RATIONALE: Alterations in the expression of neurotrophic growth factors like brain-derived neuronal factor (BDNF) and glial cell line-derived neuronal growth factor (GDNF) have been frequently associated with affective disorders. Indeed, benzodiazepine dependence is typically combined with affective disorders. Aim of the study was to investigate plasma levels of the neuronal growth factors BDNF and GDNF during benzodiazepine withdrawal in patients suffering from comorbidity of benzodiazepine dependence and depressive disorder. METHODS: In total, 11 patients were included in the study. Seven patients completed benzodiazepine withdrawal. RESULTS: We found that BDNF plasma levels were significantly increased in the benzodiazepine-dependent patients (p = 0.011) compared to a healthy control group (14 age- and sex-matched persons) and decreased significantly (p = 0.029) due to benzodiazepine withdrawal, whereas GDNF plasma levels did not differ (p = 0.886) and change (p = 0.180) significantly. CONCLUSION: In conclusion, we assume that benzodiazepines may partly act by similar neurobiological mechanisms like antidepressant medication, which may explain the high frequency of benzodiazepine dependence in affective disorders.