Bariatric surgery in morbidly obese patients, restrictive gastrointestinal resection in patients, who suffer from gastric cancer or who, for suicidal purposes, ingested toxic substances has an influence on the absorption process of drugs in the gastrointestinal tract. A 77-year-old patient with gastric cancer is described, who was submitted to total gastrectomy. While he was hospitalised in a somatic hospital because of severe undernutrition due to malabsorption, a depressive episode accompanied by a somatic syndrome (F32.11) was diagnosed. Only a treatment with 45 mg/day mirtazapine resulted in a clearcut clinical response. Although the antidepressant was administered as whole tablets, plasma concentrations of mirtazapine were within those observed in patients not submitted to surgery. A review of the literature about the pharmacokinetics of antidepressants and antipsychotics in patients submitted to surgery in the gastrointestinal tract is presented. Treatment recommendations are proposed which should help to minimise risks for pharmacotherapy and optimise treatment response in these patients. In particular, therapeutic drug-monitoring is recommended before and after surgery, as adaptation processes may modify the fate of the drug in the organism.