To determine the characteristics of the activation syndrome (AS) that predict the emergence or worsening of suicidal ideation (SI) in the first month of antidepressant treatment with tianeptine, as well as the temporal relationship between both conditions. Method: A naturalistic sample of 2422 depressed outpatients starting a new antidepressant treatment with tianeptine was assessed at 2, 4 and 6 weeks of follow-up using validated questionnaires. Four main dimensions of AS were examined: impulsivity, sleep problems, anxiety and agitation.Results: The emergence of an AS was more likely in long-lasting depressive episodes, but less likely if the patient responded to the antidepressant or benzodiazepines were added as an add-on treatment. Treatment-emergent SI was strongly associated to the presence of an AS, particularly in case of sleep problems (OR = 8.42) or impulsivity upsurges (OR = 3.89), even after adjustment for all relevant confounding factors.Conclusions: Our findings suggest a dose-effect mechanism modulating the relationship between treatment-related SI and AS. AS symptoms may need to be monitored closely in the weeks that follow the introduction of an antidepressant treatment.