Three cases of drug-related death during treatment for stimulant-induced psychosis

Long-term use of stimulant drugs can cause schizophrenia-like psychotic symptoms including hallucinations and delusions in the syndrome known as stimulant-induced psychosis. Therefore, treatment for stimulant-induced psychosis follows the approach for schizophrenia and primarily involves the use of antipsychotic drugs that antagonize dopamine release. However, multiple studies suggest that pharmacotherapy and psychosocial therapy for stimulant-induced psychosis have limited therapeutic efficacy, leading to poor long-term prognosis characterized by recurrence and chronicity of psychiatric symptoms, social isolation, and an extremely high risk of suicide. Here we report three forensic autopsy cases of patients with stimulant-induced psychosis whose cause of death was considered to be due to overdose of prescription medications. All three patients had received treatment with antipsychotic drugs during their lifetimes, but they had poor medication adherence and had discontinued treatment. Two deaths were directly due to drug overdose (Case 1, chlorpromazine and quetiapine poisoning; Case 2, zotepine and tramadol poisoning). In the third case, the direct cause of death was hanging, but markedly elevated blood concentrations of quetiapine and trazodone suggested that drug intoxication may have contributed to death. Elucidating the pathophysiology of stimulant-induced psychosis and selecting and developing effective treatments are essential, and long-term mental health care and social support to prevent isolation are crucial for preventing unfortunate deaths.