title: Confirming false adverse reactions to drugs by performing individualized, randomized trials.
abstract: One-patient, randomized, double-blind, controlled trials (N-of-1 RCTs) have traditionally been used to assess the efficacy of treatment. At the Drug Safety Clinic, Toronto, this methodology is used to evaluate adverse effects related to medication use, specifically when the symptoms are vague and are in response to more than one medication. Two patients are described with histories of drug allergies to multiple medications; as well, guidelines for conducting N-of-1 trials are summarized. The first patient had a history of prolonged periorbital and generalized weakness lasting up to one week after exposure to a variety of drugs. Because of the ambiguous results of local anesthetic skin testing, an N-of-1 trial was performed using lidocaine without preservative. Two short-lived episodes of blepharospasm and lethargy were observed with placebo; no subjective or objective reaction occurred with active drug. The second patient had a history of prolonged weakness and drowsiness after exposure to many medications; she had been told that she was allergic to all drugs with a benzene ring. During the first N-of-1 trial, generalized weakness was observed with 10 mg of dimenhydrinate and all four placebo doses. During the second N-of-1 challenge using codeine, no unwarranted reactions occurred with either active or placebo drug. Traditional testing of these patients to disprove the clinical symptoms is often difficult because of the anxiety level associated with the patients' past experiences. N-of-1 trials provide a useful alternative for the management of patients with nonspecific symptomatology attributed to drug ingestion.
authors.affiliation: Division of Clinical Pharmacology, Sunnybrook & Women's College Health Sciences Centre, University of Toronto, Ontario.
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Knowles
authors.forename: Jack P
authors.initials: JP
authors.lastname: Uetrecht
authors.forename: Neil H
authors.initials: NH
authors.lastname: Shear
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000779:Anesthetics, Local / Q000009:adverse effects; D003061:Codeine / Q000009:adverse effects; D004111:Dimenhydrinate / Q000009:adverse effects; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000523:psychology; D005260:Female; D006801:Humans; D007428:Intradermal Tests; D008012:Lidocaine / Q000009:adverse effects; D015990:Placebo Effect; D010919:Placebos / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D000779:Anesthetics, Local; D010919:Placebos; D008012:Lidocaine; D004111:Dimenhydrinate; D003061:Codeine