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A double-blind comparison of tianeptine, imipramine and placebo in the treatment of major depressive episodes

Published online by Cambridge University Press:  16 April 2020

GB Cassano ,
G Heinze ,
H Lôo ,
J Mendlewicz ,
M Paes de Sousa  and
On behalf of the Study Group
GB Cassano
Affiliation:
Institute of Psychiatry, University of Pisa, via Roma 67,1-56100 Pisa, Italy
G Heinze
Affiliation:
Instituto Mexicano de Psiquiatria, Call Mexico-Xochimilco no 101, San Lorenzo Huipulco Delegacion Tlapan, 14370Mexico City, Mexico
H Lôo
Affiliation:
SHU, Hôpital Sainte-Anne, 1 rue Cabanis, 75014Paris, France
J Mendlewicz
Affiliation:
Sleep Laboratory, Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Route de Lennik 808, 1070Brussels, Belgium
M Paes de Sousa
Affiliation:
Department of Psychiatry, Hospital de Santa Maria, Av Egas Moniz, 1600 Lisbon, Portugal
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Summary

In the course of the international development of tianeptine (T), depressed patients were recruited by 18 centres from Belgium, Italy, Mexico, Portugal, Spain and Switzerland in a double-blind parallel group study versus placebo (P) and imipramine (I). Efficacy and safety of tianeptine were evaluated in 187 depressed inpatients (56% female, 44% male), who fulfilled criteria for either major depression, single episode (24.6%) or recurrent (66.8%), or depressed bipolar disorder (8.6%). After a seven-day run-in placebo pre-inclusion period, patients were treated in double-blind conditions with tianeptine (37.5 mg/d) or imipramine (150 mg/d) or placebo for 14 days, including an increasing daily dose period of three days. After the fourteenth day and until the end of the sixth week of treatment, a flexible dosage was introduced in accordance with the therapeutic efficacy and/or the potential adverse events (T: 25–50 mg/d; I: 100–200 mg/d; P; 2–4 capsules). Discontinuation of treatment occurred in 57 patients (30.5%) with more inefficacy on placebo and tianeptine (P: 16/23; T: 11/17; I: 7/17), and more side-effects on imipramine (P: 1/23; T: 1/17; I: 7/17). Final MÅDRS scores in intention-to-treat analysis were 22.3 ± 1.5, 17.3 ± 1.6 and 18.4 ± 1.5 for placebo, tianeptine and imipramine, respectively. Statistical analysis demonstrated the antidepressive efficacy of tianeptine and imipramine versus placebo (P = 0.012 and P = 0.034, respectively), and no difference between tianeptine and imipramine. In patients treated for 42 days (n = 129) the MÅDRS scores dropped from 62.3% on tianeptine, 54.2% on imipramine and 48.5% on placebo. These results confirmed the efficacy of tianeptine (37.5 mg/d) in the treatment of major depression and depressed bipolar disorder when compared to placebo. No difference was found between tianeptine and imipramine (150 mg/d) for the efficacy and between tianeptine and placebo for all safety criteria. The following adverse events were significantly more frequent with imipramine than with tianeptine or placebo: dry mouth (P < 0.001), constipation (P = 0.007), and hot flushes (P = 0.011). No difference in adverse events was found between tianeptine and placebo. While the usual cardiovascular signs of tricyclic antidepressants were observed in the imipramine group, no difference between tianeptine and placebo was shown in respect to heart rate or blood pressure (supine or standing). The assessment of haematological, renal, metabolic and hepatic parameters confirmed the safety of tianeptine.

Keywords

depressiontianeptineimipramineplacebocontrolled trial
Type
Original article
Information
European Psychiatry , Volume 11 , Issue 5 , 1996 , pp. 254 - 259
Copyright
Copyright © Elsevier, Paris 1996

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