ABSTRACT
Constipation is highly prevalent (30%–60%) in older adults taking atypical antipsychotics (AAPs), a rate insufficiently explained by anticholinergic effects alone. This paper proposes an integrated model centered on the impaired defecation reflex, which weakens with age and is further compromised by AAP–induced multi-neurotransmitter imbalance. AAPs interfere with the descending pain inhibitory pathway, disrupting the central dopamine (DA) and serotonin (5–HT) systems vital for initiating the defecation reflex via the sacral parasympathetic nuclei (SPN). Furthermore, enhanced GABAergic inhibition is implicated, potentially contributing to observed sex differences. This central impairment is compounded by gut dysbiosis–common in this population-which is hypothesized to damage neural circuits and weaken the reflex via the gut–brain axis. We advocate for a holistic management approach beyond traditional laxatives. Targeting the gut microbiota with specific butyrate-producing probiotics represents a novel, hypothesis-generating strategy. This intervention may restore central dopaminergic function, thereby strengthening the compromised defecation reflex. This integrated framework-addressing monoaminergic and gut microbiota mechanisms-provides a more complete understanding for future research and clinical strategies.