[Value of tianeptine in treating major recurrent unipolar depression. Study versus placebo for 16 1/2 months of treatment].
OBJECTIVE
The aim of this study was to assess the efficacy of tianeptine vs placebo in the long-term treatment of unipolar major recurrent depression.


METHODS
286 patients who met DSM-III-R criteria for major depression with a Hamilton Depression Rating Scale (HDRS-21 items) score > or = 17, and with a history of at least one previous episode within the last 5 years, were treated in an open trial with tianeptine for 6 weeks. 185 patients who responded to treatment at day 42 (intent-to-treat) were randomly assigned to tianeptine 37.5 mg/day (n = 111), or placebo (n = 74). Among these patients 173 were strict responders to tianeptine (per-protocol-population), as defined in the present study by a 50% reduction in the HDRS score, a global score lower than 15 and confirmation by clinical evaluation. Both groups were comparable except for the severity of the depressive episode (significantly more severe in the tianeptine group (33%) than in the placebo group (18%)) (p = 0.018). Relapses and recurrences were defined by a HDRS score > or = 15, and/or a CGI score > or = 4, the recurrences being confirmed by the clinician. Patients were subsequently evaluated at day 63, and the 3rd, 6th, 9th, 12th, 15th and 18th month.


RESULTS
Special attention was given to the number of relapses and recurrences, and to the delay of onset (Kaplan Meier Method). Between day 42 and 18th month (intent-to-treat group), the rate of relapses and recurrences was significantly higher in the placebo group (36%), than in the tianeptine group (16%) (p = 0.002). Long term comparison of the rate of patients without recurrence or relapse, also showed a significant difference in favour of tianeptine (p < 0.001). The difference between teh 2 groups increased within time. Secondary analysis of relapses and recurrence in the intent-to-treat group showed a significantly higher rate of relapses for the placebo group (p = 0.002); the rate of patients without recurrences in the long term appeared to be at the limit in the intent-to-treat group (p = 0.067) but significant in the per-protocol-group, in favour of tianeptine (p = 0.36). Furthermore, no difference was observed between the 2 groups, in terms of tolerance. Secondary effects attributed to treatment by investigators were rare and benign in each group.


CONCLUSIONS
These data support the use of tianeptine in the long term treatment of unipolar major recurrent depression. Relapses and recurrences were 2 to 3 times less frequent with tianeptine as compared to placebo. Furthermore, prolonged treatment with tianeptine appeared to be very well tolerated.
Daléry
J
J
CHS Le Vinatler, Bron.
Dagens-Lafant
V
V
De Bodinat
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000009:adverse effects; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D012008:Recurrence; D013841:Thiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine