Takahiko NagamineDivision of Psychiatric Internal Medicine, Seiwakai-Kitsunan Hospital 3381 Suzenji, Yamaguchi City, JapanAbstract: Aspiration pneumonia is a major cause of death in patients with dysphagia, often accompanied by psychiatric symptoms. The inhibition of swallowing and cough reflexes, which contribute to a significant risk for aspiration, may be related to decreased levels of substance P. Clinical studies indicate a strong association of an increased mortality in psychiatric patients with the use of antipsychotics. The present study documented fewer positive episodes of swallowing reflex in patients treated with haloperidol for schizophrenia (7/11; 63.6%) than those treated with risperidone (10/11; 90.9%). In addition, patients treated with risperidone had serum substance P levels comparable with control subjects (29.0 ± 7.8 pg/mL, 29.6 ± 7.6, respectively; p = 0.9), while patients treated with haloperidol had significantly lower serum substance P levels (20.6 ± 5.5 pg/mL; p < 0.01). Among patients on haloperidol, those with negative episodes of reflex (4/11; 36.4%) had serum substance P levels at 15.8 ± 1.0 pg/mL, in contrast with those with positive episodes (7/11; 63.6%) who had serum levels at 23.4 ± 4.9 pg/mL. However, in the patient group treated with risperidone, serum substance P levels in the majority of patients with positive episodes of reflexes (10/11, 90.9%; 30.1 ± 7.2 pg/mL) was found to be as high as in control subjects, all with positive episodes (5/5, 100%; 29.6 ± 7.6 pg/mL) (p = 0.866), and higher than in one patient with negative reflex (1/11, 9.1%; 18.0 ± 0.0 pg/mL). These results suggest that the decreased serum substance P levels are strongly associated with the use of haloperidol, as well as decreased swallowing reflexes. This suggests that serum substance P levels may be a useful predictive marker for the increased risk of developing aspiration, or subsequently aspiration pneumonia. Moreover, this increased incidence of aspiration may contribute to an increased mortality in patients following antipsychotic therapy. Risperidone, which has little influence on serum substance P productions, may be a more appropriate first-line drug of choice for treatment of schizophrenia.Keywords: schizophrenia, aspiration pneumonia, substance P, risperidone, haloperidol