Medication side effects in anxious patients: negative placebo responses?

The purpose of the present study was to detect any problems among anxious patients in switching from alprazolam to extended release alprazolam. Fifty-four patients with an anxiety disorder, stabilized on alprazolam, entered the study. During the first 2 weeks, all patients took alprazolam as usual. During the second 2 weeks, they all took the same dosage of the extended release formulation. They were evaluated weekly with standard clinical measures and were asked to report any adverse medical events. The clinical measures showed modest, steady improvement over the course of the study. Patients reporting adverse medical events increased from 26% of the sample to 60% after the switch of dosage forms. Most of these events were anxiety-like (48%) or sedative (37%). Patients who developed sedative events took slightly higher mean doses of alprazolam. Patients who developed anxiety-like events had higher baseline scores on the Somatization, Anxiety and Phobia clusters of the SCL-90. The results suggest that more anxious patients confronted with a change of regimen commonly generate anxiety symptoms that they attribute to the medication, i.e., negative placebo responses, perhaps especially if they have a tendency toward somatization. A study designed to sort out pharmacological and psychological effects and further explore the mechanisms at work is indicated.