Regular and long-term injections of botulinum toxin (BoNT) are considered the first line therapy for essential blepharospasm (BEB), but no data exists on the long-term effect of this therapy on depressive symptoms and quality of life. This study aims to prospectively evaluate the long-term effects of BoNT therapy on depressive symptoms as well as on daily activities, emotional well-being and quality of life using validated questionnaires (BEB-scale, Beck`s Depression Inventory (BDI)). 86 patients diagnosed with BEB were followed up for a median of 4 years. Clinical symptoms improved significantly after BoNT-injections. Everyday activities and subjective assessment of the overall situation improved gradually under long-term BoNT therapy. Significant correlations (p < 0.0001; r-values between 0.498 and 0.706) were found between the BDI and items of the BEB-scale. No significant antidepressive effect of long-term BoNT therapy was found with a low median BDI total score (5/max. 63), but up to 31.3% of BEB patients had a BDI score ≥ 11, indicating clinically relevant depressive symptoms. Of these, 65.4% had no known history of depression. Although, several studies reported an antidepressant effect of botulinum toxin injections in patients with major depression, this effect does not seem to be present in patients with BEB despite clinical improvement of symptoms. A high prevalence of previously undetected depressive symptoms was found in BEB patients. As this may influence BoNT therapy success, identifying potential depressive symptoms at the time of BEB diagnosis and initiating appropriate treatment seems important.