A DOUBLE-BLIND COMPARISON OF TIANEPTINE, IMIPRAMINE AND PLACEBO IN THE TREATMENT OF MAJOR DEPRESSIVE EPISODES

In the course of the international development of tianeptine (T), depr essed patients were recruited by 18 centres from Belgium, Italy, Mexic o, Portugal, Spain and Switzerland in a double-blind parallel group st udy versus placebo (P) and imipramine (I). Efficacy and safety of tian eptine were evaluated in 187 depressed inpatients (56% female, 44% mal e), who fulfilled criteria for either major depression, single episode (24.6%) or recurrent (66.8%), or depressed bipolar disorder (8.6%). A fter a seven-day run-in placebo pre-inclusion period, patients were tr eated in double-blind conditions with tianeptine (37.5 mg/d) or imipra mine (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 ac cordance with the therapeutic efficacy and/or the potential adverse ev ents (T: 25-50 mg/d; I: 100-200 mg/d; P: 2-4 capsules). Discontinuatio n 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-ef fects 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. Statisti cal analysis demonstrated the antidepressive efficacy of tianeptine an d imipramine versus placebo (P = 0.012 and P = 0.034, respectively), a nd no difference between tianeptine and imipramine. In patients treate d for 42 days (n = 129) the MADRS scores dropped from 62.3% on tianept ine, 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 depr ession and depressed bipolar disorder when compared to placebo. No dif ference 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 imi pramine than with tianeptine or placebo: dry mouth (P < 0.001), consti pation (P = 0.007), and hot flushes (P = 0.011). No difference in adve rse events was found between tianeptine and placebo. While the usual c ardiovascular signs of tricyclic antidepressants were observed in the imipramine group, no difference between tianeptine and placebo was sho wn in respect to heart rate or blood pressure (supine or standing). Th e assessment of haematological, renal, metabolic and hepatic parameter s confirmed the safety of tianeptine.