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

Placebo- and Nocebo-Effects in Cognitive Neuroenhancement: When Expectation Shapes Perception

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Effects of in vitro Amitriptyline, Fluoxetine, Tranylcypromine and Venlafaxine on Saphenous Vein Grafts

“…Moreover, we demonstrated that amitriptyline relaxed the isolated human SV graft independently of the endothelium. In a clinical study on the determination of placebo and baseline-controlled side effects of amitriptyline, the amitriptyline group reported a high level of side effects, depending on xerostomia, dizziness and subjective blood circulation [14] . Side effects, depending on the blood circulation disorder, were consistent with our findings.…”

Classics in Chemical Neuroscience: Amitriptyline

“…Less fatal, though serious, adverse effects strongly associated with amitriptyline include anticholinergic effects (dry mouth, slight dizziness), constipation, tachycardia, and confusion. − These are most likely due to the compound’s antagonism of adrenergic, muscarinic, and histaminergic receptors, contributing to the side effects of dizziness, memory impairments, and drowsiness, respectively …”