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Serotonin–dopamine antagonists (SDAs) inhibit dopaminergic transmission in the mesolimbic system less than in the nigrostriatal dopaminergic pathway, which relates to the extrapyramidal side-effects of these drugs. The SDAs seem to have an adequate receptor binding profile for the management of the behavioral and psychiatric symptoms of dementia. However, clinicians are discouraged from prescribing SDAs for elderly patients because of an advisory statement from the US Food and Drug Administration that warns about an increased mortality rate among elderly patients treated with atypical antipsychotics.We conducted a retrospective study involving 16 elderly patients (mean age 84.9 years; range 67–94 years) with delirium who were treated with one of two SDAs, namely perospirone (4–12 mg/day) or risperidone (1–2 mg/day). The time-course of their psychiatric symptoms was assessed using subcategories of the Delirium Rating Scale (DRS) before treatment and on Days 10 and 24 of treatment.Total DRS scores were significantly decreased from baseline in both treatment groups. Both agents led to significant improvements from baseline in psychomotor behavior and lability of mood. Of interest, perospirone decreased hallucinations and delusions and improved sleep–awake cycle disturbances compared with baseline. No serious side-effects were seen with either drug.Both perospirone and risperidone are effective in the management of delirium in elderly patients. The improvement in the sleep–awake cycle with perospirone may be derived from its short pharmacological half-life.