A Diagnostic and Therapeutic N-of-1 Randomized Trial

Abstract

The objective of this paper is to study the effect of amitriptyline on a young woman with symptoms of lightheadedness, palpitations, somnolence and fatigue. We conducted a single case (N-of-1) randomized trial including three pairs of treatment periods. Each pair included one four-week period when the patient was receiving amitriptyline and one four-week period when the patient was receiving placebo. The clinical setting was a secondary care internal medicine practice. During active treatment periods, amitriptyline was given in a dose of 100 mg each evening. Efficacy symptoms included lightheadedness, headaches and somnolence/fatigue. Side-effects of dry mouth and constipation were also monitored. Each symptom was rated on a seven point scale in which higher numbers denoted fewer symptoms. For the combined efficacy score, the mean difference in scores and the associated standard error was in favour of amitriptyline. The most profound effect was on sleepiness. These differences represent clinically important treatment effects. Dry mouth and constipation were worse on the active drug, but differences did not reach statistical significance. Our experience suggests the usefulness of N-of-1 randomized trials in outpatient medical practice, including psychiatric practice.