There is evidence that the brain-derived neurotrophic factor (BDNF) has implications for the pathophysiology of major depressive disorders (MDD). Measures of BDNF levels are highly dependent on the methodologies used and these vary among different studies. Therefore, the aim of this study was to carry out a descriptive analysis of the methodologies used to measure BDNF in clinical trials (CT) in patients with the diagnosis of major depression. We conducted a qualitative systematic review of CT that included samples of subjects diagnosed with major depression and evaluated the BDNF levels as an outcome. The search was performed on Pubmed, Scielo, Psychinfo and Lilacs. The selected articles were analyzed according to the CONSORT Statement and their methods of BDNF collection and analysis were described. Twenty-eight studies were included in the final analysis. Of those, 6 trials (21.4%) involved non-pharmacological interventions and only half had the MDD diagnosis based on structured interview. Trials used different methods to evaluate BDNF levels: most of them verified serum BDNF levels, 17 (60.7%) trials mentioned that measured BDNF levels in duplicate and 9 (32.1%) collected blood in fasting. A variety of methods for BDNF collection and analysis was used in the different studies, making it difficult to compare results. However, despite of the methodology, BDNF seems to increase after treatment for major depression.