Drug-induced hallucination: a case/non case study in the French Pharmacovigilance Database

Abstract

Background and Objectives: Hallucinations are sensory perceptions which occur without external stimuli. There are associated with psychiatric disease but also can be related to organic disease and drug or toxic exposure. The purpose of our study was to investigate the association between exposure to medications and the reporting of hallucinations using data from the spontaneous-reporting French Pharmacovigilance Database (FPVD). Methods: We used the case/noncase method in the FPVD. Cases were all the observations of hallucination with the LLT term "perception disturbances", registered into the FPVD from January 1985 to Jan 2013. Data were expressed as odds ratio (OR) with their 95% confidence intervals. Results: Among the 469,181 reports of adverse effects recorded between 1985 and 2013, 4,086 are hallucinations. For about 50% of these hallucinations were experimented by patient older than 65 years old. A statistically significant OR was found with several medications included rasagiline (OR 17.6 [95%CI 10.4-29.8]), zolpidem (OR 12.9 [95%CI 11.3-14.8]), methylphenidate (OR 9.3 [95%CI 5.9-14.6]) and baclofene (OR 5.4 [95%CI 3.7-7.8]). An increased risk of hallucinations was also observed with non central nervous system drugs, including ertapenem (OR 24.0 [95%CI 14.2-40.5]), voriconazole (OR 12.9[95%CI 10.2-16.5]) and valacyclovir (OR 9.1 [95%CI 6.9-11. 9]). Conclusions: This pharmacoepidemiological study describes an association between drugs and hallucinations. This relationship involves not only some already suspected drugs but also other drugs less known to induce such an adverse reaction. Despite the mandatory limits of this kind of study, these data should lead to special precautions in patient at risk.

Isotretinoin‐induced visual hallucinations in a patient with acne vulgaris

“…Dementia, delirium, tumor, epilepsy, serotonergic syndrome, Charles‐Bonnet syndrome, inappropriate release of antidiuretic hormone, hyponatremia, and drugs can cause hallucinations. Drug‐induced hallucinations are often visual, as in our patient 3,4 . Drugs reported to cause hallucinations include zolpidem, fluoroquinolones, valacyclovir, narcotic analgesics, levodopa, benzodiazepine, antidepressants, methylphenidate, proton pump inhibitors, voriconazole, and oxybutynin 3 .…”

Opioid-induced Hallucinations: A Review of the Literature, Pathophysiology, Diagnosis, and Treatment

“…A study using the French Pharmacovigilance Database, which recorded 469,181 reports of adverse effects between 1985 and 2013, found that 482 patients reported hallucinations of the total 12,184 patients who had received opioids. 42 Although the duration of opioid therapy was not standardized, these data provide suggestion to the overall incidence of opioid-induced hallucinations. 42 Tramadol was involved most often with an incidence of 240, an odds ratio of 6.3, and 95% confidence interval of 5.5 to 7.2, whereas morphine was next with an incidence of 143, an odds ratio of 4.4, and 95% confidence interval of 3.7 to 5.2.…”

“…42 Although the duration of opioid therapy was not standardized, these data provide suggestion to the overall incidence of opioid-induced hallucinations. 42 Tramadol was involved most often with an incidence of 240, an odds ratio of 6.3, and 95% confidence interval of 5.5 to 7.2, whereas morphine was next with an incidence of 143, an odds ratio of 4.4, and 95% confidence interval of 3.7 to 5.2. The increased incidence associated with tramadol may occur because along with its opioid-agonist properties, it also inhibits reuptake of norepinephrine and serotonin.…”

Pharmacovigilance Signals of the Opioid Epidemic over 10 Years: Data Mining Methods in the Analysis of Pharmacovigilance Datasets Collecting Adverse Drug Reactions (ADRs) Reported to EudraVigilance (EV) and the FDA Adverse Event Reporting System (FAERS)

“…However, following its extensive use for chronic pain relief and also in drug-abuse cases, dependency and, after long-term use, the occurrence of withdrawal symptoms were observed. Tramadol was associated with visual and auditory hallucinations, psychotic disorder, and confusional state, which might resemble the withdrawal symptoms of serotonin reuptake blockers rather than opioid blockers, and this may be related to tramadol's mechanism of action as a serotonin and epinephrine reuptake blocker [47,48]. Consistently, a report by the Adverse Drug Reactions Advisory Committee of Australia found that confusion, hallucinations, convulsions, and serotonin syndrome were the most serious adverse reactions recorded among all tramadol-related reports [49,50].…”