title: Sensitivity of Quantitative Signal Detection in Regards to Pharmacological Neuroenhancement.
abstract: Pharmacological neuroenhancement (PNE) is a form of abuse and has not yet been addressed by methods of pharmacovigilance. In the present study, we tested if quantitative signal detection may be sensitive in regards to PNE. We evaluated the risk of drug abuse and dependence (DAAD) related to substances that are known to be used for PNE and divided this group into agents with (methylphenidate) and without a known abuse potential outside the field of PNE (atomoxetine, modafinil, acetylcholine esterase inhibitors, and memantine). Reporting odds ratios (RORs) were calculated using a case/non-case approach based on global and country-specific drug safety data from the Uppsala Monitoring Centre (UMC). Both control substances (diazepam and lorazepam) and methylphenidate were statistically associated with DAAD in all datasets (except methylphenidate in Italy). Modafinil was associated with DAAD in the total dataset (ROR, 2.7 (95% confidence interval (CI), 2.2-3.3)), Germany (ROR, 4.6 (95% CI, 1.8-11.5)), and the USA (ROR, 2.0 (95% CI, 1.6-2.5)). Atomoxetine was associated with DAAD in the total dataset (ROR, 1.3 (95% CI, 1.2-1.5)) and in the UK (ROR, 3.3 (95% CI, 1.8-6.1)). Apart from memantine, which was associated with DAAD in Germany (ROR, 1.8 (95% CI, 1.0-3.2)), no other antidementia drug was associated with DAAD. Quantitative signal detection is suitable to detect agents with a risk for DAAD. Its sensitivity regarding PNE is limited, although atomoxetine and modafinil, which do not have a known abuse potential outside PNE, and no antidementia drugs, whose use in PNE is presumably low, were associated with DAAD in our analysis.
authors.affiliation: Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany. maximilian.gahr@uni-ulm.de.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Gahr
authors.affiliation: Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany. bernhard.connemann@uni-ulm.de.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Connemann
authors.affiliation: Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany. carlos.schoenfeldt@uni-ulm.de.
authors.forename: Carlos
authors.initials: C
authors.lastname: Schönfeldt-Lecuona
authors.affiliation: Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany. rene.zeiss@uni-ulm.de.
authors.forename: René
authors.initials: R
authors.lastname: Zeiss
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000069445:Atomoxetine Hydrochloride / Q000009:adverse effects; D001315:Australia / Q000453:epidemiology; D001559:Benzhydryl Compounds / Q000009:adverse effects; D002170:Canada / Q000453:epidemiology; D000697:Central Nervous System Stimulants / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000453:epidemiology / Q000209:etiology*; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects; D005602:France / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008559:Memantine / Q000009:adverse effects; D008774:Methylphenidate / Q000009:adverse effects*; D000077408:Modafinil; D060735:Pharmacovigilance; D013030:Spain / Q000453:epidemiology; D019966:Substance-Related Disorders / Q000145:classification / Q000453:epidemiology / Q000209:etiology; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D064690:Wakefulness-Promoting Agents / Q000009:adverse effects
chemical_list: D018759:Adrenergic Uptake Inhibitors; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D064690:Wakefulness-Promoting Agents; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D000077408:Modafinil; D008559:Memantine
keywords: addictovigilance; atomoxetine; brain doping; methylphenidate; modafinil