Background: Depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5). One of them must be either Depressed mood or Anhedonia, named main criteria. Although the secondary symptoms can be divided into somatic and non-somatic clusters, the DSM-5 identify depression in all or none fashion. In contrast, depression severity is a continuous variable. Therefore, it is commonly assessed with scales such as the Hamilton Depression Rating Scale (HAMD). Previously, we reported that patients with moderate depression (MD) exhibit greater impairments in cardiac-autonomic modulation than severely depressed (SD) patients. However, clinicians usually do not use scales.Objective: To verify whether the DSM-5 symptoms would be able to discriminate SD from MD and MD from non-depressed (ND) subjects.Material and Methods: Depression was diagnosed based on the Structured Clinical Interview for DSM-5® Disorders. The HAMD evaluated depression severity. In depressed subjects, MD and SD were defined considering the HAMD scores. ND was defined considering both the absence of DSM-5 criteria for depression and the HAMD score. Among 782 outpatients, 46 SD were found. MD and ND subjects were randomly sampled to match the demographic variables of the SD group.Results: Discriminant analysis showed that Depressed Mood was the most reliable symptom to discriminate ND from MD. Anhedonia discriminated SD from MD. Among the secondary DSM-5 criteria, the somatic cluster discriminated ND from MD and the non-somatic cluster SD from MD patients.Discussion: The presence of the somatic cluster in MD may indicate decreased vagal tone and/or increased sympathetic tone, leading to higher cardiovascular risk. As SD is associated with the non-somatic cluster, these patients are at risk of committing suicide. The DSM-5 symptoms exhibited by the patient may help the choice of adequate pharmacological treatment. This would avoid the use of antidepressants that unnecessarily increase cardiac risk in MD. When the symptom cluster suggests SD, the treatment must focus on the prevention of suicide.Conclusions: Depression severity may be inferred based on the DSM-5 criteria. The presence of the Anhedonia main criterium accompanied by non-somatic criteria indicate SD. The Depressive Mood criterium followed by somatic criteria suggest MD.