Not all side effects associated with tricyclic antidepressant therapy are true side effects

Patients with functional gastrointestinal disorders treated with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it is unclear whether these are drug side effects or reflect a behavioral tendency to report symptoms. We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms.

Female patients in a multicenter National Institutes of Health trial for functional bowel disorders completed a 15-item symptom questionnaire at baseline (before randomization), 2 weeks after they were given desipramine (n = 81) or placebo (n = 40), and at study completion (12 weeks). Patients were asked about the severity and frequency of 15 symptoms. Results were analyzed from 57 patients given desipramine who completed the questionnaires.

Symptoms reported as side effects to have occurred more frequently and also worsened at week 2 in the group given desipramine included dizziness, dry mouth/thirstiness, lightheadedness, jittery feelings/tremors, and flushing. Symptoms that did not change in severity or showed improvement at week 2 in the group given desipramine included morning tiredness, nausea, blurred vision, headaches, appetite reduction, and trouble sleeping. Psychologic distress but not desipramine blood level correlated with symptom reporting.

Most symptoms often attributed to side effects of desipramine were present before treatment; only a few, related to anticholinergic effects, worsened 2 weeks after treatment, suggesting that most so-called side effects were not associated specifically with desipramine use. Such symptoms might instead be associated with psychologic distress.