A 73-year-old male patient with delusional disorder, somatic type (DDST) who had a delusion of skin infestation with insects was presented. He was taking multiple medications to treat concomitant physical diseases. Milnacipran was selected as the treatment drug because of its low drug-interaction profile. Milnacipran treatment at the doses of 25 to 50 mg/d decreased the infestation delusion significantly, without an adverse effect or event suggestive of a drug interaction. The effectiveness of the drug was confirmed coincidentally by repeated recurrences and improvements after his deliberate discontinuation and restart of the drug, respectively. The present report suggests that milnacipran is effective for a patient with DDST and that this drug may be the first choice when the patient is taking multiple medications.