Antipsychotic Abuse, Dependence, and Withdrawal in the Pediatric Population: A Real-World Disproportionality Analysis

Abstract

Antipsychotic drugs (APs) aim to treat schizophrenia, bipolar mania, and behavioral symptoms. In child psychiatry, despite limited evidence regarding their efficacy and safety, APs are increasingly subject to off-label use. Studies investigating addictology-related symptoms in young people being scarce, we aimed to characterize the different patterns of AP misuse and withdrawal in children and adolescents relying on the WHO pharmacovigilance database (VigiBase®, Uppsala Monitoring Centre, Sweden). Using the standardized MedDRA Query ‘drug abuse, dependence and withdrawal’, disproportionality for each AP was assessed with the reporting odds ratio and the information component. A signal was detected when the lower end of the 95% confidence interval of the information component was positive. Results revealed mainly withdrawal symptoms in infants (under 2 years), intentional misuse in children (2 to 11 years), and abuse in adolescents (12 to 17 years). Olanzapine, risperidone, aripiprazole, and quetiapine were disproportionately reported in all age groups, with quetiapine being subject to a specific abuse signal in adolescents. Thus, in adolescents, the evocation of possible recreational consumption may lead to addiction-appropriate care. Further, in young patients with a history of AP treatment, a careful anamnesis may allow one to identify misuse and its role in the case of new-onset symptoms.

Multi-omic network analysis identifies dysregulated neurobiological pathways in opioid addiction

“…The network also includes known drugs of abuse ( e.g. , opioids, ethanol, promethazine) and widely prescribed drugs with potential for misuse, including antipsychotics ( e.g., aripriprazole 33,34 ( OPRM1 ), dosulepin 35 ( ADRA1D ), olanzapine 33 ( GABRG3 ), pipamperone 33 ( ADRA1D ), quetiapine 33,36 ( ADRA1D ) and benzodiazepines ( e.g. , alprazolam 37 , lorazepam 38 , temazepam 38 that all target GABRE and GABRG3 ).…”

“…This includes the drug spironolactone (targeting CACNB2 and PGR), which has recently been investigated for treating AUD 30 , and multiple approved antidepressants 31,32 such as amitriptyline (ADRA1D, NTRK2, OPRM1), amoxapine (ADRA1D, GABRE, GABRG3), and esketamine (BDNF, NTRK2). The network also includes known drugs of abuse (e.g., opioids, ethanol, promethazine) and widely prescribed drugs with potential for misuse, including antipsychotics (e.g., aripriprazole 33,34 (OPRM1), dosulepin 35 (ADRA1D), olanzapine 33 (GABRG3), pipamperone 33 (ADRA1D), quetiapine 33,36 (ADRA1D) and benzodiazepines (e.g., alprazolam 37 , lorazepam 38 , temazepam 38 that all target GABRE and GABRG3). A number of opioids are also present in the drug-gene target network based on their characterized effects on OPRM1.…”

Trends and off-label utilization of antipsychotics in children and adolescents from 2016 to 2021 in China: a real-world study

“…Meanwhile, these guidelines have indicated that early use of antipsychotics (APs) could reduce or delay the onset of psychosis. According to the underlying mechanism, Aps are categorized into typical and atypical antipsychotics, also known as first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), for the treatment of schizophrenia, bipolar disorders and other behavioral disorders [8,9]. Compared to FGAs, SGAs have fewer neurological adverse reactions but are associated with a greater risk of metabolic adverse events [10,11].…”