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

Abstract

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 MADRS 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 MADRS 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.

Tianeptine and paroxetine in major depressive disorder, with a special focus on the anxious component in depression: an international, 6‐week double‐blind study†

“…Tianeptine is an atypical tricyclic compound, for which antidepressant ef®cacy has been well established, particularly in comparison with amitriptyline (Lôo et al, 1988;Guel® et al, 1989), imipramine (Cassano et al, 1996),¯uoxetine (Alby et al, 1993;Lôo et al, 1999) and placebo (Cassano et al, 1996;Costa e Silva et al, 1997;Dalery et al, 2001). Preclinical and clinical studies suggest that it may have some anxiolytic properties in depressed patients.…”

Tianeptine and fluoxetine in major depression: a 6‐week randomised double‐blind study

“…The antidepressant activity of tianeptine has been demonstrated in several short-term controlled trials versus placebo, imipramine, amitriptyline, fluoxetine, paroxetine and sertraline (Cassano et al, 1996;Costa e Silva et al, 1997;Guelfi et al, 1989;Lôo et al, 1999;Waintraub et al, 2000;Lepine et al, 2001;Szádóczky and Füredi, 2000).…”

Ansatz der glutamatergen Modulation erweitert die Therapieoptionen

“…Insgesamt ist Tianeptin gut verträglich, das Nebenwirkungspro l ist dem von Placebo ähnlich, lediglich Kopfschmerzen waren signi kant häu ger als unter Placebo [30,31,51] (Abb. 4).…”