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Novel hypotheses, appreciating the etiology of the disease, are on demand for the development of more effective and safe antidepressants

When amitriptyline is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required

Importantly, circulating HTY metabolites, mainly HTY sulfate and HTY glucuronides, reach plasma concentrations several-fold higher than parent HTY and retain cardiovascular-related bioactivity