
Reference Guy, Ban and McEvoyHackett et al, 1967 Efficacy and safety data are not available
Reference Hackett, Gold and KlineHaider, 1967 Amitriptyline v. amitriptyline/chlordiazepoxide
Reference HaiderHanin, 1985 Same efficacy/safety data of Kocsis et al (Reference Klieser and Lehmann1986)
Reference HaninHealy et al, 1984 Same efficacy/safety data of Carney et al (Reference Byrne1984)
Reference Healy, Carney and LeonardHerceg et al, 1979 Psychotherapy trial
Reference Herceg, Prusoff and WeissmanHoenig & Visram, 1964 Not randomised trial
Reference Hoenig and VisramHollister et al, 1964 Efficacy and safety data are not available
Reference Hollister, Overall and JohnsonHorden et al, 1963 Same efficacy/safety data of Burt et al (Reference Burke, Sainsbury and Mezo1962)
Reference Horden, Holt and BurtHorden et al, 1964 Same efficacy/safety data of Burt et al (Reference Burke, Sainsbury and Mezo1962)
Reference Horden, Burt and GordonHutchinson & Smedberg, 1963 Efficacy and safety data are not available
Reference Hutchinson and SmedbergJakitowicz, 1991 Not randomised trial
Reference JakitowiczKatz et al, 1987 Same efficacy/safety data of Kocsis et al (Reference Klieser and Lehmann1986)
Reference Katz, Koslow and MaasKatz et al, 1993 Amitriptyline v. oxaprotiline v. levoprotiline
Reference Katz, Lott and LandauKieback, 1982a Efficacy and safety data are not available
Reference KiebackKieback, 1982b Efficacy and safety data are not available
Reference KiebackKiloh et al, 1962 Not randomised trial
Reference Kiloh, Ball and GarsideKlein et al, 1998 Amitriptyline is not one of the randomised treatments
Reference Klein, Mannuzza and KoplewiczKoch, 1990 Efficacy and safety data are not available
Reference KochKocsis et al, 1990 Same efficacy/safety data of Kocsis et al (Reference Klieser and Lehmann1986)
Reference KocsisKonig et al, 1994 Amitriptyline is not one of the randomised treatments
Reference König, Heinrich and DiehlKopera, 1980 Efficacy and safety data are not available
Reference KoperaKoszewska et al, 1994 Not randomised trial
Reference Koszewska, Beresewicz and PuzynskiKowalski et al, 1985 People without a primary diagnosis of depression
Reference Kowalski, Stanley and DennersteinKrakowski, 1968 Not randomised trial
Reference KrakowskiKramer et al, 1989 People without a primary diagnosis of depression
Reference Kramer, Vogel and DiJohnsonKupfer et al, 1977 Amitriptyline v. placebo
Reference Kupfer, Hanin and SpikerKupfer et al, 1979 Amitriptyline v. placebo
Reference Kupfer, Coble and RubinsteinKuss et al, 1984 Amitriptyline v. amitriptyline-N-oxide
Reference Kuss, Jungkunz and HolsboerLambourn & Rees, 1974 Efficacy and safety data are not available
Reference Lambourn and ReesLeyburn, 1967 Not randomised trial
Reference LeyburnLiisberg et al, 1978 Amitriptyline v. sustained release amitriptyline
Reference Liisberg, Mose and AmdisenLloyd et al, 1981 Efficacy and safety data are not available
Reference Lloyd, Zisook and ClickLyons et al, 1985 Amitriptyline is not one of the randomised treatments
Reference Lyons, Rosen and DyskenMaier et al, 1989 Efficacy and safety data are not available
Reference Maier, Philipp and SchlegelMarey et al, 1991 Not randomised trial
Reference Marey, Ganry and DelalleauMarjerrison et al, 1969 Efficacy and safety data are not available
Reference Marjerrison, Deza and SilzerMartin & Leahy, 1968 Same efficacy/safety data of Leahy & Martin (Reference Lauritsen and Madsen1967)
Reference Martin and LeahyMathur, 1975 Crossover design
Reference MathurMattila et al, 1978 Crossover design
Reference Mattila, Liljequist and SeppalaMcConaghy & Joffe, 1968 Same efficacy/safety data of McConaghy et al (Reference McCallum and Meares1965)
Reference McConaghy and JoffeMcNair et al, 1984a Crossover design
Reference McNair, Kahn and FrankenthalMcNair et al, 1984b Crossover design
Reference McNair, Kahn and FrankenthalMindham, 1981 Amitriptyline is not one of the randomised treatments
Reference MindhamMontgomery et al, 1978 Efficacy and safety data are not available
Reference Montgomery, Cronholm and ÅsbergMoyes et al, 1980 Efficacy and safety data are not available
Reference Moyes, Ray and MoyesMuck-Seler et al, 1991 Efficacy and safety data are not available
Reference Muck-Seler, Jakovljevic and DeanovicMurphy, 1975 Efficacy and safety data are not available
Reference Myers and BranthwaiteMyers & Calvert, 1976 Amitriptyline is not one of the randomised treatments
Reference MurphyMyers & Branthwaite, 1992 Efficacy and safety data are not available
Reference Myers and CalvertNahunek et al, 1964 Not randomised trial
Reference Nahunek, Bartova and IngrovaOliver-Martin et al, 1975 Amitriptyline is not one of the randomised treatments
Reference Oliver-Martin, Marzin and BuschsenschutzOltman & Friedman, 1963 Not randomised trial
Reference Oltman and FriedmanOltman & Friedman, 1964 Not randomised trial
Reference Oltman and FriedmanOse, 1971 Noxiptiline as the experimental drug
Reference OsePearce & Rees, 1974 Amitriptyline is not one of the randomised treatments
Reference Pearce and ReesPeet et al, 1977 Efficacy and safety data are not available
Reference Peet, Tienari and JaskariPennese et al, 1993 People without a primary diagnosis of depression
Reference Pennese, Palombo and ScurtiPeselow et al, 1986 Not randomised trial
Reference Peselow, Goldring and StanleyPetrie et al, 1980 Amitriptyline is not one of the randomised treatments
Reference Petrie, Wilson and BanPost & Goodwin, 1974 Efficacy and safety data are not available
Reference Post and GoodwinPreskorn et al, 1984 Efficacy and safety data are not available
Reference Preskorn, Othmer and LaiPressman & Weiss, 1961 Not randomised trial
Reference Pressman and WeissPrusoff et al, 1976 Same efficacy/safety data of Weissman et al (Reference Waite, Grundy and Arie1975)
Reference Prusoff, Weissman and TannerPugh, 1983 Same efficacy/safety data of Pugh et al (Reference Preskorn, Silkey and Beber1982)
Reference PughRajotte et al, 1966 Opipramol as the experimental drug
Reference Rajotte, Bordeleau and TetreaultRao et al, 1996 Same efficacy/safety data of Moller et al (Reference Moises, Kasper and Beckmann1995)
Reference Rao, Ruhrmann and ReteyRechlin, 1994 Efficacy and safety data are not available
Reference RechlinRees & Risdall, 1976 Not randomised trial
Reference Rees and RisdallReisby et al, 1977 Amitriptyline is not one of the randomised treatments
Reference ReisbyRenfordt & Bush, 1976 Efficacy and safety data are not available
Reference Renfordt and BushReynolds et al, 1969 Not randomised trial
Reference Reynolds, Craggs and Joyston-BechalRickels et al, 1974 Amitriptyline v. placebo
Reference Robinson, Cooper and HowardRobinson et al, 1972 Not randomised trial
Reference Rickels, Csanalosi and ChungRobinson et al, 1985 Amitriptyline v. phenelzine
Rockcliffe, 1971 Not randomised trial
Reference RockliffRouillon et al, 1989 Amitriptyline is not one of the randomised treatments
Reference Rouillon, Phillips and SerrurierRydzynski, 1966 Amitriptyline is not one of the randomised treatments
Reference RydzynskiSaletu et al, 1979 Efficacy and safety data are not available
Reference Saletu, Marx and GrunbergerSanger, 1969 People without a primary diagnosis of depression
Reference SangerSchweizer, 1993 People without a primary diagnosis of depression
Reference SchweizerSimpson et al, 1972 Amitriptyline v. thiothixene
Reference Simpson, Amin and AngusSims, 1972 Sustained-release amitriptyline v. amitriptyline
Reference SimsSnow & Rickels, 1964 Crossover design
Reference Snow and RickelsStassen et al, 1996 Not randomised trial
Reference Stassen, Angst and Delini-StulaStjean et al, 1966 Amitriptyline is not one of the randomised treatments
Reference Stjean, Ban and ScottStratas, 1984 Efficacy and safety data are not available
Reference StratasStromberg et al, 1991 People without a primary diagnosis of depression
Reference Stromberg, Suokas and SeppalaSullivan et al, 1977 Efficacy and safety data are not available
Reference Sullivan, Dackis and StanfieldSwann et al, 1990 Same efficacy/safety data of Kocsis et al (Reference Klieser and Lehmann1986)
Reference Swann, Secunda and StokesSymes, 1967 Amitriptyline is not one of the randomised treatments
Reference SymesTaragano et al, 1997 People without a primary diagnosis of depression
Reference Taragano, Lyketsos and MangoneTrick, 1975 Same efficacy/safety data of (Reference Taragano, Lyketsos and MangoneTrick 1975,Reference Toru, Takamizawa and KariyaTrick 1975)
Reference TrickVan De Merwe et al, 1984a Efficacy and safety data are not available
Reference Van De Merwe, Silverstone and AnkierVan De Merwe et al, 1984b Efficacy and safety data are not available
Reference Van De Merwe, Silverstone and AnkierVan Scheyen & Van Kammen, 1979 Efficacy and safety data are not available
Reference Van Scheyen and Van KammenVartanyan, 1984 Efficacy and safety data are not available
Reference VartanyanVeith et al, 1982 Efficacy and safety data are not available
Reference Veith, Bloom and BielskiVinar & Grof, 1964 Not randomised trial
Reference Vinar and GrofVogel et al, 1976 Efficacy and safety data are not available
Reference Vogel, Bente and FederVon Arnold & Foitl, 1961 Not randomised trial
Reference Von Arnold and FoitlVon Arnold & Heves, 1967 Not randomised trial
Reference Von Arnold and HevesVon Bergener, 1968 Efficacy and safety data are not available
Reference Von BergenerVon Plavec & Steininger, 1968 Not randomised trial
Reference Von Plavec and SteiningerVon Rosenberg, 1974 Noxiptiline as the experimental drug
Reference Von RosenbergWeiss & Pressman, 1961 No random allocation
Reference Weiss and PressmanWeissman, 1976 Same efficacy/safety data of Weissman et al (Reference Waite, Grundy and Arie1975)
Reference Weissman and GallantWelner et al, 1980 Not randomised trial
Reference Welner, Welner and RobinsWheatley, 1967 Imipramine v. phenobarbitone, amitriptyline v. amitriptyline/chlordiazepoxide
Reference WheatleyWilkins et al, 1989 Efficacy and safety data are not available
Wilson et al, 1963 Amitriptyline is not one of the randomised treatments
Reference WilsonWittenborn et al, 1973 Efficacy and safety data are not available
Reference Wittenborn, Kiremitci and WeberYamamoto et al, 1972 Amitriptyline is not one of the randomised treatments

Although all trials reported that patients had been randomly allocated, in six cases the concealment of allocation was inadequate with some bias possible. In four studies only physicians, but not patients, were blind to treatments, in nine cases neither physicians nor patients were blind, while the other 173 studies were double-blind. The median sample size was 50 patients (10% percentile 24, 25% percentile 40, 75% percentile 80, 90% percentile 153; range 10-531). The median length of trials was four weeks (25% percentile 4, 50% percentile 4, 75% percentile 6; range 3-12); the number of studies with more than four weeks of follow-up increased from 28 (30%) to 62 (67%) after 1980. In 67 trials (36%) authors adopted diagnostic criteria and a specification of severity of depression to enrol patients; in 55 trials (30%) authors adopted only a specification of severity, while in the remaining 34% of studies patients were enrolled on the basis of physicians' implicit criteria to define patients with depression or because they were judged to require antidepressant therapy. Fifty-nine per cent of studies published before 1980 used implicit criteria v. 9.6% of those published after this date. Overall, 108 trials (60%) used operational criteria for depression. Nearly half of the studies (47%) provided a comprehensive description of patients' side-effects, while 23 (12%) trials gave inadequate details. The outcome assessment was performed with valid and reliable instruments in 70% of the sample; the use of valid instruments in studies published before and after 1980 increased from 51 (55%) to 81 (86%).

Efficacy of amitriptyline

Data extracted from 82 RCTs showed that the proportion of patients who responded to amitriptyline was 2.4% higher than for control TCA/heterocyclic antidepressants (NNTB 42, 95% CI NNTH 357 to ∞ to NNTB 20) (see Table 2). This difference corresponds to an overall odds ratio which favoured amitriptyline (Peto odds ratio 1.11, 95% CI 0.99-1.25), but with only borderline statistical significance. The estimate of the efficacy of amitriptyline and control TCAs/heterocyclic antidepressants on a continuous outcome, performed on 699 and 661 patients respectively, revealed an effect size which also significantly favoured amitriptyline (SMD=0.177, 95% CI 0.005-0.350). Head-to-head comparisons indicated that amitriptyline, in comparison with imipramine, is associated with a greater proportion of responders; in comparison with dothiepin, however, the proportion of responders was significantly lower (see Table 2).

Table 2

Amitriptyline (AMI) in comparison with tricyclic (TCA) or heterocyclic antidepressants: proportion of responders, number of patients evaluated on a continuous outcome and estimates of efficacy

Responders/total randomised1 Patients evaluated on a continuous outcome2 Responders (intention to treat) Peto-odds ratio3 Mean score at end-point SMD4 (95% CI)
(No. of trials) TCA AMI (No. of trials) TCA AMI
Control TCA/heterocyclic drug
Amineptine (1) 21/26 14/25 (2) 42 47 0.32 (0.10-1.04) 0.397 (-2.78 to 3.58)
Amoxapine (11) 180/298 199/303 (1) 17 21 1.28 (0.91-1.81) 0.099 (-0.54 to 0.74)
Clomipramine (1) 20/35 13/37 (1) 35 37 0.42 (0.17-1.05) -0.236 (-0.70 to 0.23)
Desipramine (3) 41/77 39/69 (2) 43 39 1.20 (0.62-2.31) 0.422 (-0.01 to 0.86)
Dothiepin (5) 87/114 74/116 (2) 46 47 0.54 (0.31-0.96) 0.015 (-0.39 to 0.42)
Doxepin (8) 100/161 103/170 (-) 1.00 (0.63-1.59) -
Imipramine (9) 141/285 177/293 (-) 1.71 (1.20-2.43) -
Lofepramine (6) 129/189 116/187 (3) 57 54 0.75 (0.49-1.16) -0.002 (-0.48 to 0.47)
Maprotiline (12) 217/343 207/340 (5) 71 68 0.90 (0.65-1.26) 0.324 (-0.06 to 0.71)
Mianserin (5) 70/133 65/109 (3) 39 38 1.37 (0.82-2.29) 0.252 (-0.20 to 0.71)
Minaprine (1) 15/30 17/30 (1) 28 30 1.30 (0.48-3.56) 0.173 (-0.34 to 0.69)
Nortriptyline (4) 55/104 55/93 (2) 33 32 1.36 (0.77-2.40) -0.140 (-0.63 to 0.35)
Protriptyline (1) 17/51 27/49 (-) 2.40 (1.09-5.26) -
Tianeptine (2) 204/285 218/280 (1) 103 108 1.40 (0.95-2.06) 0.180 (-0.09 to 0.45)
Trazodone (7) 149/271 149/276 (4) 145 98 0.94 (0.66-1.33) 0.273 (0.01 to 0.54)
Trimipramine (1) (/13 7/13 (1) 17 17 0.54 (0.11-2.52) 0.251 (-0.42 to 0.93)
Viloxazine (3) 25/57 35/60 (1) 23 25 1.76 (0.84-3.67) 0.379 (-0.19 to 0.95)
Combination (2) 25/68 17/37 (-) 1.59 (0.69-3.71) -
Overall comparison 1.11 (0.99-1.25) 0.177 (0.005-0.350)
Test of heterogeneity χ2=108.4 (d.f.=81), Z=1.78, P<0.05 χ2=63.2 (d.f.=28), Z=2.01, P<0.05

Data from 17 RCTs showed that the proportion of patients who responded to amitriptyline was 2.8% higher than for SSRIs (NNTB 35, 95% CI NNTH 53 to ∞ to NNTB 13) (see Table 3). This difference corresponded to an overall odds ratio which favoured amitriptyline (Peto odds ratio 1.14, 95% CI 0.92-1.38), but not significantly. The estimate of the efficacy of amitriptyline and SSRIs on a continuous outcome, performed on 1041 and 1061 patients, respectively, revealed a small effect size which significantly favoured amitriptyline (SMD=0.106, 95% CI 0.02-0.19). No significant differences emerged from direct comparisons between amitriptyline and one of the SSRIs (see Table 3).

Table 3

Amitriptyline (AMI) in comparison with selective serotonin reuptake inhibitors (SSRIs): proportion of responders, number of patients evaluated on a continuous outcome and estimates of efficacy

Responders/total randomised1 Patients evaluated on a continuous outcome2 Responders (intention to treat) Mean score at end-point
(No. of trials) SSRI AMI (No. of trials) SSRI AMI Peto odds ratio3 (95% CI) SMD4 (95% CI)
Control SSRI
Fluoxetine (5) 77/146 70/145 (9) 336 341 0.83 (0.52-1.33) 0.113 (-0.04 to 0.27)
Fluvoxamine (1) 16/35 22/34 (2) 40 43 2.13 (0.83-5.46) 0.291 (-0.41 to 0.99)
Sertraline (-) (2) 173 174 - 0.109 (-0.10 to 0.32)
Paroxetine (9) 266/487 267/455 (7) 468 483 1.21 (0.93-1.58) 0.114 (-0.04 to 0.27)
Citalopram (2) 104/206 112/210 (1) 24 20 1.11 (0.76-1.63) -0.077 (-0.67 to 0.52)
Overall comparison 1.14 (0.94-1.38) 0.106 (0.02-0.19)
Test of heterogeneity χ2=11.27 (d.f.=16), Z=1.31, P=0.79 χ2=19.65 (d.f.=20), Z=2.42, P=0.48

Tolerability of amitriptyline

Data from 125 RCTs showed that 20% of patients treated with amitriptyline failed to complete the study, in comparison with 21.5% of patients who received another tricyclic/heterocyclic antidepressant (NNTB=69, 95% CI NNTH 385 to ∞ to NNTB 32). This difference corresponded to an overall odds ratio non-significantly favouring amitriptyline (Peto odds ratio 1.09, 95% CI 0.98-1.22) (see Table 4). However, the estimate of the proportion of patients who experienced side-effects during the study was 13% higher for amitriptyline than for control TCAs/heterocyclic antidepressants (NNTH=7.6, 95% CI NNTH 6 to NNTH 11) (see Table 4), corresponding to an odds ratio which significantly favoured the control TCAs/heterocyclic antidepressants. Head-to-head comparisons failed to detect statistically significant differences in terms of drop-outs between amitriptyline and one of the TCA/heterocyclic antidepressants (see Table 4). However, amitriptyline was associated with more side-effects than dothiepin, maprotiline, mianserin, minaprine and nortriptyline (see Table 4).

Table 4

Amitriptyline (AMI) in comparison with tricylcic/heterocyclic antidepressants (TCAs): proportion of drop-outs, proportion of patients with side-effects and estimates of tolerability

Responders/total randomised1 Patients evaluated on a continuous outcome2 Drop-outs3 Patients with side-effects
(No. of trials) TCA AMI (No. of trials) TCA AMI Peto odds ratio4 (95% CI) Peto odds ratio4 (95% CI)
Control TCA/heterocyclic
Amineptine (2) 8/48 7/47 (1) 6/26 10/25 1.14 (0.38-3.39) 0.46 (0.14-1.49)
Amoxapine (13) 94/359 89/363 (3) 59/97 63/95 1.09 (0.77-1.54) 0.77 (0.41-1.44)
Clomipramine (3) 73/148 59/151 (1) 18/35 16/37 1.52 (0.95-2.41) 1.38 (0.55-3.47)
Desipramine (4) 10/82 13/74 (-) 0.72 (0.28-1.84) -
Dothiepin (8) 12/196 18/200 (5) 51/115 70/119 0.68 (0.32-1.47) 0.51 (0.29-0.88)
Doxepin (13) 88/427 103/433 (4) 46/76 61/92 0.84 (0.60-1.17) 0.77 (0.39-1.50)
Imipramine (6) 25/172 24/177 (2) 17/71 25/85 1.34 (0.71-2.51) 0.73 (0.35-1.50)
Lofepramine (8) 54/236 61/234 (2) 12/31 19/31 0.85 (0.55-1.32) 0.39 (0.14-1.08)
Maprotiline (18) 86/557 88/550 (7) 136/224 154/212 0.97 (0.69-1.35) 0.59 (0.40-0.88)
Mianserin (12) 123/410 96/377 (3) 73/135 101/131 1.27 (0.91-1.77) 0.34 (0.20-0.57)
Minaprine (2) 115/429 31/162 (2) 117/429 67/162 1.50 (0.98-2.29) 0.55 (0.37-0.82)
Nomifensine (1) 1/17 1/12 (-) 0.69 (0.04-12.1) -
Nortriptyline (8) 27/235 26/232 (4) 42/124 52/102 1.01 (0.56-1.83) 0.51 (0.30-0.87)
Protriptyline (-) (1) 38/51 33/49 - 1.41 (0.60-3.33)
Tianeptine (3) 80/349 65/345 (-) 1.28 (0.89-1.85) -
Trazodone (10) 79/357 72/362 (2) 53/113 54/110 1.14 (0.79-1.65) 0.92 (0.54-1.55)
Trimipramine (2) 11/58 13/57 (1) 3/21 5/20 0.76 (0.30-1.97) 0.51 (0.11-2.36)
Viloxazine (7) 24/140 21/148 (1) 14/19 16/22 1.32 (0.69-2.55) 1.05 (0.27-4.12)
Combinations (5) 84/409 32/164 (1) 68/89 37/46 1.05 (0.66-1.69) 0.79 (0.34-1.86)
Overall comparison 1.09 (0.98-1.22) 0.62 (0.53-0.73)
Test of heterogeneity χ2=118.1 (d.f.=109) χ2=53.3 (d.f.=39)
Z=1.60, P<0.05 Z=5.90, P=0.06

Data from 40 RCTs comparing amitriptyline and SSRIs showed that 29.8% of patients treated with amitriptyline failed to complete the study, in comparison with 27.7% of patients treated with SSRIs (NNTH=49, 95% CI NNTB 180 to ∞ to NNTH 22). This difference corresponds to an overall odds ratio of 0.86 (95% CI 0.75-0.98), which significantly favoured SSRIs (see Table 5). The estimate of the proportion of patients who experienced side-effects during the study was 11.6% higher for amitriptyline than for SSRIs (NNTH=8.6, 95% CI NNTH 6 to NNTH 15) (see Table 5), corresponding to an odds ratio which significantly favoured the SSRIs.

Table 5

Amitriptyline (AMI) in comparison with selective serotonin reuptake inhibitors (SSRIs): proportion of drop-outs, proportion of patients with side-effects and estimates of tolerability

Drop-outs/total randomised1 Patients with side-effects/total randomised2 Drop-outs Patients with side-effects
(No. of trials) SSRI AMI (No. of trials) SSRI AMI Peto odds ratio3 (95% CI) Peto odds ratio3 (95% CI)
SSRI
Fluoxetine (15) 124/540 148/551 (1) 7/20 16/21 0.79 (0.59-1.04) 0.20 (0.06-0.66)
Fluvoxamine (3) 17/81 19/77 (-) 49/115 52/113 0.84 (0.39-1.83) -
Sertraline (6) 264/650 228/568 (2) 221/366 251/360 0.97 (0.76-1.23) 0.87 (0.50-1.50)
Paroxetine (13) 205/897 217/882 (4) 131/206 169/210 0.89 (0.71-1.12) 0.70 (0.51-0.96)
Citalopram (3) 55/230 75/230 (2) 0.64 (0.42-0.96) 0.43 (0.28-0.66)
Overall comparison 0.86 (0.75-0.98) 0.61 (0.48-0.76)
Test of heterogeneity χ2=49.6 (d.f.=39), Z=2.27, P=0.11 χ2=14.7 (d.f.=8), Z=4.35, P=0.06

Overall efficacy and tolerability of amitriptyline in comparison with all antidepressant drugs

A funnel plot (Fig. 1) showed no evidence of publication bias being a problem in the data collected. The overall estimate of the efficacy of amitriptyline in comparison to TCAs/heterocyclic drugs and SSRIs showed a 2.5% difference in the proportion of responders in favour of amitriptyline (NNTB=40, 95% CI NNTB 21 to NNTB 694) (see Fig. 2), which corresponded to an intention to treat odds ratio of 1.12 (95% CI 1.01-1.24). The estimate of the efficacy of amitriptyline and control antidepressants on a continuous outcome confirmed the slightly superior efficacy profile of amitriptyline: the estimate of the SMD significantly favours amitriptyline (see Fig. 2).

Fig. 1

Funnel plot of estimated logarithmic odds ratio against the size of the study. Broken horizontal line represents the overall estimate of the logarithmic odds ratio (0.11).

Fig. 2

Overall estimate of the efficacy and tolerability of amitriptyline (AMI) in comparison to all other antidepressant drugs.

The drop-out rate in patients taking amitriptyline and the control antidepressants was very similar, yielding an overall odds ratio of 0.99 (95% CI 0.91-1.08). However, the estimate of the proportion of patients who experienced side-effects during the study was 13.1% higher for amitriptyline than control antidepressants (NNTH=7.6, 95% CI NNTH 6 to NNTH 10), corresponding to an odds ratio which significantly favoured the control antidepressants (see Fig. 2).

DISCUSSION

Implications for research

This systematic review suggests that amitriptyline should remain in its position as the gold-standard antidepressant. Using a highly conservative approach to estimate efficacy — in which drop-outs were included in the analysis — we estimated that amitriptyline is slightly more efficacious than all other antidepressants grouped together. The same applied when the analysis was subdivided according to pharmacological class of the comparison drug — although the comparison with SSRIs failed to reach statistical significance. This measure of outcome takes into consideration drop-outs from therapy, so it cannot be explained by differential completion of the study protocol. The additional efficacy outcome — using effect sizes of continuous outcomes — showed a similar picture, but now with a statistically significant difference against the SSRIs. The tolerability data confirm that amitriptyline is associated with more side-effects than, but similar drop-outs to, other TCAs, and more side-effects and more drop-outs than SSRIs.

Methodological concerns

There are reasons for interpreting these results with caution. Included studies are heterogeneous in terms of selection criteria, allocation concealment, setting and out-come measures. A certain variability in the overall quality of the primary research might therefore have influenced the overall comparison. This systematic review did not investigate heterogeneity by grouping trials according to patient characteristics or trial quality and performing subgroup analyses. This approach was not adopted because it would have inevitably decreased the power of the analysis, thus providing ambiguous results; in addition, increasing the number of comparisons would have increased the possibility of detecting significant differences only by chance. The present analysis, which pools data from different trials carried out in many populations, has the advantage of generating information which can be applied to a very diverse range of patients (Reference Oxman, Cook and GuyattOxman et al, 1994).

Implications for practice

How should these data be translated into clinical practice? It certainly seems reasonable to conclude that amitriptyline is as good as — if not better than — the other TCAs and heterocyclic antidepressants, with the possible exception of dothiepin (Reference Eccles, Freemantle and MasonEccles et al, 1999). It seems reasonable to suggest that either amitriptyline or dothiepin should remain the first-line TCA. More controversial is the role of TCAs alongside SSRIs. The results from randomised trials suggest that amitriptyline probably has the edge in terms of efficacy over SSRIs. Given that publication bias is likely to work in favour of newer compounds, it is possible that unpublished data would further improve amitriptyline's position. Those who advocate first-line use of an SSRI point to two additional strands of evidence — the danger of TCAs in overdose and the fact that they are often in practice prescribed at sub-therapeutic doses. Although the widespread prescribing of SSRIs has to be viewed as a public health measure to prevent suicide, it is likely to be prohibitively expensive; in addition, data showing that the widespread use of SSRIs decreases suicide rates are lacking (Reference Barbui, Campomori and D'AvanzoBarbui et al, 1999). The advice should probably remain that SSRIs are the first-line treatment to be given to patients at high risk of committing deliberate self-harm. The problems of TCAs being prescribed in low doses has attracted considerable attention, as evidence suggests that in real situations TCAs are rarely taken appropriately. However, the guidelines on ‘adequate’ dosing — which suggest at least 125 mg of amitriptyline have to be prescribed for it to be effective — are themselves based on inadequate research. Recent systematic reviews indicate that low-dose TCAs are as effective as SSRIs in treating depression (Canadian Coordinating Office for Health Technology Assessment, 1997a ), and studies directly comparing low- and high-dose TCAs show only very modest benefits of high doses (Reference Bollini, Pampallona and TibaldiBollini et al, 1999).

Clinical Implications and Limitations

CLINICAL IMPLICATIONS

  • ▪ Amitriptyline is at least as effective as the other tricyclic and heterocyclic antidepressants.

  • ▪ Slightly more patients treated with amitriptyline make a recovery than with selective serotonin reuptake inhibitors.

  • ▪ Amitriptyline is less well tolerated than selective serotonin reuptake inhibitors.

LIMITATIONS

  • ▪ Included trials are heterogeneous in terms of patients, settings and outcome measures.

  • ▪ Heterogeneity has not been investigated by performing subgroup analyses.

  • ▪ The variability in the quality of the original studies might have influenced the overall comparison.

ACKNOWLEDGEMENTS

We would like to thank Hugh McGuire, CCDANCTR Trial Search Coordinator, for assisting in developing the search strategy of this research. Thanks in addition to Nick Freemantle for sharing relevant references and to Jennifer Hillebrand for assistance in extracting data from non-English articles.

Footnotes

†

See editorial, pp. 99–100, this issue.

Declaration of interest

None.

References

References

Altman, D. G. & Bland, J. M. (1996) Detecting skewness from summary information. British Medical Journal, 313, 1200.CrossRefGoogle ScholarPubMed
Altman, D. G. (1998) Confidence intervals for the number needed to treat. British Medical Journal, 317, 1309–1312.CrossRefGoogle ScholarPubMed
Anderson, I. M. & Tomenson, B. M. (1995) Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis. British Medical Journal, 310, 1433–1438.Google Scholar
Barbui, C., Campomori, A., D'Avanzo, B., et al (1999) Antidepressant drug use in Italy since the introduction of SSRIs: national trends, regional differences and impact on suicide rates. Social Psychiatry and Psychiatric Epidemiology, 34, 152–156.CrossRefGoogle ScholarPubMed
Bollini, P., Pampallona, S., Tibaldi, G., et al (1999) Effectiveness of antidepressants. Meta-analysis of dose–effect relationships in randomised clinical trials. British Journal of Psychiatry, 174, 297–303.CrossRefGoogle ScholarPubMed
Canadian Coordinating Office for Health Technology Assessment (1997a) Selective Serotonin Reuptake Inhibitors (SSRIs) for Major Depression. Part I. Evaluation of the Clinical Literature. Ottawa: Canadian Coordinating Office for Health Technology Assessment.Google Scholar
Canadian Coordinating Office for Health Technology Assessment (1997b) Selective Serotonin Reuptake Inhibitors (SSRIs) for Major Depression. Part II. The Cost-Effectiveness of SSRIs in Treatment of Depression. Ottawa: Canadian Coordinating Office for Health Technology Assessment.Google Scholar
Eccles, M., Freemantle, N. & Mason, J. (1999) North of England Evidence-Based Guideline Development Project: summary version of guidelines for the choice of antidepressants for depression in primary care. Family Practice, 16, 103–111.CrossRefGoogle ScholarPubMed
Garattini, S., Barbui, C. & Saraceno, B. (1998) Antidepressant agents: from tricyclics to serotonin reuptake inhibitors. Psychological Medicine, 28, 1169–1178.Google Scholar
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology. DHEW Pub. No. (ADM)76–338. Rockville, MD: National Institute of Mental Health.Google Scholar
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23, 56–62.Google Scholar
Hotopf, M., Lewis, G. & Normand, C. (1996) Are SSRIs a cost-effective alternative to tricyclics? British Journal of Psychiatry, 168, 404–409.CrossRefGoogle ScholarPubMed
Hotopf, M., Hardy, R. & Lewis, G. (1997) Discontinuation rates of SSRIs and tricyclic antidepressants: a meta-analysis and investigation of heterogeneity. British Journal of Psychiatry, 170, 120–127.CrossRefGoogle ScholarPubMed
Montgomery, S. A. & Åsberg, M. (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382–389.Google Scholar
Montgomery, S. A. & Kasper, S. (1995) Comparison of compliance between serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis. International Clinical Psychopharmacology, 9 (suppl. 4), 33–40.Google Scholar
Oxman, A. D., Cook, D. J. & Guyatt, G. H. (1994) Users' guides to the medical literature. IV. How to use an overview. Journal of the American Medical Association, 272, 1367–1371.Google Scholar
Review Manager (RevMan) (1999) Version 4.0 for Windows. Oxford: Cochrane Collaboration.Google Scholar
Song, F., Freemantle, N., Sheldon, T. A., et al (1993) Selective serotonin reuptake inhibitors: meta-analysis of efficacy and acceptability. British Medical Journal, 306, 683–687.Google Scholar

APPENDIX

Potentially relevant studies identified by the electronic search and subsequently excluded from the meta-analysis Google Scholar
Abou-Saleh, M. T. & Coppen, A. (1983) Classification of depression and response to antidepressive therapies. British Journal of Psychiatry, 143, 601–603.Google Scholar
Abram, H. C., Kanter, V. B., Rosen, I., et al (1963) A controlled clinical trial of imipramine (Tofranil) with outpatients. British Journal of Psychiatry, 109, 286–293.Google Scholar
Altamura, A. C., Mauri, M. C., Colacurcio, F., et al (1988) Trazodone in late-life depressive states: a double-blind multicentre study versus amitriptyline and mianserin. Psychopharmacology, 95, S34–S36.CrossRefGoogle Scholar
Angst, J. (1963) Vergleich der antidepressiven eigenschaften von amitriptylin und imipramin. Psychopharmacologia, 4, 389–401.CrossRefGoogle Scholar
Anonymous (1971) Multihospital controlled comparison of the therapeutic effects of four antidepressants. Activitas Nervosa Superiora, 13, 166–167.Google Scholar
Anton, R. F. & Burch, E. A. (1993) Response of psychotic depression subtypes to pharmacotherapy. Journal of Affective Disorders, 28, 125–131.Google Scholar
Arfwidsson, L., d'Elia, G., Laurell, B., et al (1972) Comparison of chlorimipramine and imipramine in ambulatory treatment of depression. Acta Psychiatrica Scandinavica, 48, 367–376.Google Scholar
Bagheri, H., Picault, P., Schmitt, L., et al (1994) Pharmacokinetic study of yohimbine and its pharmacodynamic effects on salivary secretion in patients treated with tricyclic antidepressants. British Journal of Clinical Pharmacology, 37, 93–96.Google Scholar
Bagheri, H., Schmitt, L., Berlan, M., et al (1997) A comparative study of the effects of yohimbine and anetholtrihione on salivary secretion in depressed patients treated with psychotropic drugs. European Journal of Clinical Pharmacology, 52, 339–342.CrossRefGoogle ScholarPubMed
Baldini, J. T. & Neary, E. R. (1970) Controlled trials of an amitriptyline–fluphenazine combination in depressive neuroses and psychoses: a collaborative study. Current Therapy Research, 12, 84–93.Google Scholar
Ball, J. R. B. & Kiloh, L. G. (1959) A controlled trial of imipramine in treatment of depressive states. British Medical Journal, 2, 1052–1055.CrossRefGoogle ScholarPubMed
Ban, T. A., Fujimori, M., Petrie, W. M., et al (1982) Systematic studies with amoxapine, a new antidepressant. International Pharmacopsychiatry, 17, 18–27.Google Scholar
Baumann, U., Eckmann, F. & Stieglitz, R. D. (1985) Self-rating data as a selecting factor in clinical trials of psychotropic drugs. European Archives of Psychiatry and Neurological Sciences, 235, 65–70.CrossRefGoogle ScholarPubMed
Bercel, N. A. (1967) Clinical trial of protriptyline. International Journal of Neuropsychiatry, 3, 365–378.Google Scholar
Beresewicz, M., Bidzinska, E., Koszewska, I., et al (1991) Results of using tricyclic antidepressive drugs in the treatment of endogenous depression (comparative analysis of seven drugs). Psychiatria Polska, 25, 13–18.Google Scholar
Bergener, M. (1968) L'application du test de “randomization” en pharmaco-psychiatrie. Evolution Psychiatrique, 33, 707–720.Google Scholar
Bialos, D., Giller, E., Jatlow, P., et al (1982) Recurrence of depression after discontinuation of long-term amitriptyline treatment. American Journal of Psychiatry, 139, 34–38.Google ScholarPubMed
Blaine, G. (1975) Double-blind comparison of doxepin and amitriptyline in depressed menopausal outpatients receiving estrogen replacement therapy. In Sinequan (Doxepin HCl) (ed. Mendels, J.), pp. 43–50. Amsterdam: Excerpta Medica.Google Scholar
Blashki, T. G., Mowbray, R. & Davies, B. (1971) Controlled trial of amitriptyline in general practice. British Medical Journal, 1, 133–138.Google Scholar
Bolzani, L. & Slivar, G. (1967) Clinical study of an anxiolytic antidepressive drug. Psychiatria et Neurologia, 153, 301–307.Google Scholar
Bowden, C. L., Koslow, S., Maas, J. W., et al (1987) Changes in urinary catecholamines and their metabolites in depressed patients treated with amitriptyline or imipramine. Journal of Psychiatry Research, 21, 111–128.CrossRefGoogle ScholarPubMed
Branconnier, R. J., Cole, J. O. & Ghazvinian, S. (1981) The therapeutic profile of mianserin in mild elderly depressives. Psychopharmacology Bulletin, 17, 129–130.Google Scholar
Brick, H., Doub, W. H. & Perdue, W. C. (1965) A comparison of the effects of amitriptyline and protriptyline on anxiety and depressive states in female prisoners. International Journal of Neuropsychiatry, 1, 325–336.Google ScholarPubMed
Brown, W. A., Haier, R. J. & Qualls, C. B. (1980) Dexamethasone suppression test identifies subtypes of depression which respond to different antidepressants. Lancet, i, 928–929.Google Scholar
Browne, M. W., Kreeger, L. C. & Kazamias, N. G. (1963) A clinical trial of amitriptyline in depressive patients. British Journal of Psychiatry, 109, 692–694.CrossRefGoogle ScholarPubMed
Burch, J. E., Ahmed, O., Hullin, R. P., et al (1988) Antidepressive effect of amitriptyline treatment with plasma drug levels controlled within three different ranges. Psychopharmacology Berlin, 94, 197–205.Google Scholar
Burgess, C. D., Montgomery, S., Wadsworth, J., et al (1979) Cardiovascular effects of amitriptyline, mianserin, zimelidine and nomifensine in depressed patients. Postgraduate Medical Journal, 55, 704–708.CrossRefGoogle ScholarPubMed
Casper, R. C. (1994) The pattern of physical symptom changes in major depressive disorder following treatment with amitriptyline or imipramine. Journal of Affective Disorders, 31, 151–164.Google Scholar
Chaplan, A. (1975) Doxepin in anxious/depressed outpatients with gastrointestinal symptoms: double-blind comparison of doxepin and perphenazine/amitriptyline. In Sinequan (Doxepin HCl) (ed. Mendels, J.), pp. 32–42. Amsterdam: Excerpta Medica.Google Scholar
Charney, D. S., Heninger, G. R. & Sternberg, D. (1984a) Serotonin function and mechanisms of action of antidepressant treatment. Effects of amitriptyline and desimipramine. Archives of General Psychiatry, 41, 359–365.Google Scholar
Charney, D. S., Heninger, G. R. & Sternberg, D. (1984b) The effect of mianserin on alpha-2 adrenergic receptor function in depressed patients. British Journal of Psychiatry, 144, 407–416.Google Scholar
Claghorn, J. L., Schroeder, J. & Goldstein, B. J. (1984) Comparison of the electrocardiographic effect of dothiepin and amitriptyline. Journal of Clinical Psychiatry, 45, 291–293.Google Scholar
Collard, J., Dufrasne, M., Fraipont, J., et al (1978) Un nouvel agent antidepressif: la dothiepin. Revue Médicale de Liège, XXXIII, 275–279.Google Scholar
Cooke, R. G., Warsh, J. J., Stancer, H. C., et al (1984) The non-linear kinetics of desipramine and 2-hydroxydesipramine in plasma. Clinical Pharmacology and Therapeutics, 36, 343–349.Google Scholar
Coppen, A. (1978) Amitriptyline plasma-concentration and clinical effect. A World Health Organization Collaborative Study. Lancet, i, 63–66.CrossRefGoogle Scholar
Coppen, A. Gupta, R., Montgomery, S., et al (1976) Mianserin hydrochloride: a novel antidepressant. British Journal of Psychiatry, 129, 342–345.Google Scholar
Coppen, A. Gupta, R., Montgomery, S., et al (1987) A new antidepressant agent. Mianserin hydrochloride. Zeitschrift für Allgemeinmedizine, 54, 1569–1573.Google Scholar
Croughan, J. L. (1988) Sociodemographic and prior clinical course characteristics associated with treatment response in depressed patients. Journal of Psychiatry Research, 22, 227–237.Google Scholar
Davidson, J., McLeod, M., LawYone, B., et al (1978) A comparison of electroconvulsive therapy and combined phenelzine–amitriptyline in refractory depression. Archives of General Psychiatry, 35, 639–642.Google Scholar
De Montigny, C., Cournoyer, G., Morissette, R., et al (1983) Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression. Correlations with the neurobiologic actions of tricyclic antidepressant drugs and lithium ion on the serotonin system. Archives of General Psychiatry, 40, 1327–1334.Google Scholar
Denker, S. J. (1971) Behandlingsforsok med imipramin-N-oxid och amitriptylin-N-oxid. Nordisk Psykiatrisk Tidsskrift, 25, 463–470.Google Scholar
Elwan, O., Taher, Y., Allam, M., et al (1976) A comparative study of antidepressants in the treatment of depressive states. Journal of International Medical Research, 4, 202–210.Google Scholar
Fernstrom, M. H. & Kupfer, D. J. (1988) Antidepressant-induced weight gain: a comparison study of four medications. Psychiatry Research, 26, 265–271.CrossRefGoogle ScholarPubMed
Friedel, R. O., Veith, R. C., Bloom, V., et al (1979) Desipramine plasma levels and clinical response in depressed outpatients. Communications in Psychopharmacology, 3, 81–87.Google ScholarPubMed
Friedman, J., McCallum, P. & Meares, R. (1980) 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, 14, 115–119.CrossRefGoogle ScholarPubMed
Ghose, K., Coppen, A. & Turner, P. (1976) Autonomic actions and interactions of mianserin hydrochloride and amitriptyline in patients with depressive illness. Psychopharmacology, 49, 201–204.Google Scholar
Giedke, H., Gaertner, H., Breyer-Pfaff, U., et al (1986) Amitriptyline and oxaprotiline in the treatment of hospitalised depressed patients. Clinical aspects, psychophysiology, and drug plasma level. European Archives of Psychiatry and Neurological Sciences, 235, 329–338.Google Scholar
Giedke, H., Heimann, H. & Rein, W. (1987) Changes in slow evoked potentials in depressed patients treated with amitriptyline and oxaprotiline. Review in Electroencephalography and Neurophysiology Clinic, 17, 279–287.Google Scholar
Giller, E., Bialos, D., Harkness, L., et al (1985) Long-term amitriptyline in chronic depression. Hillside Journal of Clinical Psychiatry, 7, 16–33.Google Scholar
Glassman, A. H., Perel, J. M., Shostak, M., et al (1977) Clinical implications of imipramine plasma levels for depressive illness. Archives of General Psychiatry, 34, 197–204.Google Scholar
Glatzel, J. (1967) Clinical experiences with a new thymoleptic. Schweizer Archiv für Neurologie, Neurochirurgie und Psychiatrie, 100, 167–178.Google Scholar
Goldberg, H. L., Rickels, K. & Finnerty, R. (1981) Treatment of neurotic depression with a new antidepressant. Journal of Clinical Psychopharmacology, 1 (suppl. 6), 35S–38S.Google Scholar
Goodwin, F. K., Prange, A. J., Post, R. M., et al (1982) A potentiation of antidepressant effects by L-triiodothyrpsine in tricyclic non responders. American Journal of Psychiatry, 139, 34–38.Google Scholar
Guy, W., Ban, T. A., McEvoy, J. P., et al (1982) A collaborative study of a new antidepressant, viloxezine, in neurotic and endogenous depressives. International Pharmacopsychiatry, 17, 36–42.CrossRefGoogle ScholarPubMed
Hackett, E., Gold, R. L., Kline, N. S., et al (1967) Controlled evaluation of psychotropic drugs in a private psychiatric practice. Doxepin vs. amitriptyline (Elavil). Psychosomatics, 8, 162–165.Google Scholar
Haider, I. (1967) A comparative trial of Ro 4–6270 and amitriptyline in depressive illness. British Journal of Psychiatry, 113, 993–998.Google Scholar
Hanin, I. (1985) Cerebrospinal fluid levels of amitriptyline, nortriptyline, imipramine and desmethylimipramine. Journal of Affective Disorders, 9, 69–78.CrossRefGoogle Scholar
Healy, D., Carney, P. A. & Leonard, B. E. (1984) Biochemical correlates of antidepressant response. Results of a trazodone versus amitriptyline trial. Psychopathology, 17 (suppl. 2), 82–87.Google Scholar
Herceg, B. R. L., Prusoff, B. A. & Weissman, M. M. (1979) Pharmacotherapy and psychotherapy in acutely depressed patients: a study of attrition patterns in a clinical trial. Comprehensive Psychiatry, 20, 315–325.Google Scholar
Hoenig, J. & Visram, S. (1964) Amitriptyline versus imipramine in depressive psychoses. British Journal of Psychiatry, 110, 840–845.CrossRefGoogle ScholarPubMed
Hollister, L. E., Overall, J. E., Johnson, M., et al (1964) Controlled comparison of amitriptyline, imipramine and placebo in hospitalised depressed patients. Journal of Nervous and Mental Disease, 139, 370–375.Google Scholar
Horden, A., Holt, N. F., Burt, C. G., et al (1963) Amitriptyline in depressive states. Phenomenology and prognostic considerations. British Journal of Psychiatry, 109, 815–825.Google Scholar
Horden, A., Burt, C. G., Gordon, W. F., et al (1964) Amitriptyline in depressive states: six-month treatment results. British Journal of Psychiatry, 110, 641–647.Google Scholar
Hutchinson, J. T. & Smedberg, D. (1963) Treatment of depression: a comparative study of E.C.T. and six drugs. British Journal of Psychiatry, 109, 536–538.Google Scholar
Jakitowicz, J. (1991) The amitriptyline plasma level and therapeutic response in patients with affective illness. Psychiatria Polska, XXV, 13–20.Google Scholar
Katz, M. M., Koslow, S. H., Maas, J. W., et al (1987) The timing, specificity and clinical prediction of tricyclic drug effects in depression. Psychological Medicine, 17, 297–309.Google Scholar
Katz, R. J., Lott, M., Landau, P., et al (1993) A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant. Biological Psychiatry, 33, 261–266.CrossRefGoogle ScholarPubMed
Kieback, D. (1982a) Vergleich der Hamilton Rating Scale for depression (HRS) mit der v. Zerssen-Befindlichkeitsskala (BS) am Beispiel einer klinischen profung von trazodon versus amitriptylin. Pharmacopsychiatry, 15, 97–101.CrossRefGoogle Scholar
Kieback, D. (1982b) Zur problematik psychologischer testverfahren in der pharmakopsychiatrie. Pharmacopsychiatry, 15, 175–180.Google Scholar
Kiloh, L. G., Ball, J. R. & Garside, R. F. (1962) Prognostic factors in treatment of depressive states with imipramine. British Medical Journal, 1, 1225–1227.Google Scholar
Klein, R. G., Mannuzza, S., Koplewicz, H. S., et al (1998) Adolescent depression: controlled desimipramine treatment and atypical features. Depression and Anxiety, 7, 15–31.Google Scholar
Koch, H. (1990) Steady-state plasma levels during antidepressant therapy with amitriptyline and amitriptylinoxide. Israel Journal of Psychiatry and Related Sciences, 27, 48–56.Google Scholar
Kocsis, J. H. (1990) Response to treatment with antidepressants of patients with severe or moderate nonpsychotic depression and of patients with psychotic depression. American Journal of Psychiatry, 147, 621–624.Google Scholar
König, W., Heinrich, T. & Diehl, B. (1994) A double-blind comparison of amitriptylinoxide versus doxepine in the treatment of severe depression. Progress in Neuropsychopharmacology and Biological Psychiatry, 18, 491–496.Google Scholar
Kopera, H. (1980) Cardiac effects of mianserin: results of clinical pharmacological investigations. Current Medical Research and Opinion, 6 (suppl. 7), 36–43.Google Scholar
Koszewska, I., Beresewicz, M., Puzynski, S., et al (1994) Psychotropic profile of essential antidepressants (amitriptyline, imipramine, desimipramine, chlorimipramine). Psychiatria Polska, XXVIII, 27–38.Google Scholar
Kowalski, A., Stanley, R. O., Dennerstein, L., et al (1985) The sexual side-effects of antidepressant medication: a double-blind comparison of two antidepressants in a non-psychiatric population. British Journal of Psychiatry, 147, 413–418.Google Scholar
Krakowski, A. J. (1968) Activity study of doxepin. A new antidepressant. Psychosomatics, 9, 89–95.Google Scholar
Kramer, M. S., Vogel, W. H., DiJohnson, C., et al (1989) Antidepressants in depressed schizophrenic inpatients. A controlled trial. Archives of General Psychiatry, 46, 922–928.Google Scholar
Kupfer, D. J., Hanin, I., Spiker, D. G., et al (1977) Amitriptyline plasma levels and clinical response in primary depression. Clinical Pharmacology and Therapeutics, 22, 904–911.CrossRefGoogle ScholarPubMed
Kupfer, D. J., Coble, P. A. & Rubinstein, D. (1979) Changes in weight during treatment for depression. Psychosomatic Medicine, 41, 535–544.Google Scholar
Kuss, H. J., Jungkunz, G. & Holsboer, F. (1984) Amitriptyline: looking through the therapeutic window. Lancet, i, 464–465.CrossRefGoogle Scholar
Lambourn, J. & Rees, J. A. (1974) A general practitioner study of dothiepin and amitriptyline. Journal of International Medical Research, 2, 210–213.CrossRefGoogle Scholar
Leyburn, P. (1967) A critical look at antidepressant drug trial. Lancet, ii, 1135–1137.Google Scholar
Liisberg, P., Mose, H., Amdisen, A., et al (1978) A clinical trial comparing sustained release amitriptyline and conventional amitriptyline tablets in endogenously depressed patients with simultaneous determination of serum levels of amitriptyline and nortriptyline. Acta Psychiatrica Scandinavica, 57, 426–435.Google Scholar
Lloyd, C., Zisook, S., Click, M., et al (1981) Life events and response to antidepressants. Journal of Human Stress, 7, 2–15.Google Scholar
Lyons, J. S., Rosen, A. J. & Dysken, M. W. (1985) Behavioural effects of tricyclic drugs in depressed inpatients. Journal of Consulting and Clinical Psychology, 53, 17–24.Google Scholar
Maier, W., Philipp, M., Schlegel, S., et al (1989) Diagnostic determinants of response to treatment with tricyclic antidepressants: a polydiagnostic approach. Psychiatry Research, 30, 83–93.Google Scholar
Marey, C., Ganry, H., Delalleau, B., et al (1991) Effects thérapeutiques de la tianeptine chez les patients déprimés et anxieux avec ou sans alcoolisme associé. Presse Médicale, 20, 1828–1836.Google Scholar
Marjerrison, G., Deza, P. C. & Silzer, J. C. K. (1969) Verbal behaviour changes with depression treatment. Canadian Psychiatric Association Journal, 14, 503–508.Google Scholar
Martin, I. C. A. & Leahy, M. R. (1968) Prediction in anti-depressant therapy. British Journal of Psychiatry, 114, 1289–1291.Google Scholar
Mathur, G. N. (1975) A double-blind comparative clinical trial of maprotiline and amitriptyline. Journal of International Medical Research, 3 (suppl. 2), 71–74.Google Scholar
Mattila, M. J., Liljequist, R. & Seppala, T. (1978) Effects of amitriptyline and mianserin on psychomotor skills and memory in man. British Journal of Clinical Pharmacology, 5, 53S–55S.CrossRefGoogle ScholarPubMed
McConaghy, N. & Joffe, A. D. (1968) Correlation of clinical features of depressed out-patients with response to amitriptyline and protriptyline. British Journal of Psychiatry, 114, 103–106.Google Scholar
McNair, D. M., Kahn, R. J., Frankenthal, L. M., et al (1984a) Amoxapine and amitriptyline. I. Relative speed of antidepressant action. Psychopharmacology, 83, 129–133.Google Scholar
McNair, D. M., Kahn, R. J., Frankenthal, L. M., et al (1984b) Amoxapine and amitriptyline. II. Specificity of cognitive effects during brief treatment of depression. Psychopharmacology, 83, 134–139.Google Scholar
Mindham, R. H. S. (1981) Continuation therapy with tricyclic antidepressants in relapsing depressive illness. Bibliotheca Psychiatrica, 160, 49–55.Google Scholar
Montgomery, S., Cronholm, B., Åsberg, M., et al (1978) Differential effects on suicidal ideation of mianserin, maprotiline and amitriptyline. British Journal of Clinical Pharmacology, 5, 77S–80S.Google Scholar
Moyes, I. C. A., Ray, R. L. & Moyes, R. B. (1980) Plasma levels and clinical improvement – a comparative study of clomipramine and amitriptyline in depression. Postgraduate Medical Journal, 56 (suppl. 1), 127–129.Google Scholar
Muck-Seler, D., Jakovljevic, M. & Deanovic, Z. (1991) Effect of antidepressant treatment on platelet 5-HT content and relation to therapeutic outcome in unipolar depressive patients. Journal of Affective Disorders, 23, 157–164.Google Scholar
Murphy, J. E. (1975) A double-blind general practice trial of maprotiline (Ludiomil) against amitriptyline in the treatment of reactive depression. Journal of International Medical Research, 3 (suppl. 2), 97–100.Google Scholar
Myers, E. D. & Branthwaite, A. (1992) Out-patient compliance with antidepressant medication. British Journal of Psychiatry, 160, 83–86.Google Scholar
Myers, E. D. & Calvert, E. J. (1976) The effect of forewarning on the occurrence of side-effects and discontinuance of medication in patients on dothiepin. Journal of International Medical Research, 4, 237–240.Google Scholar
Nahunek, K., Bartova, D. & Ingrova, L. (1964) Endogenic depressive states treated with prothiaden. Activitas Nervosa Superiora (Praha), 4, 178–179.Google Scholar
Oliver-Martin, R., Marzin, D., Buschsenschutz, E., et al (1975) Concentrations plasmatiques de l'imipramine et de la desmethylimipramine et effet antidepresseur au cours d'un traitement côntrole. Psychopharmacologia, 41, 187–195.CrossRefGoogle Scholar
Oltman, J. E. & Friedman, S. (1963) Evaluation of nortriptyline in the treatment of affective disorders (and comparison with other drugs). American Journal of Psychiatry, 120, 988–989.Google Scholar
Oltman, J. E. & Friedman, S. (1964) Factors influencing results with antidepressant drugs. American Journal of Psychiatry, 121, 895–897.CrossRefGoogle Scholar
Ose, E. (1971) Et kontrollert klinsk forsok med det nye antidepressivum noxiptilin sammenlignet med amitriptylin. Nordisk Psykiatrisk Tidsskrift, 25, 382–390.CrossRefGoogle Scholar
Pearce, J. B. & Rees, W. L. (1974) A double-blind comparison of three times daily and single night dosage of the tricyclic anti-depressant dothiepin. Journal of International Medical Research, 2, 12–19.Google Scholar
Peet, M. Tienari, P. & Jaskari, M. O. (1977) A comparison of the cardiac effects of mianserin and amitriptyline in man. Pharmacopsychiatry, 10, 309–312.Google Scholar
Pennese, F., Palombo, V., Scurti, R., et al (1993) Post-stroke depression: predictable factors to therapy outcome in a clinical trial comparing dothiepin to amitriptyline. Giornale di Gerontologia, 41, 353–358.Google Scholar
Peselow, E. D., Goldring, N., Stanley, M., et al (1986) The dexamethasone suppression test (DST) in predicting response to desipramine and amitriptyline in depressed outpatients. International Clinical Psychopharmacology, 1, 17–23.Google Scholar
Petrie, W. M., Wilson, W. H., Ban, T. A., et al (1980) Mianserin: determination of therapeutic dose range. International Pharmacopsychiatry, 15, 111–117.Google Scholar
Post, R. M. & Goodwin, F. K. (1974) Effects of amitriptyline and imipramine on amine metabolites in the cerebrospinal fluid of depressed patients. Archives of General Psychiatry, 30, 234–239.CrossRefGoogle ScholarPubMed
Preskorn, S. H., Othmer, S. C., Lai, C. W., et al (1984) Tricyclic-induced electroencephalogram abnormalities and plasma drug concentrations. Journal of Clinical Psychopharmacology, 4, 262–264.Google Scholar
Pressman, M. D. & Weiss, L. B. (1961) Experiences with elavil: treatment of fifty-one cases of depression. American Journal of Psychiatry, 118, 74–75.Google Scholar
Prusoff, B. A., Weissman, M. M., Tanner, J., et al (1976) Symptom reduction in depressed outpatients treated with amitriptyline or maprotiline: repeated measurement analysis. Comprehensive Psychiatry, 17, 749–754.Google Scholar
Pugh, R. (1983) An association between hostility and poor adherence to treatment in patients suffering from depression. British Journal of Medical Psychology, 56, 205–208.Google Scholar
Rajotte, P., Bordeleau, J. M., Tetreault, L., et al (1966) A double-blind comparative study of opipramol and amitriptyline in neurotic and endogenous depressions. Canadian Psychiatric Association Journal, 11 (suppl.), 159–168.Google Scholar
Rao, M. L., Ruhrmann, S., Retey, B., et al (1996) Low plasma thyroid indices of depressed patients are attenuated by antidepressant drugs and influence treatment outcome. Pharmacopsychiatry, 29, 180–186.Google Scholar
Rechlin, T. (1994) The effect of amitriptyline, doxepin, fluvoxamine, and paroxetine treatment on heart rate variability. Journal of Clinical Psychopharmacology, 14, 392–395.Google Scholar
Rees, J. A. & Risdall, P. C. (1976) An evaluation of a once daily dosage regime of dothiepin hydrochloride. Journal of International Medical Research, 4, 319–325.Google Scholar
Reisby, N. (1977) Imipramine: clinical effects and pharmacokinetic variability. Psychopharmacology, 54, 263–272.Google Scholar
Renfordt, E. & Bush, H. (1976) Neue Strategien psychiatrischer urteilsbildung durch anwendung audiovisueller techniken. Pharmakopsychiatrie Nevropsychopharmakologie, 9, 67–75.Google Scholar
Reynolds, E., Craggs, D. F., Joyston-Bechal, M. P., et al (1969) Physicians' preferences in a blind trial of imipramine and amitriptyline. British Journal of Psychiatry, 115, 1175–1179.CrossRefGoogle Scholar
Rickels, K., Csanalosi, I., Chung, H. R., et al (1974) Amitriptyline in anxious–depressed outpatients: a controlled study. American Journal of Psychiatry, 131, 25–30.Google Scholar
Robinson, D. S., Cooper, T. B., Howard, D., et al (1985) Amitriptyline and hydroxylated metabolite plasma levels in depressed outpatients. Journal of Clinical Psychopharmacology, 5, 83–88.Google Scholar
Robinson, S., Dasberg, H. & Winnik, H. Z. (1972) Clinical and electroencephalographic effects of anafranil treatment in depression. Diseases of the Nervous System, 33, 268–272.Google Scholar
Rockliff, B. W. (1971) Measurements of drug effects in newly hospitalised depressives. Diseases of the Nervous System, 32, 532–537.Google Scholar
Rouillon, F., Phillips, R., Serrurier, D., et al (1989) Recurrence of unipolar depression and efficacy of maprotiline. Encephale, 15, 527–534.Google ScholarPubMed
Rydzynski, Z. (1966) Badania nad wlasnosciami przeciwdepresyjnymi prothiadenu. Neurologia, Neurochirurgia I Psychiatria Polska, XVI, 1159–1162.Google Scholar
Saletu, B., Marx, B., Grunberger, J., et al (1979) Double-blind clinical and psychological test investigations in depressed out-patient with mianserin and Limbitrol. Excerpta Medica ICS, 462, 8–18.Google Scholar
Sanger, M. D. (1969) The treatment of anxiety and depression in the allergic patient. Annals of Allergy, 25, 506.Google Scholar
Schweizer, E. (1993) The role of antidepressants in the treatment of generalised anxiety disorder (GAD). European Neuropsychopharmacology, 3, 213–214.Google Scholar
Simpson, G. M., Amin, M., Angus, J. W., et al (1972) Role of antidepressants and neuroleptics in the treatment of depression. Archives of General Psychiatry, 27, 337–345.Google Scholar
Sims, A. C. (1972) Trial of a sustained release form of amitriptyline in the treatment of depressive illness. British Journal of Psychiatry, 120, 65–67.Google Scholar
Snow, L. H. & Rickels, K. (1964) The controlled evaluation of imipramine and amitriptyline in hospitalised depressed psychiatric patients. Psychopharmacologia, 5, 409–416.Google Scholar
Stassen, H. H., Angst, J. & Delini-Stula, A. (1996) Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses. Pharmacopsychiatry, 29, 87–96.Google Scholar
Stjean, A., Ban, T. A. & Scott, J. (1966) The effect of proptriptyline–perphenazine combination in chronic psychiatric patients. Current Therapeutic Research, 8, 483–486.Google Scholar
Stratas, N. E. (1984) A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder. Journal of Clinical Psychiatry, 45, 466–469.Google Scholar
Stromberg, C., Suokas, A., Seppala, T., et al (1991) Echocardiographic and psychometric effects of amitriptyline or imipramine plus alcohol. European Journal of Clinical Pharmacology, 40, 349–354.CrossRefGoogle ScholarPubMed
Sullivan, J. L., Dackis, C. & Stanfield, C. (1977) In vivo inhibition of platelet MAO activity by tricyclic antidepressants. American Journal of Psychiatry, 134, 188–190.Google Scholar
Swann, A. C., Secunda, S. K., Stokes, P. E., et al (1990) Stress, depression, and mania: relationship between perceived role of stressful events and clinical and biochemical characteristics. Acta Psychiatrica Scandinavica, 81, 389–397.Google Scholar
Symes, M. H. (1967) Monochlorimipramine: a controlled trial of a new antidepressant. British Journal of Psychiatry, 113, 671–672.Google Scholar
Taragano, F. E., Lyketsos, C. G., Mangone, C. A., et al (1997) A double-blind, randomised, fixed-dose trial of fluoxetine vs. amitriptyline in the treatment of major depression complicating Alzheimer's disease. Psychosomatics, 38, 246–252.Google Scholar
Trick, K. L. K. (1975) Double-blind comparison of maprotiline with amitriptyline in the treatment of depressive illness. International Pharmacopsychiatry, 10, 193–198.Google Scholar
Van De Merwe, T. J., Silverstone, T., Ankier, S. I., et al (1984a) A double-blind non-crossover placebo-controlled study between group comparison of trazodone and amitriptyline on cardiovascular function in major depressive disorder. Psychophatology, 17 (suppl. 2), 64–76.Google Scholar
Van De Merwe, T. J., Silverstone, T., & Ankier, S. I., (1984b) Electrophysiological and haemodynamic changes with trazodone, amitriptyline and placebo in depressed outpatients. Current Medical Research Opinion, 9, 339–351.Google Scholar
Van Scheyen, J. D. & Van Kammen, D. P. (1979) Clomipramine-induced mania in unipolar depression. Archives of General Psychiatry, 36, 560–565.Google Scholar
Vartanyan, F. E. (1984) Effects of antidepressants in different populations. Farmakologie Toksicologie, 47, 13–17.Google Scholar
Veith, R. C., Bloom, V., Bielski, R., et al (1982) ECG effects of comparable plasma concentration of desimipramine and amitriptyline. Journal of Clinical Psychopharmacology, 2, 394–398.Google Scholar
Vinar, O. & Grof, P. (1964) Clinical experience with prothiadene. Activitas Nervosa Superiora (Praha), 6, 179–180.Google Scholar
Vogel, H. P., Bente, D., Feder, J., et al (1976) Mianserin versus amitriptyline. A double-blind trial evaluated by the AMP system. International Pharmacopsychiatry, 11, 25–31.Google Scholar
Von Arnold, O. H. & Foitl, G. (1961) Die behandlung der endogenen depression mit amitriptyline. Wiener Medizinische Wochenschrift, 16, 272–274.Google Scholar
Von Arnold, O. H. & Heves, H. P. (1967) Die behandlung der endogenen depression mit monochlorimipramin. Wiener Medizinische Wochenschrift, 79, 3–6.Google Scholar
Von Bergener, M. (1968) Klinische prufung antidepressiv wirksamer substanzen im döppelblindversuch. Arzneimittel Forschung, 18, 245–249.Google Scholar
Von Plavec, J. & Steininger, E. (1968) Protriptylin in klinischer und ambulanter anwendung bei verschiedenen formen der depression. Wiener Medizinische Wochenschrift, 118, 983–985.Google Scholar
Von Rosenberg, L. (1974) Döppelblindprufung von drei antidepressiva. Arzneimittel Forschung, 24, 207–213.Google Scholar
Weiss, L. B. & Pressman, M. D. (1961) A comparison of imipramine and amitriptyline in the treatment of depression. Psychosomatics, 2, 293–296.Google Scholar
Weissman, M. M. (1976) Some problems in clinical trials of new antidepressant agents. A. Issues in the evaluation of new drugs: a double-blind trial of maprotiline and amitriptyline in outpatient depressives. In Depression (ed. Gallant, D. M.), pp. 233–250. New York: Spectrum Publications.Google Scholar
Welner, A., Welner, Z. & Robins, E. (1980) Effect of tricyclic antidepressants on individual symptoms. Journal of Clinical Psychiatry, 41, 306–309.Google Scholar
Wheatley, D. (1967) Influence of doctors‘ and patients’ attitudes in the treatment of neurotic illness. Lancet, 2, 1133–1135.Google Scholar
Wilkins, J. N., Spar, J. E. & Carlson, H. E. (1989) Desimipramine increases circulating growth hormone in elderly depressed patients: a pilot study. Psychoneuroendocrinology, 14, 195–202.Google Scholar
Wilson, I. (1963) A controlled study of treatment of depression. Journal of Neuropsychiatry, 4, 331–337.Google Scholar
Wittenborn, J. R., Kiremitci, N. & Weber, E. P. (1973) The choice of alternative antidepressants. Journal of Nervous and Mental Disease, 156, 97–108.Google Scholar
Yamamoto, J., Kline, F. M. & Burgoyne, R. W. (1972) Double-blind drug study in depressed outpatients. Rocky Mountain Medical Journal, 69, 71–74.Google Scholar
Randomised controlled trials included in the meta-analysis Google Scholar
Aberg, A. & Holmberg, G. (1977) Controlled trial of a new antidepressive, amoxapine, in comparison with amitriptyline. Current Therapeutic Research, 22, 304–315.Google Scholar
Altamura, A. C., Mauri, M. C. & Rudas, N., et al (1989a) Clinical activity and tolerability of trazodone, mianserin, and amitriptyline in elderly subjects with major depression: a controlled multicenter trial. Clinical Neuropharmacology, 12 (suppl. 1), S25–S33.Google Scholar
Altamura, A. C., De Novellis, F., Guercetti, G., et al (1989b) Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial. International Journal of Clinical Pharmacology Research, 9, 391–396.Google Scholar
Amin, M. M., Brahm, E., Bronheim, L. A., et al (1973) A double-blind, comparative clinical trial with Ludiomil (CIBA 34,276–Ba) and amitriptyline in newly admitted depressed patients. Current Therapeutic Research, 15, 691–699.Google Scholar
Amin, M. M., Cooper, R., Khalid, R., et al (1978) A comparison of desipramine and amitriptyline plasma levels and therapeutic response. Psychopharmacology Bulletin, 14, 45–46.Google Scholar
Anderson, J., Lambert, N. G. & Pigott, P. V. (1972) An evaluation of fluphenazine with nortriptyline in anxiety and depression. Practitioner, 208, 511–517.Google Scholar
Anton, R. & Burch, E. A. (1990) Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression. American Journal of Psychiatry, 147, 1203–1208.Google Scholar
Ather, S. A., Ankier, S. I. & Middleton, R. S. W. (1985) A double-blind evaluation of trazodone in the treatment of depression in the elderly. British Journal of Clinical Practice, 39, 192–199.Google Scholar
Balestrieri, A., Benassi, P., Cassano, G. B., et al (1971) Clinical comparative evaluation of maprotiline, a new antidepressant drug. International Pharmacopsychiatry, 6, 236–248.Google Scholar
Bascara, B. (1989) A double-blind study to compare the effectiveness and tolerability of paroxetine and amitriptyline in depressed patients. Acta Psychiatrica Scandinavica, 80 (suppl. 350), 141–142.Google Scholar
Battegay, R., Hager, M. & Rauchfleisch, U. (1985) Double-blind comparative study of paroxetine and amitriptyline in depressed patients of a university psychiatric outpatient clinic. Neuropsychobiology, 13, 31–37.Google Scholar
Beaini, A. Y., Hindmarch, I., Snaith, R. P. (1980) A re-examination of the clinical effects of imipramine and amitriptyline in depressive illness. Journal of Affective Disorders, 2, 89–94.Google Scholar
Beckmann, H. & Goodwin, F. K. (1975) Antidepressant response to tricyclics and urinary MHPG in unipolar patients. Archives of General Psychiatry, 32, 17–21.Google Scholar
Bennie, E. H. & Schiff, A. A. (1976) A comparison of amitriptyline and fluphenazine/nortriptyline preparation in anxiety-depressive states. Scottish Medical Journal, 21, 204–209.Google Scholar
Bersani, G., Rapisarda, V., Ciani, N., et al (1994) A double-blind comparative study of sertraline and amitriptyline in outpatients with major depressive episodes. Human Psychopharmacology, 9, 63–68.Google Scholar
Bianchi, G. N., Barr, R. F. & Kiloh, L. G. (1971) A comparative trial of doxepin and amitriptyline in depressive illness. Medical Journal of Australia, 1, 843–846.Google Scholar
Bignamini, A. & Rapisarda, V. (1992) A double-blind multicentre study of paroxetine and amitriptyline in depressed outpatients. International Clinical Psychopharmacology, 6 (suppl. 4), 37–41.Google Scholar
Blacker, R., Shanks, N. J., Chapman, N., et al (1988) The drug treatment of depression in general practice: a comparison of nocte administration of trazodone with mianserin, dothiepin and amitriptyline. Psychopharmacology, 95, S18–S24.Google Scholar
Botros, W. A., Ankier, S. J., Priest, R. G., et al (1989) Clinical assessment and performance tasks in depression: a comparison of amitriptyline and trazodone. British Journal of Psychiatry, 155, 479–482.Google Scholar
Browne, M. W. (1969) A comparison of two drug treatments in depressive illness. British Journal of Psychiatry, 115, 693–696.Google Scholar
Burke, B. V., Sainsbury, M. J. & Mezo, B. A. (1967) A comparative trial of amitriptyline and trimipramine in the treatment of depression. Medical Journal of Australia, 1, 1216–1218.Google Scholar
Burrows, G., Norman, T. R. & Davies, B. M. (1980) A comparative study of amoxapine and amitriptyline for depressive illness. Australian Family Physician, 9, 762–766.Google Scholar
Burt, C. G., Gordon, W. F., Holt, N. F., et al (1962) Amitriptyline in depressive states: a controlled trial. Journal of Mental Science, 108, 711–729.Google Scholar
Byrne, M. M. (1989) Meta-analysis of early Phase II studies with paroxetine in hospitalized depressed patients. Acta Psychiatrica Scandinavica, 80 (suppl. 350), 138–139.Google Scholar
Carman, J. S., Ahdieh, H., Wyatt-Knowles, E., et al (1991) A controlled study of mianserin in moderately to severely depressed outpatients. Psychopharmacology Bulletin, 27, 135–139.Google Scholar
Carney, P. A., Healy, D. & Leonard, B. E. (1984) A double-blind study to compare trazodone with amitriptyline in depressed patients. Psychopathology, 17 (suppl. 2), 37–38.Google Scholar
Chouinard, G. (1985) A double-blind controlled trial of fluoxetine and amitriptyline in the treatment of outpatients with major depression. Journal of Clinical Psychiatry, 46, 32–37.Google Scholar
Christiansen, P. E., Behnke, K., Black, C. H., et al (1996) Paroxetine and amitriptyline in the treatment of depression in general practice. Acta Psychiatrica Scandinavica, 93, 158–163.Google Scholar
Click, M. A. & Zisook, S. (1982) Amoxapine and amitriptyline: serum levels and clinical response in patients with primary unipolar depression. Journal of Clinical Psychiatry, 43, 369–371.Google Scholar
Cohn, C. K., Shrivastava, R., Mendels, J., et al (1990) Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. Journal of Clinical Psychiatry, 51 (suppl. B), 28–33.Google Scholar
Cournoyer, G., de Montigny, C., Quellette, J., et al (1987) A comparative double-blind controlled study of trimipramine and amitriptyline in major depression: lack of correlation with 5-hydroxytryptamine reuptake blockade. Journal of Clinical Psychopharmacology, 7, 385–393.Google Scholar
Dahl, L. E., Dencker, S. J. & Lundin, L. (1981) A double-blind study of dothiepin hydrochloride (Prothiaden) and amitriptyline in outpatients with masked depression. Journal of International Medical Research, 9, 103–107.Google Scholar
Daly, R. J. & Browne, P. J. (1979) Mianserin in the treatment of depressive illness: a comparison with amitriptyline. Irish Journal of Medical Science, 148, 145–148.Google Scholar
De Ronchi, D., Rucci, P., Lodi, M., et al (1998) Fluoxetine and amitriptyline in elderly depressed patients. A 10-week, double-blind study on course of neurocognitive adverse events and depressive symptoms. Archives of Gerontology and Geriatrics, 6 (suppl.), 125–140.Google Scholar
Deering, R. B. & Vallè-Jones, J. C. (1974) A general practitioner double-blind study of dothiepin hydrochloride (‘Prothiaden’) and amitriptyline in depression. Current Medical Research Opinion, 2, 471–473.Google Scholar
Del Zompo, M., Bernardi, F., Burrai, C., et al (1990–91) A double-blind study of minaprine versus amitriptyline in major depression. Neuropsychobiology, 24, 79–83.Google Scholar
Delaunay, J. & Meynard, J. (1978) Essai clinique et comparatif de la dosulepine et de lamitriptyline. Annales Medico-Psycholigique, 136, 1201–1207.Google Scholar
Dell, A. J. (1977) A comparison of maprotiline and amitriptyline. Journal of International Medical Research, 5 (suppl. 4), 22–24.Google Scholar
Demyttenaere, K., Van Ganse, E., Gregoire, J., et al (1998) Compliance in depressed patients treated with fluoxetine or amitriptyline. International Clinical Psychopharmacology, 13, 11–17.Google Scholar
Donlon, P., Biertuemphel, H. & Willenbring, M. (1981) Amoxapine and amitriptyline in the outpatient treatment of endogenous depression. Journal of Clinical Psychiatry, 42, 11–15.Google Scholar
Doongaji, D. R., Bal, S., Rajkumar, S., et al (1993) Multicentre double-blind comparison of lofepramine and amitriptyline in the treatment of major depressive disorders in Indian patients. British Journal of Clinical Research, 4, 45–53.Google Scholar
Dorman, T. (1980) Clinical trial comparison of a sustained release form of amitriptyline with dothiepin. Journal of International Medical Research, 8, 286–292.Google Scholar
Dorn, M. (1980) Psychopharmaka in der praxis. Döppelblindprufung lofepramin gegen amitriptylin. Zeitschrift für Allgemeinmedizin, 56, 133–139.Google Scholar
Edwards, J. G., Dinan, T. G., Waller, D. G., et al (1996) Double-blind comparative study of the antidepressant, unwanted and cardiac effects of minaprine and amitriptyline. British Journal of Clinical Pharmacology, 42, 491–498.Google Scholar
Fawcett, J., Zajecka, J. & Kravitz, H. (1989) Fluoxetine vs amitriptyline in adult inpatients with major depression. Current Therapeutic Research, 45, 821–832.Google Scholar
Feighner, J. P., Jacobs, R. S., Jackson, R. E., et al (1983) A double-blind comparative trial with mianserin and amitriptyline in outpatients with major depressive disorders. British Journal Clinical Pharmacology, 15, 227S–237S.Google Scholar
Ferrari, G., Berardi, D., Berlinzani, L., et al (1987) A double-blind comparative trial with viloxazine and amitriptyline in inpatients with major non-psychotic depressive disorders. Current Therapeutic Research, 42, 1088–1095.Google Scholar
Forrest, A. D., Affleck, J. W., McGibb, I. A., et al (1964) Comparative trial of nortriptyline and amitriptyline. Scottish Medical Journal, 9, 341–344.Google Scholar
Forrest, A. W. (1975) A comparison between daily and nightly dose regimen of amitriptyline and maprotiline (Ludiomil) in the treatment of reactive depression in general practice. Journal of International Medical Research, 3 (suppl. 2), 120–125.Google Scholar
Fruensgaard, K., Hansen, C. E., Korsgaard, S., et al (1979) Amoxapine versus amitriptyline in endogenous depression. A double-blind study. Acta Psychiatrica Scandinavica, 59, 502–508.Google Scholar
Gasperini, M., Gatti, F., Bellini, L., et al (1992) Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. Neuropsychobiology, 26, 186–192.Google Scholar
Geretsegger, C., Stuppaeck, C. H., Mair, M., et al (1995) Multicentre double-blind study of paroxetine and amitriptyline in elderly depressed inpatients. Psychopharmacology, 119, 277–281.Google Scholar
Goldberg, H. L. & Finnerty, R. J. (1977) Which tricyclic for depressed outpatients, imipramine pamoate or amitriptyline? Disorders of the Nervous System, 38, 785–789.Google Scholar
Goldberg, H. L. & Finnerty, R. J. (1980) Trazodone in the treatment of neurotic depression. Journal of Clinical Psychiatry, 41, 430–434.Google Scholar
Goldstein, B. J. & Pinosky, D. G. (1969) Clinical evaluation of doxepin in anxious depressed outpatients. Current Therapeutic Research, 11, 169–177.Google Scholar
Gomez-Martinez, I. (1968) Preliminary double-blind clinical trial with a new antidepressive doxepin. Current Therapeutic Research, 10, 116–118.Google Scholar
Gravem, A., Amthor, K. F., Astrup, C., et al (1987) A double-blind comparison of citalopram (Lu 10–171) and amitriptyline in depressed patients. Acta Psychiatrica Scandinavica, 75, 78–86.Google Scholar
Grof, P., Saxena, B., Cantor, R., et al (1974) Doxepin versus amitriptyline in depression: a sequential double-blind study. Current Therapeutic Research, 16, 470–476.Google Scholar
Grof, P., Saxena, B., Daigle, L., et al (1977) Dopaminergic agonist nomifensine compared with amitriptyline: a double-blind clinical trial in acute primary depressions. British Journal of Clinical Pharmacology, 4, 221S–225S.Google Scholar
Guelfi, J. D., Pichot, P. & Dreyfus, J. F. (1989) Efficacy of tianeptine in anxious–depressed patients: results of a controlled multicentre trial versus amitriptyline. Neuropsychobiology, 22, 41–48.Google Scholar
Guy, W., McEvoy, J. M., Ban, T. A., et al (1983) A double-blind clinical trial of mianserin versus amitriptyline: differentiation by adverse symptomatology. Pharmacotherapy, 3, 45–51.Google Scholar
Harding, T. (1973) A comparative clinical trial of oral clomipramine (Anafranil) against amitriptyline. Journal of International Medical Research, 1, 343–346.Google Scholar
Harris, B., Szujelecka, T. K. & Anstee, J. A. (1991) Fluvoxamine versus amitriptyline in depressed hospital out-patients: a multicentre double blind comparative trial. British Journal of Clinical Research, 2, 89–99.Google Scholar
Hekimian, L. J., Friedhoff, A. J. & Deever, E. (1978) A comparison of the onset of action and therapeutic efficacy of amoxapine and amitriptyline. Journal of Clinical Psychiatry, 30, 633–637.Google Scholar
Hutchinson, D. R., Tong, S., Moon, C. A., et al (1992) Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline. International Clinical Psychopharmacology, 6 (suppl. 4), 43–51.Google Scholar
Invenizzi, G., Aguglia, E., Bertolino, A., et al (1994) The efficacy and safety of tianeptine in the treatment of depressive disorder: results of a controlled double-blind multicentre study vs. amitriptyline. Neuropsychobiology, 30, 85–93.Google Scholar
James, B. (1982) A double-blind comparative clinical study of amoxapine and amitriptyline in depressed, hospitalised patients. New Zealand Medical Journal, 95, 391–393.Google Scholar
Jaskari, M. O., Ahlfors, U. G., Ginman, L., et al (1977) Three double-blind comparative trials of mianserine (ORG GB 94) and amitriptyline in the treatment of depressive illness. Pharmacopsychiatry, 10, 101–103.Google Scholar
Jessel, H. J., Jessel, I. & Wegener, G. (1981) Therapie von alterendepressiven patienten. Lofepramin und amitriptylin unter döppelblindbedingungen. Zeitschrift für Allgemeinmedizin, 57, 784–788.Google Scholar
Judd, F. K., Moore, K., Norman, T. R., et al (1993) A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness. Australian and New Zealand Journal of Psychiatry, 27, 49–55.Google Scholar
Kamijima, K., Koyama, T., Mita, T., et al (1997) Clinical evaluation of sertraline hydrochloride, a selective serotonin reuptake inhibitor in the treatment of depression and depressive state: A double-blind, group comparison study of sertraline by hydrochloride vs amitriptyline hydrochloride. Japanese Journal of Neuropsychopharmacology, 19, 529–548.Google Scholar
Kampman, R., Nummikko-Pelkonen, A. & Kuha, S. (1978) Tricyclic antidepressants in the treatment of depression. Acta Psychiatrica Scandinavica, 58, 142–148.Google Scholar
Kaumier, H. S. & Haase, H. J. (1980) A double-blind comparison between amoxapine and amitriptyline in depressed in-patients. International Journal of Clinical Pharmacology Therapy and Toxicology, 18, 177–184.Google Scholar
Kay, N. & Davies, B. (1974) A controlled trial of maprotiline (Ludiomil) and amitriptyline in general practice. Medical Journal of Australia, 1, 704–705.Google Scholar
Keegan, D., Bowen, R. C., Blackshaw, S., et al (1991) A comparison of fluoxetine and amitriptyline in the treatment of major depression. International Clinical Psychopharmacology, 6, 117–124.Google Scholar
Kerr, T. A., McClelland, H. A., Stephens, D. A., et al (1984) Trazodone. A comparative clinical and predictive study. Acta Psychiatrica Scandinavica, 70, 573–577.Google Scholar
Khan, A. U. (1981) A comparison of the therapeutic and cardiovascular effects of a single nightly dose of Prothiaden (dothiepin, dosulepin) and Lentizol (sustained-release amitriptyline) in depressed elderly patients. Journal of International Medical Research, 9, 108–112.Google Scholar
Khan, M. C., Ancill, R. J. & Davey, A. (1982) Treatment of severe depressive illness: a double-blind comparison of mianserin and long-acting amitriptyline. British Journal of Clinical Practice, 36, 240–242.Google Scholar
Kiloh, L. G., Bartrop, R. W., Franklin, J. A., et al (1979) A double-blind comparative trial of viloxazine and amitriptyline in patients suffering from endogenous depression. Australian and New Zealand Journal of Psychiatry, 13, 357–360.Google Scholar
Klieser, E. & Lehmann, E. (1988) Experimental comparison between the effect of standardised trazodone–amitriptyline and placebo treatment in vitalised depressive patients. Psychopharmacology, 95, S3–S5.Google Scholar
Kline, N. S. (1982) A controlled comparison of trimipramine and amitriptyline. Journal of Clinical Psychiatry, 43, 100–104.Google Scholar
Kocsis, J. H., Hanin, I., Bowden, C., et al (1986) Imipramine and amitriptyline plasma concentrations and clinical response in major depression. British Journal of Psychiatry, 148, 52–57.Google Scholar
Kuhs, H. & Rudolf, G. A. E. (1989) A double-blind study of the comparative antidepressant effect of paroxetine and amitriptyline. Acta Psychiatrica Scandinavica, 80 (suppl. 350), 145–146.Google Scholar
Kyle, C. J., Petersen, H. E. H. & Overo, K. F. (1998) Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Depression and Anxiety, 8, 147–153.Google Scholar
Laakmann, G. (1991) Selective re-uptake-hemmung und ihre bedeutung für die depression. Berlin: Springer-Verlag.Google Scholar
Laakmann, G., Blaschke, D., Engel, R., et al (1988) Fluoxetine vs amitriptyline in the treatment of depressed out-patients. British Journal of Psychiatry, 153 (suppl. 3), 64–68.Google Scholar
Lapierre, Y. D., Sussman, P. & Ghadirian, A. (1980) Differential antidepressant properties of trazodone and amitriptyline in agitated and retarded depression. Current Therapeutic Research, 28, 845–854.Google Scholar
Lauritsen, B. J. & Madsen, H. (1974) A multinational, double-blind trial with a new antidepressant maprotiline (Ludiomil) and amitriptyline. Acta Psychiatrica Scandinavica, 50, 192–201.Google Scholar
Laursen, A. L., Mikkelsen, P. L. & le Fievre Honore, P. (1985) Paroxetine in the treatment of depression – a randomised comparison with amitriptyline. Acta Psychiatrica Scandinavica, 71, 249–255.Google Scholar
Leahy, M. R. & Martin, I. C. A. (1967) Double-blind comparison of nortriptyline and amitriptyline in depressive illness. British Journal of Psychiatry, 113, 1433–1434.Google Scholar
Lehmann, L. S., Bowden, C. L., Redmont, F. C., et al (1982) Amitriptyline and nortriptyline response profiles in unipolar depressed patients. Psychopharmacology, 77, 193–197.Google Scholar
Lennox, I. G., Asbury, J. F. P., Couldrick, W. G. R., et al (1978) Viloxazine and amitriptyline in depressive illness. A double-blind controlled trial in general practice. Practitioner, 220, 153–156.Google Scholar
Levin, A. (1974) Maprotiline and amitriptyline in the treatment of depressive illness. A double-blind comparison. South African Medical Journal, 48, 47–49.Google Scholar
Lipsedge, M. S. & Rees, W. L. (1971) A double-blind comparison of dothiepin and amitriptyline for the treatment of depression with anxiety. Psychopharmacologia, 19, 153–162.Google Scholar
Loga, S., Milovanovic, D. & Eric, L. J. (1992) A double-blind, parallel-group comparative study of dothiepin and amitriptyline in the treatment of depression in a Yugoslavian population. Journal of Drug Development, 4, 213–218.Google Scholar
Loo, H., Malka, R., Defrance, R., et al (1988) Tianeptine and amitriptyline. Controlled double-blind trial in depressed alcoholic patients. Neuropsychobiology, 19, 79–85.Google Scholar
Lopez-Ibor Alino, J. J., Ayuso Gutierrez, J. L., Montejo Iglesias, M. L., et al (1979) Estudio clínico comparativo entre el nomifensin y la amitriptilina en el tratamiento de la depresión endogena. Actas Luso Españolas de Neurología, Psiquiatría y Ciencias Afines, VII, 123–132.Google Scholar
Lydiard, R. B., Stahl, S. M., Hertzman, M., et al (1997) A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. Journal of Clinical Psychiatry, 58, 484–491.Google Scholar
Magnus, R. V. & Schiff, A. A. (1977) Once daily treatment for mixed anxiety/depressive states: a comparison of slow release amitriptyline and fluphenazine with nortriptyline. Journal of International Medical Research, 5, 109–113.Google Scholar
Marais, G. F. T. (1974) Clinical evaluation of the antidepressants maprotiline and amitriptyline. A double-blind controlled trial. South African Medical Journal, 48, 1530–1532.Google Scholar
Marchesi, C., Ceccherininelli, A., Rossi, A., et al (1998) Is anxious-agitated major depression responsive to fluoxetine? A double-blind comparison with amitriptyline. Pharmacopsychiatry, 31, 216–221.Google Scholar
Mariategui, J., Chavez, H. & Olivares, A. (1978) Lofepramina: estudio clinico comparativo con amitriptilina. Acta Psiquiatrica Psicologica América Latina, 24, 201–209.Google Scholar
Marneros, A. & Philipp, M. (1979) A double-blind trial with amitriptyline and lofepramine in the treatment of endogenous depression. International Pharmacopsychiatry, 14, 300–304.Google Scholar
Masco, H. L. & Sheetz, M. S. (1985) Double-blind comparison of fluoxetine and amitriptyline in the treatment of major depressive illness. Advance Therapy, 2, 275–284.Google Scholar
Mason, B. J., Kocsis, J. H., Frances, A. J., et al (1990) Amoxapine versus amitriptyline for continuation therapy of depression. Journal of Clinical Psychopharmacology, 10, 338–343.Google Scholar
McCallum, P. & Meares, R. (1975) A controlled trial of maprotiline (Ludiomil) in depressed outpatients. Medical Journal of Australia, 2, 392–394.Google Scholar
McClelland, H. A., Kerr, T. A., Stephens, D. A., et al (1979) The comparative antidepressant value of lofepramine and amitriptyline. Results of a controlled trial with comments on the scales used. Acta Psychiatrica Scandinavica, 60, 190–198.Google Scholar
McConaghy, N., Kingston, W. R., Stevenson, H. G., et al (1965) A controlled trial comparing amitriptyline and protriptyline in the treatment of out-patient depressives. Medical Journal of Australia, ii, 403–405.Google Scholar
Melo de Paula, A. J., Heckert, Y., Abizaid, W., et al (1977) Amoxapina e amitriptilina – Um estudio duplo-cego em pacientes deprimidos. Folha Médica, 75, 165–169.Google Scholar
Mendels, J. (1968) Comparative trial of nortriptyline and amitriptyline in 100 depressed patients. American Journal of Psychiatry, 124, 59–62.Google Scholar
Mendlewicz, J., Linkowski, P. & Rees, J. A. (1980) A double-blind comparison of dothiepin and amitriptyline in patients with primary affective disorder: serum levels and clinical response. British Journal of Psychiatry, 136, 154–160.Google Scholar
Mendlewicz, J., Pinder, R. M., Stulemeijer, S. M., et al (1982) Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline. Journal of Affective Disorders, 4, 219–226.Google Scholar
Metha, B. M., Spear, F. G. & Whittington, J. R. (1980) A double-blind controlled trial of mianserin and amitriptyline in depression. Current Medical Research Opinion, 7, 14–22.Google Scholar
Mindham, B. A. (1977) A comparison of maprotiline (Ludiomil) and amitriptyline. Journal of International Medical Research, 5 (suppl. 4), 25–33.Google Scholar
Moises, H. W., Kasper, S. & Beckmann, H. (1981) Trazodone and amitriptyline in treatment of depressed inpatients. A double-blind study. Pharmacopsychiatry, 14, 167–171.Google Scholar
Moller, H. J., Berzewski, H., Eckmann, F., et al (1993) Double-blind multicenter study of paroxetine and amitriptyline in depressed patients. Pharmacopsychiatry, 26, 75–78.Google Scholar
Moller, H. J., Kasper, S., Muller, H., et al (1995) A controlled study of the efficacy and safety of mianserin and amitriptyline in depressive inpatients. Pharmacopsychiatry, 28, 249–252.Google Scholar
Moller, H. J., Gallinat, J., Hegerl, U., et al (1998) Double-blind, multicenter comparative study of sertraline and amitriptyline in hospitalized patients with major depression. Pharmacopsychiatry, 31, 170–177.Google Scholar
Molnar, G. (1977) Maprotiline – a double-blind study of a new tetracyclic antidepressant in severe depression. Canadian Psychiatric Association Journal, 22, 19–23.Google Scholar
Montbrun, F. & Obermair, W. (1976) Döppelblindstudie lofepramin versus amitriptylin. Therapiewoche, 26, 8722–8726.Google Scholar
Monteleone, P. & Fabrazzo, M. (1994) Blood levels of mianserin and amitriptyline and clinical response in aged depressed patients. Pharmacopsychiatry, 27, 238–241.Google Scholar
Montgomery, S. A., McAuley, R., Montgomery, D. B., et al (1980) Pharmacokinetics and efficacy of maprotiline and amitriptyline in endogenous depression: a double-blind controlled trial. Clinical Therapeutics, 3, 292–310.Google Scholar
Muller-Oerlinghausen, B., Ruther, E., Adam, H. K., et al (1979) Clinical profile and serum concentration of viloxazine as compared to amitriptyline. Pharmacopsychiatrie Nevropsychopharmakologie, 12, 321–337.Google Scholar
Murphy, J. E. & Ankier, S. I. (1980) An evaluation of trazodone in the treatment of depression. Neuropharmacology, 19, 1217–1218.Google Scholar
Murphy, J. E. & Bridgman, K. M. (1978) A comparative clinical trial of mianserin (Norval) and amitriptyline in the treatment of depression in general practice. Journal of International Medical Research, 6, 199–206.Google Scholar
Naftulin, D. H. & Ware, J. E. (1972) A behavioural and clinical evaluation of two psychotropic agents: doxepin-hydrochloride and pherphenazine–amitriptyline hydrochloride. Psychosomatics, XIII, 125–130.Google Scholar
Nelson, W. H., Orr, W. W., Stevenson, J. M., et al (1982) Hypothalamic–pituitary–adrenal axis activity and tricyclic response in major depression. Archives of General Psychiatry, 39, 1033–1036.Google Scholar
Nieto, D. & Rincon, H. P. (1973) Un nuevo antidepresivo: el C 34,276–Ba o maprotilina, primer timoanaleptico tetraciclico. Prensa Medica Mexicana, 11–12, 429–434.Google Scholar
Nugent, D. (1979) A double-blind study of viloxazine and amitriptyline in depressed geriatric patients. Clinical Trials Journal, 16, 13–17.Google Scholar
Okasha, A. & Sadek, A. (1976) A controlled, double-blind clinical trial between maprotiline and imipramine in depressive illness. Journal of the Egyptian Medical Association, 59, 557–562.Google Scholar
Peters, U. H., Lenhard, P. & Metz, M. (1990) Ambulante therapie der depression mit fluoxetin – eine multizentrische döppelblindstudie. Nervenheihunde, 9, 28–31.Google Scholar
Petrie, W. M., Ban, T. A., Wilson, W. H., et al (1982) Viloxazine in the treatment of endogenous depression. A standard (amitriptyline) controlled clinical study. International Pharmacopsychiatry, 17, 280–286.Google Scholar
Preskorn, S. H., Silkey, B., Beber, J. et al (1991) Antidepressant response and plasma concentrations of fluoxetine. Annals of Clinical Psychiatry, 3, 147–151.Google Scholar
Prusoff, B., Weissman, M. M., Charney, J., et al (1981) Speed of symptom reduction in depressed outpatients treated with amoxapine and amitriptyline. Current Therapeutic Research, 30, 843–855.Google Scholar
Pugh, R., Bell, J., Cooper, A. J., et al (1982) Does lofepramine have fewer side effects than amitriptyline? Journal of Affective Disorders, 4, 355–363.Google Scholar
Quadri, A. A., Shalini, K. & Channabasavanna, S. M. (1980) D-Amphetamine as a predictor for response to imipramine and amitriptyline. Indian Journal of Psychiatry, 22, 182–184.Google Scholar
Querol, M. (1970) Estudio doble ciego con antidepresivos. Revista de Neuro-Psiquiatría, XXXIII, 251–270.Google Scholar
Rabkin, J. G., McGrath, P. J., Quitkin, F. M., et al (1984) Mianserin versus amitriptyline for depression: a double-blind 6-week trial. Neuropsychobiology, 12, 224–228.Google Scholar
Rampello, L., Nicoletti, G., Raffaele, R., et al (1995) Comparative effects of amitriptyline and amineptine in patients affected by anxious depression. Pharmacopsychiatry, 31, 130–134.Google Scholar
Rees, J. A. & Cryer, P. C. (1976) A single-blind comparative study of once daily dothiepin (Prothiaden) and divided daily doses of amitriptyline. Current Medical Research Opinion, 6, 416–421.Google Scholar
Rego, A. & Sanchez De Vega, J. (1974) Estudio comparativo simple-ciego entre pacientes con Ludiomil (Ciba 34, 276–Ba) y su valoración con la escala de Hamilton. Archivos Neurobiologica, 37, 475–484.Google Scholar
Reimherr, F. W., Chouinard, G., Cohn, C. K., et al (1990) Antidepressant efficacy of sertraline: a double blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. Journal of Clinical Psychiatry, 51 (suppl. B), 18–27.Google Scholar
Remick, R. A., Reesal, R., Oakander, M., et al (1994) Comparison of fluvoxamine and amitriptyline in depressed outpatients. Current Therapeutic Research, 55, 243–250.Google Scholar
Richels, K. & Case, W. G. (1982) Trazodone in depressed outpatients. American Journal of Psychiatry, 139, 803–806.Google Scholar
Richels, K., Gordon, P. E., Weise, C. C., et al (1970) Amitriptyline and trimipramine in neurotic depressed outpatients: A collaborative study. American Journal of Psychiatry, 127, 126–128.Google Scholar
Richels, K., Hutchinson, J. C., Weise, C. C., et al (1972) Doxepin and amitriptyline–perphenazine in mixed anxious–depressed neurotic outpatients: a collaborative controlled study. Psychopharmacologia, 23, 305–318.Google Scholar
Richels, K., Weise, C. C., Csanalosi, I., et al (1974) Clomipramine and amitriptyline in depressed outpatients. A controlled study. Psychopharmacologia (Berl.), 34, 361–376.Google Scholar
Richels, K., Csanalosi, I., Werblowsky, J., et al (1982) Amitriptyline–perphenazine and doxepin in depressed outpatients: a controlled double-blind study. Journal of Clinical Psychiatry, 43, 419–422.Google Scholar
Richels, K., Feighner, J. P. & Smith, W. T. (1985) Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Archives of General Psychiatry, 42, 134–141.Google Scholar
Richmond, P. W. & Roberts, A. H. (1964) A comparative trial of imipramine, amitriptyline, isocarboxazid and tranylcypromine in out-patient depressive illness. British Journal of Psychiatry, 110, 846–850.Google Scholar
Rose, J. T., Leahy, M. R., Martin, I. C. A., et al (1965) A comparison of nortriptyline and amitriptyline in depression. British Journal of Psychiatry, 111, 1101–1103.Google Scholar
Rush, A. J., Weissenburger, J., Vasavada, N., et al (1988) Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline. Journal of Clinical Psychopharmacology, 8, 421–425.Google Scholar
Rush, A. J., Giles, D. E., Jarret, R. B., et al (1989) Reduced REM latency predicts response to tricyclic medication in depressed outpatients. Biological Psychiatry, 26, 61–72.Google Scholar
Rybakowski, J., Matkowski, K., Linka, M., et al (1991) Monitorowane leczenie depresji endogennej imipramina i amitriptylina. Psychiatria Polska, XXV, 111–118.Google Scholar
Sandifer, M. G., Wilson, I. C. & Gambill, J. M. (1965) The influence of case selection and dosage in an antidepressant drug trial. British Journal of Psychiatry, 111, 142–148.Google Scholar
Sedman, G. (1977) Double-blind trial of sustained-release amitriptyline compared with viloxazine in moderate to severe depressive illness. Current Medical Research Opinion, 5, 217–225.Google Scholar
Sethi, B. B., Sharma, I., Singh, H., et al (1979) Amoxapine and amitriptyline: a double-blind study in depressed patients. Current Therapeutic Research, 25, 726–737.Google Scholar
Shaw, D. M., Thomas, D. R., Briscoe, M. H., et al (1986) A comparison of the antidepressant action of citalopram and amitriptyline. British Journal of Psychiatry, 149, 515–517.Google Scholar
Shipley, J. E., Kupfer, D. J., Griffin, S. J., et al (1985) Comparison of effects of desipramine and amitriptyline on EEG sleep of depressed patients. Psychopharmacology, 85, 14–22.Google Scholar
Silverstone, J. T. (1977) A comparison of maprotiline and amitriptyline in the treatment of depression in general practice. Practitioner, 218, 279–282.Google Scholar
Sims, A. C. P. (1980) Comparison of the efficacy of sustained-release amitriptyline with maprotiline in the treatment of depressive illness. Current Medical Research Opinion, 6, 534–539.Google Scholar
Sinclair, J. M., Walsh, M. R., Valle-Jones, J. C., et al (1975) Treatment of anxiety/depressive conditions in the elderly: a double-blind comparative study of motival and amitriptyline. Age and Ageing, 4, 226–231.Google Scholar
Solis, H. G., Molina, G. B. & Pineyro, A. (1970) Clinical evaluation of doxepin and amitriptyline in depressed patients. Current Therapeutic Research, 12, 524–527.Google Scholar
Staner, L., Kerkhofs, M., Detroux, D., et al (1995) Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: a double-blind randomized trial in major depression. Sleep, 18, 470–477.Google Scholar
Stier, C. S., Neumann, M. & Elizur, A. (1982) Comparative double-blind study between maprotiline and amitriptyline in one fixed nightly dose in major depressive disorder. Current Therapeutic Research, 32, 447–456.Google Scholar
Stott, P. C., Blagden, M. D. & Aitken, C. A. (1993) Depression and associated anxiety in primary care: a double-blind comparison of paroxetine and amitriptyline. European Neuropsychopharmacology, 3, 324–325.Google Scholar
Straker, M., Davanloo, H. & Moll, A. (1966) A double-blind comparison of a new antidepressant, protryptiline, with imipramine and amitriptyline. Canadian Medical Association Journal, 94, 1220–1222.Google Scholar
Stuppaek, C. H., Geretsegger, C., Whitworth, A. B., et al (1994) A multicentre double-blind trial of paroxetine versus amitriptyline in depressed inpatients. Journal of Clinical Psychopharmacology, 14, 241–246.Google Scholar
Taverna, P. & Ferrari, G. (1969) Valutazione comparativa della nortriptilina dellamitriptilina e del placebo nel trattamento delle forme ansiose e depressive. Minerva Medica, 60, 2417–2431.Google Scholar
Toru, M., Takamizawa, M., Kariya, T., et al (1972) A double-blind sequential comparison of doxepin with amitriptyline in depressed patients. Psychosomatics, XIII, 241–250.Google Scholar
Trappe, B. (1973) Doxepin and amitriptyline–chlordiazepoxide combination in neurotic states. Psychiatria Fennica, 269–275.Google Scholar
Trick, K. L. K. (1975) Double-blind comparison of maprotiline (Ludiomil) with amitriptyline in the treatment of depressive illness. Journal of International Medical Research, 3 (suppl. 2), 67–70.Google Scholar
Tsaras, G. & Ambrus, J. (1981) Etude clinique comparative de l'association chlordiazepoxide–amitriptyline et de la maprotiline chez des patients souffrant de dépression à composante anxieuse. Revista Medica Suisse Romande, 101, 483–486.Google Scholar
Upward, J. W., Edwards, J. G., Goldie, A., et al (1988) Comparative effects of fluoxetine and amitriptyline on cardiac function. British Journal of Clinical Pharmacology, 26, 399–402.Google Scholar
Van Amerongen, P. (1979) Double-blind clinical trial of the antidepressant action of amineptine. Current Medical Research Opinion, 6, 93–100.Google Scholar
Veith, R. C., Bielski, R. J., Bloom, V., et al (1983) Urinary MHPG excretion and treatment with desipramine or amitriptyline: prediction of response, effect of treatment, and methodological hazards. Journal of Clinical Psychopharmacology, 3, 18–27.Google Scholar
Von Bauer, G. & Nowak, H. (1969) Doxepin, ein neues antidepressivum: wirkungsvergleich mit amitriptylin. Arzneimittezforschung, 19, 164–1646.Google Scholar
Waite, J., Grundy, E. & Arie, T. (1986) A controlled trial of antidepressant medication in elderly in-patients. International Clinical Psychopharmacology, 1, 113–126.Google Scholar
Watanabe, S., Yokoyama, S., Kubo, S., et al (1978) A double-blind controlled study of clinical efficacy of maprotiline and amitriptyline in depression. Folia Psychiatrica et Neurologica Japonica, 32, 1–31.Google Scholar
Weissman, M. M., Lieb, J., Prusoff, B., et al (1975) A double-blind trial of maprotiline (Ludiomil) and amitriptyline in depressed outpatients. Acta Psychiatrica Scandinavica, 52, 225–236.Google Scholar
Wheatley, D. (1975) Controlled clinical trial of a new antidepressant (ORG GB 94) of novel chemical formulation. Current Therapeutic Research, 18, 849–854.Google Scholar
Wilcox, C. S., Cohn, J. B., Katz, B. B., et al (1994) A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients. International Clinical Psychopharmacology, 9, 271–279.Google Scholar
Wright, S. & Hermann, L. (1976) Döppelblindversuch zum wirkungsvergleich von lofepramin und amitriptylin bei ambulant behandelten patienten mit depressiven zustansbildern. Arzneim Forschung (Drug Research), 26, 1167–1169.Google Scholar
Yamhure, A. & Villalobos, A. (1977) Amoxapine: a double-blind comparative clinical study of amoxapine and amitriptyline in depressed, hospitalised patients. Current Therapeutic Research, 21, 502–506.Google Scholar
Young, J. P. R., Coleman, A. & Lader, M. H. (1987) A controlled comparison of fluoxetine and amitriptyline in depressed out-patients. British Journal of Psychiatry, 151, 337–340.Google Scholar
Ziegler, V. E., Clayton, P. J. & Biggs, J. T. (1977) A comparison study of amitriptyline and nortriptyline with plasma levels. Archives of General Psychiatry, 34, 607–612.Google Scholar
Figure 0

Table 1Studies identified by the electronic search but excluded from the meta-analysis, and reason for exclusion

Figure 1

Table 2Amitriptyline (AMI) in comparison with tricyclic (TCA) or heterocyclic antidepressants: proportion of responders, number of patients evaluated on a continuous outcome and estimates of efficacy

Figure 2

Table 3Amitriptyline (AMI) in comparison with selective serotonin reuptake inhibitors (SSRIs): proportion of responders, number of patients evaluated on a continuous outcome and estimates of efficacy

Figure 3

Table 4Amitriptyline (AMI) in comparison with tricylcic/heterocyclic antidepressants (TCAs): proportion of drop-outs, proportion of patients with side-effects and estimates of tolerability

Figure 4

Table 5Amitriptyline (AMI) in comparison with selective serotonin reuptake inhibitors (SSRIs): proportion of drop-outs, proportion of patients with side-effects and estimates of tolerability

Figure 5

Fig. 1Funnel plot of estimated logarithmic odds ratio against the size of the study. Broken horizontal line represents the overall estimate of the logarithmic odds ratio (0.11).

Figure 6

Fig. 2Overall estimate of the efficacy and tolerability of amitriptyline (AMI) in comparison to all other antidepressant drugs.

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