Assessment of adverse events in clinical drug trials: Identifying amitriptyline's placebo- and baseline-controlled side effects

Abstract

Adverse events in clinical drug trials are often poorly assessed and reported. The absence of baseline assessment and structured symptom lists, as well as the fact that most drug trials are industry-sponsored are common sources of bias. In addition, adverse events are usually assessed in patient samples, which can bias results because of the misattribution of symptoms that are part of the illness to medication intake. We aimed to identify amitriptyline's placebo- and baseline-controlled side effects by examining a sample of healthy adults, using structured assessments via a symptom list. Forty healthy individuals were randomized equally to either a group taking 50 mg amitriptyline on four consecutive days or to a placebo control group. Complaints were assessed via the Generic Assessment of Side Effects Scale prior to and after four days of medication intake. Frequency of complaints and their intensity were compared after medication intake between the two groups while controlling for complaints at baseline. The amitriptyline group's participants reported having suffered from "dry mouth," "dizziness," "subjective blood circulation-associated problems," and "constipation" significantly more often. When taking into account the complaint's intensity, the amitriptyline group also reported higher intensities for "dry mouth," "dizziness," and "subjective blood circulation-associated problems." Our results emphasize the importance of a structured and well-controlled harm assessment. Future drug trials should report the placebo- and baseline-controlled side effects with a clear causal relationship to the intake of the drug under investigation, in addition to the frequency of complaints and their odds ratios. (PsycINFO Database Record

Trial registration: ClinicalTrials.gov NCT02127736.