Tramadol-associated hallucinations: a systematic review and narrative synthesis of their pathophysiology, diagnosis, and treatment

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)

“…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]. Recently, tramadol-associated hallucinations have been proposed as a clinical entity by Jean et al [49], speculating an involvement of several different mechanisms, such as muscarinic antagonism, serotonin reuptake inhibition, serotonin receptor-mediated dopamine dysregulation, and antagonistic effects on gamma-aminobutyric acid (GABA) receptors. Unfortunately, the data available to this study did not allow for an evaluation of the concomitant use of substances/drugs acting on the same neurotransmitter systems or organic diagnoses, and this might have influenced the clinical presentation recorded.…”

“…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]. Recently, tramadol-associated hallucinations have been proposed as a clinical entity by Jean et al [49], speculating an involvement of several different mechanisms, such as muscarinic antagonism, serotonin reuptake inhibition, serotonin receptor-mediated dopamine dysregulation, and antagonistic effects on gamma-aminobutyric acid (GABA) receptors.…”

(Attenuated) hallucinations join basic symptoms in a transdiagnostic network cluster analysis

“…Albeit considered a part of the subdimension 'reality distortion' of the 'psychosis superspectrum' of the HiTOP initiative (Kotov et al, 2020), hallucinations were linked to non-schizophrenia-spectrum psychotic disorders by the HiTOP initiative (Kotov et al, 2020).Moreover, hallucinations can appear in other mental or somatic disorders, and as the result of substance use, including medications (Ben-Zeev et al, 2020;Carota and Bogousslavsky, 2019;Coerver and Subramanian, 2020;Ford et al, 2014;Jean et al, 2020;Thakur and Gupta, 2020;Waters and Fernyhough, 2017). Hallucinatory experiences can also occur in hypnagogic or hypnopompic states; and, in these non-pathological forms, are most frequent in the community by far (Ohayon, 2000;Chapman and Chapman, 1980;Carota and Bogousslavsky, 2019).…”

“…The clinical and diagnostic significance of perceptual aberrations, in particular of hallucinatory experiences, for psychosis has been challenged by their association with age and developmental stage in both clinical and community samples (Maijer et al, 2019;Brink et al, 2020;Schimmelmann et al, 2015;Schultze-Lutter and Schmidt, 2016;Schultze-Lutter et al, 2017, 2020a, 2020bWalger et al, 2020), their occurrence in a broad range of other mental and somatic disorders (Carota and Bogousslavsky, 2019;Coerver and Subramanian, 2020;Jean et al, 2020;Thakur and Gupta, 2020;Waters and Fernyhough, 2017) and their unclear psychosis-predictive value (Zhang et al, 2020;Niles et al, 2019;Marshall et al, 2019). It was suggested that hallucinations might better be regarded as a common endpoint of multiple processes and that, by assessing hallucinations in different modalities together as one, as done in SIPS and PANSS, meaningful differences in etiology and phenomenology may be ignored (Pienkos et al, 2019).…”

Drug utilization review of tramadol hydrochloride in a regional hospital in South Africa; findings and implications

“…However, tramadol HCl has the ability to induce psychic and physical dependence of the morphine type leading to concerns about the risk of tramadol dependence and abuse potential especially at supratherapeutic doses (5,8,10). In addition, there are concerns including major drug interactions with an appreciable number of medicines as well as the potential for seizures, hallucinations, hypertension and respiratory depression, leading to calls for its prescribing to be carefully monitored (10)(11)(12)(13)(14)(15)(16)(17).…”