Various CNS reactions can occur with metoclopramide, some of which are dose-related. Tardive dyskinesia has been reported with long-term use. Extrapyramidal effects can include akathisia, dystonia, and, possibly, tardive dyskinesia. These effects are more likely to occur in teenagers and young adults. The incidence is higher with higher doses.
Tardive dyskinesia occurs more frequently in elderly female patients and can be irreversible.
Although tardive dyskinesia is more likely to occur after prolonged therapy or high dosage, relatively brief therapy has been associated with this effect as well. Extrapyramidal effects usually occur within 24-48 hours of treatment and generally disappear within 24 hours of discontinuation. Other adverse CNS effects include drowsiness, restlessness, fatigue, lassitude, depression, and headache. The cholinergic-like effects of metoclopramide increase gastric and duodenal motility, which can cause diarrhea. Metoclopramide can increase prolactin secretion, which can result in breast enlargement, galactorrhea, libido decreases, impotence in males, and menstrual irregularity in women.