There have been no culturally validated measures to screen for depression in Madagascar. In 2022–2023, we conducted qualitative studies in the Bay of Ranobe area in southwestern Madagascar to understand local mental health syndromes specific to this region. We found that the 8-item Patient Health Questionnaire (PHQ-8) shares symptoms with the general distress-like, depressive-like and grief-like syndromes elicited locally. We adapted the PHQ-8 to align with the unique symptoms found in the region that were missing from the measure. We administered the adapted PHQ-8 to 809 participants aged 16 and above. We found that the one-factor (Depression) model (root mean square error of approximation [RMSEA] = 0.046, standardized root mean square residual [SRMR] = 0.053, Comparative Fit Index [CFI] = 0.993 and Tucker–Lewis Index [TLI] = 0.991) had a better fit to our data than the two-factor (Cognitive–Affective and Somatic) model (RMSEA = 0.047, SRMR = 0.052, CFI = 0.994 and TLI = 0.990). The one-factor (Depression) model demonstrated good internal consistency (MacDonald’s omega coefficient
$ {\omega}_0 $ = 0.81 and ordinal alpha
$ {\alpha}_0 $ = 0.87). We conducted a multigroup confirmatory factor analysis to establish measurement invariance (MI) across four groups (sex, ethnicity, level of education and age group) and found that all levels of MI were achieved across groups. Our research provides a validated method to assess the probable prevalence of current depression in southwestern Madagascar.