Is There a Potential of Misuse for Venlafaxine and Bupropion?

Abstract

Objective: Traditionally, studies on the non-medical use of pharmaceutical products have focused on controlled substances; e.g., opiates/opioids; and benzodiazepines. Although both bupropion and venlafaxine have been reported as being misused, only anecdotal reports have been made available so far. Hence, the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs), misuse/abuse/dependence and withdrawal, venlafaxine- and bupropion-related, database was here analyzed.Methods: All EMA spontaneous reports relating to venlafaxine (2005–2016) and bupropion (2003–2016) notifications were here analyzed, to provide a descriptive analysis by source, gender, age, and type of report. The UK-based, 2000–2016, Yellow Card Scheme pharmacovigilance database, bupropion and venlafaxine withdrawal reports were compared as well with those pertaining to fluoxetine and paroxetine.Results: Out of 20,720 (bupropion) and 47,516 (venlafaxine) total number of ADRs, some 2,232 (10.8%), and 4,071 (8.5%) misuse/abuse/dependence ADRs were respectively associated with bupropion and venlafaxine. Conversely, bupropion withdrawal-related ADRs were here reported in 299/20,720 (1.44%) cases and in 914/47,516 (1.92%) cases for venlafaxine. Overall, all bupropion and venlafaxine misuse-/abuse-/dependence- and withdrawal-ADRs were related to a respective number of 264 and 447 patients. According to the Proportional Reporting Ratio (PRR) computation, in comparison with venlafaxine bupropion resulted to be more frequently misused/abused (PRR: 1.50), but less frequently associated with both dependence (PRR: 0.92) and withdrawal (PRR: 0.77) issues. Yellow Card Scheme data suggested that paroxetine and venlafaxine, in comparison with fluoxetine and bupropion, were associated with higher number of withdrawal-related reports.Conclusions: The dopaminergic, stimulant-like, bupropion activities may be associated with its possible recreational value. Present data may confirm that the occurrence of a withdrawal syndrome may be a significant issue for venlafaxine-treated patients.

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

“…Such listings showed all information related to the ADR, the patient, the drug, the reporter, and the diagnosis. In line with previous studies from our group [36][37][38][39], the ADRs considered here were, per se, voluntary and unsolicited communications [34] reported by both Regulatory Authorities of the EU Member States where the reaction occurred and/or by the Marketing Authorization Holders for those ADRs occurring outside the EEA. Individual Case Safety Reports, such as voluntary reports, refer to the format and content for the reporting of one or several suspected ADRs in relation to a medicinal product that occur in a single patient at a specific point of time [40].…”

“…Indeed, the clozapine pharmacodynamic profile may well include: (a) a dopaminergic super-sensitivity, with the risk of a dopaminergic psychosis and symptoms such as dystonias, dyskinesias, and catatonia [38,[56][57][58][59]; (b) a cholinergic rebound, inducing in vulnerable patients a rapid worsening of psychosis, agitation, confusion, insomnia, and symptoms including nausea, vomiting, diarrhea, headache, diaphoresis, and abnormal movements, such as dystonias and dyskinesias [6,54,56,57,[60][61][62][63][64]. Consistent with this, symptoms appear to regress rapidly with the help of anti-cholinergic drugs; (c) a serotonergic syndrome, which may occur even without the concomitant use of a serotonergic agent [10,39,61]. In fact, acting as a 5-HT2A antagonist, long-term clozapine use may be associated with receptor downregulation, and thus, its abrupt discontinuation might lead to receptors' upregulation [65,66]; (d) a sudden decrease in gamma-aminobutyric acid (GABA) activity, with the development of catatonic symptoms which may include, mutism, waxy flexibility, staring, posturing, mannerisms, negativism, and also restless, irrelevant speech, and psychomotor agitation [6,67].…”

“…Within the standardized MedDRA Query (SMQ) 'drug abuse, dependence and withdrawal' section, we identified the following ADRs: dependence, drug abuse, drug abuser, drug dependence, drug diversion, drug withdrawal convulsions, drug withdrawal syndrome, drug withdrawal neonatal syndrome, intentional product misuse, product use issue, substance abuse, and withdrawal syndrome. For the definition of 'abuse'; 'addiction'; 'dependence'; and 'misuse' please refer to references [35][36][37][38][39][40]. Moreover, in accordance with MedDRA, 'withdrawal' is identified in association with the abrupt cessation or reduction in intake of a drug in a habituated person.…”

New/emerging psychoactive substances and associated psychopathological consequences

“…1 Antidepressants Antidepressants emerged as being misused, raising public health concerns on their prescription control policies (Evans and Sullivan, 2014). Bupropion inhibits both the NA and DA reuptake (Schifano and Chiappini, 2018a) and, being a cathinone derivative, presents with stimulant activities (Baumeister et al, 2015;Evans and Sullivan, 2014). It may be consumed orally, insufflated, or injected, with high dosages provoking a 'high' similar to cocaine (Vento et al, 2013).…”

“…Adverse effects range from nasal pain to irritability, agitation, cardiac toxicity, hallucinations and seizures. Vulnerable users are inmates and patients with past histories of substance misuse (Schifano and Chiappini, 2018a) (Table 1). Amitriptyline anecdotally emerged as the most abused among tricyclic antidepressants giving, at high dosages, 'pleasant feelings' and euphoria.…”