In a prospective, non-blinded, uncontrolled, multicenter, post-marketing, observational study (FRIENDS; NCT02043197), fluvoxamine (50-300 mg/day for 90 days) was effective for the treatment of depression in 299 adult patients (age ≥18 years) with neurological disorders at baseline. The therapeutic effect of fluvoxamine was measured by means of changes in the Hospital Anxiety and Depression Scale depression and anxiety scores (HADS-D and HADS-A, respectively), global severity of illness, and clinical condition (measured using the Clinical Global Improvement [CGI] scale). The mean HADS-D subscale score at baseline in the per-protocol cohort (n=296) was 11.7±3.1 points and the corresponding mean HADS-A score was 12.6±3.2. Significant (P<0.0001) improvements in both scores were recorded during fluvoxamine treatment and later follow-up. Most patients (>85%) recorded reductions versus baseline in both indices. In the CGI-based assessment, most evaluated patients (>200) experienced moderate to very substantial clinical improvement, with no or limited side effects. Significant improvements were also recorded in the exploratory outcomes of sleep quality, assessed using the Insomnia Severity Index, and cognitive function, assessed using the Montreal Cognitive Assessment (P<0.0001 vs baseline for both). No death or serious adverse drug reactions were reported during the study. The results of this observational study affirm that fluvoxamine is effective and well tolerated for the treatment of depression in the context of neurological disorders. The effects on the exploratory endpoints of this research merit evaluation in controlled trials.