Mirtazapine, escitalopram, and valproic acid are newer antidepressant drugs than traditional tricyclic antidepressants and are supposed to be less toxic. Nevertheless, intoxication cases due to their overdosage have been repeatedly reported. In the case presently reported, a 64-year-old woman with a previous history of chronic depression was found dead in her apartment. Several packages of pharmaceutical drugs were found, including mirtazapine, escitalopram, and valproic acid. During the autopsy, no evidence of natural disease or trauma was found to account for this death. In order to determine whether massive drug assumption might have determined a lethal intoxication, heart blood, urine, and gastric content were collected and submitted to toxicological analysis. Specific liquid chromatography-tandem mass spectrometry protocols were purposely developed and validated. Blood concentrations of mirtazapine, escitalopram, and valproic acid were 20.3, 65.5, and 417 mg/L, respectively, whereas urine concentrations were 17.0, 94.5, and 423 mg/L, respectively. High concentrations of these drugs were also detected in the gastric content, confirming their ingestion shortly before death. The agreement between authoptic examination by forensic pathologists and toxicological findings are consistent with the suicidal hypothesis, where the death arose by drug intoxication due to simultaneous high-dosage ingestion of mirtazapine, escitalopram, and valproic acid.